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[Acetylcholine and the primary input of acupuncture sensation--influence of peripheral acetylcholine on the role of electroacupuncture analgesia]. In order to investigate the correlation between the peripheral ACh and the primary input of acupuncture sensation, in the paper the cholinesterase inhibitor--Neostigmine and the ACh synthesis blocker--Hemicholine, which are unable to pass through blood brain barrier, and ACh were used as tools to increase or decrease the level of ACh in peripheral nerve system of rats. The results indicated that: 1) The effect of electroacupuncture analgesia can be enhanced by subcutaneous injection of neostigmine which related to the dosage used. 2) The influence of electroacupuncture analgesia can be markedly inhibited by intraperitoneal injection of Hemicholine. 3) This influence of suppression by Hemicholine can be reversed at once when acetylcholine in combination with neostigmine was injected. But could not reverse by neostigmine alone. It suggested that the effect of electroacupuncture analgesia and the primary input of acupuncture sensation were significantly related to the level and content of ACh in periphery.

The hyperaemic response to a transient reduction in cerebral perfusion pressure. A modelling study. A mathematical model of cerebral blood flow and the cerebrospinal fluid circulation is described which permits the study of phenomena caused by dynamic changes in cerebrovascular autoregulatory or cerebrospinal fluid compensatory reserves. A transient decrease in cerebral perfusion pressure was produced by carotid artery compression. Comparison of the computer simulations with clinical and experimental data, reported elsewhere, suggests that the transient hyperaemic response (THR) is proportional to the strength of the autoregulatory response. The relationships between the magnitude and time course of the THR, and the period and level of reduction in CPP were studied. This model suggests that simple clinical tests based on the examination of THR using transcranial Doppler velocity measurements are of potential value for the non-invasive assessment of the autoregulatory reserve.

Plasma-membrane-independent pool of the alpha subunit of the stimulatory guanine-nucleotide-binding regulatory protein in a low-density-membrane fraction of S49 lymphoma cells. We report that compartmentalisation of the stimulatory guanine-nucleotide-binding regulatory protein (Gs) exists in S49 lymphoma cells. In addition to the previously reported cytosolic form of the alpha subunit of Gs (Gs alpha) [Ransnäs, L. A., Svoboda P., Jasper, J. R. & Insel, P. A. (1989) Proc. Natl Acad. Sci. USA 86, 7900-7903], three membrane-bound forms of Gs alpha were identified through rate-zonal centrifugation in sucrose density gradients, Gs alpha-specific anti-peptide serum and an adenylate cyclase complementation assay. The sedimentation profile of the first pool of Gs alpha in the high-density portion of the gradient (1.13-1.16 g/cm3) is identical with that of beta-adrenergic-receptor binding, Na/K-ATPase and adenylate cyclase activity, and may therefore be identified as plasma-membrane fragments. The second pool, which was recovered in the middle portion of the gradient (1.09-1.11 g/cm3), contains a much lower total amount of Gs alpha and correlates with the endoplasmic reticulum (microsomal) enzyme markers, NADPH-cytochrome-c reductase and glucose-6-phosphatase. The identity of the third pool of Gs alpha located at the top of the gradient (1.06-1.08 g/cm3), is unknown. The Golgi apparatus marker, UDPgalactose:N-acetylglucosamine glycosyltransferase, was partially recovered in this area; however, this enzyme was also present in the high-density portion of the gradient. Complete absence of specific adenylate cyclase and Na/K-ATPase activity indicates that this low-density (light) membrane form of Gs alpha is distinct from any plasma-membrane fragments. Furthermore, sedimentation at 100,000 x g proves its particulate (membrane) character. The light membrane form of Gs alpha subunit is functionally active in an adenylate cyclase complementation assay using cyc- membranes devoid of Gs alpha. Overall, our data indicates that a substantial portion of Gs alpha is localized in membrane pools other than plasma membrane.

[Smallpox vaccine, then and now. From the "cow lymphe" to the cell-culture vaccine]. There have been few changes in the preparation of smallpox vaccine since Eduard Jenner described his method of preventive inoculation in 1798. Jenner's vaccine, "the matter", was maintained in man by arm to arm passage. The only major achievement in production methods was the introduction of an animal host for virus propagation. The skin of living calves or sheep was inoculated with seed virus and the "pulp" harvested three to four days later. The disadvantages of this procedure are evident: massive bacterial contamination in spite of rigorous cleanliness and excessive amounts of undesired tissue debris in the crude material to be used for vaccine production. In spite of these obvious disadvantages the method is still in use all over the world. Advances in tissue culture techniques have led to the production of all modern vaccines for use in animals and in the human from this substrate with low initial content of foreign protein and of primary sterility. The only exception today is conventional smallpox vaccine. Sporadic attempts to produce smallpox vaccine in tissue culture have been recently and successfully made in England, Holland and Yugoslavia. The Bavarian State Institute of Vaccination has adopted Vaccinia strain Elstree to primary cultures of chick embryo fibroblasts. The virus propagation in roller bottles permits the economical production of a high titered vaccine with a stability equal to that of calf origin. The cell culture harvest is bacteriologically steril and has a minimal content of foreign protein. Within the past two years this cell culture vaccine has totally replaced the old "calf lymph". Vaccination takes are equal, complications have so far not come to our attention.

[Lipid composition of erythrocytes in iron deficiency anemia]. The assay of lipid composition in red blood cells of 51 patients with iron-deficiency anemia (IDA) was conducted with the use of horizontal thin-layer chromatography, and the state of the end blood flow was studied with the ai of conjunctival biomicroscopy. It was found that in IDA patients the content of total lipids, phospholipids, free fatty acids, cholesterol, sphingomyelins, cardiolipins and phosphatidic acids increased and that of triglycerides decreased. The content of the rest fractions of total lipids in IDA patients was practically not changed. Variations in lipid composition of red blood cells lead to disorders in their functional activity. In IDA patients it is clinically expressed in the development of the sludge phenomenon that aggravates tissue hypoxia in women with this disease.

Stroke topography and outcome in relation to hyperglycaemia and diabetes. In a prospective study to analyse stroke topography and outcome in diabetics and to determine the prognostic value of blood glucose and glycosylated haemoglobin estimation, we evaluated 176 patients with acute stroke. The patients were classified into four groups on the basis of history, fasting glucose, and glycosylated haemoglobin: euglycaemic patients with no history of diabetes, stress hyperglycaemia, newly diagnosed diabetics, and known diabetics. A high prevalence of undiagnosed diabetes was shown. No difference was found in the type or site of stroke between the four groups. No difference was found in the site of symptomatic or incidental lesions on computerised axial tomography. Patients with stress hyperglycaemia and known diabetics had more severe strokes. Mortality was higher in patients with stress hyperglycaemia, newly diagnosed diabetics, and the combined diabetes groups. This increased mortality was evident in the hyperglycaemic and diabetic groups, even after excluding patients with cerebral haemorrhage. Stroke severity and mortality also increased independently with blood glucose in the euglycaemic group. We conclude that there is a correlation between admission glucose concentration, diabetes, and poor stroke outcome, which may not be attributed to stroke type or location.

Metabolic fate of administered 1,25-dihydroxycholecalciferol in controls and in patients with hypoparathyroidism. In four healthy controls and three patients with hypoparathyroidism serum-1,25-dihydroxycholecalciferol (1,25-D.H.C.C.) concentrations, after oral or intravenous administration, declined biphasically with a rapid-phase half-time of about 14 hours. Repeated oral doses of 1 mug 1,25-D.H.C.C. (2-4 nmol) produced serum concentrations well below the assayed normal range but were nevertheless effective in raising serum-calcium. It is suggested that orally administered 1,25-D.H.C.C. acts directly on the intestinal mucosal-cell nucleus to promote calcium absorption. 1,25-D.H.C.C. is more rapidly eliminated from the body than vitamin D, and it is predicted that any hypercalcaemia caused by 1,25-D.H.C.C. therapy should be of relatively short duration.

The effect of structured and unstructured leader roles on internal and external group participants. This study assessed the impact of structured and unstructured leader roles on measures of outcome for Ss who differed on the pretest dimension "locus of control." On the basis of their pretest locus of control scores, Ss were assigned to a structured or an unstructured marathon group. The treatment in the two 16-hour -arathons consisted of a defined series of exercises; the only difference between the two groups was the degree of leader control over member participation. As predicted, internal Ss in the unstructured group rated the leader and the group more psoitively than did external Ss, while the reverse responsivity occured in the structured group. Significant Locus of Control X Treatment interactions indicated that internal and external Ss reflected differential shifts in general anxiety, general depression, and locus of control as a function of treatment. The relationship between changes in self-actualization and locus of control and changes in conflict-handling styles and negative affects differed as a function of locus of control and treatment condition. The overall results coupled with prior findings tentatively support the appropriateness of an unstructured leader role for internal scores and a structured leader role for external scorers.

Liquid chromatography with fluorescence detection of lasalocid sodium in feeds and premixes. Lasalocid sodium is extracted directly from feeds and premixes with the mobile phase solution, an aliquot is chromatographed, and the concentration (peak height) of lasalocid sodium is measured by high pressure liquid chromatography with fluorescence detection. Chromatography and detection are completed in about 7 min. The results agree well with those found by the official AOAC fluorometric method, 42.A08--42.A13. The method offers an alternative to the AOAC method and has the capability of processing almost twice as many samples. The average recovery of 4 levels (0.0008, 0.0040, 0.0080, and 0.0120%) of lasalocid sodium from feeds is 100%. Replicate assays of typical poultry mashes and pellets containing about 0.0080% lasalocid sodium yielded coefficients of variation of 2.68--3.35%.

Radiocontrast-associated renal dysfunction: a comparison of lower-osmolality and conventional high-osmolality contrast media. Nephropathy is an established untoward event associated with intravascular administration of conventional high-osmolality contrast media (HOM). It has not been shown previously that lower-osmolality contrast media (LOM) are less nephrotoxic in a clinical setting. We evaluate the ability to replace HOM with LOM (in lower-extremity angiography) to reduce the incidence of nephropathy. We use multiple definitions for contrast-induced nephropathy (six different magnitudes of rise of serum levels of creatinine or blood urea nitrogen in various periods). The incidences of nephrotoxic effects with LOM vs HOM in patients with presumed risk factors, including preexisting renal insufficiency and diabetes, are evaluated also. When all patients are considered, the incidence of contrast-induced nephropathy for LOM vs HOM (defined as an increase in serum creatinine level greater than 0.3 mg/dl and greater than 20% on day 1, 2, or 3 and on day 5, 6, or 7, is 7% vs 26% (p = .001). When only patients with preangiography azotemia are considered, the incidence of contrast-induced nephropathy for LOM vs HOM is 10% vs 41% (p = .017); for diabetic patients, regardless of preangiography creatinine level, the incidence is 10% vs 31% (p = .012). Although contrast-induced nephropathy may develop even in a patient with no risk factors who receives LOM, LOM is associated with a decreased incidence of this condition, to various degrees, depending on the presence of risk factors.

Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Liver parenchymal cells continuously extract high amounts of bile acids from portal blood plasma. This uptake process is mediated by a Na+/bile acid cotransport system. A cDNA encoding the rat liver bile acid uptake system has been isolated by expression cloning in Xenopus laevis oocytes. The cloned transporter is strictly sodium-dependent and can be inhibited by various non-bile-acid organic compounds. Sequence analysis of the cDNA revealed an open reading frame of 1086 nucleotides coding for a protein of 362 amino acids (calculated molecular mass 39 kDa) with five possible N-linked glycosylation sites and seven putative transmembrane domains. Translation experiments in vitro and in oocytes indicate that the transporter is indeed glycosylated and that its polypeptide backbone has an apparent molecular mass of 33-35 kDa. Northern blot analysis with the cloned probe revealed crossreactivity with mRNA species from rat kidney and intestine as well as from liver tissues of mouse, guinea pig, rabbit, and man.

Human proximal tubular cells modulate allogen responses of leukocytes in vitro. The interaction between proximal tubular cells and leukocytes was examined. In co-cultures of tubular cells and allogenic leukocytes, tubular cells expressed MHC antigens and ICAM-1. A small number of leukocytes adhered to tubular cells and induced cytotoxic damage. Thus, 65% of the tubular cells were viable after co-culturing with allogenic leukocytes. These cells had low alloreactive capacity, which was not due to lack of interleukin-1 or interferon-gamma. The presence of tubular cells modulated the immune response of leukocytes by reducing the effect of mitogen by 80%, allogens by 65% and interleukin-2 by 40%. A soluble factor released in the co-cultures was a likely mediator, since addition of supernatants from co-cultures suppressed mitogen responses by 27% compared to leukocytes cultured alone. This mediator might be prostaglandin, because addition of indomethacin to co-cultures increased the growth response of leukocytes.

[Umbilical Doppler velocimetry in prolonged pregnancies]. One-hundred and eighty-seven single pregnancies, at full term determined accurately and confirmed by ultrasound before 17 weeks of amenorrhea and which were proceeding normally were monitored every 2 days after the expected end of term. This was done by conventional methods and in 132 cases by determining a placental resistance index (R = D/S). All the deliveries were carried out under monitoring and the infants examined by a pediatrician. The umbilical index at 280 to 300 days of gestation was found to be constant and equal to R = 0.52 +/- 0.041 (n +/- D) and the signs of fetal distress and post-maturity increased beyond term. In the first 80 pregnancies studies in this way, the determination of the value of the index R was not included in the decision-making process. Twelve of the 14 cases of fetal heart rate arrhythmia during delivery and all recorded cases of post-mature clinical signs and neonatal acidosis occurred when the index was above RI = 0.54. The next 107 pregnancies were randomly divided into two groups. In the 52 pregnancies in which the Doppler revealed an index at two consecutive determinations in excess of 0.54, this was taken to be a criterion for the induction of childbirth. In this group, some of the women gave birth earlier, without any increase in the number of Caesareans and this resulted in fewer post-mature infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Episodic secretion of arginine vasopressin. The plasma arginine vasopressin (pAVP) response to osmotic stimulation was studied in dogs and sheep by sampling at frequent intervals during steady-state dehydration and during water diuresis. Frequent sampling also was conducted after continuous infusion or bolus injection of 5 or 20 g/100 ml NaCl. A pulsatile pattern of pAVP was observed after such infusions or injections and in some animals after water deprivation. This pattern was not seen after water loading or in mildly dehydrated animals. The short term changes in pAVP during continuous infusion of 5 g/100 ml NaCl could not be correlated with variations in plasma tonicity. Rather, they appeared to reflect discontinuous hypothalamic posterior pituitary release of AVP. Thirst was evoked by a lower dose of 5 g/100 ml NaCl than was required for consistent stimulation of pAVP release, and the thirst response frequently was observed prior to the peak AVP response after bolus injection of 5 and 20 g/100 ml NaCl.

Expression of the ETS2 and transferrin receptor genes in Philadelphia-positive chronic myeloid leukemia patients with a reciprocal t(3;21). The translocation t(3;21)(q26;q22) is a rare recurring clonal abnormality, either preceding or associated with blast crisis in Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients. We previously localized the chromosomal breakpoints at 3q26.2 and 21q22.2, using high resolution chromosomal analysis. Two genes of interest are localized near the breakpoints, the transferrin receptor gene and the ETS2 proto-oncogene. Their chromosomal localizations, determined by in situ hybridization on normal metaphase cells, were 3q29 and 21q22.3, respectively. They underwent a reciprocal translocation in patients with t(3;21). Their structures were not altered by the translocation, and both were expressed to varying levels in t(3;21) patients. Southern blotting investigations showed that the structure of other single-copy genes, including FIM3, localized near the breakpoints, were not affected by the translocation. An analysis of ETS2 expression performed on CML patients without t(3;21) showed the presence of the transcript in 100% of the blast crises, but only in 20% of the chronic-phase patients. Thus ETS2 expression may either be linked to or play a role in CML progression.

Nature of the regions involved in the insertion of newly synthesized protein into the outer membrane of Escherichia coli. Outer membrane proteins are synthesized by cytoplasmic membrane-bound polysomes, and inserted at insertion sites which cover about 10% of the total outer membrane when cells grow with a generation time of 1 h. A membrane fraction enriched in outer membrane insertion regions was isolated and partly characterized. The rat at which newly inserted proteins are transferred from such insertion regions into the rest of the outer membrane was found to be very fast; the new protein content of insertion regions and that of the remaining outer membrane equilibrate completely within about 20 s at 25 degrees C. Given the rather rigid structure of the outer membrane and the multiple interactions between outer membrane components and the murein layer, lateral diffusion of newly inserted proteins from insertion sites to the remaining outer membrane is not likely to explain this rapid equilibration. Instead, the data support a model in which insertion regions move along the cell surface, leaving behind stationary, newly inserted outer membrane proteins.

Hemodynamic evaluation in patients with superficial temporal artery-middle cerebral artery anastomosis--stable xenon CT-CBF study and acetazolamide. Sixteen patients with minor completed stroke in the chronic stage underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. The acetazolamide-activated regional cerebral blood flow (rCBF) was measured 20 minutes after the injection using inhalation of stable xenon and computed tomographic scanning (Xes CT-CBF study) pre- and postoperatively. Eleven patients (Group 1) showed immediate improvement in neurological state within a few days of the operation, while five (Group 2) showed no improvements. Preoperative rCBF in the ischemic areas without infarction was 30.8 +/- 3.0 ml/100 gm/min in Group 1 and 53.0 +/- 5.2 ml/100 gm/min in Group 2. Preoperative vasodilatory capacity with acetazolamide in Group 1 was 5.7 +/- 8.6 and significantly increased to 19.8 +/- 4.9 after surgery. In Group 2, pre- and postoperative vasodilatory capacity was 12.7 +/- 3.1 and 14.9 +/- 2.9, respectively, and there was no significant change. These results suggested that minor stroke patients with moderate decrease of affected side rCBF (less than 40 ml/100 gm/min) and with hemodynamic impairment may have the surgical indication for STA-MCA anastomosis.

Human bone marrow lymphocytes. III. Polyclonal activation of B lymphocytes in human bone marrow measured by a direct plaque-forming cell assay. Lymphocytes from the bone marrow and peripheral blood of the same normal individuals were assayed simultaneously for blast transformation as well as polyclonal activation with differentiation to antibody-forming cells after stimulation with pokeweed mitogen. Blastogenic responses were measured by tritiated thymidine incorporation and antibody-forming cell assay. There was no significant difference between the blastogenic responses of lymphocytes in the peripheral blood compared to the bone marrow of the same individuals. However, differentiation to antibody-forming cells measured by the plaque-forming cell response was significantly greater in lymphocytes in the bone marrow as compared to peripheral blood of the same individuals. These studies demonstrate that the lymphocytes in human bone marrow are at a stage of differentiation whereby they can be readily induced to differentiation toward antibody production by polyclonal activation, even more so than peripheral blood lymphocytes. This supports the concept that the bone marrow is a major source of immunoglobulin production in man.

The TIS11 primary response gene is a member of a gene family that encodes proteins with a highly conserved sequence containing an unusual Cys-His repeat. The TIS11 primary response gene is rapidly and transiently induced by both 12-O-tetradecanoylphorbol-13-acetate and growth factors. The predicted TIS11 protein contains a 6-amino-acid repeat, YKTELC. We cloned two additional cDNAs, TIS11b and TIS11d, that contain the YKTELC sequence. TIS11, TIS11b, and TIS11d proteins share a 67-amino-acid region of sequence similarity that includes the YKTELC repeat and two cysteine-histidine containing repeats. TIS11 gene family members are not coordinately expressed: (i) unlike TIS11, the TIS11b and TIS11d mRNAs are detectable in quiescent Swiss 3T3 cells and are not dramatically induced by 12-O-tetradecanoylphorbol-13-acetate; (ii) cycloheximide superinduction does not occur for TIS11b and TIS11d; and (iii) unlike TIS11, TIS11b expression is extinguished in PC12 pheochromocytoma cells.

Collagen metabolism in infected colonic anastomoses. Infection of the peritoneum has an adverse effect on the healing of colonic anastomoses. It has been suggested that infection results in a disturbance of colonic collagen metabolism, but the precise nature of the biochemical disorder is uncertain. Colonic collagen metabolism was studied in infected anastomoses in the left colon of rats. The rats were labeled with radioactive proline from an early stage of growth, and infected anastomoses were compared with anastomoses of the control group of uninfected rats. Infection resulted in significant changes in collagen metabolism during the early phase of colonic healing. There was a significant reduction in the amount of salt soluble collagen in infected anastomoses on the third postoperative day compared with anastomoses of the control group, and reduced amounts of acid soluble collagen and insoluble collagen were found in infected anastomoses on the seventh postoperative day. These observations suggest that the defective healing of infected colonic anastomoses results either from an increased lysis of newly formed--salt soluble--collagen or from a reduction in the intracellular formation of collagen.

Predictability of FEV1 after pulmonary resection for bronchogenic carcinoma. The aim of this study was to review the reliability of prediction of postoperative FEV1 in patients with bronchogenic carcinoma using a Tc-99m perfusion scan and simple spirometry. Over a 27-month period, 40 patients without known recurrent disease had their FEV1 measured. One quarter of the postoperative values for FEV1 differed from predicted values by less than 5% (2/11 pneumonectomies, 5/23 lobectomies, 3/6 segmental resections) and half differed by no more than 10% of predicted FEV1 (4/11 pneumonectomies, 12/23 lobectomies, 3/6 segmentectomies). One tenth of the predicted values differed by more than 30% and up to 760 mls (1/11 pneumonectomies, 2/23 lobectomies, 1/6 segmentectomy). Disease recurrence, phrenic nerve paralysis, exacerbation of obstructive pulmonary disease and poor collaboration during spirometry explained the most severe erroneous results. Age, preoperative smoking, tumour stage and histology, absence of symptoms at the time of diagnosis and adjuvant radiotherapy showed no statistically significant effect on predictability. Twenty-one patients had a postoperative Tc-99m pulmonary scan simultaneous to the spirometric control. Overestimation of postoperative FEV1 was associated with heterogeneous distribution of ventilation and perfusion.

Aminopeptidase B in human serum. The activity of arginine aminopeptidases in human serum was studied with special reference to the possible involvement of enzymes resembling aminopeptidase B (APB). The serum samples were obtained from 10 patients with various acute inflammatory processes, both during the acute phase and after treatment with penicillin. The administration of penicillin to the patients did not result in noticable changes in the chromatographic pattern of the APB-like enzyme. The disappearance of the acute symptoms did not significantly affect the overall specific activity of arginine aminopeptidases in serum. The results showed that human serum does contain, contrary to earlier reports, an enzyme corresponding to APB, even though in very low concentrations. The low enzyme activity was revealed by prolonged reaction times and by the use of larger samples in chromatography than earlier. The APB-like enzyme in serum may have derived from blood cells.