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Biomedical subjects

M Stern

Publications and source records attributed to M Stern.

At least 181 records · Page 10Linked to original sources

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↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗

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↗

Fetal cleft lip repair in rabbits: long-term clinical and cephalometric results.

We have developed a model for fetal cleft lip (CL) repair in rabbits. To date, the in utero CL procedure has been performed on 174 fetuses in 98 pregnant does. Details of the model, wound healing characteristics, and early growth results have been published previously. In this study, we report long-term clinical and cephalometric findings in 23 fetuses who underwent the fetal CL procedure, were born alive, and survived until completion of growth. The surgically created and repaired CL in fetal rabbits described here resulted in healing without scar formation. The deformity varies from an incomplete to a severe complete cleft, resembling the clinical spectrum of spontaneous clefts in humans. Cephalometric studies indicate that there were no statistically significant differences in premaxillary width, anterior maxillary length, or anterior and posterior maxillary width among control, unrepaired, and repaired animals. Documentation of this phenomenon in higher animals is necessary before the technique can be applied to humans with cleft lip.

Animals↗

[Healing of bronchial anastomoses in single and double pulmonary transplantations].

Bilateral single lung transplantation (BSLT) (the procedure of choice for double lung replacement) and single lung transplantation (SLT) have at present a low incidence of anastomotic problems. In our experience, we have recorded no death related to anastomotic problems and 4 complications occurred for 33 anastomoses with a follow up of at least 2 months. A stent was temporarily inserted for two patients. The decrease of anastomotic complications is confirmed in the literature. It is one of the reasons why the number of SLT and BSLT performed all over the world increases rapidily to the detriment of heart lung transplantation.

Adult↗

Apoptosis in human eosinophils. Programmed cell death in the eosinophil leads to phagocytosis by macrophages and is modulated by IL-5.

Eosinophils are believed to injure tissues in a variety of allergic disease by virtue of their highly histotoxic contents and metabolites. They are readily observed in tissues during the allergic response yet the mechanisms governing the duration of tissue residence and route of removal remain obscure. We have previously reported in vitro and in vivo evidence that neutrophils undergo apoptosis (programmed cell death) and are recognized and ingested as intact cells by macrophages. We report that eosinophils, purified from the peripheral blood of asymptomatic healthy atopics, undergo apoptosis in vitro. After 72 to 96 h in culture, 57.0 +/- 6.2% (mean +/- SE) of the eosinophil population showed characteristic morphologic changes of apoptosis. Electrophoresis of the DNA from these cells demonstrated the typical "ladder" pattern of internucleosomal DNA cleavage, the hallmark of apoptosis-associated endonuclease activation. The rate of eosinophil apoptosis, slower than that reported for neutrophils, was delayed (by 80 +/- 6 h) in the presence of recombinant human IL-5, a cytokine previously reported to prolong eosinophil life in vitro but not known to modulate apoptosis. Aged, apoptotic eosinophils, but not fresh or aged preapoptotic eosinophils, were recognized and ingested as intact cells by macrophages. Apoptosis and ingestion by macrophages may represent a mechanism whereby the tissue longevity and removal of eosinophils is controlled.

Cell Death↗

Enterocytozoon bieneusi infection in acquired immunodeficiency syndrome-related sclerosing cholangitis.

Acalculous cholecystitis and sclerosing cholangitis due to Cryptosporidium sp, and cytomegalovirus have been described in patients with the acquired immunodeficiency syndrome (AIDS). However, in about 40% of cases of AIDS-related biliary disease, no opportunistic pathogen is identified. The current case report describes the first case, to the best of the authors' knowledge, of AIDS-related sclerosing cholangitis associated with microsporidiosis. Enterocytozoon bieneusi was detected in the duodenum and bile by means of light microscopy and confirmed by electron microscopy. Microsporidian infection should be suspected in patients with AIDS-related sclerosing cholangitis as well as in cases of diarrhea in which none of the usual pathogens are found.

Acquired Immunodeficiency Syndrome↗

Fetal cleft lip repair in rabbits: histology and role of hyaluronic acid.

This study examines the histologic and biochemical features of wound healing in a cleft lip model in the mid-third-trimester fetal rabbit. At days 1, 2, and 4 after the procedure, control, unrepaired, and repaired fetal heads were obtained, sectioned, and stained for histologic examination. The localization of hyaluronic acid in the wound was documented using a cartilage-derived hyaluronic acid-binding protein. In both repaired and unrepaired wounds, the fetal cleft healed without inflammatory cell infiltration or scar formation. Six months after birth, the repaired cleft showed complete regeneration of muscle across the wound and the collagen fibers were of normal density and orientation. Decreased hyaluronic acid deposition was observed in unrepaired clefts as compared with adjacent tissue; no such difference was detected in repaired clefts. Our findings support the hypothesis that a cleft lip repaired in utero heals without the scarring that accompanies postnatal repair. This may explain the lack of maxillary growth restriction after in utero cleft lip repair.

Animals↗

An ELISA-like assay for hyaluronidase and hyaluronidase inhibitors.

Hyaluronic acid (HA) is a prominent molecule in the extracellular matrix and is enriched whenever there is rapid tissue proliferation, regeneration and repair. HA is degraded in part by hyaluronidases (HA'ases) that are not well characterized. We have developed a novel ELISA-like rapid assay for HA'ases and their inhibitors. The assay is based on a high affinity biotinylated HA-binding peptide derived from tryptic digests of proteoglycan core protein of bovine nasal cartilage and the avidin-biotin reaction. HA-coated plates were incubated with serial dilutions of Streptomyces HA'ase, and the undegraded HA was measured. This established a standard curve for HA'ase activity against which all unknown enzyme samples were compared. The assay is easily modified to also serve a measure of HA'ase inhibitors. For detection of inhibitors, aliquots of sample were preincubated with a known activity of HA'ase and inhibition of HA degradation by the mixture was measured. We have used this assay to document the presence of potent HA'ase inhibitors in fetal calf sera. These techniques will aid in the purification and characterization of Ha'ases and their inhibitors.

Animals↗