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Long-term enhancement of evoked potentials in raccoon somatosensory cortex following co-activation of the nucleus basalis of Meynert complex and cutaneous receptors. Long-term enhancement of the evoked potential was induced in the primary somatosensory cortex of anaesthetized raccoons after mechanical stimulation of the skin was paired with electrical stimulation of the nucleus basalis of Meynert (NBM). Sets of 4 pulses, 0.5 ms duration at 300 Hz were delivered at 2-s intervals to the basal forebrain 80 ms before the glabrous skin on the 4th digit of the contralateral forepaw was stimulated mechanically. The average waveform of 30 evoked potentials was separated into an initial positive, a negative and a second positive component. During pairing of the skin and NBM stimuli, the area under the initial positive component was smaller than before or after pairing. The negative and second positive waves were unchanged. One minute after pairing, the initial positive wave returned to control values and continued to increase until the end of the experiment 50 min later, at which time it was 300% above control. The negative and second positive waves increased after the pairing to between 130 and 200% and remained at that level for the duration of the experiment. The effective NBM site for stimulation was the area rich in cholinergic neurons corresponding to the NBM. In control animals, repeated stimulation of the skin or NBM alone, or their random, unpaired stimulation together, did not enhance the somatosensory evoked potential. The results suggest that the NBM input enhances the efficacy of cortical responses to cutaneous input and thus may play a role in cortical neuronal plasticity.

Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual and auditory evoked responses during penicillin-induced generalized spike-and-wave activity in cats. In 13 healthy adult cats chronically implanted with parasagittal electrodes applied to the dural surface, curarization was performed and baseline recordings of the visual evoked response (VER), auditory evoked response (AER), and brainstem auditory evoked response (BAER) were made. Following the procedure of Prince and Farrell (1969), the animals were then given intramuscular doses of 300,000 to 500,000 U/kg of penicillin with the subsequent development of diffuse, bilaterally symmetrical, photosensitive spike-and-wave discharges in the EEG from 1 to 1 1/2 hr later and concomitant facial myoclonus, arrest of movement, and "absence-like" staring in non-curarized animals. The VER, AER, and BAER were monitored at 15-min intervals for several hours during which time the VER consistently decreased in amplitude up to the time at which the first spike-and wave bursts could be elicited by photic stimulation, approximately 1 hr after injection, after which all early components (0-200 msec) of the VER were progressively increased from 150 to 300% until spontaneous spike-and-wave bursts were consistently recorded (1 1/2-2 hr). Coincident with this change, a marked increase in late components (200-500 msec) was also observed. Both th early diminution and later augmentation of the VER were equally observable in visual and nonvisual cortex. Changes in the AER were also recorded with the development of this model, and were similar to those of the VER but of a lesser degree. The amplitudes of waves I through V of the BAER were found to increase from 28 to 88% maximal at 1 1/2 hr following penicillin injection. These data and the similarity of this model to human petit mal epilepsy argue against increased inhibitory impulses to the visual system during the ictal discharge being responsible for the subjective loss of visual information during petit mal absence. If the amplitude of the evoked response is directly related to the functional integrity of a sensory system, this suggests that the impairment of sensory input, or absence, during spike-and-wave paroxysm is due to interference with sensory processing rostral to the brainstem ascending auditory pathway, and probably does not occur in primary sensory cortex but rather in cortical or subcortical association tracts.

Frequency analysis of CD4+CD8+ T cells cloned with IL-4. The coexpression of both CD4 and CD8 molecules on T cells occurs in the peripheral blood at a low frequency and can be generated transiently on CD4+ peripheral blood T cells by treatment with lectin which induces CD8 biosynthesis and cell surface expression. We have cloned T cells in a nonselective fashion from normal subjects in the presence of either IL-2, rIL-4 and IL-2, or rIL-4 and have examined the phenotypic expression of CD4 and CD8. The addition of excess rIL-4 increased the expression of CD8 on the surface of CD4+ T cell clones but did not increase CD4 expression on CD8+ T cell clones. There were three patterns of CD4 and CD8 expression observed: high density CD8 with no CD4 expression; high density CD4 with low CD8 expression; or high density CD4 with higher cell surface CD8 expression which was regulated by the presence of rIL-4. CD4+ T cell clones originally cultured in IL-2 and rIL-4 and subsequently grown in IL-2 alone exhibited decreased expression of the CD8 molecule. The increased expression of CD8 did not correlate with NK activity or lectin-dependent cytotoxicity in an antigen independent system. In addition, rIL-4 alone or in combination with IL-2 appeared to accelerate the growth curve of T cell clones as compared to IL-2 alone. These results show that IL-4 can upregulate CD8 expression on CD4+ T cell clones while not effecting CD4 expression on CD8+ T cell clones. As class I MHC is the ligand for the CD8 molecule, expression of CD8 induced by IL-4 on CD4+ T cells may allow for increased nonspecific cell to cell contact during the course of an inflammatory response.

Significance of serum IgM anti-HBc in chronic hepatitis B virus infection. Because of widely differing reports on the significance of IgM anti-HBc in chronic hepatitis B virus (HBV) infection, paired sera and liver biopsies from 49 patients with chronic HBV infection were analysed for serum IgM anti-HBc, HBsAg titre, HBeAg/anti-HBe, HBV DNA, serum aspartate transaminase, intrahepatic HBcAg expression, and liver histology. High levels of IgM anti-HBc, in the diagnostic range of acute hepatitis B (greater than 1.2), were detected in seven patients (14.3%) and a total of 34 patients (69.6%) had an index of more than 0.2. No correlation was found between IgM anti-HBc and the serum markers of active viral replication or HBsAg titre but it correlated significantly with intrahepatic expression of cytoplasmic HBcAg (r2 = 0.165, P = 0.002). IgM anti-HBc also correlated with active liver histology (P = 0.015) but there was a considerable overlap of the IgM anti-HBc index values between the various disease groups, indicating a poor specificity. Serial assessment of IgM anti-HBc in eight patients treated with interferon-alpha (four responders) showed an increase in IgM anti-HBc in three out of four patients corresponding to the e-seroconversion period followed by a drop in IgM anti-HBc levels. However, an increase in IgM anti-HBc was also seen in one non-responder, indicating that this feature is not unique to interferon-alpha responders. These data indicate that serum IgM anti-HBc cannot be used alone as a certain diagnostic measure of HBV replication nor in the prediction of liver histology.

Impedance of intrathoracic airway models during low-frequency periodic flow. The total pulmonary and lower airway impedances of the normal adult lung were simulated from 0.5 to 10 Hz using a distributed parameter model of the complete tracheobronchial tree. The model includes branching asymmetry; distributed representation of gas compliance, inertance, viscous effects, and inertial distortion of velocity profiles; and nonrigid airway walls. The model predicts closely similar resistance and frequency dependence of resistance but substantially greater reactances than observed by Finucane et al. (J. Appl. Physiol. 38: 517--530, 1975). Increases in resistance with frequency could be explained by changes in the distribution of flow among parallel inhomogeneities (47%), inertial distortion of velocity profiles (35%), changes in the serial distribution of flow due to gas compliance (11%), and airway wall compliance (7%). The disparity between measured and simulated reactance is attirbutable to artifact in the previously reported reactance measurement.

Role of pineal melatonin and melatonin-induced-immuno-opioids in murine leukemogenesis. The relationship between the pineal gland, melatonin and melatonin-induced-immuno-opioids with the response of C57Bl/6 mice to A-RadLV induced T cell lymphomas was investigated. Mice were injected at day 0 with A-RadLV and from day 10 they were treated chronically with melatonin 4 mg/kg body weight, naltrexone 1 mg/kg or phosphate buffered saline, throughout the experiment. In another protocol, groups of mice were a) surgical pinealectomized at day-14, b) functional pinealectomized (24:24 hours light) from day -20 and c) sham pinealectomized. At day 0 each group was inoculated intrathymically with A-RadLV. The results show that melatonin accelerated (p < 0.005) leukemogenesis whereas the surgical pinealectomy and the functional pinealectomy delayed it (p < 0.005 and p < 0.01). Moreover, the action of melatonin was blocked by naltrexone (p < 0.005), indicating the involvement of melatonin-induced-immuno-opioids in the development of the lymphomas.

Questionable methods of cancer management. Immuno-augmentative therapy (IAT). "Immuno-augmentative therapy" is a method of cancer management developed by Lawrence Burton, PhD. Dr. Burton states that IAT can control all forms of cancer by restoring natural immune defenses. He claims to accomplish this by injecting protein extracts isolated with processes that he has patented. However, experts believe that the substances he claims to use cannot be produced by these procedures and have not been demonstrated to exist in the human body. He has not published detailed clinical reports, divulged the details of his methods, published meaningful statistics, conducted a controlled trial, nor provided independent investigators with specimens of his treatment materials for analysis. During the mid-1980s, several cases were reported where patients of Dr. Burton developed serious infections following IAT.

Overproduction and purification of the Tn10-specified inner membrane tetracycline resistance protein Tet using fusions to beta-galactosidase. Tetracycline resistance in the Enterobacteriaceae is mediated by a number of genetically related, usually plasmid-borne, determinants which specify an efflux system involving an inner membrane protein, Tet. Attempts to overproduce the Tn10 (Class B)-encoded Tet in Escherichia coli by cloning the structural gene tet downstream of the lambda PL promoter under regulation by temperature-sensitive lambda repressor cI857 were unsuccessful; induction at 42 degrees C resulted in filamentous, non-viable cells containing little detectable overproduction of the protein. However, cells containing tet fused to lacZ were resistant to tetracycline at 30 degrees C and synthesized modest amounts of a large fusion protein when induced at 42 degrees C. Fusion of the N-terminal half or the first 38 amino acids of tet to lacZ did lead to increased production of fusion proteins. Fusions could be purified by size or by LacZ immunoaffinity or substrate-affinity chromatography. In the latter method, selected detergents were required to counteract nonspecific binding of Tet to the adsorbant. Amino acid sequencing of the N-terminus of Tet-LacZ fusion proteins indicated that most molecules were blocked at this terminus. The sequence of an unblocked subpopulation was consistent with that expected from the nucleotide sequence. A collagen peptide linker, genetically placed between tet and lacZ, allowed recovery of purified Tet protein after collagenase treatment of the purified fusion protein.

Cerebral concussion in sport. Management and prevention. This article explains the various stresses (tensile, compressive, and shearing) that can affect the brain, and how they may produce the different types of brain injury. The biomechanical forces and dynamics that produce coup versus contra coup injury are covered, as are the common intracranial athletic head injuries, i.e. concussion and the various intracranial haematomas (epidural, subdural, subarachnoid and intracerebral). Though less common in occurrence, because their outcome is so catastrophic, space is also devoted to the recognition, the treatment and (especially in the latter case) the prevention of the malignant brain oedema syndrome of the adolescent and the second impact syndrome of the adult. A major emphasis of this paper is the recognition of the 3 grades of cerebral concussion and the delineation of clear guidelines as to when it is safe to return to collision sports after sustaining such injuries, for the first, second or third time during a given season. Clear guidelines are also presented as to when to discontinue collision sport competition for the remainder of the season after multiple concussions. Because of the concern for the second impact syndrome, the requirement to never allow an athlete with postconcussion syndrome symptoms to return to competition is emphasised. Also covered is the prevention of head injuries, which sports are at greatest risk, and the need for additional research on the cumulative effects of concussion.

Effects of warning-signal modality on the contingent negative variation (CNV). CNVs were recorded during the S1-S2 interval of a prolonged simple reaction task. In the task, a warning stimulus S1 is followed by an imperative stimulus S2, to which the subject makes a motor response. The differential effects of a visual and an auditory S1 were investigated under two interstimulus interval (ISI) durations (1 and 3 sec). Under the 3 sec ISI condition, the form of the slow negative wave demonstrated clearly a biphasic character: an orientation wave (O wave) following S1 with a peak latency at about 650 msec and an expectancy wave (E wave), which reaches its largest amplitude towards the end of the ISI. Under the 1 sec ISI condition the two components of the CNV are confounded. The O wave had a fronto-central distribution, while the E wave was located precentrally. The O wave was enhanced after an auditory S1, as compared to a visual S1.

Auditory projections to the inferior colliculus of the rat are present by birth. Despite extensive literature on the anatomical organization of the adult mammalian auditory system, the ontogeny of internuclear connections is still obscure. We studied the postnatal development of afferent brainstem connections to the inferior colliculus in rat pups using WGA-HRP and DiI as tracers. At birth, connections to the inferior colliculus from the cochlear nuclei and nuclei of the superior olivary complexes and the lateral lemnisci are present. During successive development, there are no obvious changes in the quantity of labeled neurons or the basic labeling pattern. These results provide evidence that all input connections from auditory brainstem nuclei to the rat's inferior colliculus are established prenatally.

Recovery after cold cardioplegic arrest of isolated blood-perfused hearts excised from non-anesthetized pigs. An isolated blood-perfused pig heart model has been established in order to evaluate the recovery of hearts obtained from slaughterhouse domestic pigs avoiding anesthesia and direct experiments on animals. Eleven hearts subjected to 9 min of normothermic ischemia were infused with cold modified Bretschneider solution. After 180 min of cardioplegic-induced global ischemia (including 9 min of normothermic ischemia) 8 hearts were reperfused for 120 min. Left ventricular function (measured isovolumetrically by means of a balloon, and expressed as developed left ventricular pressure, positive and negative dP/dt) was stable during the whole reperfusion period. Lactate production was abolished after 25 min of reperfusion, while there was a small glucose extraction during the whole reperfusion period. Slight deterioration of the mitochondria was found during the induced cardiac arrest, however, reversing during the reperfusion. Thus, due to the stability of left ventricular function, improved metabolism and ultrastructure during the reperfusion period, the model with no use of laboratory animals, and without any influence of anesthesia, seems to be suitable for testing the pure effect on the performance of the left ventricle of drugs and substrates added to the reperfusate during the reperfusion period.

The role of prostaglandins in the spontaneous motility of the fallopian tube. Spontaneous isometric contractions of the human fallopian tube were measured in vitro. The tubes were obtained during the follicular phase of the menstrual cycle in 16 experiments and during the luteal phase in 23 experiments. The area under the curve and the frequency of spontaneous isometric contractions, together with the amount of prostaglandins E and F produced by the tube, were measured. Using each tissue as its own control, the effects of adding indomethacin or papeverine to the tissue both were assessed. Indomethacin, a prostaglandin synthetase inhibitor, significantly reduced the prostaglandin output without affecting the tubal motility. By contrast, papaverine, which is a smooth muscle relaxant but not an inhibitor of prostaglandin synthesis, significantly reduced both motility and prostaglandin output. It is concluded that prostaglandins do not have a direct role in the regulation of the spontaneous motility of the human fallopian tube.

A retrospective study on the perceived need for and actual use of psychiatric consultations in older medical patients. The authors examined the (under) utilization of the psychiatric consultation service for patients aged sixty to seventy-five who were hospitalized for medical reasons, and explored whether one could retrospectively document and identify a greater need for psychological support than the one reflected in the number of actual consultations requested. Three questions were addressed: 1) the psychiatric consultation rate; 2) the frequency of unrecognized medical, psychiatric, and psychosocial complicating factors; and 3) whether the distribution of these factors differed by gender. Records of 203 consecutively-admitted elderly patients hospitalized on medical wards were reviewed by two experienced general hospital psychiatrists for any indication of medical, psychiatric, and psychosocial risk factors. The frequency of actual psychiatric consultations was also recorded. Three or more risk factors were noted in the records of 36 percent of all patients. Consultation was sought for only 3 percent. Gender differences in type and distribution of risk factors were identified. Indicators and profiles that define probable need for psychiatric consultation were identified and briefly discussed. More well-designed, prospective studies testing these indicators and profiles are needed.

Studies on bacterial cell wall inhibitors. VIII. Mode of action of a new antibiotic, azureomycin B, in Bacillus cereus T. Azureomycin B, a new antibiotic which contains sugar, amino acid and phenol moieties and inhibits Gram-positive bacteria, was found to be a specific inhibitor of peptidoglycan synthesis in bacteria. The antibiotic lysed growing cells of Bacillus cereus T at a concentration of 10 micrograms/ml but did not affect resting cells. Microscopical observation revealed swelling and lysis of the bacterial rods when treated with azureomycin B. The incorporation of [3H]diaminopimelic acid or [14C]glucosamine into acid-insoluble fraction of growing cells of Bacillus cereus T was strongly inhibited in the presence of azureomycin B, but that of [14C]leucine, [3H]thymidine or [3H]uridine were not, at least until 5 minutes after the beginning of the incubation. The antibiotic caused accumulation of a nucleotide precursor in the cells which was identified as UDP-MurNAc-L-Ala-D-Glu-meso-Dpm-D-Ala-D-Ala. Thus the site of action was suggested to lie between this nucleotide and peptidoglycan in the pathway of peptidoglycan synthesis.

Role of TGF-beta 1 in experimental glomerulonephritis. Glomerulonephritis is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli. We have shown that TGF-beta 1 is unique in regulating the production of proteoglycans and matrix glycoproteins by glomerular cells in vitro. In an experimental model of glomerulonephritis in rats we found increased proteoglycan and fibronectin synthesis by cultured nephritic glomeruli, which was greatly reduced by addition of antiserum to TGF-beta 1. Conditioned media from glomerular cultures induced elevated proteoglycan synthesis when added to normal cultured mesangial cells. This stimulation was blocked by addition of TGF-beta antiserum. Glomerular histology showed mesangial matrix expansion with a time course that roughly paralleled that of the elevated proteoglycan synthesis by the nephritic glomeruli was increased. Administration of anti-TGF-beta 1 at the time of induction of glomerulonephritis suppressed the elevated extracellular matrix production and dramatically attenuated histological manifestations of the disease. Our results provide direct evidence for a causal role of TGF-beta 1 in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.

The value of helicopter transportation for trauma patients. Helicopters have been used for the evaluation of civilian casualties since the 1960s. This trend has been increasing and a number of helicopter emergency services have now commenced in the UK. Despite these developments, little attention has been paid to their exact role, and the potential benefits to patients. In addition, the costs of such services are high, and the risks to patients and staff from air accidents are considerable. Similar or improved results may be obtained through the use of more cost-effective ground-based units. Judicious placement of both helicopter emergency services and land-based 'flying squads' in an integrated accident service may contribute usefully to better care of patients. However, enthusiasm for helicopters should not lead to a waste of resources and should be accompanied by careful consideration, planning and audit of their use.

Dorsal raphe stimulation produces inhibitory effect on trigeminal nucleus neurons. Inhibitory effects of conditioning stimulation of the dorsal raphe nucleus (DR) on the neuron activity in the rostral part of spinal trigeminal nucleus (STN) were studied in cats for the purpose of comparison with the inhibition induced by locus coeruleus (LC) stimulation. DR conditioning stimulation reduced the orthodromic field potential in STN elicited by inferior alveolar nerve stimulation, and enhanced the antidromic field potential in the trigeminal nerve evoked by STN stimulation; but the inhibitory effects of DR stimulation were considerably weaker than those of LC stimulation. In tracking experiments near the raphe nucleus, conditioning stimulation of DR itself produced the most pronounced decrease in the STN field potential. Orthodromic spike number of STN relay neurons was significantly reduced by DR conditioning stimulation; however, the threshold for the conditioning stimulus to the DR was much higher than that to the LC. Antidromic spike generation of the STN neurons was unaltered by conditioning stimulation of both DR and LC. DR stimulation elicited a field potential in STN, which followed high frequency stimuli up to 200 HZ. A single fiber action potential was also obtained in STN by DR stimulation. STN stimulation produced a field potential in DR, which followed high frequency stimuli. It is suggested from these findings that conditioning stimulation of DR produces a direct inhibition of transmission in STN neurons; however, this stimulation has less effect on these neurons than does stimulation of the LC.

Frozen-section analysis of allograft renal biopsy specimens. Reliable histopathologic data for rapid decision making. Rapid tissue diagnosis during acute events associated with renal transplantation is often necessary to permit immediate decisions regarding initiation or modification of therapy. To achieve this, we performed frozen section analyses with cryoprotected alcoholic Bouin's-fixed tissue, which permits evaluation within 2.5 hours. During a 30-month period, 200 allograft biopsies were performed; 68 frozen sections were obtained when deemed necessary by the clinical team. We compared frozen-section diagnoses with those following regular evaluation of the biopsy specimen. Agreement in diagnoses occurred in 61 (88.4%) of 69 specimens. Acute rejection was the dominant diagnosis (n = 39); others were acute tubular necrosis, cyclosporine toxicity, chronic rejection, and infection. Major misdiagnoses included acute vascular processes (three capillary and/or venous thromboses and one vascular inflammation); acute cellular rejection was missed in two cases, reflecting a sampling error. Secondary diagnoses not of immediate therapeutic importance were detected in seven frozen sections and missed in nine. These included chronic glomerulopathies, nephrosclerosis, and mild chronic rejection. Although acute vascular phenomena may be difficult to recognize in frozen sections, we conclude that allograft biopsy frozen-section analysis is a valuable part of the care of transplant recipients.

Transcriptional regulation of the Tn5276-located Lactococcus lactis sucrose operon and characterization of the sacA gene encoding sucrose-6-phosphate hydrolase. The Lactococcus lactis sucrose operon was located on the conjugative transposon Tn5276 and the nucleotide sequence of the sacA gene, encoding sucrose-6-phosphate hydrolase, and its surrounding regions was determined. Northern blot analysis showed that the sucrose operon contains two divergent transcriptional units of 3.2 and 3.6 kb, the expression of which is considerably higher in cells grown on sucrose than in cells grown on glucose. This was confirmed by primer extension studies which demonstrated that transcription is initiated at two sucrose-inducible promoters with a back-to-back organization. The 3.2-kb transcriptional unit includes the sacB gene which most probably encodes the sucrose-specific enzyme II of the phosphotransferase system, and may contain the gene encoding fructokinase. The 3.6-kb transcriptional unit includes genes sacA and sacR. The protein encoded by the sacR gene is likely to be involved in the regulation of the sac operon expression, since its deduced N terminus is homologous to helix-turn-helix DNA-binding domains found in several regulatory proteins.

Neurology in Islamabad Children's Hospital--present status and problems. Pediatric neurologic disease is still progressive health problem in developing countries, Disorders of mental and motor development (34.8% of total 5234 neurological patients in 1988-89), seizure disorders (25.8%) and infections of the nervous system (18.9%) are the most common neurological problems in the Islamabad Children's Hospital (ICH), Pakistan. These figures differ from those in children's Hospitals in developed countries such as Japan. ICH needs to establish a good neurology department with better physiotherapy and rehabilitation centre, a workshop and a facilitated physiological laboratory. The global situation can be controlled by improving the basic life and fundamental factors to improve the hygiene and general health status of mothers and their children. The provision of rural rehabilitation services is also needed. Also international technical cooperation and support would be helpful.

Metabolic deficiencies and SIDS. The role of inherited metabolic defects in SIDS is controversial: some workers think that they may account for the cause of death in about 10% of cases. Many maintain that this is a gross overestimate, but it cannot be denied that the sudden onset and rapid deterioration known to occur in some metabolic disorders during the first year of life can mimic SIDS. This may remain undetected unless postmortem material is examined in specialist centres with individual metabolic disorders in mind. Defects in energy metabolism and the maintenance of glucose homeostasis frequently show this pattern of presentation precipitated by minor clinical infection. These disorders include the glycogen storage disorders, gluconeogenic enzyme defects, and the defects of fatty acid oxidation. Several reports have appeared since 1984 linking fatty acid oxidation defects with SIDS. Estimates of their prevalence vary, due partly to methodological heterogeneity and partly to the limited size of individual studies which have not permitted adequate statistical analysis. Nevertheless, the lack of adequate information has not precluded a great deal of debate. Over the past seven years a group in Sheffield has studied the occurrence of these defects in SIDS using three distinct approaches: retrospective analysis of SIDS cases, prospective analysis of SIDS cases, prospective analysis of urine obtained from siblings of SIDS cases during the first week of life. The result of these studies would suggest that the contribution to SIDS made by medium chain acyl CoA dehydrogenase deficiency may be in the region of 1%. Additional related metabolic disorders may account for a further as yet undefined small percentage. The eventual resolution of some of these uncertainties may be provided by harmonizing the results of existing studies and by DNA analysis of materials obtained at necropsy in SIDS cases.

Acute lung injury induced by phospholipase A2. Structural and functional changes. On the basis of the observation that serum levels of phospholipase A2 (PLA2) are elevated in pancreatitis and systemic sepsis, and the association of these conditions with the subsequent development of acute lung injury, the present investigation examined the structural and physiologic consequences of intratracheal administration of PLA2 to adult male rats. Rats received direct intratracheal instillation of either control vehicle or 40,000 units/kg of PLA2 repurified from Naja naja venom. Animals treated with PLA2 showed higher cumulative mortality (33% versus 0%, n = 79; p less than 0.01) than did their control littermates. The PLA2-treated animals showed histologic evidence of acute lung injury characterized by interstitial and alveolar edema, accumulation of inflammatory cells, and alveolar wall thickening, which reached maximal severity 48 h after enzyme instillation. Forty-eight hours after PLA2 administration experimental animals had lower arterial oxygen tensions (73.9 +/- 7.66 mm Hg versus 96.7 +/- 2.52 mm Hg, mean +/- SEM; p less than 0.01), higher alveolar-arterial oxygen gradients (35.3 +/- 6.3 mm Hg versus 18.8 +/- 1.42 mm Hg, p less than 0.01), and higher wet-dry lung weight ratios (5.08 +/- 0.26, mean +/- SEM, n = 7 versus 3.29 +/- 0.08, n = 3; p less than 0.002) than did control animals. Lung lavage from experimental animals 48 h after PLA2 instillation showed increased total cell counts [(26.6 +/- 5.04) x 10(6) cells versus (4.69 +/- 1.48) x 10(6) cells; p less than 0.01], an increased percentage of neutrophils (34.2 +/- 4.6% versus 1.25 +/- 0.25%, mean +/- SEM; p less than 0.01), and increased protein concentrations in lavage fluid (0.38 +/- 0.06 mg/ml, mean +/- SEM, n = 4 versus 0.27 +/- 0.02 mg/ml, n = 5; p less than 0.05). The histologic and physiologic abnormalities had largely resolved by 240 h. These results suggest that PLA2 may be a potent mediator of lung inflammation and that intratracheal administration of PLA2 to adult rats may provide a useful experimental model of acute lung injury.

The relationship between pituitary-gonadal function and sexual behavior in healthy aging men. Few studies have assessed the role of pituitary and gonadal hormones on age-related changes in sexual behavior in healthy men. We conducted a retrospective and prospective evaluation of sexual function and behavior in 77 healthy married men aged 45 to 74 years. The subjects were studied in the sleep laboratory for four nights with the last night devoted to sequential blood sampling every 20 minutes. Significant age-related decreases in sexual desire, sexual arousal and activity, and increases in erectile problems were noted. Aging was negatively correlated with bioavailable testosterone (bT), was positively correlated with luteinizing hormone (LH), and was not related to total testosterone, estradiol, and prolactin. Bioavailable testosterone, and the ratio of bT over LH showed a close association with several sexual behavior dimensions while total testosterone, estradiol, and prolactin demonstrated few or no behavioral relationships. The age-related effect of bT was, however, a more important determinant of the reported behavioral differences than were the effect of bT independent of age. There was no evidence that changes in circulating hormones contribute to erectile disorders in healthy aging men.

The protein phosphatase inhibitor, okadaic acid, inhibits phosphatidylcholine biosynthesis in isolated rat hepatocytes. There is evidence that phosphatidylcholine (PC) biosynthesis in hepatocytes is regulated by a phosphorylation-dephosphorylation mechanism. The phosphatases involved have not been identified. We, therefore, investigated the effect of okadaic acid, a potent protein phosphatase inhibitor, on PC biosynthesis via the CDP-choline pathway in suspension cultures of isolated rat hepatocytes. Okadaic acid caused a 15% decrease (P less than 0.05) in [Me-3H]choline uptake in continuous-pulse labeling experiments. After 120 min of treatment, the labeling of PC was decreased 46% (P less than 0.05) with a corresponding 20% increase (P less than 0.05) in labeling of phosphocholine. Cells were pulsed with [Me-3H]choline for 30 min and subsequently chased for up to 120 min with choline in the absence or presence of okadaic acid. The labeling of phosphocholine was increased 86% (P less than 0.05) and labeling of PC decreased 29% (P less than 0.05) by 120 min of chase in okadaic acid-treated hepatocytes. The decrease of label in PC was quantitatively accounted for in the phosphocholine fraction. Incubation of hepatocytes with both okadaic acid and CPT-cAMP did not produce an additive inhibition in labeling of PC. Choline kinase and cholinephosphotransferase activities were unaltered by treatment with okadaic acid. Hepatocytes were incubated with digitonin to cause release of cytosolic components. Cell ghost membrane cytidylyltransferase (CT) activity was decreased 37% (P less than 0.005) with a concomitant 33% increase (P less than 0.05) in released cytosolic cytidylyltransferase activity in okadaic acid-treated hepatocytes. We postulate that CT activity and PC biosynthesis are regulated by protein phosphatase activity in isolated rat hepatocytes.

Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). Mice carrying mutations at the Sl (steel) and W (dominant white spotting) loci develop abnormalities on 3 migratory embryonic stem cell populations: hematopoietic stem cells, neural crest-derived melanocytes, and primordial germ cells. Transplantation experiments have indicated that the Sl locus affects the microenvironment where stem cells migrate, proliferate, and differentiate, while the W locus affects the migratory cells themselves. The Sl locus encodes for a multipotent growth factor known as stem cell factor. The W locus encodes the c-kit protein tyrosine kinase receptor whose ligand is the stem cell factor. We have investigated the incidence and organ distribution of experimental metastases after systemic intra-arterial injection of B16-G3.26 melanoma cells into mutant Sl/Sld and W/Wv mice. Both mutant mouse strains had a markedly lower incidence of ovarian metastases when compared with their congenic +/+ mice. In contrast to the rare colonization of the ovaries, Sl/Sld and W/Wv mice developed metastases in the myocardium, kidney, and stomach--anatomic sites that were infrequently or never affected in their congenic nonmutant mice. The only organs in which the average number of metastatic colonies differed between Sl/Sld and W/Wv mice were the bone marrow and kidneys. The average number of colonized bones per mouse in the Sl/Sld group was 5.0 +/- 3.1 (SD), compared with 12.7 +/- 5.3 in the W/Wv group. The average number of metastatic nodules in the kidneys of Sl/Sld mice was 24.6 +/- 9, while W/Wv mice had 15.5 +/- 2.5. Mutant mice with multiple metastatic nodules in the kidneys, heart, and stomach were also found to have forestomach papillomas, an enlarged duodenum, kidney abnormalities, and small body size. The results of this study provide useful information on potential mechanisms of interaction of metastatic cells with their target organs, and suggest that there are additional organ defects associated with the mutations in the Sl and W loci. They also document the importance of mutant mice in metastasis research.

Sequential measurement of beta 2-microglobulin levels, p24 antigen levels, and antibody titers following transplantation of a human immunodeficiency virus-infected kidney allograft. A renal allograft recipient developed symptoms suggestive of AIDS. Serological studies revealed that the donor was positive for human immunodeficiency virus (HIV). Retrospective testing of stored sequential serum samples showed that the recipient was negative for HIV pretransplant; anti-p24 and anti-p41 antibodies appeared 10 and 49 days posttransplant, respectively. The recipient's serum beta 2-microglobulin levels were elevated 14 days posttransplant, with normal renal function, 35 days before the detection of anti-p24 antibody. p24 Antigen was detected for the first time 21 days posttransplant. In addition to p24 antigen, elevated serum beta 2-microglobulins may be a useful marker for HIV infection prior to seroconversion.

Formal genetics of Fanconi's anemia. The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature. 1. The result of segregation analysis is compatible with the hypothesis of a simple autosomal recessive mode of inheritance. 2. The number of sporadic cases is not greater than expected. 3. Among the affected siblings in the sibships analyzed, males are somewhat more frequent than females. However, this sex difference is also found among the unaffected siblings, and it is not statistically significant. 4. Contrary to assertions made in the literature, there is no clustering of affected in the sequence of siblings, no maternal age effect, and no preference of higher birth orders. 5. A high intrafamilial correlation for age at onset, and (very probably) number and severity of malformations points to genetic heterogeneity. Apart from the standard type, an especially mild type with late onset, few malformations, and a relatively benign course seems to exist. Its counterpart is possibly an especially severe type with early onset, many malformations, and a malignant course. However, definite conclusions on the special character of this heterogeneity will require application of additional methods.

Characterization of multiple forms of phosphoinositide-specific phospholipase C from bovine aorta. Three forms (I, II and III) of phospholipase C were separated from the cytosol of bovine aorta by chromatography on Blue Sepharose. All three forms showed an increase of enzyme activity when free Ca2+ in the assay was raised between 40 microM and 9 mM. The pH optimum was in the range of 6.0 to 6.5 for each subtype. Marked differences in thermostability were found when the three enzyme forms were pre-incubated at 50 degrees C prior to the assay. All three forms were able to hydrolyse phosphatidylinositol as well as phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate. In contrast, when phosphatidylcholine was used as substrate, no enzyme activity was observed. Spermine and spermidine, but not putrescine, were able to stimulate form I and III; neomycin sulphate inhibited all three subtypes.

Structure of the gene encoding human casein kinase II subunit beta. Casein kinase II (CKII) is a ubiquitous serine/threonine protein kinase with numerous key functions in cell metabolism and growth. The human CKII has a tetrameric structure; two catalytic subunits (alpha and alpha') form the holoenzyme together with two presumably regulatory subunits (beta). The gene encoding CKII subunit beta was isolated from human genomic DNA and analyzed for its primary structure using exclusively nonradioactive procedures. The gene was found to span 4.2 kilobase pairs and to be composed of seven exons. Exon sizes range from 76 (exon 5) to 329 base pairs (bp) (exon 1), intron sizes from 145 (intron V) to 965 bp (intron II). All exon-intron junctional sequences conform to the canonical GT-AG rule. Primer extension analysis determined three transcription initiation sites, at 951, 919, and (minor) 840 bp upstream of the translation start site. The translation start is located early in the second exon; exon 1 is untranslated. The 3'-cleavage/polyadenylation signal sequence (AA-TAAA) is in the last exon at position 4173 bp relative to the first transcription initiation site. The coding sequence for CKII beta comprises 648 nucleotides identical to the published CKII beta-cDNA sequence (Jakobi, R., Voss, H., and Pyerin, W. (1989) Eur. J. Biochem. 183, 227-233). The upstream promoter region of the CKII beta gene contains multiple potential gene regulatory sequence elements, noticeable DNA structures, and the characteristics of a housekeeping gene (more than one transcription initiation site, lack of a TATA-box, presence of a CpG island, occurrence of multiple GC boxes and of nonstandard positioned CCAAT boxes). The CKII beta gene promoter shares common features with that of mammalian protein kinases and is closely related to the regulatory subunit gene promoter of cAMP-dependent protein kinase.

Auditory lateralization in monkeys: an examination of two cues serving directional hearing. In assigning binaural ongoing time differences (phase) as the cue for localization of low frequencies, and binaural intensity differences as the cue for localization of high frequencies, the duplex theory has successfully accounted for human directional hearing of tones. Sensitivity of monkeys to these cues was examined in two experiments. The dependencies on frequency of interaural intensity difference thresholds (lateralization experiment I) and time difference thresholds (lateralization experiment II) were determined behaviorally on three monkeys (M. nemestrina). The range of frequencies was from 125 Hz to 8 kHz in experiment I and from 250 Hz to 2 kHz in experiment II. The results indicate that the duplex theory is applicable to monkeys. However, monkeys are less sensitive than man to both binaural cues. The shortest time disparity monkeys discriminate is 42 microseconds at 1.5 kHz and the smallest intensity difference is 3.5 dB at 500 Hz. Good agreement between the present findings and localization measurements [C. H. Brown et al., J. Acoust. Soc. Am. 63, 1484-1492 (1978)] suggests: (a) that monkeys utilize time disparity cues through higher frequencies than man; and (b) that inaccurate localization by monkeys at high frequencies reflects decreasing sensitivity to interaural intensity cues.

An adjustable collimator for stereotactic radiosurgery. Stereotactic radiosurgery utilizing a linear accelerator is now carried out using small non-coplanar beams to produce a high-dose volume that is approximately spherical in shape. It is desirable to shape the high-dose region so that it is similar to the target volume thereby reducing the amount of healthy tissue irradiated by a high dose. An adjustable collimator has been developed that can be employed to control the target volume height and diameter. Based on film dosimetry and measurements made with a small parallel-plate ionization chamber it was determined that the beams produced by the collimator have properties that make them suitable for radiosurgery. The basic dosimetry parameters (output factors and tissue maximum ratios, TMR) needed for patient treatment were evaluated. It was found that the diameter and length of the high-dose region produced by the patient rotation method are related to the light-field size at 100 cm from the x-ray target. A more favourable dose distribution was found for the adjustable collimator as compared to treating the same volume by use of the two-target method.

Addition of protease inhibitors to culture medium of neuroblastoma cells induces both neurite outgrowth and phosphorylation of microtubule-associated protein MAP-1B. The addition of two synthetic peptides with antiprotease activity to the culture medium of mouse neuroblastoma cells results in the promotion of neurite outgrowth. One of these peptides has a sequence corresponding to the reactive center of protease nexin-1 and inhibits both trypsin and thrombin. Its effect on neuroblastoma cells is similar to that found on serum withdrawal from the culture medium, giving rise to cells with one or two long neurites, and is reversed upon the addition of thrombin to the culture medium. The sequence of the other peptide is present in one of the precursor proteins of the main component of the amyloid plaques of Alzheimer's disease patients' brains, and corresponds to protease nexin-2. It can inhibit trypsin but fails to inhibit thrombin at low doses. Its effect on neuroblastoma cells is slightly different from that observed after serum deprivation, as a significant proportion of stellate cells, with short and branched neurites, is observed. An increase in the phosphorylation of microtubule-associated protein MAP-1B, which accompanies neurite outgrowth induced by serum deprivation, is also observed upon addition of the two antiprotease synthetic peptides, although the nexin-2 (amyloid) peptide induces a less marked increase in phosphorylated MAP-1B than does the nexin-1 peptide. These results may be correlated with the different antiprotease activities of both synthetic peptides, thus suggesting a role for a balance between trypsin-like and thrombin-like proteases and their inhibitors in eliciting neurite outgrowth under normal and pathological conditions.

Gas-solid chromatographic determination of moisture in lyophilized pharmaceutical products. A gas-solid chromatographic procedure is described for the analysis of low levels of moisture in individual lyophilized vials of pharmaceutical products. Dry ethanol, which contains methanol as the internal standard, is injected through the septum of the vial to dissolve the lyophilized contents. An aliquot of this solution is then withdrawn and injected onto a Porapak QS column at 110 degrees C where the components are separated and detected using thermal conductivity detection. A solvent blank correction allows quantitation of the water in the individual vial. The method is conveniently applied to samples containing as little as 50 microgram water/vial, and as many as 25 vials can be assayed/day. A simple technique is also described for removing water from the ethanol solvent to less than 100 ppm, using a molecular sieve.

Dissociation, cross-linking, and glycosylation of the coated vesicle proton pump. In order to refine further our structural model of the coated vesicle (H+)-ATPase (Arai, H., Terres, G., Pink, S., and Forgac, M. (1988) J. Biol. Chem. 263, 8796-8802), we have extended our structural analysis to identify peripheral and glycosylated subunits of the pump as well as to identify subunits which are in close proximity in the native (H+)-ATPase complex. Treatment of the purified, reconstituted (H+)-ATPase with 0.30 M KI in the presence or absence of ATP or MgATP results in the release of the 73-, 58-, 40-, 34-, and 33-kDa subunits, leaving behind the 100-, 38-, 19-, and 17-kDa subunits in the membrane. Because the former group of polypeptides is released from the membrane in the absence of detergent, they correspond to peripheral membrane proteins. To determine which subunits are in close proximity, cross-linking of the purified (H+)-ATPase was carried out using the cleavable, bifunctional amino reagent 3,3'-dithiobis(sulfosuccinimidylpropionate) followed by two-dimensional gel electrophoresis. These studies indicate that contact regions exist between the 73- and 58-kDa subunits as well as between the 17-kDa subunit and the 40-, 34-, and 33-kDa subunits. To test for glycosylation of the (H+)-ATPase, the detergent-solubilized complex was treated with neuraminidase followed by electrophoresis and blotting using a peanut lectin/horseradish peroxidase conjugate. Galactose-inhibitable staining of the 100-kDa subunit, together with affinity chromatography of the intact (H+)-ATPase on peanut lectin agarose, indicates that the 100-kDa subunit is glycosylated, most likely at a site exposed on the luminal side of the membrane. These results, together with those presented in the preceding paper (Adachi, I., Arai, H., Pimental, R., and Forgac, M. (1990) J. Biol. Chem. 265, 960-966), were used in the construction of a refined model of the coated vesicle (H+)-ATPase.

[Serum lipid and apolipoprotein levels in patients with chronic pancreatitis]. Serum lipid and apolipoprotein (apo A-I, A-II, A-IV, B, C-II, C-III, E and H) levels were determined in 26 patients with chronic pancreatitis without complications such as liver disease or diabetes mellitus. These patients were divided into two groups, CP-I (n = 16) and CP-II (n = 10), according to the clinical criteria for chronic pancreatitis. HDL-cholesterol and apo A-I levels in CP-I and CP-II groups significantly decreased compared to those in sex- and age-matched healthy controls (p less than 0.05), whereas there were not significant differences in triglyceride and total cholesterol levels between these groups and controls. On the other hand, apo A-IV levels in CP-I and CP-II were 7.1 +/- 1.0 mg/dl and 8.3 +/- 1.5 mg/dl, respectively and these values were significantly lower than 11.2 +/- 1.8 mg/dl in controls (p less than 0.001). In this study, the serum lipids apparently showed normal levels in patients with chronic pancreatitis who had no severe complication, and the markedly low apo A-IV levels in these patients were considered to be mainly due to the decrease of lipid absorption from the intestine.

The distribution of the DHFR genes in trimethoprim-resistant urinary tract isolates from Taiwan. Between July 1987 and June 1989, 1054 urinary isolates of enterobacteria from Kaohsiung, Taiwan were studied for their trimethoprim resistance. Trimethoprim resistance was defined as MIC greater than 4 micrograms/ml and high-level resistance by MIC greater than 1000 micrograms/ml. The incidence of trimethoprim resistance increased from 33.6% in 1987 to 42.1% in 1989. Among the resistant strains studied, 90% were resistant to high levels of trimethoprim. An increase in the proportion of resistant strains (33.9-46.3%) exhibiting high-level non-transferable trimethoprim resistance was noted. The distribution of the dihydrofolate reductase (DHFR) genes by colony hybridization in 374 trimethoprim-resistant isolates revealed the presence of type I and type V DHFR genes in most of these isolates (45.4% and 10.4% respectively). Type I was predominant in Escherichia coli whereas type V was frequently seen in Enterobacter spp. None showed homology with the type II and type III DHFR probe DNA. In addition, transposon Tn7 was present in 7.8% of 374 trimethoprim-resistant enterobacteria.

Effect of Caralluma tuberculata on the cytological and biochemical changes induced by cyclophosphamide in mice. Treatment with Caralluma tuberculata extract induced complex biochemical and cytological changes in mice. Its cytotoxicity in the bone marrow cells of mice was comparable with that of the standard drug cyclophosphamide (CP); however, unlike CP, C. tuberculata was not clastogenic (as shown by the micronucleus assay). A dose-dependent decrease in the RNA content of liver and testes was produced by C. tuberculata treatment whereas there was no effect on the content of nucleic acid and protein in the brain. In the extract-treated animals there was a significant and dose-dependent increase in the DNA content of the liver, with a negligible effect on the protein content. Combined treatment with C. tuberculata and CP showed that C. tuberculata diminished the effect of CP on DNA levels; however, RNA levels were further suppressed, resulting in increased cytotoxicity. Pretreatment with C. tuberculata extract significantly reduced the clastogenicity of CP. These results indicated the involvement of different phytoconstituents acting by different routes.

Hormonal changes and mood in the puerperium. This investigation is an attempt to test the common supposition that postpartum emotional disturbance is related to hormone changes. A group of 27 normal pregnant women were assessed three times before delivery and sixteen times in the six weeks following delivery. During the first two interviews baseline data on personality and other personal variables were obtained. On each occasion blood was taken and three measures of clinical status and mood were completed. Plasma LH, FSH, total oestrogen and progesterone results are presented in detail and the results of prolactin assays mentioned more briefly. An attempt to correlate hormone findings and clinical findings is described. This failed to produce any strong evidence that hormones are related to mood at this time, although hormone changes were correlated weakly with a few specific symptoms. Some of the unexpected clinical findings and technical difficulties of the study are discussed, with special reference to possible further research in this area.

Theoretical conversion yields for penicillin synthesis. The efficiency of conversion of the carbon-energy source to product is of primary importance in many fermentation processes. In order to assess the efficiency of a process, one must know how close the actual conversion yield is to the theoretical maximum. Theoretical conversion yields are useful, therefore, as guides in improving a process. This knowledge is particularly important today because the cost of raw materials is rapidly rising. In this study, the biochemical pathway of penicillin synthesis was used to estimate the theoretical yield of penicillin from glucose, ammonia, and sulfate. These values are compared with experimental data from the literature. An analysis of the role of glucose in the synthesis of cell mass and penicillin and in the maintenance of cells makes it possible to assess the efficiency of carbon-source utilization and to direct further advances in penicillin fermentations.

Androgen receptor and the testes influence hypertension in a hybrid rat model. The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic acid level in cellular lipids determines the amount of prostaglandins synthesized during cell growth in tissue culture. Methylcholanthrene transformed mouse fibroblast cells can be induced to synthesize prostaglandins by a short term incubation with various vasoactive agents including serum, bradykinin and thrombin or in response to mechanical detachment from the culture dish. The ability of the cells to synthesize prostaglandins upon stimulation changes during growth of the culture on the dish; the response is maximal on the first day after inoculation and decreased sharply thereafter. Feeding of the cells with fresh growth medium enhances prostaglandin production induced by all stimuli. The difference in the cell response during growth is probably not due to change of prostaglandin synthetase activity since the specific enzyme activities assayed with microsomal preparations of cells harvested from the first and third day culture are similar. However, analysis of the cellular content of arachidonic acid after saponification of the total lipid extract of cells harvested at different days of growth reveals that the level of arachidonic acid per cell during growth is parallel to the response to stimuli. It is maximal on the first day and decreases sharply on the second day and stays low on the third day. Our study suggests that the level of arachidonic acid in the cell governs the extent of prostaglandin synthesis upon stimulation.

Phospholipid binding and self-association of the major apoprotein of human and baboon high-density lipoproteins. The purpose of this study was to establish a relationship between self-association and phospholipid binding of the human and the baboon apoA-I protein. The enthalpy changes on binding dimyristoyl lecithin and lysolecithin to either the human or the baboon native apoA-I protein were measured in a microcalorimeter. An endothermal process, most pronounced for the human apoprotein, was observed at low phospholipid levels. At higher phospholipid to protein ratios the binding was exothermal. Gel filtration experiments on Sephadex G-200 showed that the native apoprotein of both species consists of dimers and tetramers. The baboon native apoA-I protein contained a higher amount of dimers. After preincubation of the apoA-I protein with lysolecithin, the enthalpy changes measured on subsequent binding of dimyristoyl lecithin were shifted towards more exothermal values compared to the curve for the native apoprotein. The amplitude of this shift corresponds to that of the endothermal process observed on binding dimyristoyl lecithin to the native apoprotein. This process was attributed to a phospholipid-induced disaggregation of the apoA-I protein. Gel filtration data showed a decreased extent of aggregation in the apoA-I protein preincubated with lysolecithin. This sample consisted exclusively of dimers. Ultracentrifugal flotation of the complexes formed between the apoA-I protein, and respectively dimyristoyl lecithin and sphingomyelin indicated that preincubation with lysolecithin increased the extent of complex formation. These results suggest that the dimeric form of the apoA-I protein possesses the highest affinity for phospholipids. Any dissociation of higher polymers enhances the phospholipid-binding capacity of the human and the baboon apoA-I protein.

Meningococcal carriage and vaccination in army recruits in Italy. The effect of Neisseria meningitidis group A and C polysaccharide vaccine on nasopharyngeal carriage was studied in the training center for army medical officers in Florence. Nasopharyngeal swabs were cultured for N. meningitidis at the time of vaccination (one week after entry to service) and again seven weeks later in a follow-up cohort of 171 men. During the two surveys the overall carriage did not showed significant difference (respectively 16% and 12%); while the percentage of isolates belonging to the serogroup C showed a significant reduction from 6% to 0.6% (P less than 0.01). No increased prevalence of meningococci belonging serogroups other than A or C was observed during the two surveys. The cumulative carriage was 20%. Out of the 35 carriers during the whole study period, only 5 (14%) belonged to the same serogroup. These findings show that meningococcal vaccine may inhibit the nasopharyngeal carriage of group specific meningococci in army recruits.

A comparison of cryptophytan phycocyanins. The spectroscopically different phycocyanins present in the type strain of Hemiselmis virescens, Millport 64, and in a second strain of this cryptophytan species, Plymouth 157, have been purified and compared. They are similar in native molecular weight and in subunit structure, both containing alpha and beta subunits with molecular weights of approximately 10000 and 19000 respectively. However, they do not have the same chromophore composition. Both subunits of the phycocyanin of Plymouth 157 contain two bilins with absorption maxima at 600 and 660 nm, respectively. Only the beta subunit of Milllport 64 carries these chromophores; its alpha subunit bears another chromophore, with absorption maxima at 368 and 694 nm. The spectroscopic differences between the two native phycocyanins can be entirely accounted for by their differing chromophore compositions. The phycocyanin of Millport 64 is the only biliprotein so far described which contains three chemically different chromophores.

Possible involvement of different GTP-binding proteins in noradrenaline- and thrombin-stimulated release of arachidonic acid in rabbit platelets. Noradrenaline (NA) stimulated the release of arachidonic acid (AA) from the [3H]AA-labelled rabbit platelets via alpha 2-adrenergic receptors, since the effect of NA was inhibited by yohimbine. The stimulatory effect of NA in digitonin-permeabilized platelets was completely dependent on the simultaneous presence of GTP and Ca2+. The NA- and thrombin-stimulated releases of AA were markedly decreased by the prior ADP-ribosylation of the permeabilized platelets with pertussis toxin. Antiserum directed against the pig brain Go (a GTP-binding protein of unknown function), recognizing both alpha 39 and beta 35,36 subunits, but not alpha 41, of pig brain, reacted with 41 kDa and 40 kDa bands, with not one of 39 kDa, in rabbit platelet membranes. Anti-Go antiserum inhibited guanosine 5'-[gamma-thio]triphosphate-, A1F4(-)-, NA- and thrombin-stimulated AA releases in the membranes. Although the effect of thrombin was inhibited by low concentrations of anti-Go antiserum, high concentrations of the antiserum was needed for inhibition of the NA effect. Antiserum directed against the pig brain G1 (inhibitory G-protein), recognizing both alpha 41 and beta 35,36 subunits, but not alpha 39, of pig brain, reacted with the 41 kDa band in platelets. Anti-G1 antiserum inhibited only the effect of NA. Reconstitution of the platelet membranes ADP-ribosylated by pertussis toxin with Go, not Gi, purified from pig brain restored the thrombin-stimulated release of AA. In contrast, reconstitution of those membranes with Gi, not Go, restored the NA-stimulated release of AA. These results indicate that different GTP-binding proteins, Gi- and Go-like proteins, may be involved in the mechanism of signal transduction from alpha 2-adrenergic receptors and thrombin receptors to phospholipase A2 in rabbit platelets.

Treatment of comatose patients by mechanical hyperventilation. In case of cranial trauma, early respiratory troubles either of central or peripheral origin often accelerate the deterioration of the neurological situation. The different values of PCO2, PO2, pH and alcaline reserve measured on samples of CSF in comatose patients prove the central acidosis related to metabolic and vascular disorders in the damaged areas. Our results confirm the correlation between the importance of this disturbances and the severity of the trauma. It is thus necessary to insure patients of satisfactory respiration conditions. The tracheobronchial cleansing is applicable to intubated or tracheotomized patients by an instillation of 5ml of simple or bicarbonated physiological serum 4 to 6 times a day, followed by repeated aspirations and associated to a preventive endotracheal instillation of 80 mg of Gentamycin 4 times a day. Moreover we use controlled respiration which does not modify the gazometric parameters in the CSF but which assures patients a normoxia and moderate hypocapnia with a decrease of intracranial hypertension. Treatment by controlled hyperventilation must be precocious, because the recuperation at the level of the damaged zones is very slow.

Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus. Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump.

Nursing case management: application to neuroscience nursing. The changing health care environment has challenged nurses to develop creative care delivery systems that provide for quality, comprehensive, cost-effective care in a time of restricted reimbursement and diminishing human and material resources. Nursing case management has been identified as one such approach to health care delivery that has resulted in quality, patient-centered care and improved resource utilization. The case management plan, critical path and discharge planning sheet are primary tools in this care delivery model. Because of the diverse case types and variety of patient care settings, neuroscience nursing is an ideal arena for implementing a nursing case management model of care.

Epidemiology of acute lower respiratory tract infections, especially those due to Haemophilus influenzae type b, in The Gambia, west Africa. Mortality surveys undertaken in rural areas of The Gambia, a small country on the west coast of Africa, indicate that acute lower respiratory tract infections (ALRI) are the most frequent cause of death among children and that approximately 1 in 25 rural Gambian children dies from an ALRI before the age of 5 years. Community surveys suggest that each child experiences an average of one episode of ALRI accompanied by radiographic changes before reaching this age. Etiologic studies have shown that pneumococci, Haemophilus influenzae type b (Hib), and respiratory syncytial virus are the most important causes of ALRI in Gambian children who present to a hospital, and the same three organisms are probably the major causes of severe ALRI in rural communities. Hib probably accounts for 5%-10% of cases of severe ALRI in Gambian children, and because the incidence of severe ALRI is high, an effective Hib conjugate vaccine might save as many childhood deaths by preventing pneumonia as by preventing meningitis.

Organization of specific DNA sequence elements in the region of the replication origin and matrix attachment site in the chicken alpha-globin gene domain. The distribution of specific DNA sequence elements in a 2.9 kb HindIII fragment of chicken DNA containing the replication origin and the upstream matrix attachment site (MAR) of the alpha-globin gene domain was investigated. The fragment was shown to contain a CR1-type repetitive element and two stably bent DNA sequences. One of them colocalizes with the previously described MAR element and with the recognition site for a proliferating-cell-specific, DNA-binding protein. The melting pattern of a set of subfragments of the region proved to be non random. No correlation between the distribution of readily melting sequences and bent DNA was found. The possible importance of curved, low-melting and repetitive DNA sequences for the organization of the upstream boundary of the alpha-globin gene domain and the function of the replication origin is discussed.

Motility studies of the cervical esophagus with intrathoracic gastric conduit after esophagectomy. Gastric emptying, upper esophageal sphincter pressure and intrathoracic gastric motility were studied in esophagectomized patients, ten with a gastric conduit in the posterior mediastinum and ten with a conduit in the retrosternal space. In addition, the clinical state was reassessed more than 6 months after esophageal reconstruction. Gastric emptying, assessed with Tc-99m Sn colloid in a semisolid test meal, did not differ between the two groups. In manometric studies a high-pressure zone distal to the upper esophageal sphincter was associated with dysphagia. A high-pressure zone at the anastomosis was found in 60% of the retrosternal group and 20% of the posterior mediastinal group. As regards food intake, the posterior mediastinal route seems to be preferable in esophageal replacement, since it permits more physiologic motility of the conduit.

Utilization of mental health services. I. Patienthood and the prevalence of symptomatology in the community. We explored the association between patienthood and prevalence of symptomatology in the community. Base line data on prevalence were obtained through the use of a household survey. Characteristics of survey respondents (N equals 938) and patients admitted from the surveyed area to a Connecticut Mental Health Center during a 12-month period (N equals 808) were compared. High utilization of facilities was associated with the prevalence of symptoms in the community, particularly where defining characteristics were descriptors of disadvantaged social status. A second set of variables correlated with mental health center use but not with the prevalence of symptoms in the community. By and large, these characteristics describe a lack of social supports not necessarily related to social status. Finally, certain groups were underrepresented as patients even though comprising polulations-at-risk in terms of levels of symptom impairment in the community.

Specific types of colonic fermentation may raise low-density-lipoprotein-cholesterol concentrations. To assess the effects of increased colonic fermentation on serum lipids, eight healthy volunteers were placed on two identical 2-wk metabolic diets, one of which was supplemented with lactulose (18-25 g/d). Lactulose raised day-long concentrations of breath hydrogen and serum glutamine as indicators of increased colonic fermentation by 78 +/- 13% (P less than 0.001) and 24.7 +/- 9.5% (P less than 0.05), respectively). Unexpectedly, however, fasting serum total and low-density-lipoprotein cholesterol and apolipoprotein B concentrations were higher at 2 wk by 8.9 +/- 1.5% (P less than 0.001), 10.9 +/- 2.2% (P less than 0.005), and 18.9 +/- 5.9% (P less than 0.02), respectively, compared with the control diet. With lactulose, mean free fatty acid concentrations were reduced over the day by 19.5 +/- 5.9% (P less than 0.02), with no change in mean day-long blood glucose, serum insulin, or C-peptide concentrations. We conclude that certain rapidly fermented substrates may raise rather than lower serum lipids, possibly through increasing the amount of acetate absorbed from the colon.

Effect of substance P on detrusor muscle in rats with diabetic cystopathy. Diabetic cystopathy (DCP) is a well known complication in diabetes mellitus (DM). In the present experimental study, DM was induced in rats by streptozotocin and DCP was confirmed on cystometry. In vitro studies on detrusor strips from diabetic rats showed an increased contractile response to substance P (SP) compared with controls, indicating denervation supersensitivity. A decreased response to capsaicin in diabetic detrusor strips indicated a decreased neuronal content of SP or a diminished number of SP-containing sensory nerves. This suggests that DM induces alterations in nerves containing SP which may be at least partly responsible for sensory loss and the development of DCP.

The recognition of a recombinant human Fc epsilon fragment by the subclasses of IgG autoanti-IgE: disproportional subclasses distribution of complexed autoantibody. Circulating IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma where it is suggested to be potentially involved in the removal of IgE-allergen complexes. Since such a putative role will largely be determined by the subclass profile of complexed (i.e. IgE-bound) IgG anti-IgE, a study was undertaken to determine the subclass distribution of complexed IgG anti-IgE antibody in the sera of asthmatic patients. The study exploits the heat-labile property of IgE by heating (30 min at 56 degrees C) serum to liberate bound anti-IgE, pre- and post-heated sera are then assayed for IgG subclass anti-recombinant human Fc epsilon (rFc epsilon) activities by ELISA and any heat-induced increase in antibody activity is taken as a measure of complexed anti-IgE. This has revealed a disproportionately high amount of IgG4 in complexed (but not free) IgG anti-IgE. The propensity of IgG4 to form complexes with IgE has important biological consequences, particularly with regard to the activation of C1q and Fc gamma R by other subclasses.

Rifampin plus trimethoprim: bactericidal activity and suppression of resistance in human urine in vitro. The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine. Drug concentrations used were similar to those attainable in human urine. The combination was more effective than the individual drugs and than a combination of Tmp plus sulfamethoxazole (Smx). Tmp was bactericidal in urine and blocked the emergence of Ramp-resistant bacteria. Ramp was responsible for most of the bactericidal action of the combination but also potentiated the bactericidal activity of Tmp. Ramp suppressed the selection of thy- (Tmp-resistant) bacteria. Under the experimental conditions, Smx+Tmp was not more bactericidal than Tmp alone for most of the test organisms, despite strong synergy between the two at subinhibitory concentrations.

Catecholamine and neuropeptide Y levels in tissues from young Dahl rats following 5 days low- or high-salt diet. The mesenteric vasculature of Dahl salt-sensitive (DS) rats on high-salt diet is supersensitive to nerve stimulation and to norepinephrine. The current experiments were undertaken to examine whether the enhanced sensitivity to nerve stimulation is due solely to the postsynaptic supersensitivity to norepinephrine, to increased sympathetic innervation, to altered transmitter release or to the presence of another transmitter acting as a potentiator. Catecholamine content and neuropeptide Y (NPY) presence were determined in tissues from young (approximately 5 weeks old) male Dahl rats exposed to 5 days of high (7%) or low (0.45%) salt diet. Catecholamine content from mesenteric artery, renal artery, caudal artery, right atrium, aorta, vas deferens and adrenal gland was quantified by high-pressure liquid chromatography with an electrochemical detector. A strain difference, independent of diet, between young DS and Dahl salt-resistant (DR) rats was seen only in adrenal epinephrine content. DS high-salt (+) rats displayed reduced norepinephrine content relative to DR+ in the mesenteric artery and right atrium. The release of norepinephrine from isolated mesenteric vasculature into the perfusate in response to transmural stimulation showed no significant differences between DS+ and DR+ preparations under basal, or deoxycorticosterone acetate (DOCA; 30 microM) perfusion conditions. The addition of 5 microM cocaine to the DOCA perfusion, while increasing total norepinephrine outflow in all preparations, failed to differentiate between DS+ and DR+. NPY immunofluorescence along mesenteric artery sections of DS+ and DR+ rats was not significantly different. Thus, in the tissues examined, enhanced responsiveness of vascular smooth muscle may not be explained by hypernoradrenergic innervation, elevated NPY innervation or altered release of transmitter.

Insensible water loss in resting adults in Kandy, Sri Lanka. Sixty three adults (44 men) were observed over a 4 hour period in Kandy to measure insensible water loss. Six adult men were similarly studied over 24 hours. The average loss per day, computed from the 4 hour studies was 1,333 ml for men and 1,230 ml for women. The 24 hour study showed an average loss of 1,423 ml. A reasonable working estimate for insensible water loss for resting adults in Kandy would be about 1,000 to 1,200 ml per day. However, when renal excretion of water is impaired, it is safer to err on the side of mild dehydration than to attempt complete hydration.

[Morphometrical-statistical structure analysis of human striatum, pallidum and subthalamic nucleus]. 1. A morphometric-statistical analysis was carried out of fifteen hemispheres of thirteen normal brains of human adults. 2. A comparison of the volumes and the cell densities studied in serial sections is only meaningful if the results are corrected for shrinkage, which varies interindividually to a great extent. 3. The mean of the fresh volume of the striatum of the male subjects (10.2 cm3) was 12% higher than that of the female subjects (9.0 cm3), the difference not being significant. The putamen was 13% bigger on the average than the caudate nucleus. The size of the two nuclei was strictly correlated (r = 0.81). 4. The relative volume of the striatum in percent of the hemisphere volume amounted to 1.87% in males and 1.97% in females, of the putamen 0.99% (male) and 1.05% (female), of the caudate nucleus 0.88% and 0.92%, respectively. 5. The mean of the numerical density of small striatal nerve cells (kl. Nz) -- corrected for shrinkage -- came to 1100 kl. Nz/mm3, without evidence of being dependent of sex or age. 6. The corrected numerical density of the large striatal nerve cells (gr. Nz) had a mean of 65 gr. Nz/mm3 with a wide range of 49 to 78 gr. Nz/mm3, without a significant influence of sex or age. 7. The relation of kl. Nz/gr. Nz was on an average of 171:1 with a range of 130:1 to 258:1. 8. The mean of the corrected numerical density of glial cells (Gz) was found to be 41000 Gz/mm3 with a range of 34500 to 49200. Neither a difference between sexes nor a dependency of age was found. 9. The glia index (Gz/Nz) showed a mean of 37:1 with a range of 3.2:1 to 4.7:1. 10. The total number of small striatal cells averaged 100 million for males and 105 Million for females; for the large striatal cells the means were 670 thousand (male) and 570 thousand (female). Differences due to sex failed to be significant. 11. The total number of glial cells decreases with age. The mean of 408 million for males exceeded the mean of 380 million for females by 7% but without significance. 12. The volumetric density of nerve cells of males (4.03 Vol.-%) and females (4.14 Vol.-%) differed very little. 13. The mean fresh volume of a single small nerve cell in the striatum was calculated to be about 3600 mum3, ranging from 2600 to 4600 mum3. 14. The striatal nerve cells reached a total volume of 423 mm3 in males and 374 mm3 in females. 15. The mean of the diameter of the nucleus of the small nerve cells was calculated to be 8.64 mum in males and 8.70 mum in females.

Characterization of the venom from Crotalus molossus nigrescens Gloyd (black tail rattlesnake): isolation of two proteases. The venom from Crotalus molossus nigrescens contains many activities including: hyde powder azure proteinase; N-benzoyl-arginine-ethyl-ester hydrolase; phospholipase; phosphodiesterase; desoxyribonuclease; fibrinogen coagulase; collagenase, fibrinolytic activity, and hemorrhagic factors. The venom, assayed with amounts of venom up to 50 micrograms protein per assay, does not contain acetylcholinesterase, phosphatase, amylase, ribonuclease, tyrosyl-ester hydrolase or hyaluronidase activities. The venom is lethal to mice with an i.p. LD50 of 2.35 mg/kg mouse. Fractionation of soluble venom by Sephadex G-75 separates at least five families of components. Fractions I-III contains all the enzymes, and fraction V have six small peptides. Further separation of fractions II-III on diethyl-amino-ethyl-cellulose columns at pH 8.0 and 8.3 gave pure proteinase E with a mol. wt of 21,390 and the following N-terminal amino acid sequence; Phe-Ala-Lys-Arg-Tyr-Val-Glx-Leu-Val-Ile-Val-Ala. A thrombin-like enzyme with a mol. wt of 75,000 was also purified from this venom by means of affinity and ion exchange chromatographies.

Magnitude estimation of contact force when objects with different shapes are applied passively to the fingerpad. Stimuli with spherically curved surfaces were presented passively to the fingerpads of human subjects. There were 28 stimuli, consisting of all combinations of 4 different curvatures and 7 different contact forces; these were presented in random order. Subjects scaled their perceived magnitude of the contact force using magnitude estimation. Perceived force increased markedly with an increase in experimentally applied contact force. An increase in curvature resulted in a slight increase in perceived contact force. Thus, when humans are passively presented with objects changing in both shape and contact force, they are able to extract information about the force. Because of the passive nature of the task, all such information must be conveyed to the brain by the cutaneous mechanoreceptors.

Assessment of voiding dysfunction in men with acute epididymitis. Fifteen men with a recent attack of acute epididymitis were examined urodynamically and endoscopically after the symptoms had resolved. Thirteen of the 15 patients had abnormal voiding. Two patients had stricture formation in the posterior urethra, one had benign prostatic hyperplasia, one had bladder neck sclerosis, and 4 had detrusor-external sphincter dyssynergia. Three patients including the one with prostatic enlargement presented abdominal straining exceeding 50 cm H2O during micturition. The cause of an obstructive voiding pattern could not be established in 3 patients. The results support the theory of urethrovasal reflux due to a high hydrostatic pressure at the collicular level as a pathophysiological factor in acute epididymitis.

Pulse wave reflection at the collapsed segment of an artery in Riva-Rocci's method. The contours of pressure and flow of a pulse wave arriving at the entrance of a collapsed segment of an elastic tube can be described by application of the basic laws of reflection. The collapsed segment acts like a valve. It is opened by the pressure of the pulse wave when the pressure within the tube becomes higher than the "collapse pressure", i.e. the pressure exerted on the segment from outside. This opening of the collapsed segment suddenly changes the sign of the pulse wave reflection from positive to negative; thus a typical contour change of the pulse proximal to the segment is observed. The most obvious effect is a reduction of the pulse pressure. The extent of this reduction is a function of the collapse pressure. A typical example of this phenomenon can be observed in an artery proximal to the segment which is collapsed due to pressure exerted by an inflated Riva-Rocci cuff. The effect is explained by the assumption that the sign of reflection changes when the pressure of the pulse wave crosses the level of the cuff pressure. This explanation is supported by the results of model experiments.

Histochemical characteristics of the anal sacs of the cat. The histochemistry of polysaccharides and proteins and the distribution of RNA were investigated in the glands and mature secretion of the anal sacs of the cat. Glycogen was extremely abundant in the epithelial lining of the lumen and efferent duct of the anal sac and also in ducts of sebaceous glands of the sacs constantly formed in the place of degenerating acini. Little glycogen was found in the unchanged sebaceous acini. The apocrine glands of the anal sacs were substantially richer in glycogen than the apocrine sweat glands of the skin and were in an active state. A high concentration of acid mucopolysaccharides was present in the mature secretion, and their source was the apocrine glands. The phases of the secretory cycle alternated in different cells and secretory portions of the apocrine glands highly asynchronously. Carboxylated acid mucopolysaccharides were more abundant than sulfated. Sialomucin, hyaluronic acid, and chondroitin sulfate could be identified in the secretion. Neutral and acid mucopolysaccharides were present in the mature secretion in the form of complexes with one another in approximately equal proportions; neutral polysaccharides consisted chiefly of glycogen. Besides polysaccharides, the apocrine glands produce large quantities of protein, in which the mature secretion was rich. This protein was predominantly basic, and the secretion contained very little acid protein. Maturing cells of the sebaceous acini, and also other specific sebaceous glands, were characterized by a much higher protein concentration than in ordinary sebaceous glands.

Correlation between the serine sensitivity and the derepressibility of the ilv genes in Escherichia coli relA- mutants. Upon addition of excess one carbon metabolites (including serine)bacteria stop growing because of isoleucine starvation. After such treatment stringent bacteria rapidly resume normal growth whereas relaxed mutants remain unable for some time to grow. We show here that this is due to a lack of derepressibility of ilv genes after the starvation period. Results are also presented which show that RNA polymerase structural mutants may be selected among the clones resistant to a mixture of serine, methionine and glycine, in relA- strains. Finally circumstancial evidence suggests that the one carbon metabolism may be involved in a process controlling isoleucine metabolism.

Use of psychological and neuropsychological variables in selection of patients for epilepsy surgery. Cortical resection surgery for epilepsy is costly, involves risk, and does not result in significant seizure relief in a number of patients. Therefore, it is important to develop methods which will as accurately as possible identify in advance those persons who will or will not be helped by this procedure. From a review of the literature and from a presentation of original data, it is concluded that psychological/neuropsychological variables are valid predictors of cessation of seizures following surgery but that they are only infrequently used. A multidisciplinary, multivariate statistical approach, using EEG findings and psychological/neuropsychological variables in combination, provides the most accurate predictions which are superior to those derived from using either EEG variables or psychological/neuropsychological variables alone. This approach also avoids much of the predictive instability encountered when single variables are evaluated. Since psychological/neuropsychological variables are obtained at low cost and are non-invasive, further evaluation of their role as predictors of seizure relief following surgery is needed.

Behavioral contagion in sibships. A behavior is "contagious" if one person is more likely to exhibit it when a relevant other person has already done so. In this sense, behavioral contagion is commonly thought to contribute to many social problems, such as drug abuse and teenage promiscuity. In this paper we focus on behavioral contagion in sibships. Borrowing a model from the theory of contagious diseases, we show that contagion will cause prevalence to increase with sibship size. This model also allows us to estimate the magnitude of the contagious factor relative to non-contagious factors. Finally, we develop two statistical tests for the presence of contagion. Results are presented for participation in a skill-development program and four child-psychiatric conditions: neurosis, hyperactivity, somatization, and conduct disorder. Evidence is presented that program participation is probably contagious and conduct disorder possibly so. The other three child-psychiatric conditions are shown not to be contagious. Implications for research and practice are discussed.

A bovine rotavirus serotype 1: serologic characterization of the virus and nucleotide sequence determination of the structural glycoprotein VP7 gene. Bovine rotavirus T449 was isolated from feces of a calf with diarrhea. Serological characterization by serotype-specific monoclonal antibodies showed that the T449 virus belonged to serotype 1. This is the first report of a bovine rotavirus that does not belong to serotype 6, 8, or 10. The serotype 1 designation was confirmed by using an immunoperoxidase focus neutralization assay. The gene encoding the major neutralization antigen (VP7) was cloned and its nucleotide sequence was determined. The sequence obtained was 1062 bp in length and contained an open reading frame corresponding to 326 amino acid residues. Comparative analysis of the deduced amino acid sequence with the corresponding sequence of the human serotype 1 rotavirus strain, Wa, revealed a 90% identity. When compared to the predicted amino acid sequence of VP7 protein of the other serotypes an overall divergence of 20 to 25% was detected. These data show that the serological typing agrees with the result of the genetic analysis.

Spontaneous milk ejection during lactation and its possible relevance to success of breast-feeding. In a woman suckling twins it became apparent that both suckling-induced and precisely timed, spontaneous bursts of milk ejection were occurring. Observations on days 14, 28, 56, and 112 of lactation disclosed highly significnat increases in intervals between episodes of spontaneous milk ejection. Furthermore, at all stages of lactation the interval between a feed and the next episode of spontaneous ejection was significantly longer than the interval between spontaneous ejections. The decrease in frequency of episodes of spontaneous milk ejection during lactation may be related to the decreasing release of prolactin in response to suckling. Spontaneous milk-ejection episodes are felt only when the breast is full and may signal its readiness for a further suckling episode. Such bursts of milk ejection may stimulate the suckling response in babies, suggesting that rigid three- or four-hour feeding regimens may be unphysiological and pose a threat to the success of breast-feeding in the early postnatal period.

Ribulose bisphosphate carboxylase from methanol-grown Paracoccus denitrificans. Paracoccus denitrificans grows on methanol as the sole source of energy and carbon, which it assimilates aerobically via the reductive pentose phosphate cycle. This gram-negative bacterium grew rapidly on 50 mM methanol (generation time, 7 h, 30 degrees C) in excellent yield (3 g of wet-packed cells per liter of culture). Electron microscopic studies indicated that the late-log-phase cells were coccoid, having a thick envelope surrounding a layer of more diffuse electron-dense material and a relatively electron-transparent core. Ribulose bisphosphate carboxylase in the 15,000 X g supernatant of fresh cells had specific activities (micromoles of CO2 fixed per minute per milligram of protein) of 0.026, 0.049, 0.085, 0.128, and 0.034 during the lag, early, mild-, and late log, and late stationary phases, respectively. The enzyme was purified 40-fold by pelleting at 159,000 X g, salting out, sedimentation into a 0.2 to 0.8 M linear sucrose gradient, and elution from a diethylaminoethyl-Sephadex column. The enzyme was homogeneous by the criteria of electrophoresis on polyacrylamide gels polymerized from several acrylamide concentrations and sedimentation behavior. The molecular weight of the native enzyme, as measured by gel electrophoresis and gel filtration, averaged 525,000. Sodium dodecyl sulfate dissociated the enzyme into two types of subunits with molecular weights of 55,000 and 13,600. The S20,w of the enzyme was 14.0 Km values for ribulose bisphosphate and CO2 were 0.166 and 0.051 mM, respectively, and the enzyme was inhibited to the extent of 94% by 1 mM 6-phosphogluconate.

Role of pH in salivary histidine-rich polypeptide antifungal germ tube inhibitory activity. Purified synthetic salivary histidine-rich polypeptides (HRPs) 2, 3, 4, 5 and 6 were found to inhibit Candida albicans conversion of blastospores to germ tubes. HRP-4 was the best inhibitor within the pH 5 to 7 range tested and all of the HRPs were observed to lose potency as the pH was raised from 5 to 7. The pH pattern obtained with a synthetic homologous histidine peptide suggested that the protonated form of the histidine imidazole residues of the HRPs was important to the germ tube antifungal activity. Similar pH inhibition profiles of germ tube formation by parotid saliva and the HRPs were also observed.

Anti-idiotypic antibodies mimic bovine viral diarrhea virus antigen. Polyclonal rabbit anti-idiotypic antibodies (anti-ids) against two neutralizing murine monoclonal antibodies (mAbs) specific to a bovine viral diarrhea virus (BVDV) glycoprotein, 53 kDa, were produced, purified, and characterized. Each anti-id inhibited the binding of its respective mAb to BVDV antigen in a competitive ELISA and blocked the immunoprecipitation of the 53 kDa protein by the mAb. The anti-ids also inhibited the virus-neutralizing activity of their homologous mAbs. These results suggest that the anti-ids bear an internal image of a BVDV antigen and mimic neutralizing epitopes on the 53 kDa protein. Treatment of MDBK cells with the anti-ids inhibited BVDV infection, indicating that they block a cellular component, such as a virus receptor, required for virus adsorption or entry. Inhibition of the homologous mAb and lack of inhibition of the heterologous mAb indicate that the anti-ids are specific for the unique antigen-binding sites on the mAbs.

[Calcium-antagonism, a new principle in coronary vasodilation]. As in all other vessels, coronary contractile tone depends on the availability of Ca ions. Thus, Ca-antagonistic drugs such as verapamil, prenylamine or nifedipine produce a loss of muscle tone in depolarized coronary strips. One molecule of these compounds successfully blocks the action of thousands of Ca ions in excitation-contraction coupling. Nitroglycerine and other nitrites exert a similar action, though in their case relaxation is more rapid, incomplete and spontaneously reversible. In analogy to their well-known Ca-synergistic action on heart muscle fibres, cardiac glycosides are also capable of increasing the coronary vascular tone even in very low concentrations. If, however, suitable doses of Ca-antagonistic compounds are simultaneously administered, the hearts are protected against this unpleasant coronary side effect without an appreciable loss of the inotropic glycoside action on the myocardium.

[Quantitative pharmaco-EEG study of nootropics]. A treatment of geriatric disorders is one of the current major problems socially as well as medically. Thus nootropics have become one of the biggest topics in drug developments. Unfortunately, it is still very difficult to assess brain dysfunctions and therapeutic efficacies of these drugs objectively. Giurgea has proposed a new drug category, "nootropic", as those substances which possess an anti-dementia action, yet the general concept remains obscure. The present author expand the concept that those substances which improve the vigilance level to be included. The author has been engaged with computer assisted pharmaco-electroencephalography and research of nootropics for last several years. Based on the own experiences, the author presented the CNS effects of five different substances such as meclofenoxate, amantadine, piracetam, teniloxazine and WEB-1881, which were regarded as nootropics from various reasons. Single dose of each substances was administered in healthy young volunteers, and teniloxazine was given to geriatric patients. EEG changes induced by these substances in normal subjects were an increase of alpha activity, particularly in higher frequency range above 9.5 Hz, and an associated decrease of slow activity and of fast activity, which are different from those of the other psychotropic drugs. Multivariate analysis of variance (MANOVA) of EEG parameters has confirmed that the response of WEB-1881 was most manifest in frontal area. This suggests that WEB-1881 might activate linguistic learning and memory process. In the patient study, the induced EEG changes were an increase of alpha activity associated with a decrease of slow activity, while fast activity did not show any changes. However, the EEG changes in the patient study were quite similar to those of normal volunteer study for the most part. It is relevant to infer the efficacy of nootropics in geriatric patients from acute normal volunteer study. In physiological aging process, alpha activity gradually decreases. The EEG changes induced by nootropics are the reverse of this process, suggesting the antagonistic efficacy in the geriatric changes. Therefore, quantitative pharmaco-EEG is one of the best tools in the screening for the CNS efficacy of nootropic or anti-dementia substance in the meantime.

An evaluation of the usefulness of primary tumour expression of MCA and CA15-3 as prognostic indicators in breast carcinoma. CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) show potential as clinically useful serum markers of breast carcinoma. Recently, immunohistochemical versions of these monoclonal antibodies have become available but few data are available as to their clinical usefulness. The aims of this study were (i) to assess CA15-3 and MCA expression by primary breast tumours and to correlate tumour immunoreactivity with tumour behaviour, and (ii) to investigate the relationship between immunohistological staining and oestrogen receptor (ER) status. Pathological material from 39 stage 1 (node free) breast carcinoma patients was assessed. The mean age was 51.3 (range 34-70) years, 19 were premenopausal and the mean duration of follow-up was 3.6 years (range 0.8-14 years). In each case two further sections were stained with antisera to the CA15-3 and MCA antigens. Staining of primary tumour was achieved in 38 cases. Low (less than 30% tumour cell staining) and intermediate (30-60% of cells staining) grade immunoreactivity with both monoclonals correlated with significantly shorter disease free intervals (P less than 0.05). Neither monoclonal can predict ER status. We conclude that the use of monoclonal antibodies to CA15-3 and MCA in staining primary breast carcinoma tumours and their axillary nodes may be a significant (P less than 0.05) prognostic indicator of future tumour behaviour and that this requires further evaluation.

A 31P nuclear magnetic resonance study of Crithidia luciliae. 31P NMR has been used to observe phosphorus-containing compounds in both perchloric acid and KOH extracts and in whole cell suspensions of Crithidia luciliae. Cells were grown in Bone and Steinert medium, or in a modified RPMI culture medium and harvested after about 72 h in mid- to late log phase. 31P NMR spectra of the perchloric acid extracts indicated that 3-phosphoglycerate, which is normally at low concentrations in most cells, was the dominant phosphorus-containing compound in the sugar phosphate region. 3-Phosphoglycerate is the end product of glycosomal glycolysis and our finding is consistent with previous observations of the failure to detect prior glycolytic intermediates. Other metabolites observed were ATP, ADP, NAD(P)+, phosphoenolpyruvate and low molecular weight polyphosphates (PPn, n less than 20). The presence of high-molecular-weight polyphosphates was established by spectra recorded on extracts obtained through subsequent treatment of the insoluble fraction with KOH. 31P NMR experiments on whole cells indicated that the average main internal pH of cells in late-log growth phase was approx. pH 7.2 +/- 0.1, using the orthophosphate resonance as an indicator. The cells responded to the addition of glucose (final concentration approx. 35 mM) with a decrease in pH, both internal (delta pH = -0.9 (55 min)-1) and external (delta pH = -1.3 (15 min)-1). Polyphosphates and ATP could not be observed in whole cell experiments, although perchloric acid extracts of identically treated cells showed no significant depletion of these compounds.

Saliva and serum lithium monitoring in hospitalized children. Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring.

[Importance of heparin in thrombin-131I clearance and in the complex formation processes in animals under experimental restoration of the function of the anticoagulating system]. Thrombine-I131 infusion to animals receiving Linethol with vitamin A in the presence of both natural and atherogenic diets accelerated the clearance of thrombine-I131 and elevated the level of nonenzymatic fibrinolysis in the blood and tissue of the liver and lungs. In addition to the administration of thrombine-I131, intravenous heparin injections to animals kept for a long time on atherogenic diets and receiving Linethol with vitamin A provided for a still greater acceleration of thrombine-I131 clearance, which manifested itself in its faster absorption from blood by the liver in the form of a thrombine-I131 -- heparin complex, in an increasing total fibrinolytic activity and of its nonenzymatic fibrinolysis in blood plasma and tissues of the liver and lungs. This resulted in a partial restoration of the function of the anticoagulation system and an increase of the functional activity of the hepatic tissue directed at the consumption of the thrombine excess from the blood flow.

Vitreous, retinal and subretinal hemorrhages associated with von Willebrand's syndrome. Two patients with von Willebrand's syndrome had intraocular hemorrhages without trauma or neovascularization. A 13-year-old Japanese girl complained of sudden spotted vision in her left eye. Vitreous, peripapillary retinal, and subretinal hemorrhages were seen by ophthalmoscopy in the affected eye. In addition, a 19-year-old Japanese man had repeated vitreous hemorrhage and epistaxis. Also noted was gyrate atrophy of the choroid and retina. Analysis of the coagulation-fibrinolysis system revealed decreased activities of Factor VIII and von Willebrand's factor in both patients. The amount of von Willebrand's factor antigen also was decreased. These results suggested that the patients had von Willebrand's syndrome. The bleeding tendency in the disorder appeared to be responsible for the pathogenesis of the intraocular hemorrhages seen in these patients.

[The content of biologically active substances in the margin of a stomach ulcer being treated with a copper-vapor laser]. A study was made of the effect of laser therapy on the content of she biologically active substances serotonin, histamine, PGE2 and PGF2 alpha as well as on the adenylate cyclase system--adenylate cyclase activity and cGMP content. Direct exposure to laser produced an appreciable increase of the content of serotonin and histamine, PGE2 and PGF2 alpha, cAMP and of adenylate cyclase activity. On the healing of ulcerous defect after 5-6 sessions of laser therapy a decrease of the content of serotonin, a rise of histamine, PGE2, PGF2 alpha, cAMP accumulation and adenylate cyclase activation were recorded.

Mandibular involvement by squamous cell carcinoma of the lower alveolus: analysis and comparative study of histologic and radiologic features. Histologic analysis of squamous cell carcinoma of the lower alveolus shows 2 basic patterns of tumor spread in relation to the mandible: an infiltrative one and an expansive one. While the tumor invades the mandible by destroying the bone or through cortical defects of some spaces in the infiltrative form, the tumor does this only by eroding the bone in the expansive form, in which the degree of bone resorption seems to be proportional to tumor advancement. A comparison between radiologic and histologic features discloses that the radiologically detected bone defects are not necessarily correlated with the patterns of bone involvement. However, most lesions with erosive bone defects show the expansive pattern histologically, and the extent of the radiologically detected bone defect is roughly in accordance with the histologic extent of bone involvement. These results lead us to believe that some squamous carcinoma of the lower alveolus could be treated successfully without sacrificing the continuity of the mandible.

A preliminary report on the role of somatostatin analogue (SMS 201-995) in the management of children with tall stature. We have studied the effect of somatostatin analogue (SMS 201-995) given as a subcutaneous injection on the growth and growth hormone secretion in seven tall children (two male; five female). SMS 201-995 was given in doses of 37.5 or 50 micrograms on a once or twice-daily regimen. Growth velocity decreased from a pretreatment median of 8.3 cm/year (range 5.5-12.2) to 3.0 cm/year (range 0.2-4.5) after 6 months treatment (Wilcoxon, P = 0.02). In three of the children therapy was discontinued for the next 6 months with restoration of growth rate to pretreatment values in two of the three. Growth hormone secretion decreased as a result of SMS 201-995 therapy although one child needed a twice-daily regimen to achieve long-term suppression. Final height measurements were reduced in four of five patients with an overall reduction between 1.1 and 6.3 cm and no change in the other. No effects of treatment on fasting glucose and insulin, glycosylated haemoglobin or serum thyroxine concentrations were observed. These preliminary studies suggest that SMS 201-995 may have a role in the management of the growth of tall children but the optimum mode of administration remains to be established.

Mechanisms of idiotype suppression. I. In vitro generation of idiotype-specific suppressor T cells by anti-idiotype antibodies and specific antigen. Normal BALB/c spleen cells are unresponsive in vitro to the phosphorylcholine (PC) determinant in the presence of anti-idiotype antibodies specific for the TEPC-15 myeloma protein (T15) which carries an idiotypic determinant indistinguishable from that of most anti-PC antibodies in BALB/c mice. The possibility that idiotype-specific suppressor cells may be generated during the culture period was examined by coculturing the cells with untreated syngeneic spleen cells. Cells that had been preincubated with anti-T15 idiotype (anti-T15id) antibodies and a PC-containing antigen, R36a for 3 d, were capable of specifically suppressing the anti-PC response of fresh normal spleen cells, indicating that idiotype-specific suppressor cells were generated during the culture period. The presence of specific antigen also appeared to be necessary because anti-T15id antibodies and a control antigen, DNP-Lys-Ficoll, were not capable of generating such suppressor cells. Suppressor cells were induced only in the population of spleen cells nonadherent to nylon wool and the suppressive activity was abrogated by treatment with anti-Thy 1.2 serum and complement. These results indicate that anti-idiotype antibodies and specific antigen can generate idiotype-specific suppressor T cells in vitro. These in vitro results may reflect in vivo mechanisms of idiotype suppression.

Vein graft surveillance improves patency in femoro-popliteal bypass. Sixty-three patients undergoing femoro-popliteal bypass using autologous vein were prospectively screened for the development of graft related strictures by clinical assessment, intravenous digital subtraction angiography (IVDSA) and Duplex scanning. Eighteen strictures were identified in 14 grafts. Clinical examination detected only 11% of lesions, IVDSA detected 83% of lesions and Duplex scanning detected all 18 lesions. Seventeen lesions had occurred by 6 months from the time of operation which suggests that screening should begin early. Treatment by percutaneous transluminal angioplasty (PTA) was offered for eight strictures and dilatation was complete in all cases. No stricture recurred in the follow-up period. Cumulative patency in this series of screened and selectively treated vein grafts was compared with a previous series of 216 femoro-popliteal vein grafts and an improvement in 1 year potency of 15% was achieved (log rank test, chi 2 = 5.12, P = 0.02).

The habenular complex mediates hormonal stimulation of maternal behavior in rats. The role of the habenular complex (Hbc) in the hormonal onset and nonhormonal maintenance of maternal behavior in rats was examined. In Experiment 1, bilateral lesions were produced in the Hbc on Gestational Day (GD) 12. On GD 16, animals were hysterectomized-ovariectomized and given estradiol benzoate (EB); they were then tested for maternal behavior 48 hr later. Hbc lesions delayed the appearance of all components of maternal behavior for several days. In Experiment 2, large Hbc lesions that were produced on Postpartum Day 4 caused only 1- or 2-day deficits in maternal behavior. These data suggest that the Hbc mediates the hormonal onset of maternal behavior. During the postpartum period, however, the importance of the Hbc for maternal behavior diminishes as the hormones of pregnancy become less important.

Maturation of the lymphoid system. I. Induction of tolerance in neonates with a T-dependent antigen that is an obligate immunogen in adults. A/J mice displayed a striking ontogenetic difference in the capacity to respond to DNP-Ficoll, a T-independent antigen, and to aggregated human gamma-globulin (AHGG), a T-dependent antigen. Thus, whereas responses to DNP-Ficoll of 4-day-old mice were similar in magnitude to those of adult animals, responses to AHGG did not become pronounced until mice were some 30 to 40 days of age. The inability of young animals to respond to AHGG was reflective of a negative consequence of lymphocyte/antigen interaction, since such mice became specifically unresponsive to subsequent challenges with AHGG. Unresponsiveness induced by neonatal injection of AHGG lasted 50 to 60 days, in contrast to that induced by deaggregated HGG, which persisted some 100 days longer. The unresponsive state induced by injection of neonates with AHGG maintained itself upon adoptive transfer and did not appear to be linked to suppressive factors associated with either serum or lymphoid cells for its maintenance. Finally, AHGG was also shown to be capable of inducing unresponsiveness in neonatal, athymic mice. These results demonstrate that AHGG, the normally immunogenic form of HGG in adult mice, can serve as an effective tolerogen when administered into a neonatal environment.

The clearance of heterologous antibodies in experimental antibasement membrane antibody mediated glomerulonephritis. A study of the clearance of anti GBM antibodies is important for an understanding of the pathogenesis of Goodpasture's syndrome. This paper reports a study of the sequential clearance of heterologous anti-glomerular basement membrane antibodies in the neonatal rat. A single intraperitoneal injection was followed by rapid and linear binding of injected antibodies to glomerular basement membranes, particularly to those glomeruli in the corticomedullary region. GBM bound antibodies were cleared gradually through the mesangium and significant amounts of antibodies still remained bound after 6 months. Subsequent injections of antibodies failed to provoke morphological abnormalities. These experiments have shown that the glomerular basement membrane of neonatal and adult rats possesses similar antigenic sites. The mesangium plays a major role in the clearance of injected heterologous antibodies. The slow clearance of antibodies from the GBM indicates a strong affinity of antibodies to antigenic sites and that the removal of antibodies is intimately related to the slow metabolic turnover of the glomerular basement membrane. The findings help to explain some of the observations in human antibasement membrane antibody mediated disease of the Goodpasture's type.

Oligoclonal measles virus-specific IgG antibodies isolated from cerebrospinal fluids, brain extracts, and sera from patients with subacute sclerosing panencephalitis and multiple sclerosis. Measles virus-specific antibodies were isolated from sera, cerebrospinal fluids (CSF), and brain extracts of patients with subacute sclerosing panencephalitis (SSPE) and multiple sclerosis (MS) by absorption with measles antigens and subsequent acid elution of the antigen-antibody precipitates. Electrophoretically homogeneous measles antibodies were isolated from CSF or brain extracts in five patients with SSPE and in five out of seven patients with MS. Homogeneous IgG antibodies were also demonstrated in the sera from all SSPE patients and from three of the MS patients. The antibodies isolated from various control sera and from pooled CSF were electrophoretically heterogeneous. The results support the concept of a local synthesis in the nervous system of oligoclonal IgG antibodies to measles virus in all patients with SSPE and in some patients with MS. In SSPE, most or all oligoclonal IgG proteins of the CSF or brain carry measles antibody activities. In MS, only part of the oligoclonal IgG appears to be associated with measles antibody activity.

[Choice of bread]. Bread can vary according to the flours used, extraction rate of fermentation methods, but the wast majority of French people usually consume white bread made with wheat flour. Size more than composition is the main criterion in the choice of bread. The choice of loaves with a large diameter corresponds to the traditional consumer in rural areas, but the general tendency is in favour of long loaves with a maximum of crust. This shape is more related to the qualities sought by consumers who want a "light", "crusty", well-baked (golden brown) loaf. Thus they are more interested in the consistency than in the taste, as bread is now only an accessory to a well-flavoured dish. Despite the large drop in the consumption of bread, this search for a good consistency is strong enough to justify quite frequently a detour to a baker whose quality of bread is better. However, this desire for quality does not seem to lead to a larger individual consumption. For various reasons, since the beginning of this century, man has lost his "taste for bread" and any improvement in the "taste of bread" would not be sufficient to make him find it again.

Recurrent respiratory infections in childhood: experience with a bacterial extract plus bacterial ribosomes (Immucytal). A total of 60 children (mean age +/- SD 7.6 +/- 3.5 years, range 2 - 14.2 years) with recurrent respiratory infections were treated with bacterial wall extract plus bacterial ribosomes (Immucytal) or placebo sprayed into the nostrils and oropharynx three times a day for 1 or 2-week periods over 3.5 months. The treatment was completed by 58 subjects; two patients in the placebo-treated group were withdrawn, one for poor compliance and the other because of headaches. Respiratory symptoms improved from the first month in the Immucytal treated children, but not in the placebo group, with a reduction in the incidence of infections in the upper and lower airways. No changes were noted in respiratory function parameters. Treatment with Immucytal significantly increased serum immunoglobulin A (P less than 0.02) and immunoglobulin M (P less than 0.01) and enhanced skin response to the in vivo lymphocyte blastization test, but there was no significant change in the circulating lymphocyte subpopulations. Both physicians and the patients' parents judged the bacterial extract to be clinically better than the placebo. Immucytal, therefore, may provide a useful alternative therapy for recurrent respiratory infections in infancy.

Trends in cocaine abuse reflected in emergency room episodes reported to DAWN. Drug Abuse Warning Network. The National Institute on Drug Abuse supports the Drug Abuse Warning Network (DAWN), a voluntary data collection system through which hospital emergency room (ER) and medical examiner facilities report information on medical crises and deaths related to the use of drugs. This study is based on cocaine-related episodes seen at 453 consistently reporting hospital emergency rooms located primarily in 21 U.S. metropolitan areas. Cocaine-related medical emergencies reported to DAWN increased from 16,033 in the first half of 1987 to 25,607 in the first half of 1989; they decreased to 22,796 in the second half of 1989. In the Boston, Buffalo, Dallas, Detroit, Minneapolis, New York, Newark, Phoenix, and Washington, DC, areas cocaine-related ER episodes decreased for at least the last two consecutive semiannual periods. Consistent with the prevalence of crack, smoking was the most frequently reported route of administering cocaine. Patients who had smoked the drug generally were younger and less likely to use other drugs in combination than were those who took cocaine by other routes. The proportion of black patients increased from 57 to 63 percent in cocaine-related ER episodes overall, and from 74 to 77 percent in episodes where the drug was smoked. Heroin used in combination with cocaine was reported in 12 to 15 percent of cocaine episodes, and both drugs were injected in 75 to 78 percent of the cases where both were involved, suggesting so-called speedballing. Patients who combined heroin with cocaine were generally older than patients in cocaine episodes overall.

[Interaction of nonachlazine and noradrenaline on a model phospholipid membrane]. The binding of nonachlazine (NCL), imipramine (IMP), and noradrenaline (NA) with the model phospholipid membrane vesicles--liposomes--was studied. The binding was determined by the qunching effect of these substances on the fluorescence of 3-methoxybenzantrone (MBA) present in the membrane of the fluorescent probe. A method rendering possible calculation of the binding of the preparations under study with the membrane of the basis of the fluorescence changes was developed. The binding constant of the NCL, IMP, and NA interaction with the membrane was equal to (4.3 +/- 0.3)-10(3)M-1, (2.7 +/- 0.2)-10(3)M-1, and (0.7 +/- 0.15)-10(3)M-1, respectively. It was shown that NCL and IMP could compete with NA for the membrane binding centers. Such competitive interactions could be regarded as a probable mechanism of the block of the reverse NA transport through the synaptic and the vesicular membranes characteristic of NCL and IMP.

Activity profile of competition soccer. In order to study the movement pattern of soccer players, 14 top-level players were filmed during several competitive matches. In addition, the relationship between the observed activity during match play and blood lactate values was examined. The mean distance covered during competitive matches was 10.80 km, and the average individual difference between matches was 0.92 km, with no difference in regard to high intensity activities. Midfielders covered a 10% longer (p less than 0.05) distance (11.4 km) than defenders and forwards, with no difference concerning high intensity running. There was a significant correlation (r = 0.61, p less than 0.05) between the amount of high intensity running during the match and lactate concentration in the blood. The results suggest that high intensity running can be used for making comparisons in soccer and that the interpretation of blood lactate in soccer is limited to giving an indication of the type of activity that has been carried out a few minutes before sampling.

Resting metabolic rate and coronary-heart-disease risk factors in aerobically and resistance-trained women. This cross-sectional study compared physical characteristics, cardiovascular risk factors, and resting metabolic rate (RMR) in a cohort of 82 young women separated into three groups: sedentary (SED, n = 48), aerobically trained (AT, n = 21), and resistance trained (RT, n = 13). Body mass and fat-free mass (FFM) were not different between groups whereas percent body fat was lower in the AT (16.2 +/- 0.7%) and RT (14.7 +/- 0.8%) groups than in the SED group (21.8 +/- 0.8%). There were no between-group differences for blood pressure or blood lipids. RMRs (kJ/min) for the AT (4.31 +/- 0.06) and RT (4.25 +/- 0.09) groups were significantly greater than those for the SED group (3.99 +/- 0.05). When adjusted for differences in FFM, RMRs for the AT group (4.24 +/- 0.05) were different from those of both the RT (4.13 +/- 0.05) and SED (4.05 +/- 0.03) groups; RMRs for the RT and SED groups were not different from each other. No differences were found in cardiovascular risk in young nonobese women of differing exercise status. Aerobic training in young women seems to increase the rate of metabolic activity of resting tissues whereas resistance training does not.

Effect of ovariectomy and estradiol benzoate treatment on LH-RH induced LH and FSH release in the female rabbit. Synthetic LH-RH (0.75 and 2.5 mug/animal) was administered to mature intact and castrated female rabbits. The animals were injected for 3 consecutive days with either 40 mug estradiol benzoate (EB) dissolved in 0.5 ml propylene glycol 60%, water 40% or with the solvent alone. LH-RH was injected i.v. on the 4th day. In intact rabbits EB priming increased the pituitary LH response while LH basal levels were lowered. In the unprimed castrated rabbits, basal FSH and LH levels and the cumulative responses to LH-RH were higher than in intact control animals; EB priming lowered basal LH levels and cumulative responses to the values of intact control rabbits while both basal FSH levels and the cumulative responses were less influenced by the treatment. It is concluded that estrogen acts at both hypothalamic and pituitary levels to modify the LH responses to endogenous LH-RH, and that the complete inhibition of FSH hypersecretion in the ovariectomized rabbit probably needs another ovarian factor.

Microanalysis in biology and medicine. A review of results obtained with three microanalytical methods. Three microanalytical methods have been used : X-ray emission, secondary ion emission and electron energy loss analysis. Althouth X-ray microanalysis is the most used method, many biological problems cannot be solved because of its relatively low sensitivity and inability to analyze light elements. New possibilities are offered by Secondary Ion Mass Analysis and Electron Energy Loss Analysis. Analysis by secondary ion emission permits the study of elements at low and even trace element concentration, and even the lightest elements such as hydrogen and beryllium are detected. Electron Energy Loss Analysis makes possible the study of very small volumes, less than 500 A in diameter. These methods have been applied to the study of a variety of biological tissues (mostly lungs, kidneys and biomineralized tissues) and typical applications to pathology and cell biology will be presented.

The five-year cure rate achieved by cryosurgery for skin cancer. Cryosurgery was used to treat 3540 new basal cell and squamous cell carcinomas of the skin from 1971 to 1989; a cure rate of 98.4% was achieved. To determine the 5-year cure rate in more recent years, the results of treatment of 684 nonmelanotic skin cancers from 1980 to 1984 were reviewed. In the group of 628 basal cell carcinomas, the 5-year cure rate was 99.0%. In the group of 52 squamous cell carcinomas, the 5-year cure rate was 96.1%. In the series were also four patients with basosquamous cell carcinomas, all of whom were recurrence free for 5 years or more. The overall 5-year cure rate in the 684 cases was 98.8%. On the basis of these data and our cosmetic results, we conclude that cryosurgery is an effective treatment that compares favorably with other established methods of therapy.

Effect of lovastatin on hypercholesterolemia in chronic renal failure. Using a mouse model of chronic renal failure (CRF), the possibility of using lovastatin to treat hypercholesterolemia associated with CRF was examined. Renal failure was induced in 5 week-old, C57BL/6J mice by electrocoagulation of the right kidney surface followed by left nephrectomy 2 weeks later. Five weeks post-nephrectomy, BUN and serum total cholesterol levels were assessed and lovastatin treatment commenced. Upon sacrifice 4 weeks later, BUN, serum total cholesterol levels and hepatic HMG-CoA reductase activity were measured. Results showed that CRF induced significant increases in serum total cholesterol levels and enzyme activity. Treatment with lovastatin led to a dose-dependent reduction in serum total cholesterol levels without affecting the enzyme activity. These results suggest that the hyper-cholesterolemia in CRF is partly due to an increase in de novo cholesterol synthesis in the liver and that the lipid-lowering effect of lovastatin is mediated by an action other than the direct reduction of hepatic HMG-CoA reductase activity.