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A quantitative structure-activity relationship (QSAR) has been formulated for the inhibition of glyoxalase I from yeast by 37 S-substituted glutathiones: log 1/C = 1.23 pi' + 1.20 MR4 - 0.67 I1 - 0.14 pi'2 + 1.85 C in this expression is the molar concentration of inhibitor producing 50% inhibition, pi' is the usual hydrophobic parameter modified for certain substituents, MR4 is the molar refractivity of certain p-phenyl substituents, and I1 is an indicator variable for those congeners with an acetylated alpha-amino group. This equation should be of help in the design of more effective inhibitors which may be of value in cancer chemotherapy. | US |
To study the resistance of normotensive vascular beds in coarctation hypertension, we measured perfusion pressures of pump-perfused (blood), innervated, isolated hindlimbs of 12 rats (Group A) with 4 weeks of hypertension due to partial contriction of the abdominal aorta above the renal arteries, and of three control groups: 11 normotensive rats (Group B) with aorta sham-constricted, nine normotensive rats (Group C) with slight (5%) hindquarters atrophy due to partial constriction of the abdominal aorta below the renal arteries, and six rats with two-kidney, one clip Goldblatt hypertension (Group D). After aortic constriction, measured femoral arterial pressures in Group A rats remained normotensive. In hypertensive rats of Groups A and D, compared to normotensive Group B or C rats, hindlimb pressure-flow curves were displaced toward the pressure axis (p < 0.05). Compared to normotensive rats, drop in hindlimb resistance after acute local nerve section was increased in rats with coarctation hypertension. Residual resistance after maximal vasodilation with intraarterial sodium nitroprusside remained elevated in hypertensive rats of Groups A and D (p < 0.05), as compared to normotensive Group B or C rats; compared to Group B rats, this residual resistance in the coarcted rats of Group A was increased by 9%. Thus, in normotensive vascular beds of rats with chronic hypertension caused by aortic coarctation, resistance is elevated. The neurogenic component contributes to this high resistance, and structural vascular changes, indicated by impaired maximal vasodilation, may also contribute to the elevated resistance. It is most unlikely that these resistance changes are attributable to elevated hindlimb intravascular pressures. | US |
The effect of middle-ear dysfunction and disease on hearing and language development at one year of age was evaluated for 143 high-risk infants. These infants were categorized as normal or abnormal based on otologic history, otoscopic examinations, and on tympanometric examinations. Language was significantly related to gestational age, being delayed by approximately the amount of prematurity. Language scores were therefore adjusted for gestational age. Speech-detection threshold was not related to gestational age, and was used as the measure of hearing. Hearing levels were negatively correlated with adjusted language quotients. Infants with abnormal otologic histories reported were not different from infants with normal histories in either hearing or language development. Infants with bilateral otoscopic abnormalities had significantly higher speech-detection thresholds, but did not differ in language development from those with bilaterally normal otoscopy. Infants who were abnormal bilaterally by tympanometric examination had significantly higher speech-detection thresholds as well as significantly delayed language development. A significant effect on both hearing and language was found among those infants bilaterally abnormal by tympanometry for whom evidence of middle-ear disease was not visualized by otoscopic examination. Implications of these findings are discussed. | US |
Autoregressive analysis, a statistical technique for detecting changes in electroencephalic (EEG) and heart rate (HR) data was compared with clinical behavioral audiometric results on 10 hearing-impaired children in schools for the hard of hearing and deaf. EEG and HR data were collected in a screening paradigm involving tones of .5, 1, and 4 kc/s at 80 db SPL in a free field. An index of reliability, or acceptable level of agreement, was set at 70%. This criterion was met 5 out of 6 times. For the EEG, agreements exceeded 70% at 1 and at 4 kc/s, and for HR at all 3 frequencies. Results suggest that the autoregressive approach yields data very similar to behavioral audiometry in this population. Continued exploration of autoregressive analysis of electrophysiologic indices in determining reactivity to tones is warranted, particularly since the statistical method can be used with younger infants. | US |
Eyeblink reflexes to airpuffs to the orbit are inhibited by preliminary tones even of low intensity, and the amount of inhibition or "reflex modulation" (RM) is correlated with tone loudness. Brief pure tones were presented 100 msec prior to an airpuff to the eye and eyeblink amplitude was recorded in 7 normal-hearing adults. Tones of several levels were either in quiet or in a white noise of 73.5 dbC. As tones increased in intensity, RM increased faster to stimulation in the masked than in the unmasked ear, simulating the classical "pseudo-recruitment" in the noise-masked ear. In addition, very rapid growth of RM was found at 4 kc/s in a patient with sensorineural impairment of 70 db at that frequency as compared with the RM from a frequency with normal HTL. These data confirm the potential of RM in the objective quantification of loudness recruitment. | US |
Experiments were performed on unanaesthetized ewes in the last third of pregnancy. Fetuses and ewes had indwelling vascular catheters. In some of the experiments fetal urine was drained to the exterior by means of an indwelling vesicular catheter. Placental diffusion permeabilities were measured with 22Na+ and 36Cl- injected into eight fetuses. Volumes of distribution of Na+ and Cl- in the conceptus were Na+: 548 +/- 24, Cl-: 760 +/- 51 (ml/kg fetal wt +/- SEM). Diffusion permeabilities were Na+: 5.2 X 10(-3) +/- 0.3 X 10(-3), Cl-: 9.8 X 10(-3) +/- 0.9 X 10(-3) (ml.s-1.kg-1 +/- SEM). Ultrafiltration-reflection-coefficients of Na+ and Cl- in the placental exchange barrier were measured 17 times in seven fetuses with vesicular catheters. The transplacental e.m.f. was estimated from these results, on the assumption that the individual reflection-coefficients of Na+ should correlate with those of Cl-. The best estimate was -1.0 mV (fetus negative), and the best estimates of the placental reflection-coefficients were Na+: 0.83 and Cl-: 0.79. There was a reliable negative correlation (P < 0.01) between the calculated reflection-coefficients and the osmolality of the urine secreted by the fetus. This suggested that the concentration of vasopressin in fetal plasma affects the membrane characteristics of the placenta. The mean total osmotic force across the placental barrier of the sheep in these experiments was calculated to be 260 Pa (2 mmHg). | US |
The uterine uptake of amino acids was studied in 10 pregnant sheep with gestational ages of 114-146 days. After recovery from surgery, arterial and uterine venous samples were drawn simultaneously via indwelling catheters and analysed for amino acid and oxygen content. In seven ewes, amino acid concentrations were measured by a chromatographic technique. In four ewes, glutamate and glutamine arterio-venous differences across the uterine and umbilical circulations were measured by an enzymatic method. The uptake of neutral and basic amino acids was 66 mumol/mmol O2 and 17.3 mumol/mmol O2, respectively. Comparison of uterine and umbilical uptake shows that the bulk of the neutral and basic amino acids taken up by the pregnant uterus are transferred to the fetus. there was no significant uptake of acidic amino acids (i.e. glutamate, aspartate and taurine). glutamate was delivered from the fetus to the placenta but excretion of glutamate into the uterine circulation was negligible. Glutamine and asparagine were delivered to the fetus in amount which were two to three times larger than the placental uptake of glutamate and aspartate. Therefore placental conversion of exogenous glutamate and aspartate to glutamine and asparagine cannot account entirely for the fetal uptake of these amino acids. | US |
Sixteen patients affected with multiple endocrine neoplasia, type 2b (MEN 2b), were evaluated by clinical, neurological, nerve conduction and electromyographic, and postmortem examinations. Eight of the 11 patients examined clinically had symptoms: 5, neurogenic constipation; 1, failing vision due to hypertrophied corneal nerves; 1, neuromuscular symptoms and pes cavus; and 1, facial disfigurement. Expression of the dominantly inherited MEN 2b gene is more variable than previously known. When neuromuscular findings are present alone, the features may be those of peroneal muscular atrophy. Because 10 of the 11 patients had sufficiently full expression of the dominantly inherited gene--"Marfanlike" body build, full and fleshy lips, whitish yellow nodules (neuromas) on the tip and edges of the tongue, pes cavus, or peroneal muscular atrophy--the presence of MEN 2b was recognized and a search for the usually associated medullary thyroid carcinoma was instigated. In addition to the recognized involvement of autonomic nerves, we have confirmed that somatic motor and senory neurons may be involved. Findings at postmortem evaluation indicate that symptoms can be attributed to neuroma formation: a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior columns of the spinal cord. | US |
The influence of norepinephrine and/or acetylcholine on K uptake of the guinea pig sinus node was investigated. Both "high" (10(-6) M) and "low" (10(-9) M) mediator concentrations were employed. The following results were obtained: 1) high concentration of norepinephrine increased K uptake; 2) high concentration of acetylcholine had a similar effect; 3) simultaneous exposure to both mediators did not lead to summation of the effects; 4) low concentration of norepinephrine depressed K uptake; 5) high concentration of acetylcholine overcame the inhibitory effect of the small concentration of norepinephrine; 6) 2-deoxy-D-glucose did not abolish the stimulating effect of acetylcholine on potassium uptake; and 7) strophanthidin abolished the stimulatory effect of norepinephrine, but not that of acetylcholine. The following conclusions are drawn: 1) both neuromediators in suitable concentrations increase K uptake in the sinus node; 2) the mechanism of such an increase is different, norepinephrine increasing the active and acetylcholine increasing the passive potassium transport; 3) a low concentration of norepinephrine depresses K uptake; and 4) when the two mediators are administered together, acetylcholine suppresses the action of norepinephrine on K transport. | US |
The radiobiological parameters at the basis of radiation are: randomness of cell killing by irradiation, hypoxia and reoxygenation, does response curves, relationship of histology and radiosensitivity, doses necessary to control sub-clinical disease and gross tumor, and the rationale for combining irradiation and surgery. The volume of cancer is the determining factor in treatment planning. Since there is no correlation between the volume of the tumor and 1971 FIGO staging, staging should not be used in treatment planning but instead the volume and extent of the tumor. For the "barrel-shaped" lesions originating in the endocervix, a simple extrafascial hysterectomy is very effective after somewhat diminished irradiation. Great interest has been given to irradiating not only the pelvic wall but also the common iliac and/or paraaortic lymphatics. Since the volume of tissues irradiated to high doses of external irradiation is a limiting factor, with fields extended to L4 or T12, the total external irradiation dose cannot exceed 4,500 rad. | US |
This investigation was designed to examine self-esteem and depression in diabetic adolescent girls. One hundred nondiabetic girls age 12-16 and 105 diabetic girls age 12-16 were administered the Rosenberg Self-Esteem Scale and the Beck Depression Inventory. Results indicated no significant difference between diabetic and nondiabetic girls in self-esteem scores. Diabetic girls showed significantly more depression than nondiabetic girls. Close examination of results revealed that, in fact, diabetic and nondiabetic adolescent girls were very similar. A major finding was that depression in the diabetic group was expressed primarily through physiologic symptoms of depression as seen in the vital depression scores, rather than through the pessimism, indecision-inhibition, or self-debasement measures of depression. Results were interpreted to mean that diabetic girls did not manifest deeper depression than nondiabetic girls but, rather, a greater awareness of their physiologic status. Diabetes emerged as a focus for the expression of normal adolescent conflicts. The importance of integrating developmental issues into the treatment plans for diabetic patients is emphasized. | US |
Schmidt's syndrome (thyroid and adrenal insufficiency) and concurrent diabetes mellitus represent an intriguing multiple endocrinopathy in children. This report describes an eleven-year-old girl with diabetes of eight years' duration presenting in adrenal crisis. Serum thyroxine was undetectable, and antibodies to both thyroglobulin and adrenal tissue were found in high titer. The child's condition stabilized with hormonal replacement therapy, except for persistent growth failure. Approximately two years later she succumbed during a rapidly fulminant episode of ketoacidosis. The natural history of her illness supports recent speculation based on serologic data that juvenile diabetes mellitus may be an immunologic disorder in some children. | US |
Many of the morphologic and biochemical features of porcine coronary atherosclerosis produced by high cholesterol, high fat diet and propoylthiouracil returned to control values after cessation of the atherogenic regimen. These include disappearance of foam cells and a decrease in lipid content, DNA concentration, and DNA and protein synthesis. The morpholigic and biochemical features of te atherosclerotic lesions described herein were similar to those produced in swine and other species by a variety of inciting agents during both the progression and regression phase of the disease. These results indicate that the porcine propylthiouracil-diet model may be useful for the study of coronary lesions. Second, the similarities of response of arterial tissue in several experimental animals suggest the possibility that human coronary lesions by analogy may regress under therapeutic regimens. | US |
Aedes aegypti, on Grand Bahama Island, is restricted to certain western towns, whereas A. bahamensis is more generally distributed. During 14 years of observation, the range of A. Aegypti has extended 8 km and now includes the major tourist centre. Relocation of discarded automobile tires is an important mechanism for such spread. We suggest that the presence of A. bahamensis restrains colonization by A. aegypti, and thereby helps to protect human populations from A. aegypti-borne disease. | US |
Genetic analysis indicates that dieldrin resistance in laboratory colonies of Anopheles culicifacies is under the control of codominant alleles of a locus in linkage group 3 (chromosome 3), approximately 31 map units from Acph (acid phosphatase). | US |
Previous work of del Castillo and co-workers has shown that bilayer lipid membranes (BLM) can be used as transducers for detection of antigen-antibody reactions. The present experiments extend the previous work by incorporating complement into the BLM system. The results indicate that the antigen-antibody complex or the complement has no ability to affect the BLM system separately, but when carefully combined they will destabilize the BLM as a tool for investigating immunological reactions is suggested. | US |
The embryotoxic and teratogenic potential of sulfur dioxide (SO2) was evaluated in CF-1 and New Zealand rabbits exposed to SO2 alone or in combination with carbon monoxide (CO). The animals inhaled filtered room air (controls), SO2 (mice, 25 ppm; rabbits, 70 ppm), or SO2 plus CO (250 ppm) for 7 hr/day from days 6 through 15 (mice) and from days 6 through 18 (rabbits) of gestation. In both species, inhalation of SO2 resulted in slight toxicity in the dams and an increased incidence of minor skeletal variants among their offspring; exposure to the combination did not potentiate the increased incidence of these variants. A teratogenic effect was not discerned in either mice or rabbits exposed to SO2 alone or in combination with carbon monoxide, but the fetuses of mice exposed to the combination were significantly smaller than those exposed only to SO2. | US |
The effect of inhaled sulfuric acid (H2SO4) on embryonal and fetal development was assessed in CF-1 mice and in New Zealand white rabbits. Both species were exposed for 7 hr/day to 0, 5, or 20 mg H2SO4/m3 during the period of major organogenesis (mice, days 6 through 15 of gestation; rabbits, days 6 through 18 of gestation). Little evidence of toxicity was seen in the fetuses of mice or rabbits exposed to H2SO4. Slight maternal toxicity was seen at 20 mg H2SO4/m3 in both species. Teratogenicity was not observed in either mice or rabbits exposed to H2SO4. | US |
Chickens were exposed to SO2 in relatively low concentrations (3.4 to 18.5 parts per million (ppm)) for 1 to 14 days. A portion of their tracheas was embedded in water-soluble methacrylate, cut at 2 micrometer and stained with hematoxylin and eosin, Wright's stain, methyl green-pyronin, Alcian blue - periodic and Schiff, and for acid phosphatase. An increase was found in (a) the mucosa to wall ratio; (b) the number of mucosal cells in mitosis; (c) the number of macrophages, lymphocytes, plasma cells, and neutrophils in the epithelium and lamina propria; and (d) the number of these infiltrating cells which contained acid phosphatase. The number of mucus- and seromucus- secreting cells and vasoamine-containing cells were sometimes increased, but not consistently. The percentage of cells containing sialidase-sensitive sialomucins was elevated, and percentage of cells containing neutral mucins was reduced. These changes were only partly related to the SO2 concentration and the duration of SO2 exposure, in that increasing amounts of SO2 did not always cause increasing changes in the mucin composition. Evidently, the altered mucins sometimes protected against further mucin modification. | US |
Pregnant mice were treated with a single oral dose of [carboxy-14C]2,4,5-T (100 mg/kg; 1.22 mu Ci/mg) on day 12 of gestation and sacrificed after 0.25, 0.5, 2 and 24 hours. Maternal blood, embryos, placentas and yolk sacs were analyzed by solvent extraction, TLC, and countercurrent distribution. Expressed as percentage of the administered dose/g tissue, the unchanged 2,4,5-T found in maternal blood, placentas, yolk sacs, and embryos was 3, 0.5, 0.5, and 0.2%, respectively, after 0.25 hours, and 4, 2, 2, and 0.5%, respectively, after 24 hours. No major metabolites of 2,4,5-T were detected. Urine and feces were also collected and analyzed. Radioactivity was largely eliminated in the urine, 69-78% of the administered dose in 7 days. Feces contained 5-9% of the dose. In the urine unchanged 2,4,5-T accounted for 35-44% of the dose, and 22-23% as very polar material. Unchanged 2,4,5-T in the feces was 3-5% and 1-2% as polar material. 2,4,5-T administered to pregnant mice is largely distributed and eliminated as 2,4,5-T and very polar material. | US |
A study was undertaken of the acute effect of the inhalation of ozone (1.0-1.5 ppm) on the concentration of proteins in the airway secretions harvested from the trachea of intact anesthetized dogs. Secretions were first collected during a control day during which room air was breathed. The dogs breathed ozone (1.0-1.5 ppm) on a second day. This protocol permitted each dog to serve as its own control. During the inhalation of ozone the concentration of total aqueous-soluble proteins, as well as of albumin and IgG were not significantly effected. However, when expressed as a percentage of total protein, both albumin and IgG were significantly enriched in the secretions. The quantitative changes of certain proteins in airway secretions may be an important reflection of the pulmonary response to ozone. | US |
In a population of 158 women with a breast concern, two-thirds examined their own breasts. Most examiners (80%) practiced breast self-examination at least once a month, and over 60% had been regular examiners for more than 2 years. No significant difference in frequency of breast self-examination was found between women who had been examiners for longer and shorter time periods. Examiners had two main reasons for beginning and continuing breast self-examination: (1) an awareness that it is desirable to detect breast cancer early and (2) an awareness that they themselves could get breast cancer, while nonexaminers tended to deny this possibility. Therefore, to become examiners, nonexaminers may need to be convinced not only that early detection is effective but also that they too are at risk of breast cancer. The importance of informing, but not alarming, women about their breast cancer risk is discussed. | US |
Habit is defined as a firmly established behavior pattern marked by increasing automaticity, decreasing awareness, and partial independence from reinforcement. Reinforcement is viewed as of primary importance in the acquisition of behavior, whereas principles of associative learning enter to complement reinforcement in the maintenance of behavior. Habit is seen as a mechanism for short-circuiting the reinforcement process to avoid its overload and for providing the organism with speed and stability of response instead of the variability offered by reinforcement. The implications of this definition of habit for acquisition and alteration of health behavior are discussed; examples include smoking, obesity, alcoholism, and coronary-prone (type A) behavior. | US |
A brief review of the literature surrounding the relationship between plasma levels of tricyclic antidepressants currently available in the United States and clinical efficacy is presented. While therapeutic ranges for plasma levels of some tricyclic antidepressants are reasonably well established, the relationships between plasma levels of others and clinical efficacy require further clarification. Conditions under which plasma level measurements are clinically useful and factors that alter steady-state plasma levels are discussed. | US |
A mean decrease in plasma phenytoin concentrations of 11-14% (p less than 0.005) was observed in seven patients within 4 days after influenza vaccination. Possible mechanisms are discussed. | US |
A routine gas chromatographic assay for urinary 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), the major metabolite of phenytoin (PHT) in man, was adapted to allow quantitation of 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin (Dihydrodiol, DHD) is based on the observation that acid-catalyzed dehydration of DHD quantitatively yields a mixture of p-HPPH and m-HPPH in a reproducible molar ratio of 56:44p-HPPH: m-HPPH and on the assumption that all m-HPPH found in urine after heating with acid has been derived from DHD. The urinary DHD content was verified by a "specific" method in which urine was incubated with beta-glucuronidase and the released phenolic metabolites completely removed by extraction. Subsequent acid-catalyzed dehydration of the remaining DHD yielded p-HPPH and m-HPPH, from the sum of which the original DHD concentration in urine could be calculated. In all of the urine samples from PHT patients examined to date, there was close agreement between the DHD values obtained by the "specific" method and those calculated from m-HPPH, in the simple acid-hydrolysis method. It can be inferred that much the greater part (greater than 90%) of m-HPPH found in human urine after acid treatment has been derived from DHD. All samples of urine after acid treatment has been derived from DHD. All samples of urine from PHT patients examined have shown detectable quantities of DHD. The methods described here may be useful in a survey of PHT patients to reveal unusual patterns of PHT metabolism and to permit recognition of possible associations between such unusual patterns and the occurrence of adverse reactions. | US |
Clonazepam is an antiepileptic drug for which a number of analytical procedures have been presented, none of which have been subjected to comparison studies. We present two gas chromatographic (GC) methods involving distinct forms of detection for determining plasma or serum drug levels. Both methods involve simple extractions, common GC conditions, and routine data reduction. Both employ nitrazepam as an internal standard, require 1 ml of sample, and have a detection limit of 1 ng/ml. The two methods, GC-electron capture and GC-mass spectroscopy, are precise and accurate. Correlation of the two methods paired sample analysis gave a regression equation of y = 0.988x - 0.14 (n = 30, r = 0.971, p less than 0.001). We suggest that either method is a reasonable alternative for the clinical laboratory with the proper instrumentation. | US |
All 1998 resident infant deaths in the 1969--1977 King County, Washington birth cohort of 139,132 resident live births comprise the data base for epidemiologic comparisons of the sudden infant death syndrome (SIDS) with eight other major infant mortality components: hyaline membrane disease; respiratory distress syndrome; asphyxia of the newborn; immaturity; birth injury; congenital malformation; infection; and "all other." These components were compared with respect to age at death; sex; race; prior fetal loss; prior live-born, now dead; birth plurality; birth weight; maternal age; birth order; marital status; prenatal care; and season of death in an attempt to determine the uniqueness of these purported SIDS risk factors. Only the age at death distribution unequivocally distinguished SIDS from the other components. The combination of low maternal age and multiparity was demonstrated to be putatively synergistic for risk of SIDS, hyaline membrane disease, and respiratory disease syndrome. Only deaths from infection exhibited seasonal variation similar to SIDS. These observations probably reflect secondary associations with as yet unidentified primary risk factors relatable to maternal experience. | US |
Recent studies of patients with coronary heart disease (CHD) at baseline have shown that their cholesterol levels are much less predictive of subsequent mortality than in populations free of CHD (FCHD). One previously suggested explanation of this attenuation is that the impact of hyperlipidemia on atherosclerosis or of atherosclerosis on mortality is reduced for post-myocardial infarction patients. In this paper it is shown that an alternative explanation is selection of CHD populations from FCHD populations for higher atherosclerosis levels. Data from all known follow-up studies on patients with baseline coronary angiograms are assembled to yield relations between cholesterol, atherosclerosis and mortality in CHD and FCHD populations. These data show that the selection hypothesis is not only logically possible but is also consistent with presently available epidemiologic information on relations between these three variables. An ethically impracticable large prospective study of a FCHD population with baseline angiograms might, however, be needed to choose definitively between the selection and reduced impact hypotheses. | US |
A 98.8% response rate was achieved in a follow-up study of a community based health survey. The follow-up methodology used in contacting the residents of 1700 households in a suburban upper-middle class community is presented. Study subjects, who were predominantly white, older adults, participated in the original health survey during 1972 and 1973. When the follow-up study was conducted three years later to determine the vital status of study participants, 30% of the households had moved. Follow-up response of two sets of mailings totaled 76.1%. An additional 12.1% response was obtained by calling residents at their last known address. The final 10.5% of the contacted households were located by intensive telephone tracing. A wide variety of sources of information, both local and non-local, were used to locate these "hard to trace" households. They were different from all other contacted households with respect to mobility rate, household size, and death rate. A 15.5% underestimate of the three-year death rate would have occurred if the hard to trace group had not been contacted. These results emphasize the importance of complete follow-up in prospective studies. | US |
Studies indicate the Mini-Wright Peak Flow Meter and Pulmonary Monitor have potential utility to patients for assessing airway flow drops typical of intermittent airway disease, that instrument calibration remains stable with moderate use but that neither is able to predict absolute Peak Expiratory Flow Rate with sufficient accuracy. | US |
There is increasing evidence that an important mechanism by which platelet production is regulated depends upon a humoral substance (thrombopoietin) that affects the production of platelets by megakaryocytes. Plasma from thrombocytopenic donors increases the rate of appearance or concentrations of subsequently administered Na235SO4 or selenomethionine-75Se in platelets. Both isotopes are initially incorporated into the cytoplasm of megakaryocytes, and labeled platelets appear in the circulation after their production and release from megakaryocytes. Thrombopoiesis-stimulating activity also can be detected in the plasma of normal donors when endogenous thrombopoiesis has been suppressed in recipient assay animals by the hypertransfusion of platelets. Recent studies have indicated that certain fractions of plasma from throbocytopenic donors are also capable of stimulating thrombopoiesis in recipient animals. The nature of thrombopoietin(s) and its mechanism of action remain unknown. However, currently available data indicate that thrombopoiesis-stimulating factors may act both on diploid precursors and immature megakaryocytes and upon maturing megakaryocytes. The site of production of thrombopoietin also is unknown. Although the sensor that regulates thrombopoietin or other humoral mediators of thrombopoiesis has not been identified, it appears that platelet numbers, per se, are not the sole variable to which megakaryocytopoiesis eventually responds. | US |
Although a major regulator of thrombocytopoiesis is the number of circulating platelets, several observations suggest that independent alternative regulatory mechanisms may exist. In some situations there is a curious association of megakaryocytopenia and megakarocytic macrocytosis in spite of normal platelet counts. If macrocytosis is considered as a sign of stimulation, this association suggests a cause and effect relationship between decreased numbers and increased size of megakaryocytes. This thesis was tested by examining the delayed effects of sublethal irradiation and the acute effects of hydroxyurea in mice. It was found that megakaryocytopenia and macromegakaryocytosis occurred together and that platelets counts were either normal or only slightly reduced. Therefore it was concluded that normal numbers of platelets could be produced by decreased numbers of megakaryocytes. Megakaryocytopenia appeared to be compensated, in part, by increased size of megakaryocytes, but the mechanism by which this occurred has not been elucidated. It is postulated that a reduction in the number of cells of the megakaryocytic system is sensed by a homeostatic mechanism that then acts to stimulate the cells that are present. This stimulation may then be manifested as macrocytosis of megakaryocytes. | US |
The nature of the hemopoietic stem cell compartment has been the subject of much controversy. Data are presented to support the concept of a 'continuum' model of the stem cell compartment. The important characteristics of this model are that within the continuum there are cells with varying proliferative capacities. As cells move through the compartment, their proliferative capacity becomes more limited, their likelihood to be in cycle increases, and their commitment to a specific differentiated pathway increases. Experiments with busulfan, cyclophosphamide, 5-flurouracil, and BCNU demonstrate defects in proliferative potential of the surviving CFU-S population. These defects persist throughout the life of the animal without any evidence of recovery. The clinical implications of late stem cell failure may be important as a consideration in the use of cytotoxic agents. | US |
Prolonged replication of pluripotential stem cells and committed progenitor cells is sustained for prolonged periods in a murine marrow culture system. Alterations in stem cell replication and differentiation are observed after infection of the cultures with Friend virus and Kirsten sarcoma virus consistent with transformation of pluripotential stem cells in the first case and transformation of the macrophage component of the hemopoietic microenvironment in the second. Prolonged myelopoiesis and CFU-c proliferation was also observed in continuous human and prosimian marrow cultures, suggesting the applicability of this technique for analysis of stem cell control and in vitro leukemogenesis in species other than the mouse. | US |
These studies were to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors by the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Changes in the plasma erythropoietin levels in the reticulocyte concentration and hematocrits of irradiated and nonirradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma concentrations appeared to affect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors of chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with colony stimulating factor (CSF) containing L-cell-conditioned medium revealed granulocytic colonies and burst-like formations similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric mitosis due to loss of genetic information required for continuing division, or differences in concentrations of, or ability to recognize, inhibitory factors. These possibilities are examined in the light of results from in vivo and in vitro culture techniques. | US |
Cascades of Auger electrons are emitted in the decay of 55Fe and absorbed in tissue within a 1 micrometer radius. Cytocidal amounts of 55Fe can therefore eliminate erythroid precursors with minimal damage to adjacent cells. A single intravenous injection leads to continued erythrocytocide in mice because the isotope is reutilized and has a 2.7 year half-life. The cytocide evokes an early compensatory response from morphologically unrecognizable precursors which differentiate into pronormoblasts. These early events leave the granuloid series undisturbed but they are accompanied by a precipitous fall in pluripotent stem cell (CFU-S) numbers in bone marrow, spleen, and blood. The pretreatment levels of CFU-S are not restored. Gradual decline of CFU-S is associated with intermittently increased turnover rates and reduced settings of cell production, yet the capacity for quick restoration of blood loss is unimpaired. The precipitous initial stem cell decrease is not caused by irradiation damage, as shown in a separate experimental series that used the frozen-storage cytocide technique. Only over several weeks could 55Fe radiation accumulate to lethal levels in nondividing stem cells. This irradiation is attributed to incorporation of small amounts of 55Fe into CFU-S, from where it is slowly cleared. The stem cell loss immediately following 55Fe injection is in our interpretation caused by rapid differentiation along the erythroid pathway in a response that involves all progenitor populations. Data are consistent with the hypothesis of limited cell renewal capacity which thereby gains further support. | US |
A radioimmunoassay for erythropoietin has been developed using 125I labeled pure human erythropoietin and an anti-erythropoietin antiserum produced in a rabbit immunized with human erythropoietin. Two techniques are presented for labeling erythropoietin, both resulting in an immunologically reactive labeled reactant. One method involves the use of lactoperoxidase and the other a reagent known as IODO-GEN. The second International Reference Preparation of human erythropoietin is used as a standard and a double antibody scheme is used for the separation of the free and antibody bound labeled hormone. The radioimmunoassay is sensitive to an absolute amount of erythropoietin equivalent to 0.4 milliunits. Bioassays for erythropoietin require approximately 100 times this amount. The use of pure erythropoietin as the labeled reactant has removed certain discrepancies seen in previous attempts to develop radioimmunoassays for this hormone, e.g., sera from patients without kidneys do not give the high values previously seen. Sera from anemic individuals not only give rise to high radioimmunoassay values but also show a parallel relationship with the erythropoietin standard when halving dilutions are analyzed. Desialated erythropoietin is also reactive with the same parallelism. Bleeding of a normal individual increases the serum erythropoietin level and transfusion decreases it. Erythropoietin from a variety of laboratory animals is also reactive in the radioimmunoassay, with very high values being observed in hypoxic animals. | US |
Polymorphonuclear (PMN) leukocytes exposed to mechanical trauma in vitro will release enzymes both from azurophilic and specific granules at shear stress levels of between 75 and 150 dyn/cm2 for 10 min. In addition, at these shear stresses the leukocyte count in whole blood decreased only slightly and the number of ruptured leukocytes on Wright-stained blood films increased significantly. At higher shear stresses, enzyme release and leukocyte damage increased monotonically. Transmission electron microscopy evaluation of sheared PMNs revealed that remaining intact cells had minor morphological changes at stresses of 150 dyn/cm2. They were characterized by clublike cytoplasmic potrusions, spherical shape, and a circumferential distribution of cytoplasmic granules. At higher shear stresses (600 dyn/cm2) cell destruction was marked. Intact PMNs contained fewer cytoplasmic granules, a large number of vacuoles, and condensed nuclear chromatin. These studies show that PMN morphology and function are at least as sensitive to mechanical trauma as similar platelet alterations seen in other studies. | US |
Autorhythmometry of blood pressure by an individual over an age-span of 67 to 72 years showed a strong circadian rhythm superimposed upon significant circaseptan and circannual rhythms. Automatic BP monitoring with an Arteriosonde throughout 24-hour spans on 4 separate occasions, before and during treatment, also indicated a prominent circadian BP rhythm and a treatment-related reduction in circadian mesor. The concept of a blood pressure mesor reference for the antimesor-hypertensive treatment constitutes a valuable guideline in the control of "familial" mesor-hypertension. | US |
A prospective study was undertaken to analyze the different causes of abnormal head postures on ocular bases. Eight basic mechanisms were found in a series of 188 patients. Incomitance accounted for 62.7% of the head postures and nystagmus for 20.2%. Important diagnostic criteria for evaluating patients with head postures are discussed. | US |
Urine preferences of wild (Cavia aperea), domestic (C. porcellus), and F1 adult male guinea pigs were investigated. Males of all three types preferred female urine to male urine regardless of donor type. When given a choice between female urine of each type, males preferred conspecific urine. In choices between male urine of the three types, a conspecific preference was evident for wild and domestic but not F1 subjects. These data indicate that a loss of distinctive male and female odours had not occurred as a result of domestication. However, the urine odours of wild and domestic types have diverged. The possible effects of previous individual experience on the preferential response is discussed. | US |
The process of cooking beef substances which are mutagenic in the Ames Salmonella/microsome bioassay [1,2]. In this study, the formation and disposition of basic mutagens produced by cooking beef at different temperatures were examined. Mutagenic activity increased exponentially with cooking temperature between 137 degrees C and 252 degrees C. However, the amount of mutagenic activity remaining in the meat was only 1--7% of that which was volatilized into the air. The ingested dose of mutagens may therefore be significantly influenced by factors which restrict the dissipation of mutagens from the container, as well as by cooking temperature. Inhalation of airborne mutagens from cooking, as an alternative route of exposure, should be investigated when considered in light of some epidemiological data showing an excess of lung and bladder cancer among cooks and kitchen workers. | US |
Syrian golden hamsters were treated with N delta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO), a nitrosourea amino acid, which has induced a high incidence of breast, kidney and skin neoplasms and a low incidence of pancreatic carcinoma in rats. MNCO induced a few breast and skin carcinomas, and a high incidence of foci of atypical acinar cells and of focal ductular abnormalities in the exocrine pancreas. The latter were similar to lesions observed in rats treated with MNCO. MNCO was less toxic and less effective as a carcinogen in hamster than in the rat. | US |
Bovine heart mitochondria which have been allowed to swell in isotonic NH4+ phosphate contract in response to initiation of oxidative phosphorylation. The contraction occurs optimally at pH 6.0 and appears from inhibition studies to result from Pi uptake being slower than removal of internal Pi via phosphorylation of external ADP. Similar results are obtained when K+ + nigericin is substituted for NH4+. Mersalyl inhibition of Pi transport in respiring, nonphosphorylating mitochondria which have been allowed to swell in NH4+ phosphate reveals a contractile process having an alkaline pH optimum. This contraction resembles closely the contraction observed in salts of strong acids and presumably occurs by electrophoretic ejection of Pi anions driven by electrogenic H+ ejection. | US |
Electromyographic biofeedback is becoming widely used to help patients regain voluntary control of specific muscles affected by neuromuscular disorders. Electromyographic feedback training has been employed in the rehabilitation of patients affected by poliomyelitis, cerebrovascular accident, torticollis, nerve injury, temporomandibular joint syndrome, bruxism, and other disorders. While EMG biofeedback appears to be a promising treatment technique, the research literature on its effectiveness consists mainly of uncontrolled case reports and clinical trials. It is concluded that new studies with more sophisticated design and more careful control are needed to demonstrate that EMG biofeedback makes a unique contribution to the treatment of neuromuscular disorders. Research is needed to identify relevant patients characteristics predictive of success, specify appropriate muscle groups for the treatment of particular disorders, determine how feedback can be most efficiently combined with more conventional techniques in achieving a therapeutic effect, and establish meaningful criteria of success in the treatment of neuromuscular disorders. | US |
Symmetric yellow ("vitelliform") foveal lesions are occasionally seen in adults. These patients should not be diagnosed as having Best's vitelliform dystrophy unless the EOG light/dark ratio is severely depressed and the family history reveals a dominantly-inherited maculopathy. Adult vitelliform lesions may vary in size from one third to several disc diameters, and may be present with or without drusen. More than one etiology may be involved, but many of these lesions seem to be degenerative changes related to drusen or pigment epithelial detachment. | US |
In a randomized, blind clinical study, we tested the effect of timolol and Daranide against placebo medications among patients who had intraocular pressures greater than 30 mm Hg on the first postoperative day after aphakic keratoplasty. The study failed to show any significant difference in the pressure course. We concluded that because this type of severe secondary glaucoma is extremely difficult to treat, it should be prevented by using a donor cornea larger in size than the recipient bed. | US |
A case of foveomacular retinitis, ankylosing spondylitis, iritis, and iris dissociation is described. Only ankylosing spondylitis was present in other family members. The differential diagnosis is discussed. The iritis of ankylosing spondylitis must be considered in cases of developmental full-thickness iris holes. | US |
A modification of the Jensen procedure is presented to aid in preserving the anterior segment blood supply. It involves a union of only part of the lateral rectus muscle with the temporal halves of the superior and inferior rectus muscles. The anterior ciliary artery in the lateral rectus is not included in in the union. | US |
Fungus infiltration within hydrophilic lenses has been a rare finding. This case report confirms previous findings that fungal contamination of hydrophilic contact lens is possible. The present report, to our knowledge, is the first demonstration of the association of fungus from contaminated cosmetics with hydrophilic contact lenses. It is important to be aware of the possibility of fungal invasion of hydrophilic lenses, as well as to be able to differentiate this from the more common harmless spot formation. On the basis of this study, good lid hygiene, strict adherence to the sterilization procedure, and discontinuance of any soft hydrophilic contact lenses with spot formation seems appropriate. | US |
Three patients with acute intermittent porphyria were noted to have retinal branch vessel occlusion. Branch "vein" occlusion, segmental optic atrophy, and soft exudate were the most common ocular manifestation. Two patients had labile elevated hypertension. When patients present with retinal branch vessel occlusion and a constellation of bizarre symptoms that might include hypertension, abdominal pain, acute psychotic behavior and/or cutaneous photosensitivity, the diagnosis of acute intermittent porphyria should be considered. | US |
Intestinal epithelial cells isolated from 6-wk-old chickens maintain the capability for Na+-dependent concentrative accumulation of 3-O-methylglucose (3-OMG). Cells depleted of ATP exhibit a transient accumulation of 3-OMG in response to imposed Na+ gradients ([Na+]o greater than [Na+]i) or when transmembrane ion diffusion potentials (cell interior negative) are established. Phlorizin or lack of extracellular Na+ prevents formation of sugar gradients in every case. A nonconcentrative, non-Na+-dependent sugar transport system is also operative in these cells. The latter system is inhibited to various degrees by phloretin, theophylline, cytochalasin B, and a variety of flavonones and flavones, including apigenin. These agents also act to inhibit efflux of sugar from the cell via this pathway. The concentrative system normally operates against a "leak" of sugar through the nonconcentrative carrier. If the passive system is made inoperative by any of the agents named above, a significant enhancement of steady-state sugar gradients maintained by the cells is observed. With cytochalasin B, gradients as large as 30-fold are established. The energy inherent in cellular Na+ gradients cannot account for sugar gradients of this magnitude unless both chemical electrical driving forces are considered. When the passive leak is maximmally inhibited, more than half of the total energy required must be derived from the membrane potential. | US |
The prenyl-transfer reaction catalyzed by porcine farnesyl pyrophosphate synthetase has been studied using (E)- and (Z)-3-trifluoromethyl-2-buten-1-yl pyrophosphates as substrates and inhibitors. The rate of condensation between isopentenyl pyrophosphate (IPP) and the allylic fluoro analogues is drastically depressed relative to the normal catalytic rate observed with dimethylallyl pyrophosphate (DMAPP) or geranyl pyrophosphate (GPP). A similar depression is found in the rates of solvolysis for methanesulfonate derivatives of the fluoro analogues in aqueous actone under typical SN1 reaction conditions. Prolonged incubation of [14C] IPP and (E)- or (Z)-CF3-DMAPP with the enzyme, followed by treatment with alkaline phosphatase, gave a product that comigrated with geranylgeraniol on a polystyrene column. Both fluoro analogues showed mixed linear inhibition patterns with DMAPP or GPP as the variable substrate. We interpret these results in terms of an ionization-condensation-elimination mechanism for the prenyl-transfer reaction. | US |
N'-Acetyl-4-(hydroxymethyl)phenylhydrazine was administered as a 0.0625% solution in drinking water continuously for the life span of Swiss mice, from 6 weeks of age. Compared to that in untreated controls, in treated animals the lung tumor incidence rose from 15 to 34% in females and 22 to 48% in males, whereas the incidence of blood vessel tumors increased from 8 to 32% in females and from 5 to 30% in males. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs and angiomas and angiosarcomas of the blood vessels. The commonly eaten mushroom Agaricus bisporus contains beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine, which under certain conditions yields 4-hydroxymethylphenylhydrazine and L-glutamic acid. Since 4-hydroxymethylphenylhydrazine is relatively unstable, its acetyl derivative was synthesized for this study. The possible environmental significance of the findings is discussed. | US |
The synthesis of a fluorescent colchicine derivative permits the localization of colchicine-binding receptors in cells. Fluorescein colchicine (FC) was prepared by the addition of fluorescein isothiocyanate to deacetyl colchicine. The product, FC, was separated from the reactants by thin-layer chromatography (TLC). The purity of FC was demonstrated by TLC, UV spectral analysis, and analysis of the kinetics of photodecomposition. FC inhibited [3H] colchicine binding to purified brain tubulin. The biological activity of FC was compared to the activity of unlabeled colchicine on mitosis, motility, secretion, and myogenesis. The effects of FC were identical to those of unlabeled colchicine in all biological systems tested. The results demonstrate that FC may be substituted for colchicine in biological experiments without significant loss in specificity or effectiveness. | US |
The tissue culture-adapted strain (Mebus) of the bovine coronavirus was grown to titers of greater than 10(7) 50% tissue culture infective doses per ml in secondary bovine embryo kidney cells, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which comigrated electrophoretically with vesicular stomatitis viral RNA and therefore had an apparent molecular weight of 3.8 X 10(6). (ii) It remained as a 3.8 x 10(6)-molecular-weight molecule after heat denaturation when rapidly harvested virus was examined. (iii) It was 80% susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl, and the 20% resistant fraction was 4S to 7S in size. (iv) It was polyadenylated to the extent that 40 and 60% of the native RNA bound to polyuridylic acid-Sepharose and oligodeoxythymidylic acid-cellulose, respectively, under conditions of high (0.5 M) NaCl. | US |
Free essential fatty acids (EFA) are reported to suppress cell-mediated immunity. Because Intralipid contains a high concentration of esterified EFA, the effects of this emulsion on in vitro lymphocyte transformation were studied. Intralipid concentrations of 11.5, 115, and 230 mg% in lymphocyte cultures increased phytohemagglutinin (PHA) stimulation by an average of 8.2% (not significant [NS]), 18.1% (p < 0.01), and 11.8% (NS), respectively. These same concentrations also increased Varidase stimulation in lymphocyte cultures by an average of 11.3 (p < 0.02), 18.9 (p < 0.02), and 4.4% (NS), respectively. Control wells did not demonstrate allergic reactions to Intralipid. These data demonstrate that Intralipid can significantly increase the mitogenic response of human thymic lymphocytes and the antigenic response of human lymphocytes, in vitro. | US |
Stress or injury-induced phenomena, such as impaired wound healing and immune depression, may be related to impaired function of certain leukocyte populations. Since vitamin A prevents some aspects of stress, we studied its effect on various white cell populations in normal and injured rats. Supplemental vitamin A (150,000 IU/kg chow) to normal rats resulted in marked increases in thymic weight and lymphocytes without any effct on adrenal weight. The basal chow contains 13,700 IU vitamin A per kg. In rats subjected to moderately severe injury (dorsal wounding or unilateral femoral fracture), supplemental vitamin A greatly diminished the thymic involution observed in chow-fed controls and delayed or minimized the accompanying adrenal hypertrophy. In uninjured rats, supplemental vitamin A induced in three to four days a temporary circulatory leukocytosis characterized by lymhocytosis, monocytosis, and a relative neutropenia. These changes in the blood picture persisted one day after femoral fracture. On the second and third day postfracture the lymphocyte and neutrophil values returned to normal while the monocytosis persisted. Polyvinyl alcohol sponges implanted next to the fracture site demonstrated that supplemental vitamin A consistently increased the number of white blood cells migrating into the wound area and showed significantly larger numbers of monocytes/macrophages. These data suggest that vitamin A influences the numbers and nature of white cells involved in immune, inflammatory, and wound healing processes. In addition to the known antiglucocorticoid activity of vitamin A, these effects may represent a direct beneficial action of dietary vitamin A supplements for stressed and injured animals. | US |
Myelin was isolated from the brain stem region of rats which were administered chronically with ethanol either through intragastric tubing (8gm/kg) for 3 weeks or by giving a 15% ethanol ad lib as drink for 1 year. The protein, phospholipid and cholesterol content and the acyl group composition of major phosphoglycerides of myelin were examined. Based on the protein content, there was less myelin isolated from the chronic alcoholic brain samples as compared to controls. Intrinsic changes in membrane components were observed. The phospholipid to protein ratio of myelin was approximately 20% lower in the group subjected chronically to ethanol by drink and 10% lower in the group given ethanol through intubation technique. The cholesterol to protein ratio was also lower in the group given ethanol as drink but the intubated group was not different from controls. Changes in phosphoglyceride acyl group composition were also observed. In general, there was an increase in the proportions of 16:0, 18:0 and 18:1 and a decrease in 20:1, 20:4 and 22:6. The acyl group changes reflected an increase in cellular phospholipase A2 or a decrease in chain desaturation and elongation activity due to chronic ethanol administration. These changes are also reflective of degenerative changes possibly associated with demyelination. | US |
New X-ray data suggest how myosin rods, themselves alpha-helical coiled coils, form the thick filament backbone of crustacean muscles by additional supercoiling. Natural transformations of this structure may describe the myosin backbone in many other animals also. | US |
The effects of electrical stimulation of the cat cerebral cortex have been evaluated by light and electron microscopy following a wide variety of stimulation parameters (QD/ph of 10 - 300 muC/cm2/ph). Platinum or rhodium disc electrode arrays were bilaterally implanted subdurally on the parietal cortex and subjected to 36-hour stimulations (9 hrs./day for 4 days). Prominent among the degenerative changes shown by electron microscopy were dense crystalline inclusions that were identified as calcium hydroxyapatite (CHA) crystals by electron diffraction and energy dispersive X-ray analysis. The appearance of intracellular calcification generally paralleled the onset of other degenerative changes in stimulated tissue, including gliosis, mitochondrial swelling, lipid inclusions, degenerating cells, neuronal loss, and phagocytic activity. A preferential deposition of calcium was noted in mitochondria of several cell types and in postsynaptic dendrites. The mechanism of the apparently electroresponsive calcium deposition is obscure; however, a plausible explanation is that increased cyclic AMP levels, known to occur with electrical stimulation of nervous tissue, result in enhanced calcium plasmalemmal permeability. | US |
Combination effects of cis-dichlorodiammine platinum (II) (DDP) paired with 12 other antineoplastic agents were investigated on a human carcinoembryonic antigen producing colon carcinoma cell line in vitro. DDP was effective in increasing the killing efficiency of many different drugs. Supraadditive effects were noted with hydroxyurea, bleomycin, cis-acid, BCNU, adriamycin and mitomycin C, and a marked synergistic effect was noted with ara-C. DDP displayed simple additive effects wit 5-fluorouracil (5-FU), Ftorafur and methotrexate, and subadditive effects in simultaneous combination with vincristine. In view of its powerful cytotoxic effects on this particular cell line and of the supraadditive effects of its combinations with nitrosoureas and mitomycin C, DDP appears as a potentially useful antineoplastic agent for combination therapeutic regimens for human colon carcinoma. | US |
Neurology manuals generally recommend odor identification for simple assessment of olfaction. Nevertheless, even patients with normal olfaction (normosmics) often perform only poorly. Three experiments demonstrate that such an ambiguous outcome will disappear if the test incorporates highly familiar substances and, more important, a procedure to circumvent the olfactory-verbal gap that frequently separates an odor from its name. One multiple-choice procedure, for instance, led to 100% accuracy among normosmics. Another led to 99% accuracy among normosmics and 0% accuracy among anosmics. The investigation also reveals that scratch-and-sniff labels could possibly replace customary odorants in the clinical test. | US |
A micropressure transducer (sensitive 0.1 cm H2O) utilizing a manual servo nulling system and a micropipette (tip diameter 12-20 micron) was designed in order to measure endolymphatic and perilymphatic hydrostatic pressures in the inner ear of the guinea pig. Perilymphatic pressures were measured through the round window membrane in animals in which the ossicular structures had been removed and in those in which the middle ear structures were intact. Endolymphatic pressures were measured after removal of the middle ear structures. There was a significant (p less than 0.001) difference between perilymphatic pressures in the presence (4.7 +/- 0.36 cm H2O) and absence (2.43 +/- 0.22 cm H2O) of the middle ear structures. The endolymphatic pressure was 0.00 cm H2O when measured through the basilar membrane after disruption of the scala tympani, and was 3.34 +/- 0.57 when monitored through the spiral ligament and stria vascularis. In order to verify the accuracy of these measurements, we monitored pressures in animals whose perilymphatic pressures were artificially maintained by an external source. Recoveries were always 95-100% of the artificially applied pressure. The injection of purified cholera toxin into the scala media through the basilar membrane resulted in a significant (p less than 0.001) increase in endolymphatic pressure. | US |
Treatment with varying doses of morphine and its antagonist naloxone produced different response patterns in "spontaneous" multiunit discharges recorded from the medial thalamus and caudate nucleus of freely behaving rats previously implanted, stereotaxically, with permanent semimicro-electrodes. The changes in electrical discharges induced by incremental doses of morphine exhibited dose-related patterns, and could be reversed by naloxone. This procedure, testing several incremental doses of a drug, provides a tool with which to identify and classify the specific response patterns induced by morphine. The two structures examined in the present study exhibited four response patterns to the treatments but only one pattern of response was similar in the two nuclei. The medial thalamic units are more sensitive to morphine than those recorded from the caudate nucleus. The present finding, i.e., acute effects of morphine, provides basic information with which to examine the physiological properties underlying the chronic effects of morphine. | US |
Diurnal cycles of glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and of excretion rates of sodium, potassium, magnesium, chloride and phosphate were measured in a 22 year old man with moderately severe heart failure under standardized conditions. Cycles of GFR, ERPF and excretion of potassium, chloride, and phosphate were indistinguishable from those of normals. The phases of the sodium and probably the magnesium excretory cycles were reversed from normal. The significance of some of the observations is discussed. | US |
The labelling of surfactant phosphatidylcholine and disaturated phosphatidylcholine was studied in 19-31-days-old lambs. Following the placement of small bore tracheal catheters, the animals were given radioactively labelled palmitic acid and/or choline by intravenous injection and multiple samples were recovered from the distal airways of each animal via a small catheter. The specific activities of the phosphatidylcholine and/or disaturated phosphatidylcholine were measured in these samples of surfactant. The labelled phospholipids accumulated in the samples of surfactant in a linear fashion; the mean time required to reach maximal specific activities in phosphatidylcholine and saturated phosphatidylcholine with either palmitic acid or choline as precursor was 28 h. Subsequently the specific activities of the labelled phospholipids from the surfactant samples decreased semi-logarithmically. The mean t1/2 for phosphatidylcholine and disaturated phosphatidylcholine labelled with radioactive palmitic acid was 35 h. The saturated phosphatidylcholine labelled with radioactive choline had a t1/2 of 251 h. The results demonstrate that surfactant labelling studies can be done by multiple sampling of single large animals. | US |
The small intestine of the rat, like the liver, is a tissue with high activities of arginase, ornithine aminotransferase, and pyrroline-5-carbozylate reductase. These enzymes are thought to catalyse sequential steps in the synthesis of proline. We have compared the effect of cortisol or brief starvation on the activities of these enzymes and of soluble alanine aminotransrerase in the small intestine and liver during development. In the intestine, cortisol accelerated the increase in arginase activity, reversed the normal 2-week-long post-natal decline in that of pyrroline-5-carboxylate reductase, and delayed the normal decrease, in the third week, of ornithine aminotransferase activity. Starvation of neonates for 18 h raised the activity of arginase slightly, that of pyrroline-5-carboxylate reductase significantly, and had no effect on ornithine aminotransferase activity. Cortisol did not alter the hepatic activities of pyrroline-5-carboxylate reductase in neonates but induced premature rises in the activities of arginase and ornithine aminotransferase. Short starvation did not affect the hepatic activities of any of these enzymes. Alanine aminotransferase activity in both tissues was enhanced by cortisol but not by starvation. Thus in intestine, cortisol elicited some changes in the activity of three functionally related and one unrelated enzyme while starvation evoked changes only in pyrroline-5-carboxylate reductase. Neither stimulus appears to be specific for a metabolic pathway or to trigger a coordinated onset of proline synthesis from arginine. | US |
Acute proliferative retrolental fibroplasia (RLF) has been studied in premature infants employing a Zeiss fundus camera and fluorescein angiography. A total of 164 angiograms have been performed on 122 infants. At the present time, angiography is reserved for studying infants with peculiar or puzzling fundus pictures. A dose of 0.1-0.4 cc of 10% sodium fluoresceinate is employed, depending on the age and the weight of the baby. Fluorescein clearly outlines the major arteriovenous shunt in the retina, which is the hallmark of acute RLF. The shunt fills with fluorescein and leaks it profusely. On regression, a fine brush border of capillaries is seen in the region where the shunt previously had been located. Study of the population susceptible to RLF reveals it to be the smallest sickest babies in the premature nursery. | US |
A refined classification of the stages of the retinopathy of prematurity (RLF) based on the experience of over 7500 examinations during the past decade is presented. We have been using the basic elements of this classification since 1972 in order to evaluate the influence of vitamin E on retrolental fibroplasia (RLF). It is our impression that it provides a more accurate clinical method of following the course of the retinopathy and a tool for assessing the factors other than prematurity and hyperoxia that may play a subtle role in the development of RLF. | US |
We have shown that the absorption of tetraphenylborate into black lipid membranes formed from either bacterial phosphatidylethanolamine or glycerolmonooleate produces concentration-dependent changes in the electrostatic potential between the membrane interior and the bulk aqueous phases. These potential changes were studied by a variety of techniques: voltage clamp, charge pulse, and "probe" measurements on black lipid membranes; electrophroetic mobility measurements on phospholipid vesicles; and surface potential measurements on phospholipid monolayers. The magnitude of the potential changes indicates that tetraphenylborate absorbs into a region of the membrane with a low dielectric constant, where it produces substantial boundary potentials, as first suggested by Markin et al. (1971). Many features of our data can be explained by a simple three-capacitor model, which we develop in a self-consistent manner. Some discrepancies between our data and the simple model suggest that discrete charge phenomena may be important within these thin membranes. | US |
Groups of six mongolian gerbils were exposed to two-octave (1414-5656 Hz) band noise for 1 h at 100, 110, and 120 dB SPL. Threshold shift at several frequencies was measured 0.5, 3, 6, and 12 h, and 1-28 days after exposure. Final thresholds were determined at least two months postexposure. Extensive threshold shift was observed in all groups 0.5 h after exposure (TS0.5h). Where threshold shift increased in the initial hours after exposure, such increases were correlated with eventual permanent threshold shift (PTS). Recovery of thresholds from 1-28 days after exposure was approximately exponential, and slowest at the edges of the exposure band. PTS was seen in the 110 and 120 dB SPL groups. With TS0.5h of 50 dB or less, no PTS resulted. With TS0.5h above 50-60 dB, eventual PTS increased linearly with a slope of about 1.25 PTS/TS0.5h. Cochlear damage was evaluated by light microscopy. The relationship between hair cell loss and PTS was consistent with an inner hair cell threshold about 40 dB higher than that of outer hair cells. It is suggested that recovery from noise-induced threshold shift may involve different mechanisms in the two types of hair cells. | US |
Three children, ages 6 months, 13 months and 10 years were treated by exchange transfusions following exposure to methylmercury in the Iraq outbreak in 1971-72. Two had severe signs of poisoning and the other was clinically normal but had a high blood mercury concentration. Exchange transfusion resulted in clearance of mercury not only from blood but also from other tissues. The average amount of mercury removed in a two hour exchange was estimated as 6% of the body burden as compared to 1% of the body burden removed by normal excretion processes in 24 hours. No dramatic improvement in the clinical condition of the two poisoned patients occurred. Some improvement in motor power and function was observed during follow-up visits to their houses. | US |
Rat red blood cells will hemolyze if they are present in vitro in mixtures of rat liver microsomes in which lipid peroxidation has been initiated by NADPH. Recent work from this laboratory indicated that a toxic factor not having radical properties could be generated from the lipids of the peroxidizing microsomes. This toxic factor produced prelytic damage in rat red blood cells. In this communication we show that if Ca(++)-aggregated microsomes are first peroxidized and then sedimented by centrifugation, the resuspended peroxidized microsomes are capable of hemolyzing red cells in the absence of any further microsomal lipid peroxidation. This result shows conclusively that the microsomal lipid peroxidation step can be separated from the attack on red cells leading to frank hemolysis. Furthermore, lipids extracted from the peroxidized microsomes with chloroform-methanol account quantitatively for the degree of hemolysis produced. The active hemolytic material could not be detected in resuspended microsomal centrifugates obtained during the first 10 minutes of NADPH-stimulated microsomal lipid peroxidation. It appeared rapidly after 10 minutes. It was maximal at 20 minutes, and fell to a low level of activity by 60 minutes. Peak hemolytic activity correlated with peak generation of lipid soluble peroxides. High, but less than maximal levels of peroxides appearing at 10 minutes did not cause hemolysis, and high, but less than maximal levels remaining at 60 minutes were only weakly hemolytic. The extracted lipoidal material with hemolytic potency is more reactive than hydrogen peroxide in a peroxide assay. | US |
Diffusional motions of 1,6-diphenyl-1, 3, 5-hexatriene (DPH) were observed by differential polarized phase fluorometry. The measurements indicated that the depolarizing rotations of DPH in propylene glycol are isotropic. The results in vesicles of dimyristoyl-l-alpha-phosphatidylcholine indicated that diffusional rotations of DPH are dominated by hindered torsional motions. Combined use of both differential phase and steady-state anisotropy measurements showed that the average rotational angle of DPH, at times long compared to the fluorescence lifetime, is limited to about 23 degrees at temperatures below the transition temperature of the lipid and that these rotations become less hindered above the transition temperature. The evidence that the depolarizing rotations of DPH in a lipid bilayer are different from those in an isotropic solvent calls into question the meaning of membrane microviscosity as determined by fluorescence anisotropy. | US |
The influence of the inclusion of xylan in a medium for enumeration of total culturable rumen bacteria was investigated. Maximum colony numbers were obtained on a medium, GCSX-2, which contained 0.033% each glucose and cellobiose and 0.067% each soluble starch and xylan. This medium gave higher colony counts than either medium 98-5 of Bryant and Robinson (J. Dairy Sci. 44:1446-1456, 1961), medium 98-5 of Chung and Hungate (Appl. Environ. Microbiol. 32:649-652, 1976), containing an added lucerne (hemicellulose + cellulose) fiber substrate, or medium GCSX-2 with the added lucerne (hemicellulose + cellulose) fraction. The time of collection of rumen fluid influenced the colony counts on the media containing the lucerne fiber substrate but was without effect on medium GCSX-2. | US |
The cryptophthalmos syndrome generally consists of cryptophthalmia, dyscephaly (cleft lip and palate, nasal and ear defects, meningoencephaloceles, etc.), syndactyly, and urogenital malformations. This disorder is rare. Approximately 55 cases have been reported, with only a few described in the American literature. A three-year-old boy with this rare syndrome is described. Major clinical findings include: asymmetric bilateral cryptophthalmos, unilateral orbital cyst of the nasofrontal area, bilateral anophthalmos, right choanal atresia, right microtia, right auditory canal atresia, hypodontia, ankyloglossia, cartilaginous synchondroses of the cervical vertebrae, and bilateral acetabular dysplasia. Striking features of this case, in addition to the above, were profound mental and motor retardation. Syndactyly and renal anomalies were not observed. | US |
Studies are presented on the influence of polyamines on prostatic chromatin- and non-histone-protein-associated protein kinase reactions involving both exogenous and endogenous substrates. The activities toward the model acidic protein substrate, dephosphophosvitin, were maximal at 160--200mM-NaCl (or -KCl or -NH4Cl). Under these conditions, spermidine and spermine added in concentrations up to 2mM were essentially without effect. However, without addition of NaCl to the medium, marked stimulation of these reactions was elicited by these polyamines at 1--2mM concentrations. The stimulatory effects were not due to non-specific changes in the ionic strength or to substitution of spermine for Mg2+, as maximal stimulation by 1 mM-spermine was observed only at optimal (2--4mM) Mg2+ concentrations. Qualitatively similar effects of polyamines were observed with enzyme preparations from the prostates of castrated rats, and with chromatin and non-histone-protein preparations from other tissues besides ventral prostate. When phosphorylation of endogenous non-histone proteins of the chromatin was measured, spermine stimulated both the initial rates and the final extent of transphosphorylation, even in the presence of optimal concentration of NaCl. By contrast, spermine or spermidine had no effect on the chromatin- and non-histone-protein-associated protein kinase reactions determined with lysine-rich histones as substrates. Chemically NN-dimethylated dephosphophosvitin was a less active substrate for the chromatin-associated protein kinase, but its phosphorylation was more markedly stimulated by spermine in comparison with unmodified dephosphophosvitin. These observations hint that the polyamine stimulations of the various protein kinase reactions may be due to effects on the conformations of the non-histone protein substrates rather than on the kinases themselves. | US |
Although it carries two competent replication systems, a composite plasmid formed in vitro by linkage of the complete ColE1 and pSC101 plasmid replicons at their unique EcoRI endonuclease cleavage sites normally uses only the replication origin and functions of the ColE1 component. Restriction of ColE1 replication functions by DNA polymerase I deprivation results, however, in exclusive use of the pSC101 replication origin. When using the ColE1 replication system the composite plasmid is nevertheless incompatible with both the parent replicons. This suggests that a trans-dominant gene product is involved in plasmid incompatibility and supports negative control rather than positive control models for regulation of the initiation of DNA replication. | US |
Ten cases of cryptococcosis have been identified in a 13 year experience with more than 650 renal transplants. Eight patients had meningitis, one patient had a cerebral granuloma, and in one patient the infection appeared to be limited to the lungs. The central nervous system infection often masqueraded as brain tumor and was not suspected initially. The most useful diagnostic test was cerebrospinal fluid examination including India ink preparation. Various ther apeutic regimens with amphotericin B and 5-fluorocytosine were effective in suppressing the infection. A combination of low doses of amphotericin B, not affecting kidney function, with 5-fluorocytosine for at least 3 months was associated with remission of disease in five patients who still are alive, including three patients without recurrence for longer than one year. Five deaths 3 weeks to 4 years after the beginning of treatment were not due to cryptococcosis; death resulted from vascular disease and septiciemia in three of the four patients with known causes of death. Central nervous system cryptococcosis, with the exception of the rare cerebral granuloma, is associated with little inflammation. If early death from increased intracranial pressure or cerebral edema is prevented, prolonged therapy with amphotericin B and 5-fluorocytosine may be expected to control the infection, even in immunosuppressed patients. | US |
The theoretical relations between the induced initiation and accumulation of lac mRNA and its translation are derived, taking the kinetics of repressor-operator dissociation and enzyme maturation into account. These relations are used to evaluate observed data on lac induction and to estimate a number of parameters that characterize the transcription and translation of the beta-galactosidase gene in the bacterium Escherichia coli B/r growing at three different rates (0.7-2.1 doublings/h). | US |
The techniques of tracer dilution in the circulation, and of tracer uptake by and washout from an orgen, may be described using expressions that are general and are not dependent on specific models such as exponentials. The expressions have been applied to the measurement of cardiac output using impulse and constant rate injection techniques. Further expressions have been given for estimating organ blood flow from inflow/outflow concentration-time curves, and from the distribution of deposited tracer. Some problems with respect to the use of deposition techniques as they are ordinarily applied to the estimation of regional blood flow must be considered, particularly when there are capillary beds in series or where there is countercurrent diffusional shunting of diffusible tracers between inflow and outflow. This review deals with these various aspects of tracer theory as they relate to the measurement of blood flow. | US |
Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiari syndrome. She is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. | US |
This report reviews experience with 97 patients given liver transplants. We regard out survival statistics as unsatisfactory, but fell they should encourage further work since 22 patients have survived at least one year with a maximum survival of 5 13 YEARS. The Achilles' heel of liver transplantation os bile duct reconstruction. We presently rely upon Roux-en-Y reconstruction, or alternatively, duct-to-duct anastomosis with a T-tube stent. The prime indication for liver replacement is non-neoplastic liver disease, but a favourable malignancy for treatment may prove to be small intrahepatic duct cell carcinomas. | US |
In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. | US |
By evaluating the kinetics of radioactive labelling of nascent and finished polypeptides, the peptide-chain elongation rate for Escherichia coli B/r at three different growth rates (mu) was determined to be 17 amino acids/s for the fast-growing cells (mu equals 1.3 and 2.0 doublings/h) and 12 amino acids/s for slow-growing cells (mu equals 0.67 doublings/h). The results agree with the growth-rate-dependence of the rate of peptide-chain elongation found for the translation of newly induced beta-galactosidase messenger in this strain and under these conditions of growth [Dalbow & Young (1975) Biochem. J. 150, 13-20]. Together with the previously observed ribosome efficiency at these growth rates [Dennis & Bremer (1974) J. Mol. Biol. 84, 407-422] the results indicate that the fraction of ribosomes engaged in protein synthesis is about 0.8 at all three growth rates. | US |
Animal models of human aging problems are potentially of enormous value to gerontological research. Models of behavioral problems have not often lived up to their promise. This review examines one such model system, avoidance learning in aging rodents. This model system has become increasingly popular among behavioral gerontologists, yet it has not provided the unambiguous answers to experimental questions which investigators expected. Our effort has been to determine why the system has failed, and to provide useful suggestions for future research. At the same time we have tried to provide a comprehensive review of the relevant literature and to assess the strengths and weaknesses of studies which have been conducted in the last two decades. | US |
Findings from eight longitudinal investigations were reviewed in order to evaluate the terminal drop hypothesis. The concept of terminal drop was seen to be more useful when partitioned into its component parts: the relationship between the level of cognitive performance with survival and with distance from death, and the relationship between changes in cognitive performance and death. Health status and age at death emerged as important intervening variables in understanding the terminal drop concept. | US |
Twenty-seven patients with deep vein thrombosis whose primary therapy was randomized between streptokinase and heparin were reevaluated clinically and by ascending venography after a mean period of 7 months. Normal venograms were found in 6 (40%) of the streptokinase-treated patients and in 1 patient (8%) who had heparin therapy. Segmental valve preservation was found in 1 patient from each group. All patients with complete or partial valve preservation became asymptomatic. Vein recanalization without preservation of valves occurred in 18 patients: 8 (54%) of those on streptokinase, and 10 (83%) of those on heparin. At the time of follow-up, 11 of these 18 patients, including 8 who had had prior thrombosis, reported peripheral edema; the postphlebitic syndrome developed in 1. Factors favoring a good outcome of acute venous thrombosis were (1) no prior thrombotic disease, (2) localized thrombosis, and (3) prompt streptokinase therapy. | US |
Twenty-four patients with corneal homografts were repeatedly evaluated by the leucocyte migration test using pooled human corneal extract 0.2 mg/ml as antigen. All patients were treated with small doses of local or systemic steroids. If cloudiness of the graft developed, the doses were increased up to 40 mg methylprednisolone or 48 mg triamcinolone daily. Before transplantation, two patients showed inhibition of leucocyte migration. During the third postoperative week seventeen responded with migration inhibition. The grafts remained clear in all but one patient during this period of time. After the second postoperative month, leucocyte migration inhibition was found in none of sixteen patients whose grafts remained clear. Three of seven patients with late graft rejection exhibited migration inhibition and in two of them this response was demonstrated repeatedly several months prior to the clinical reaction. These findings suggest that the test may predict graft failure in some patients. | US |
Hyperkinetic circulation, as it is related to the clinical hypertensive diseases, is defined and its implications interpreted. These pathophysiological considerations have an important bearing in understanding the pressor mechanisms underlying hypertension and the application of therapy. Another very important consideration is the value of elucidating the mechanisms for the hyperdynamic circulation, for with a clearer understanding of these, we shall come closer to an explanation of the pathogenesis of hypertension. | US |
The influence of socioeconomic background, sex, and clinicians' race on the frequency of implementation of nonstandard phonological and grammatical structures was examined in 72 black preschoolers. In order to generalize findings to typical clinical settings, language samples were elicited by 3 black and 3 white clinicians using spontaneous, paragraph completion, and sentence repetition procedures. Results showed that socioeconomic status and sex had a strong effect on black children's usage of nonstandard phonological and grammatical forms. More striking, data suggested that the beginnings of a bidialectal capability were identifiable in the clinical setting in four- and five-year-old black children. Discriminant analysis detailed those nonstandard phonological and grammatical forms which contributed to dialect differences between lower and middle-socioeconomic black children. | US |
When the auditory feedback of a speaker's own voice is amplified the speaker reasonably tends to lower his voice. The reliability of this so called sidetone amplification effect was investigated in two experiments. In the first experiment feedback was modulated gradually during a session. In the second experiment the sidetone amplification effect was assessed over five successive days of testing. In both experiments the sidetone effect was very stable despite rather different eliciting conditions. | US |
Infant rhesus monkeys were fed either a control, dilute or low protein diet from 1 to 7 months of age, and the control diet from age 7 to 12 months. All diets were fed ad libitum. Curves were fitted for energy and protein consumption and for growth in weight, length and head circumference. Both experimental groups developed increasing deficits of energy and protein consumption during the undernutrition experiment. With nutritional rehabilitation, the animals previously fed the dilute diet immediately increased their consumption of energy and protein to levels appropriate for age. Those previously fed the low protein diet showed an increased nutrient uptake, but one more appropriate for size peers. Reduced growth velocity occurred with both experimental diets. "Catch-up" growth, and growth velocity per unit diet energy and protein was most obvious for body weight, but recovery from growth deficits was most complete for growth in head circumference. Nutrient deficits accumulated by animals fed the dilute diet were not recovered during catch-up growth; catch-up growth occurred in animals previously fed the low protein diet even though cumulative nutrient deficits were increasing. | US |
The mean and standard deviation of the first arrival time for a single mutant to reach a certain frequency and the mean age of a mutant persisting in a population have been studied using diffusion methods. These quantities are shown to be highly dependent on both the heterozygous effect and the population size. For partially recessive deleterious mutations, both the mean first arrival time and the mean age decrease with increasing selection coefficient against heterozygotes. For overdominant mutations, the mean age always increases very rapidly with increasing heterozygous advantage, while the mean first arrival time first increases rapidly with increasing heterozygous advantage to a maximum and then decreases rapidly with increasing heterozygous advantage. The standard deviation of the first arrival time is small while that of the age is large. The results of this study have been applied to study the case of the sickle cell anemia mutant in Africa. It is argued that the present prevalence may be explained without the necessity of quite so great a heterozygous advantage as .25 or higher as proposed by some workers. A reasonable range for the heterozygous advantage seems to be from .05 to .18. | US |
A non-Amish "Pennsylvania Dutch" semi-isolate was found to have a high frequency of Tay-Sachs gene. This high frequency could be ascribed to founder effect and may represent, in microcosm, how this mechanism could have produced the high gene frequency among Ashkenazi Jews. | US |
The phenotypic expression of a dominantly inherited human salivary acidic protein (Pa) has been described in acid-urea starch and in Tris-borate acrylamide gel systems. Estimates of the Pa+ allelic frequencies in American Caucasians, American blacks, and Orientals are .21, .14, and .42, respectively. The genetic and biochemical similarities to another series of proline-rich salivary proteins, Pr, and to a pair of similarly staining salivary proteins, Db (double band), are evaluated. It is concluded that either one locus or two (or three) tightly linked loci are viable explanations for this polymorphic system(s). It is suggested that the three factors, Pa, Pr, and Db, be treated as separate loci to allow clarification of their genetic relationships. | US |
A polymorphic acidic protein (Pa) has been isolated from human parotid saliva by the use of ion-exchange and gel filtration chromatography. Following these purification procedures, analytical anionic polyacrylamide disc gel electrophoresis revealed a single stainable band. Amino acid analysis demonstrated a protein particularly rich in proline, glutamic acid, and glycine, but with reduced amounts of threonine and no tyrosine. Only a very small percentage of carbohydrate was detected. Isoelectric focusing at pH 3-10 verified the acidic character of this protein with an isoelectric point in the range pH 3.9-4.5. Other salivary proteins called Pa-II, possibly related physiologically and genetically to the Pr system, were also partially purified and studied. Differences were noted between Pa and Pa-II proteins in molecular size and amino acid composition. | US |
A 6-year experience with a center-satellite system for the provision of comprehensive genetic counseling services to a large geographical area is described. A series of 12 satellite genetic clinics established throughout northern and central California have brought genetic counseling services to within a 2-hour drive for most patients. These satellite clinics are largely organized by local groups (such as National Foundation-March of Dimes chapters and county health departments) but are backed by the personnel and resources of the center at the University of California, San Francisco. Assistance is generally provided by county public health nurses who collect medical records from referring physicians and pedigrees from the family. Specimens for cytogenetic or special biochemical studies are brought back to the center, but, if possible, other laboratory determinations, radiological investigations, and specialty consultations are obtained locally. Follow-up counseling may be provided by the public health nurses, and a written summary is sent to each patient or family. The socioeconomic spectrum of the patients seen at the satellite clinics is much broader than at the central clinic, and the establishment of a satellite clinic results in a great increase in the number of cases seen from the area in which it is located. Physician time per patient and cost of services per patient are substantially the same in both central and satellite clinics. Based on population figures applicable to the state of California, it is estimated that approximately 60-70 comprehensive counseling centers, each with up to 15 satellites, could adequately provide for the foreseeable genetic counseling needs of the United States. | US |