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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 811 records · Page 45Linked to original sources

Ultrastructural, immunocytochemical, and cytogenetic characterization of a human epithelioid sarcoma cell line (RM-HS1).

A cell line (RM-HS1) derived from a human epithelioid sarcoma was established in tissue culture. Ultrastructurally, the cells show features of those found within the primary tumor. A mixed mesenchymal-epithelial phenotype, defined by reactivity with antibodies to epithelial membrane antigen and to vimentin and keratin intermediate filaments, was found in the tumor, and a similar phenotype persisted in the cultured cells. Cytogenetic analysis revealed a mode of 66 chromosomes. With the use of a variety of banding techniques together with in situ hybridization of a 3H-labeled molecular probe for 18s and 28s ribosomal RNA genes (pX1r101), the karyotypes were shown to contain extensive numerical and structural rearrangements, with up to 24 marker chromosomes.

Adult↗

Strain variations in anti-sperm antibody responses and anti-fertility effects in inbred mice.

This study provides evidence for polygenic controls of antisperm antibody levels in inbred male mice immunized with syngenic testis and epididymis. H2-linked and non-H2-linked genes were involved. Mice of H-2d haplotype were high responders, whereas those with H-2k haplotype were nonresponders; however, B10.D2/nSnJ mice (H-2d) were also nonresponders. In vitro fertilization inhibition by antisera correlated positively with the serum antisperm antibody levels, particularly with antibody of the immunoglobulin (Ig) G class. Inheritance of antibody response that inhibited in vitro fertilization (IVF) was an autosomal dominant trait, but this was not apparent for the control of antibody levels per se. Since IVF was inhibited by both IgG and fragment antigen-binding (Fab) isolated from immune sera, but not by immune IgG previously absorbed by sperm or testis, the biologic effect is antigen-specific and probably involved blockade of functional antigenic epitopes. Antisera to testis, caput sperm or cauda sperm were found to inhibit IVF to a similar degree. Inbred strains of mice that produced the highest levels of serum antisperm antibodies that inhibited IVF were A/J, SJL/J, DBA/1J and BALB/cByJ mice, and their antisera immunoprecipitated a common sperm antigen molecule of 35,000 to 40,000 Mr. In contrast, C57BL/6 and C57BL/10 mice produced significant antibody levels that had no effect on IVF, and their sera did not react with the 35,000- to 40,000-Mr peak. Moreover, among BALB/c H-2 congenic mice, only antiserum of responder BALB/cByJ (H-2d) mice immunoprecipitated the 35,000- to 40,000 Mr peak. Thus the 35,000- to 40,000-Mr protein may be of functional significance in the fertilization process.

Animals↗

Prevention of deterioration in metachromatic leukodystrophy by bone marrow transplantation.

The first girl in a family was affected with late infantile metachromatic leukodystrophy (MLD) and had the expected characteristic central nervous system progressive deterioration, which resulted in decerebration and death. The second girl (propositus) demonstrated similar symptoms and signs at the same age. Both girls had characteristically low arylsulfatase A levels. The propositus underwent allogeneic bone marrow transplantation (BMT) from a normal histocompatible sibling. Two and a half years later, the propositus has not developed the intellectual and neurologic impairment demonstrated by the first sibling, although nerve conduction has continued to worsen. These results suggest that the induction of normal enzyme levels by BMT may be retarding or inhibiting CNS deterioration. These results, confirming earlier results of others, are sufficiently promising to warrant a larger scale critical trial of BMT early in the course of MLD.

Arylsulfatases↗

Medical students' attitudes toward AIDS and homosexual patients.

More than most diseases, acquired immune deficiency syndrome (AIDS) appears to elicit highly negative, fearful, and prejudicial attitudes. In the study reported here, medical students read one of four patient vignettes. The vignettes were identical in content except that the patient was identified as having either AIDS or leukemia as either homosexual or heterosexual. The students then completed a set of objective measures that assessed their attitudes toward the patient portrayed in the vignette. Multivariate and univariate analyses of variance of their responses revealed that the students held negative and prejudiced attitudes toward both the AIDS and homosexual patients. This finding suggests that medical educators should recognize that many students have stigmatizing, negative attitudes toward homosexuals and patients with AIDS. These educators should promote greater sensitivity, knowledge, and understanding among medical students of those at risk for AIDS and AIDS patients.

Acquired Immunodeficiency Syndrome↗

Cyclic AMP-dependent protein kinase regulates sensitivity of cells to multiple drugs.

The isolation of mutant cell lines affecting the activity of cyclic AMP (cAMP)-dependent protein kinase (PK-A) has made it possible to determine the function of this kinase in mammalian cells. We found that both a CHO cell mutant with a defective regulatory subunit (RI) for PK-A and a transfectant cell line expressing the same mutant kinase were sensitive to multiple drugs, including puromycin, adriamycin, actinomycin D, and some antimitotic drugs. The mutant and transfectant cells, after treatment with a concentration of the antimitotic drug colcemid that had no marked effect on the wild-type parent cell, had a severely disrupted microtubule network. The phenotype of hypersensitivity to the antimitotic drug colcemid was used to select revertants of the transfectant and the original mutant. These revertants simultaneously regained normal multiple drug resistance and cAMP sensitivity, thus establishing that the characteristics of colcemid sensitivity and cAMP resistance are linked. Four revertants of the transfectant reverted because of loss or rearrangement of the transfected mutant RI gene. These revertants, as well as one revertant selected from the original mutant, had PK-A activities equal to or higher than that of the parent. In these genetic studies, in which linkage of expression of a PK-A mutation with drug sensitivity is demonstrated, it was established that the PK-A system is involved in regulating resistance of mammalian cells to multiple drugs.

Animals↗

Unusual renal mass in a newborn infant.

A newborn male infant had a right flank mass and hematuria. A solid renal mass was demonstrated on ultrasound and computed tomography studies, while Doppler studies suggested the diagnosis of renal vascular injury. Laparotomy disclosed avulsion of the right renal pedicle, and a right nephrectomy was performed. Traumatic renal hemorrhage should be considered in the differential diagnosis of a solid renal mass in the neonate, especially if the history or physical findings suggest trauma or if there is evidence of abdominal hemorrhage.

Birth Injuries↗

Ionophore-stimulated rat basophilic leukemia cells produce PAF-acether.

Ionophore (A23187) stimulated rat basophilic leukemia (RBL-1) cells produce a lipid mediator which caused rabbit platelets to aggregate and which by using platelet-activating factor (PAF)-acether antagonists and high-pressure liquid chromotography was shown to be PAF-acether. Thus RBL-1 cells represent a cell type suitable for studying the coordinated release of three mediators of anaphylaxis: histamine, leukotrienes C4/D4 (slow-reacting substances) and PAF-acether.

Animals↗

Unemployment, drug use, and health in late adolescence.

In order to study the health correlates of unemployment, young urban South Australians, of average age 19.6 years and with 10.5% unemployed, were asked to rate their health and report number of doctor visits of the preceding month. Information about financial state, work satisfaction, and drug use was also collected. The satisfied employed rated their health somewhat more favourably than did either the dissatisfied employed or the unemployed, but changes in work situation over the next year were not related to changes in health. Alcohol use differed according to work situation for females but not males; cigarette-smoking, which did not vary with work situation, was associated with poorer health.

Adolescent↗

The effects of dopamine infusion on regional blood flow in newborn lambs.

The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the lamb. We studied eight unanesthetized newborn lambs (mean age 7 +/- 2 days) during a 15-min baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 micrograms/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclide-labeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 micrograms/kg/min but decreased at 160 micrograms/kg/min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 micrograms/kg/min. Blood flow to all organs was unchanged at the 5 micrograms/kg/min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 micrograms/kg/min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney.

Animals↗

Stigmatization of AIDS patients by physicians.

A randomly selected sample of physicians in three large cities was asked to read one of four vignettes describing a patient. They then completed a set of objective attitude measures eliciting their reactions to the patient described in the vignette. The vignettes were identical except that the patient's illness was identified as either acquired immunodeficiency syndrome (AIDS) or leukemia and the patient's sexual preference as either heterosexual or homosexual. Harsh attitude judgements were associated with the AIDS portrayals, as well as much less willingness to interact even in routine conversation when the patient's illness was identified as AIDS. Increasing numbers of AIDS patients will be seeking medical attention from physicians in all areas of the country and it will be important for health care professions to develop programs which counter unreasonable stigma and prejudicial attitudes that may be associated with this illness.

Acquired Immunodeficiency Syndrome↗

Acute herniated nucleus pulposus with cauda equina compression syndrome following chemonucleolysis. Report of three cases.

Three cases of acute disc herniation causing cauda equina compression syndrome after chemonucleolysis are described. All three patients had myelographic blocks and, despite emergency decompression procedures, were left with residual neurological deficits. Recommendations are made regarding evaluation and therapeutic intervention, and possible etiologies of this problem are reviewed.

Acute Disease↗

Endurance training and human alpha 2-adrenergic receptors on platelets.

Trained endurance athletes have a smaller rise in blood pressure, heart rate, and catecholamine response to stress when compared to an untrained, control population. Since pre-synaptic alpha 2-adrenergic receptors modulate the control of epinephrine release from nerve terminals, and since platelets are used as models of monoaminergic neurons, we investigated changes in the number and affinity binding of alpha 2-adrenergic receptors on platelets from endurance athletes and a sedentary population using the radiolabeled ligand yohimbine. We found, compared to a control, sedentary population, trained athletes had a 45% increase in the number of platelet alpha 2-adrenergic receptors (338 +/- 39 receptors/platelet vs 233 +/- 25 receptors/platelet, P less than 0.05) with no change in the dissociation constant (2.53 nM +/- 0.2 vs 2.24 nM +/- 0.2, NS) or the ED50 concentration for the competitive displacement of 2.5 nM yohimbine by epinephrine (2.8 X 10(-6) M vs 3.34 X 10(-6) M, NS). The increase in alpha 2-adrenergic receptors found in athletes may explain their decreased catecholamine response and concomitant physiologic responses to exertion.

Adult↗

Androgen and insulin response to an oral glucose challenge in hyperandrogenic women.

To further investigate the relationship between insulin and androgen secretion in hyperandrogenic women, the authors measured the response of serum insulin and androgen concentrations to an 8 A.M. oral glucose tolerance test (OGTT) in ten hyperandrogenic (HA) women and seven midfollicular phase control subjects. Significant positive correlations were demonstrated between fasting serum insulin concentration and both androstenedione (delta 4A) and testosterone (T) concentrations, which were independent of body mass index (kg/m2). A strong negative correlation was demonstrated between fasting insulin and dehydroepiandrosterone sulfate (DHEAS) levels within the HA group (r = -0.84, P = 0.003). Significant positive correlations were also demonstrated between the cumulative sum insulin response during OGTT and the percent change from fasting baseline to 3 hours in serum delta 4A (r = 0.65, P = 0.006), T (r = 0.51, P = 0.033), and dihydrotestosterone (DHT) concentrations (r = 0.75, P less than 0.001). Our data suggests that abnormalities in insulin secretion are common in HA women and that there is a strong correlation between changes in serum concentrations of insulin and androgens during an OGTT.

Androgens↗

Treatment of premenstrual syndrome with alprazolam: results of a double-blind, placebo-controlled, randomized crossover clinical trial.

A double-blind, placebo-controlled, randomized multiple crossover study was designed to determine the effectiveness of alprazolam in the treatment of premenstrual syndrome. Patients maintained daily diaries of 22 premenstrual symptoms for one pretreatment control cycle and four treatment cycles. Alprazolam 0.25 mg or placebo was administered three times daily from cycle day 20 until the second day of menstruation, at which time the dosage was tapered by one tablet per day to minimize withdrawal effects. The results of the clinical trial indicate that alprazolam is significantly more effective than placebo in relieving the severity of premenstrual nervous tension, mood swings, irritability, anxiety, depression, fatigue, forgetfulness, crying, cravings for sweets, abdominal bloating, abdominal cramps, and headache. The low incidence of side effects makes alprazolam an acceptable treatment for premenstrual syndrome for those women unresponsive to other therapies.

Adult↗

Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology.

(C57BL/6 X A/J) F1, (SWR/J X A/J) F1 and BALB/cBy mice, thymectomized on Day 3 (D3TX) or Day 7 (D7TX) or sham thymectomized (STX), were studied for immunopathologic changes in the ovary, testis, and gastric wall. In 95% of B6AF1, 100% of SWRAF1, and 35% of BALB/cBy mice ovarian disease developed, with onset at 5-6 weeks of age. Ovarian disease was not found in D7TX or STX mice. In D3TX mice, it was associated with mononuclear infiltration and ovarian follicle destruction, leading to atrophy. Epididymovasitis was detected in 70-90% of SWRAF1, 50% of B6AF1, and 64% of BALB/cBy mice after D3TX; whereas orchitis occurred in about 20% of SWRAF1 and B6AF1 mice. In some mice epididymovasitis also developed after D7TX, but not after STX. In contrast to the negative immunohistochemical findings in diseased ovaries, typical immune complex-like deposits of mouse IgG were detected by immunofluorescence along the basement membrane of epididymal ducts and seminiferous tubules. However, maximum incidence of epididymitis preceded immune complex detection. Gastritis developed in both female (57%) and male (50%) BALB/cBy mice after D3TX, occasionally after D7TX, but not after STX. Gastric mucosa was hypertrophic with dilated glands and heavy lymphocytic infiltrations throughout all gastric layers. BALB/cBy mice with gastritis usually did not have disease in the gonads, and vice versa. This study, therefore, confirms and extends the findings of Nishizuka and colleagues.

Animals↗