Biomedical subjects

M Stern

Publications and source records attributed to M Stern.

At least 37 records · Page 2Linked to original sources

PubMed1994

rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo.

The mammalian homolog of the yeast Sec1p, n-Sec1/Munc-18 has been demonstrated to bind the presynaptic membrane protein syntaxin, a putative synaptic vesicle docking protein. To determine the role of n-Sec1/Munc-18 in neurotransmitter release in vivo, we have overexpressed the Drosophila homolog, rop, in third instar larvae and measured the electrophysiological consequences at the neuromuscular junction. A 3- to 5-fold induction of the rop protein causes a dramatic decrease in neurotransmitter release, suggesting rop may restrict the ability of vesicles to dock or of docked vesicles to fuse. Consistent with this hypothesis, rop overexpression also reduces the number of spontaneous vesicle fusions by more than 50%, and repetitive stimulation results in significant decreases in evoked responses similar to those observed in rab3a mutant mice. However, rop overexpression does not alter significantly the Ca2+ dependence of neurotransmitter release. We propose that the Drosophila n-Sec1/Munc-18 homolog plays a negative role in neurotransmitter release in vivo, in addition to its previously identified positive function, possibly by modulation of docking of synaptic vesicles or activation of a pre-fusion complex at the active zone.

Animals↗

PubMed1994

Prevalence of hypertension in Mexico City and San Antonio, Texas.

BACKGROUND: Few data are available on the prevalence of hypertension in Mexico. METHODS AND RESULTS: We compared the prevalence of mild hypertension (systolic blood pressure > or = 140 mm Hg and/or diastolic blood pressure > or = 90 mm Hg and/or use of antihypertensive medications) in 1500 low-income Mexican Americans who participated in the San Antonio Heart Study and 2280 low-income Mexicans who participated in the Mexico City Diabetes Study. The crude prevalence of mild hypertension was 17.1% in Mexican men versus 24.4% in Mexican American men (P = .001) and 17.4% in Mexican women versus 22.0% in Mexican American women (P = .005). After adjustment for age, body mass index (BMI), waist-to-hip ratio (WHR), non-insulin dependent diabetes mellitus (NIDDM), educational attainment, and percent native American genetic admixture (Caucasian and native American), the odds ratio (Mexico City/San Antonio) was 0.55 (95% CI, 0.39, 0.77; P < .001) in men and 0.81 (CI, 0.54, 1.12; P = .201) in women. In a pooled model including both men and women, the odds ratio was 0.67 (95%, CI, 0.53, 0.84; P < .001). In the pooled model, city, age, female sex, NIDDM, BMI, WHR, and low educational attainment were significantly related to the prevalence of hypertension. CONCLUSIONS: The causes for these differences in hypertension prevalence are not known but may reflect a less modernized lifestyle in Mexico City, including greater physical activity, less obesity, and the consumption of a high-carbohydrate, low-fat diet.

Adult↗

PubMed1994

Treatment of organic bipolar mood disorders in Parkinson's disease.

Two patients with long-standing idiopathic Parkinson's disease (PD), without individual or family histories of affective disorders, developed bipolar mood disorders. Both were treated with lithium and clozapine, and one responded favorably. These may be the first reported cases in which mania was treated with clozapine in PD patients.

Bipolar Disorder↗

PubMed1994

A highly unusual combination of pulmonary pathogens in an HIV infected patient.

We report on a case with an unusual combination of pulmonary pathogens including Pneumocystis carinii, Rhodococcus equi and Toxoplasma gondii in an HIV infected patient. The multiple microbiological procedures required to ascertain the etiological diagnoses of pneumonitis in HIV-seropositive subjects are discussed.

AIDS-Related Opportunistic Infections↗

PubMed1994

Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice.

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.

Animals↗

PubMed1994

Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice.

Millions of people have been exposed to silicones which are present in consumer goods such as cosmetics and toiletries, processed foods and household products. In addition, silicones have been used extensively in medical practice as a lubricant in tubing and syringes, and as implantable devices. A silicone widely used in medical practice is polydimethylsiloxane. This study was undertaken to determine the immunotoxicologic potential of long term exposure to the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity during the 180 day exposure. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein, or serum CH 50 or C3 levels. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones and polyurethane marginally reduced the level of Ig+ cells in the spleen but did not consistently alter the distribution of T cell surface markers. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, as was phagocytosis of chicken erythrocytes and Covaspheres by adherent peritoneal cells. Natural killer cell activity was depressed in all silicone treatment groups and in mice implanted with polyurethane. No silicone or polyurethane treatment group displayed altered susceptibility to a challenge with Listeria monocytogenes, Streptococcus pneumoniae or the B16F10 tumor. The only consistent effect of 180 day exposure to silicone materials or polyurethane was a modest depression of natural killer cell activity.

Animals↗

PubMed1994

Immunotoxicity of nitrobenzene in female B6C3F1 mice.

Nitrobenzene (NBZ) is primarily employed as an oxidizing agent in the synthesis of analine and benzene compounds. It produces myelotoxic effects and effects on erythrocytes in both animal models and man. Reported hepatosplenomegaly and effects on the bone marrow are indicators that NBZ may be immunotoxic. In these studies, female B6C3F1 mice were exposed to 30, 100 and 300 mg/kg of NBZ in corn oil by gavage for 14 consecutive days. To assess the immunotoxic potential of NBZ, body and organ weights were determined and selected immunologic and host resistance responses were studied. In these studies, the liver and spleen appeared to be the primary target organs. Both liver and spleen weights were dose dependently increased. Gross histopathologic examinations revealed significant changes in the spleen, consisting of severe congestion of the red pulp areas with erythrocytes and reticulocytes. Serum chemistry profiles showed increases in alanine aminotransferase and aspartate aminotransferase activities, indicating liver toxicity. Hematologic studies showed a decrease in erythrocyte number and a concomitant increase in mean corpuscular hemoglobin and mean corpuscular volume. A dose-dependent increase in peripheral reticulocytes was also seen. DNA synthesis was enhanced, as was the number of formed elements and the number of monocyte/granulocyte stem cells in the bone marrow of treated mice. IgM responses were decreased and the phagocytic activity of macrophages in the liver was dose dependently increased with a concomitant decrease in the activities in the spleen and lung. Other immunological parameters examined were unchanged. Host resistance to microbial or viral infection was not markedly altered by NBZ; however, there were trends towards increased susceptibility where T-cell function contributes to host defense. These data indicate that NBZ-induced hemolysis and liver injury are linked to the observed alterations in bone marrow activity.

Administration, Oral↗

PubMed1994

Immunotoxicity of mono-nitrotoluenes in female B6C3F1 mice: I. Para-nitrotoluene.

para-Nitrotoluene (p-nitrotoluene) is used primarily as an intermediate in the production of various dyes, explosives, pharmaceuticals, and in the production of rubber and agricultural products. Previous investigations indicated that p-nitrotoluene was mutagenic in the Ames Test and that other mono-substituted nitrotoluenes bound covalently to hepatic macromolecules. The objective of these studies was to evaluate the potential immunotoxicity of p-nitrotoluene in mice exposed by the oral route. Mice exposed to p-nitrotoluene (200-600 mg/kg) daily for 14 days showed modest dose-dependent increases in liver and spleen weights. The livers of mice exposed subchronically to 400 and 600 mg/kg showed a mild to moderate swelling of the hepatocytes adjacent to the central veins; this swelling appeared to be reversible and there was no evidence of necrosis. The proportion of monocytes in blood was decreased in mice treated with p-nitrotoluene or toluene. Serum chemistries, bone marrow cellularity and the number of CFU-M and CFU-GM were unaffected. Immunologic investigations showed p-nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a 24% decrease in the percentage of CD4+ T lymphocytes in the spleen. There was no dose-dependent alteration of peritoneal macrophage numbers or differential count, unstimulated natural killer cell activity, response to B cell mitogen LPS, C3 activity or interferon levels. Exposure of mice to p-nitrotoluene decreased resistance to Listeria monocytogenes but not to Streptococcus pneumoniae, Plasmodium yoelii or the B16F10 melanoma, and increased resistance to the PYB6 tumor. These studies indicated that the immune system is an important target for toxicity of p-nitrotoluene. The decreased host resistance to L. monocytogenes can be attributed to the decrease in T lymphocytes and to a decreased delayed hypersensitivity response to KLH.

Administration, Oral↗

PubMed1994

Immunotoxicity of mono-nitrotoluenes in female B6C3F1 mice: II. Meta-nitrotoluene.

The nitrotoluenes are chemicals used in dyes, agricultural products, pharmaceuticals and explosives. In the present studies, the toxicology and immunotoxicity of meta-nitrotoluene (m-nitrotoluene) were evaluated. Mice, exposed to m-nitrotoluene at dose levels of 200, 400 and 600 mg/kg/body weight for 2 weeks by gastric gavage, gained body weight over the treatment period to a slightly greater extent than the control groups. Of the selected organs weighed, the liver and kidney of mice exposed to m-nitrotoluene were increased in weight while the thymus weight was decreased. The liver of mice exposed to m-nitrotoluene, but not ortho-nitrotoluene, showed slight to moderate swelling of the hepatocytes adjacent to the central veins. The hepatocyte swelling appeared to be reversible and there was no evidence of necrosis. The hematology and serum chemistries examined were unaffected by m-nitrotoluene exposure although there were modest decreases in the percentage of polymorphonuclear leukocytes and eosinophils in differential blood counts. Bone marrow cellularity and the number of CFU/M and CFU/GM were unaffected by m-nitrotoluene exposure. m-Nitrotoluene suppressed the IgM response to sRBC and the DHR response to KLH. There was a slight (8%) decrease in the percentage of B lymphocytes in the spleen. The response to the T cell mitogens was suppressed by as much as 39%. Fc-mediated adherence and phagocytosis of chicken erythrocytes and NK cell activity were increased dose dependently in mice exposed to m-nitrotoluene. Several immune parameters were unaffected by exposure to m-nitrotoluene, including the IgG response to sRBC, responses to the B cell mitogen LPS and to allogeneic cells, and serum interferon levels. Resistance to Streptococcus pneumoniae and Plasmodium yoelii were unaffected also. Resistance to the tumor model PYB6 was increased. Exposure of mice to m-nitrotoluene decreased resistance to Listeria monocytogenes. The decreased resistance to L. monocytogenes may be related to an effect on T cells, evidenced by a decrease in T cell numbers and in the DHR.

Administration, Oral↗

PubMed1994

Immunotoxicity of 2,4-diaminotoluene in female B6C3F1 mice.

2,4-Diaminotoluene (DAT) has been demonstrated to be a potent carcinogen. The present studies were carried out to determine the toxic and immunotoxic potential of DAT. Mice exposed to DAT at 25-100 mg/kg per day for 14 days by gavage showed a 42% increase in liver weight and a slight decrease in spleen weight. Histopathologic evaluation of selected organs showed the liver to be the major target with morphological changes which were dose dependent. The high dose (100 mg/kg) was associated with moderate centrilobular necrosis. No abnormal structure was noted in the spleen, lungs, thymus, kidney or mesenteric lymph nodes. The liver toxicity was associated with an elevation in alanine aminotransferase activity. The only change noted in selected hematologic parameters was a 64% increase in peripheral blood leukocytes. Mice exposed to DAT showed a decreased IgM and IgG response to sheep erythrocytes. The decrease was not a function of a decreased number of B cells because the number of B cells increased dose dependently. Proliferative capacity of immunocompetent cells was not impaired by exposure to DAT as measured by the response to several mitogens. The delayed hypersensitivity response to keyhole limpet hemocyanin in mice exposed to DAT was increased. Natural killer cell activity was decreased dose dependently and may represent a spleen cell pool shift because the number of B cells increased in the presence of a decreasing spleen size. Serum C3 was suppressed at the high dose of DAT. Phagocytosis by splenic macrophages, but not peritoneal macrophages, was inhibited by DAT exposure. DAT exposure for 14 days decreased host resistance to the bacteria, Streptococcus pneumoniae and Listeria monocytogenes, while host resistance to the pulmonary tumor model, B16F10, and the PYB6 fibrosarcoma was unaffected by DAT exposure. These data indicate that DAT is hepatotoxic and perturbs the differentiation and maturation of leukocytes.

Administration, Oral↗

PubMed1994

Neurocysticercosis: an old disease with new questions.

Cysticercosis is a parasitic infection of the central nervous system that occurs in some geographic regions and is transmitted through contaminated food or by the fecal-oral route. Treatment depends on the degree of central nervous system involvement. Ventricular cysts require surgery. Parenchymal involvement requires systemic antiparasitic therapy. Computed tomography and magnetic resonance imaging are used to image patients with neurocysticercosis. Magnetic resonance imaging is more sensitive for cerebral involvement than in computed tomography. Computed tomography is more sensitive to calcifications than is magnetic resonance imaging.

Brain Diseases↗

PubMed1994

[Evaluation of the right ventricular function for lung transplantation. Value of the electron beam scanner].

Several invasive or not invasive technics were used to evaluate right ventricular insufficiency associated to severe chronic pulmonary insufficiency. But none of them were very accurate and now the use of EBT appears as a real improvement. We performed a prospective study with 50 patients waiting for a lung transplantation and we compared the values of right ventricular function obtained by EBT to those obtained by nuclear medicine and catheterism. Accuracy of EBT for left ventricule evaluation has already been proved. Stroke volumes calculated by EBT in right and left ventricules are similar and this constitutes a good validation of the method for right ventricule evaluation. Correlations with hemodynamic measurements are poor and nuclear medicine technics underestimate the ejection fraction. So, EBT is recommended for right ventricular study before and after lung transplantation.

Adult↗

PubMed1994

Transference-countertransference: realizing a love by not actualizing it.

This paper deals with the nature and function of transference and countertransference, with respect to transference love. After a summary of the major views on the nature of transference and its function in the analytic process, the paper presents a case in which this issue of transference love was pertinent and how the therapist dealt with these feelings.

Adult↗

PubMed1993

Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release.

Synaptotagmin (syt), a synaptic vesicle-specific protein known to bind Ca2+ in the presence of phospholipids, has been proposed to mediate Ca(2+)-dependent neurotransmitter release. We have addressed the role of syt in neurotransmitter release in vivo by generating mutations in synaptotagmin (syt) in the fruitfly and assaying the subsequent effects on neurotransmission. Most embryos that lack syt fail to hatch and exhibit very reduced, uncoordinated muscle contractions. Larvae with partial lack-of-function mutations show almost no evoked excitatory junctional potentials (EJPs) in 0.4 mM Ca2+ and a 15-fold reduction in EJP amplitude in 1.0 mM Ca2+ when compared with heterozygous controls. In contrast, we observe an increase in the frequency of spontaneous miniature EJPs in the mutants. These results provide in vivo evidence that syt plays a key role in Ca2+ activation of neurotransmitter release and indicate the existence of separate pathways for evoked and spontaneous neurotransmitter release.

Alleles↗

PubMed1993

Purification and characterization of human serum hyaluronidase.

Hyaluronidase from fresh human serum was purified to apparent homogeneity in a two-step procedure. Potent serum inhibitors of hyaluronidase activity were removed during the course of the purification. Isolation of the enzyme was expedited by the use of a newly devised ELISA-like assay. Enzyme activity was measured by following the rates of hydrolysis of hyaluronan (HA) adsorbed onto microtiter wells. Following enzymatic digestion, the remaining HA was measured using a cartilage-derived biotinylated HA-binding protein and an avidin-peroxidase reaction. Molecular sieve chromatography yielded a doublet of proteins with apparent molecular sizes of 42 and 50 kDa. The molecular size of the major band of protein obtained on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions was 59 kDa. Under reducing conditions, however, the size increased to 72 kDa. The pH optimum of the enzyme was 3.7. Sodium chloride concentrations greater than 100 mM were inhibitory. Activity of the serum enzyme was further characterized with a new HA-substrate gel procedure. The serum enzyme activity is different from the liver-derived activity. The tissue source of this circulating enzyme is unknown.

Chromatography↗

PubMed1993

Long-term viability of the temporalis muscle/fascia flap used for temporomandibular joint reconstruction.

Temporalis muscle/fascia axial flaps (TFs) were used in 115 temporomandibular joints (TMJs) in 81 patients to correct ankylosis (n = 25 joints), traumatic defects (n = 8), congenital anomalies (n = 4), defects resulting from tumor resection (n = 2), degenerative joint disease (n = 52), autoimmune arthritides (n = 21), and lateral capsule flaccidity (n = 3). The follow-up period ranged from 6 months to 5.5 years. Seven patients (8.6% of the group; 10 TMJs) were reevaluated for recurrent symptoms (pain and decreased motion), with a mean of 1.7 years (range = 1 to 3 years) postoperatively. Four of these patients (seven TMJs) had magnetic resonance imaging (MRI) as part of their diagnostic workup and four patients (five TMJs) required a second operative procedure. This study reports the results of the MRI, intraoperative, and histologic evaluations of the TFs in these seven patients. The MRIs showed vascularized tissue between the condyle and roof of the glenoid fossa in all seven joints examined. The signal was consistent with muscle and/or fat as opposed to scar tissue. All flaps examined at the time of surgery (arthroscopy, n = 1; arthrotomy, n = 4) were in place and had the gross appearance of normal muscle. Histologic examination of biopsies of four flaps indicated the presence of viable muscle with normal-appearing nuclei. The results of this study indicate that the TF does survive when it is carefully dissected and inferiorly based to preserve blood supply.

Fascia↗

PubMed1993

Fetal cleft lip repair in lambs: histologic characteristics of the healing wound.

Sequential surgical procedures in cleft lip/palate (CL/P) patients result in scar formation that is believed to be associated with midface growth retardation. By use of a previously developed fetal lamb model, wound healing characteristics were investigated after in utero CL repair. It is hypothesized that scarless healing after fetal CL repair occurs without inflammation and scar formation. CL wounds were created in mid-second-trimester fetal lambs and either repaired in three layers (mucosa, muscle, and skin) or left unrepaired. Fetuses were then harvested at 7, 14, and 21 days postoperatively, and the wound site was examined microscopically. When created at 75 days' gestation (term = 145 days), fetal lamb CL wounds heal rapidly without inflammation and scar formation. By day 21 postoperatively, there was complete regeneration of skin, muscle, and mucosa, as well as epidermal appendages. With this model, it will be possible to compare the effects of scarless fetal CL repair with those of postnatal repair on midface growth.

Animals↗

PubMed1993

Medical students' differential use of coping strategies as a function of stressor type, year of training, and gender.

The cognitive-transactional model of stress was used to study the process by which medical students cope with stress. The study examined the coping responses employed by male and female first- and fourth-year medical students as a function of those situations they appraised as most stressful. Multivariate analyses of variance (MANOVAs) revealed that preferred coping strategies varied by stressor type and year of training. In dealing with medical-school-related stressors, first-year students used self-blame and problem-solving styles of coping more than did fourth-year students. When dealing with interpersonal stressors, however, fourth-year students tended to use confrontive coping more than did first-year students. Surprisingly, whether the student was a man or a woman had no impact on coping responses. The findings underscored the importance of the moderating impact of the appraisal process on the coping strategies employed to manage stressful situations. Implications for medical education, as well as for future research on coping with stress, are discussed.

Adaptation, Psychological↗