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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 181 records · Page 10Linked to original sources

Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

Adolescent↗

MR cholangiography in children and young adults with biliary disease.

OBJECTIVE: Our objective was to describe the MR cholangiography findings for young patients with suspected biliary disease who underwent half-Fourier acquisition fast spin-echo technique with respiratory triggering. SUBJECTS AND METHODS: Twenty-eight MR cholangiography studies were performed in 22 patients on a 1.5-T MR unit. Ten of these 22 patients had undergone liver transplantation. RESULTS: MR cholangiography revealed abnormalities of both the extrahepatic and the intrahepatic major and minor bile duct systems, despite the small diameter of the duct system in this group of patients. Four patterns of biliary disease were shown: global dilatation of extrahepatic or intrahepatic ducts (n = 7); segmental, uniform dilatation of central or peripheral intrahepatic ducts (n = 9); segmental, nonuniform dilatation of central or peripheral intrahepatic ducts (n = 2); and fusiform ectasia with segmental, irregular intrahepatic dilatation and bile lakes (n = 2). The findings of eight studies were interpreted as normal. The four patterns of abnormalities were correlated with the results from percutaneous transhepatic cholangiography, T-tube cholangiography, and liver biopsy and with clinical and surgical information, as available. CONCLUSION: MR cholangiography is a noninvasive technique for evaluation of biliary disease. The improved resolution afforded by respiratory triggering permits evaluation of both major and minor bile ducts, even in young, uncooperative subjects. Four patterns of abnormalities were prospectively identified, correlated with other information, and used to direct clinical treatment.

Adolescent↗

The hPMS2 exon 5 mutation and malignant glioma. Case report.

Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features. Molecular genetic analysis revealed allelic loss of chromosome 19q in the patient's second tumor but no allelic loss of chromosome 1p. Prominent microsatellite instability was also found in this tumor, consistent with a germline mismatch repair defect. Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. The authors therefore evaluated whether sporadic glioblastomas and oligodendrogliomas undergo mutations of this region of the hPMS2 gene. However, single-strand conformation polymorphism analysis of hPMS2 exon 5 failed to reveal mutations in 20 sporadic glioblastomas and 16 sporadic oligodendroglial gliomas. Thus, although it is possible that the germline hPMS2 exon 5 mutation may predispose to glioblastomas with an oligodendroglial component, the same genetic defect is not commonly involved in sporadic oligodendrogliomas or glioblastomas.

Adenomatous Polyposis Coli↗

Homeless mothers and depression: misdirected policy.

This paper is a critique of recent service-intensive shelter programs for homeless mothers and the policies that underlie these shelters. We first document the process by which mental health problems and family homelessness became so closely but mistakenly linked. We then demonstrate empirically that shelter programs for homeless families nonetheless presume that mental health problems are part of the causal nexus of family homelessness and indiscriminately deliver mental health services to homeless mothers. Simultaneously, shelter programs encourage the isolation of their residents from what they presume to be their "problematic" social networks. We show that, while mental health services had little impact on depression levels among homeless mothers, isolation from social networks did increase depression among homeless mothers. Our findings suggest that policy should put more emphasis on rapid reintegration into the community through providing housing, and it should put less emphasis on providing services.

Adolescent↗

[Effect of concentration temperature of kiwi fruit pulp on color, chlorophyll and ascorbic acid].

A study was established to evaluate concentration temperatures (25, 30, 35, 40 and 45 degrees C) on kiwi fruit pulp concentrated to 32 degrees Brix, with vacuum regulation. Munsell and sensorial colour, ascorbic acid and chlorophyll amount remanent were analyzed. Both, 25 and 30 degrees C concentration temperatures treatments, in the most of variables, experimented low deteriorate and differ with the other treatments. Ascorbic acid measurements had not significative differences (P < 0.95). Chlorophyll assays showed a decreased (70%) in the amount remanent over 35 degrees C in comparison to 25 degrees C treatments. 40 and 45 degrees C treatments showed traces of chlorophyll. Sensorial colour did not showed variations on 25 and 30 degrees C treatments; they were classified as bright green. Other treatments present colour deteriorate: 35 degrees C treatment was green-yellowish classified, and 45 degrees C treatments brown-greenish categories. Munsell colour showed the same relations, were increasing the concentration temperatures, decrease the green colour and increase the yellow colour.

Ascorbic Acid↗

Techniques to improve compliance in hemo- and peritoneal dialysis patients.

"I would like some input on how other technicians effectively deal with non-compliancy among some of our more stubborn patients," wrote a technician recently in an e-mail note to NN&I. "... Any strategies that may enable us to show that compliancy is for (the patient's) own good, and not just because we are trying to be hard on them." In this article, the second in a two-part series, authors Batson and Schwartz suggest some practical interventions that renal staff can use for both hemo- and peritoneal dialysis patients. The authors cover theories of compliance in Part I (6/99, NN&I).

Humans↗

Alpha2-adrenoreceptor agonists are neuroprotective in a rat model of optic nerve degeneration.

PURPOSE: The neurodegenerative progression of glaucoma is considered to be related not only to primary risk factors such as the elevation of intraocular pressure, but also to mediators of secondary neuronal degeneration. In the present study, the neuroprotective activity of the alpha2-adrenoreceptor agonists brimonidine, AGN 191103, and clonidine were examined in an animal model that simulates secondary neuronal degeneration of the optic nerve in a way thought to be independent of elevation of intraocular pressure. The beta-blocker timolol, currently used clinically to decrease intraocular pressure, was also examined for neuroprotective activity at dosages corresponding to the effective antihypertensive dosage. METHODS: A single dose of each of the tested compounds was administered intraperitoneally immediately after partial crush injury of the rat optic nerve. Secondary degeneration was measured by determining injury-induced deficits with and without the drug. This was achieved electrophysiologically by measurement of compound action potential amplitude, and morphometrically by counting the retrogradely labeled retinal ganglion cells, representing viable optic nerve axons, in wholemounted retinas. RESULTS: All three alpha2-adrenoreceptor agonists, but not timolol, exhibited neuroprotective effects. Treatment immediately after injury with each of these agonists resulted in a dose-dependent attenuation of the injury-induced decrease in compound action potential amplitude. Moreover, after treatment with 100 microg/kg brimonidine administered intraperitoneally, the loss of retinal ganglion cells 2 weeks after injury was three times lower than in saline-treated animals. CONCLUSIONS: In addition to their known effect of lowering intraocular pressure, alpha2-adrenoreceptor agonists, unlike timolol, exert a neuroprotective effect. Use of the rat optic nerve model of partial crush injury can serve as a method of screening compounds that are potentially capable of alleviating the progression of secondary neuronal degeneration.

Action Potentials↗

Association of chronic sublethal hypoxia with ventriculomegaly in the developing rat brain.

Bronchopulmonary dysplasia remains a major cause of neurodevelopmental handicap in preterm infants. Because bronchopulmonary dysplasia may be associated with prolonged hypoxemia without obvious changes in systemic blood pressure, we developed an animal model of chronic sublethal hypoxia to test the hypothesis that this insult results in significant alterations in corticogenesis in the developing brain. Three groups of newborn rats were placed in a chamber with FIO2 9.5% on postnatal day 3 (P3). One group was sacrificed at P13; a second group was sacrificed at P33, and the third group was removed at P33 and reared in normoxia until sacrifice at P63. Control rats were those raised in room air for the corresponding periods of time. Rats were transcardially perfused and the brains were embedded in celloidin and prepared for morphometric analysis using standard stereology methods. Although experimental rat pups in the third group demonstrated 'catch-up' of body weight following return to normoxia, these studies demonstrated both failure of brain growth (p<0.01) and progressive cerebral ventriculomegaly (p<0.01). Decreased subcortical white matter (p<0. 05) and corpus callosum size (p<0.01) were noted at P63 in pups reared under conditions of chronic hypoxia. Decreases in cortical volume (p<0.05) were noted at all three experimental time points for hypoxic-reared pups when compared to control animals. These data suggest that chronic sublethal hypoxia may lead to severe impairments in corticogenesis in an animal model of developing brain.

Animals↗

Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation.

PURPOSE: To review the treatment of cirrhotic patients with hepatocellular carcinoma in the era of liver transplantation and to determine the most appropriate approach to the treatment of patients at different stages of disease. DATA SOURCES: A MEDLINE search of English-language articles published between 1981 and 1997 and the clinical experience of the Mount Sinai Liver Transplant Program. STUDY SELECTION: Selected studies were 1) original articles reporting results of resection and transplantation in the treatment of hepatocellular carcinoma in cirrhotic patients and 2) initial reports from major transplantation centers of multimethod therapies combining chemotherapy with transplantation. DATA EXTRACTION: Study designs were assessed with careful attention to methods and aims. Relevant data on patient population, tumor stage distribution, treatment, survival, and rate of recurrent disease were extracted and analyzed. DATA SYNTHESIS: Options for the treatment of hepatocellular carcinoma in cirrhotic patients vary according to tumor stage and severity of underlying liver disease. Resection remains an important method primarily in eastern countries, where the screening of high-risk populations has been associated with early detection of small asymptomatic lesions. Long-term survival after resection, however, is low. In western countries, liver transplantation is becoming the treatment of choice in patients with advanced cirrhosis and small, unresectable lesions; resection is reserved for cirrhotic patients with small, peripheral lesions and preserved hepatic function. Minimally invasive procedures (such as percutaneous ethanol injection and transarterial chemoembolization) have been developed to treat unresectable tumors. Transarterial chemoembolization may also be effective in patients with advanced cirrhosis and unresectable lesions who are awaiting transplantation. CONCLUSIONS: The efficacy of liver transplantation for hepatocellular carcinoma has been proven mainly in patients with advanced cirrhosis and small lesions. Future studies may clarify the role of approaches combining neoadjuvant chemotherapy with transplantation for large (stage III) tumors.

Algorithms↗

GTP-dependent conformational changes associated with the functional switch between Galpha and cross-linking activities in brain-derived tissue transglutaminase.

GTP and Ca2+, two well-known modulators of intracellular signaling pathways, control a structural/functional switch between two vital and mutually exclusive activities, cross-linking and Galpha activity, in the same enzyme. The enzyme, a brain-derived tissue-type transglutaminase (TGase), was recently cloned by us in two forms, one of which (s-TGN) lacks a C-terminal region that is present in the other (l-TGN). Immunoreaction with antibodies directed against a peptide present in the C-terminus of l-TGN but missing in s-TGN suggested that this site, which is located in the C-terminal fourth domain, undergoes conformational changes as a result of interaction between l-TGN and GTP. Site-directed mutagenesis suggested that the third domain is involved in mediating the inhibition of the cross-linking activity. These results were supported by molecular modeling, which further suggested that domains III and IV both participate in conformational changes leading to the functional switch between the Ca2+-dependent cross-linking activity and the Galpha activity.

Animals↗

Accumulation of passively transferred primed T cells independently of their antigen specificity following central nervous system trauma.

The central nervous system (CNS) enjoys a unique relationship with the immune system. Under non-pathological conditions, T cells move through the CNS but do not accumulate there. CNS trauma has been shown to trigger a response to CNS self-antigens such as myelin basic protein (MBP). Here, we examined whether the injured CNS tissue undergoes changes that permit T cell accumulation. We found that injury to CNS white matter, such as the optic nerve, led to a transiently increased accumulation of T cells (between days 3 and 21). In Lewis rats with unilaterally injured optic nerves, systemic administration of passively transferred T cells recognizing either self-antigen (MBP) or non-self-antigen (ovalbumin) resulted in accumulation of the T cells in injured optic nerve, irrespective of their antigenic specificity. The effect of the T cells on the damaged nerve, the lack of selectivity in T cell accumulation and the mechanism underlying non-selective accumulation are discussed.

Animals↗