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Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 145 records · Page 8Linked to original sources
PubMed1996

Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase.

Superoxide-mediated clastogenesis is characteristic for various chronic inflammatory diseases with autoimmune reactions and probably plays a role in radiation-induced clastogenesis and in the congenital breakage syndromes. It is consistently prevented by exogenous superoxide dismutase (SOD), but not by heat-inactivated SOD, indicating that the anticlastogenic effect is related to the catalytic function of the enzyme. Increased superoxide production by activated monocytes/macrophages is followed by release of more long-lived metabolites, so-called clastogenic factors, which contain lipid peroxidation products, unusual nucleotides of inosine, and cytokines such as tumor necrosis factor alpha. Since these components are not only clastogenic, but can stimulate further superoxide production by monocytes and neutrophils, the genotoxic effects are self-sustaining. It is shown here that anticlastogenic effects of exogenous SOD are preserved despite extensive washing of the cells and removal of all extracellular SOD. Using flow cytometry and confocal laser microscopy, rapid adherence of the fluorescently labeled enzyme to the cell surface could be observed with slow uptake into the cell during the following hours. The degree of labeling was concentration and time dependent. It was most important for monocytes, compared with lymphocytes, neutrophils, and fibroblasts. The cytochrome c assay showed significantly diminished O2- production by monocytes, pretreated with SOD and washed thereafter. The preferential and rapid binding of SOD to monocytes may be of importance not only for the superoxide-mediated genotoxic effects, described above, but also from a therapeutic standpoint. It can explain the observation that beneficial effects of injected SOD lasted for weeks and months despite rapid clearance of the enzyme from the blood stream according to pharmacodynamic studies.

Animals↗
PubMed1996

Physical mapping of chromosome 8p22 markers and their homozygous deletion in a metastatic prostate cancer.

Numerous studies have implicated the short arm of chromosome 8 as the site of one or more tumor suppressor genes inactivated in carcinogenesis of the prostate, colon, lung, and liver. Previously, we identified a homozygous deletion on chromosome 8p22 in a metastatic prostate cancer. To map this homozygous deletion physically, long-range restriction mapping was performed using yeast artificial chromosomes (YACs) spanning approximately 2 Mb of chromosome band 8p22. Subcloned genomic DNA and cDNA probes isolated by hybrid capture from these YACs were mapped in relation to one another, reinforcing map integrity. Mapped single-copy probes from the region were then applied to DNA isolated from a metastatic prostate cancer containing a chromosome 8p22 homozygous deletion and indicated that its deletion spans 730-970 kb. Candidate genes PRLTS (PDGF-receptor beta-like tumor suppressor) and CTSB (cathepsin B) are located outside the region of homozygous deletion. Généthon marker D8S549 is located approximately at the center of this region of homozygous deletion. Two new microsatellite polymorphisms, D8S1991 and D8S1992, also located within the region of homozygous deletion on chromosome 8p22, are described. Physical mapping places cosmid CI8-2644 telomeric to MSR (macrophage scavenger receptor), the reverse of a previously published map, altering the interpretation of published deletion studies. This work should prove helpful in the identification of candidate tumor suppressor genes in this region.

Adenocarcinoma↗
PubMed1996

Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22.

The structure and expression pattern of a human gene located within a homozygously deleted region of a metastatic prostate cancer have been characterized. Multiple cDNA fragments of this gene were isolated by hybrid capture with yeast artificial chromosome clones covering the deletion region. Eleven coding exons spanned 205-220 kb of the 730- to 970-kb deletion. The predicted amino acid sequence was 43% identical to that of an anonymous Caenorhabditis elegans gene and 20% identical to an accessory or regulatory subunit of the oligosaccharyltransferase enzyme complex in Saccharomyces cerevisiae. Hydrophobicity profiles of all three gene products were similar and showed four putative membrane-spanning domains in the molecules' C-terminal halves, suggesting a general conservation of function. The gene was expressed as an approximately 1.5-kb mRNA in most nonlymphoid human cells/tissues including prostate, lung, liver, and colon. Expression was detected in many epithelial tumor cell lines, but was undetectable by Northern blot or RT-PCR in 14 of 15 colorectal, 1 of 8 lung, and 1 of 4 liver cancer cell lines. Lack of expression in tumor cell lines was highly correlated with hypermethylation of a CpG island located at the gene's 5' end. These findings form a basis for further work on this candidate tumor suppressor gene.

Adenocarcinoma↗
PubMed1996

A new organotypic culture method to study the actions of steroid hormones on the nervous system.

A new organotypic culture method for growing slices of nervous system tissue, based on the use of hyaluronic acid as a growth supporting milieu, is described. This method allows cultures derived from either fetuses or newborns to grow and develop with markedly reduced amounts of added serum. Organotypic cultures from fetal rat hypothalamus were exposed to 17 beta estradiol and compared to control cultures exposed to the ethanol vehicle. When exposed to estradiol, cultures showed an outgrowth of thick nerve fibers that was accompanied by an elevation in the number of microtubules present in the neuronal processes, an increment in the number of synapses, and an increased morphological differentiation of synaptic terminals. Freeze-fracture analysis of neuronal membranes from estradiol-treated cultures revealed a significant increase in the number of exoendocytotic images and a decrease in the number of intramembranous particles. Estradiol's effects parallel those found in in vivo studies, indicating that hyaluronic acid-based organotypic cultures represent an appropriate model to study hormonal influences on the developing nervous system.

Animals↗
PubMed1996

[Enforced psychiatric hospitalization for dementia by the district psychiatrist].

Dementia syndromes in the elderly are characterized by progressive deterioration and clinical and functional heterogeneity. At times a psychiatric picture prevails, and at other times, somatic as well as cognitive aspects. Accordingly, management is conducted in separate facilities, psychiatric or geriatric, which are not closely connected. The Israel Mental Health Act practically permits psychiatric commitment of every case of dementia at a certain stage of the illness. We describe a 75-year-old woman with dementia who was committed to a psychiatric hospital by order of the district psychiatrist. After attenuation of psychiatric symptoms, she remained in hospital unnecessarily. Further deterioration in physical, as well as cognitive condition, required transfer to a nonpsychiatric facility. However, due to difficulties in transfer from psychiatric to geriatric facilities, this was not accomplished. We therefor suggest broadening the authority of the district psychiatrist to include transfer of patients with dementia to appropriate, nonpsychiatric, long-term treatment facilities on termination of psychiatric treatment.

Aged↗
PubMed1996

[Homosexuality].

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Homosexuality↗
PubMed1996

Why flush?

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Aged↗
PubMed1996

Action of steroid hormones on growth and differentiation of CNS and spinal cord organotypic cultures.

During the prenatal period, gonadal steroid environment induces dramatic sexually dimorphic changes in the nervous system. We have used in vitro methods to study the mechanism and timing of hormonal influences on neuronal sprouting and myelination during the prenatal period. Organotypic cultures of hypothalamus and lumbar spinal cord (SC) slices from rat fetuses were grown on plasma clot or in hyaluronic acid and exposed to estrogen (17 beta estradiol) and testosterone (T) during cultivation. Both steroid hormones were active: 17 beta estradiol enhanced sprouting of hypothalamic neuronal fibers and increased the amount of synapses. In SC cultures T induced regeneration of thick nerve processes and an early onset of myelination, mainly of peripheral myelin.

Animals↗
PubMed1996

Cloning and comparative mapping of a gene from the commonly deleted region of DiGeorge and Velocardiofacial syndromes conserved in C. elegans.

We have identified and cloned a gene, ES2, encoding a putative 476 amino acid protein with a predicted Mr of 52,568. The gene is localized within the DiGeorge/Velocardiofacial syndrome locus on 22q11.2 and is deleted in all the patients in which a deletion within 22q11 could be demonstrated, with the exception of one patient. ES2 is expressed in all the tissues studied. Sequence comparison showed identity with five ESTs and at the amino acid level the sequence was highly similar to, and collinear with, a hypothetical C. elegans protein of unknown function. Mutation analysis was performed in 16 patients without deletion, but no mutation has been found. The cDNA sequence is conserved in mouse and is localized on MMU16B1-B3, known to contain a syntenic group in common with HSA 22q11.2.

Abnormalities, Multiple↗
PubMed1996

[Stunned myocardium or hibernating myocardium? Apropos of a case].

The authors relate a case report of unstable angina pectoris accompanied by a well-documented stunned myocardium phenomenon. Stunned and hibernating myocardium resulting from an acute or chronic coronary ischaemia on the myocardium are notions which widely govern revascularisation indications, especially after a myocardial infarction. At present, their detection is based on isotopic methods and stress echocardiography.

Angina, Unstable↗
PubMed1996

Effects of M2 antagonists on in vivo hippocampal acetylcholine levels.

There is evidence that muscarinic receptors of the M2 subtype are presynaptic autoreceptors that modify the release of acetylcholine (ACh) through a negative feedback mechanism. Blocking these receptors by selective antagonists may therefore lead to increased ACh release. This in vivo microdialysis study examined the effects of three M2 antagonists, AF-DX 116, AF-DX 384, and AQ-RA 741, on hippocampal cholinergic neurotransmission. Drug (2, 4, 8, or 16 microM) or vehicle (Ringer's solution) was perfused via a microdialysis probe into the CA1 hippocampal region of conscious male Fischer 344 rats. Levels of ACh and choline were assessed by HPLC-EC. When the dose was expressed in K1 multiples, all drugs (except AQ-RA 741 at the two highest concentrations) were found to be on the same linear dose-response curve. Choline levels were not affected by drug administration. All three compounds elevated ACh levels in a similar K1-normalized dose-response fashion, strongly supporting the concept that the proposed presynaptic mechanism of action is indeed based on the same M2 receptor. Such elevations of ACh may not only improve performance on memory tasks, but may also have therapeutic advantages in conditions of cholinergic hypofunction, such as Alzheimer's disease.

Acetylcholine↗
PubMed1996

Local anesthesia in outpatient knee arthroscopy: a comparison of efficacy and cost.

This study was performed to compare the efficacy, cost-effectiveness, and safety of general, regional, and local anesthesia when performing outpatient knee arthroscopy. The study consisted of two portions. A retrospective review of 256 outpatient knee arthroscopies was performed. The types of anesthesia used were general endotracheal, regional (epidural or spinal), and local. Comparisons were made between operative procedure, anesthesia procedure time, need for supplemental anesthesia, recovery room time and cost, pharmaceutical cost, and complications. A prospective study consisted of 100 consecutive outpatient knee arthroscopies performed using local anesthesia. Data identical to the retrospective portion were obtained. Visual analog scales were used in a patient questionnaire completed at the first postoperative visit to assess patient satisfaction with local anesthesia. The retrospective data showed similar demographics and operative procedures performed in the three study groups. The difference between operative time and total anesthetic time for the local group was 35 minutes less than for regional, and 23 minutes less than for the general group. These differences were statistically significant (P < or = .05). Total pharmaceutical cost was significantly less for the local group (P < or = .05). Recovery room cost for the local anesthesia group averaged $134 compared with $450 for regional and $527 for general. This difference was significant (P < or = .05). There were 19 complications with general anesthesia, 16 with regional anesthesia, and 2 with local. There were two regional and two local cases that needed subsequent general anesthesia. The prospective data showed nearly identical time and cost data. The patient questionnaire showed nearly universal acceptance and satisfaction with the use of local anesthesia. The use of local anesthesia for outpatient knee arthroscopy is safe, effective, and well accepted. The use of local anesthesia was shown to save a minimum of $400 per case compared with the other anesthetic methods studied.

Adult↗
PubMed1996

Effect of intrajejunal elemental diet perfusion on local secretion of soluble CD4 and CD8.

The effects of nutrients on the mucosal immune system are poorly understood. The aim of this work was to study the cellular mucosal immune response to intrajejunal perfusion of an elemental diet (ED) or a control (C) electrolyte solution by measuring jejunal secretion of soluble CD4 (sCD4) and sCD8. sCD4 and sCD8 are markers of helper/inducer and suppressor/cytotoxic regulatory functions of T cells, respectively. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with C for 80 min and then with ED containing 21.3 g/l of free amino acids and 104.2 g/l of oligosaccharides for 100 min. Jejunal fluid and serum concentrations of sCD4 and sCD8 were measured and their jejunal outputs calculated. When compared with C perfusion, jejunal perfusion with the ED resulted in a significant increase of sCD8 but not sCD4 jejunal secretion rates. sCD8 jejunal values increased early after ED perfusion and stayed at roughly the same level during the perfusion. Serum concentrations of sCD4 and sCD8 were not modified during ED perfusion. These data support the hypothesis that ED suppresses the immunologic tone of the gut, which could explain its beneficial effect in the management of intestinal inflammatory disease.

Adult↗
PubMed1996

Biochemical cure of recurrent acromegaly by resection of cervical spinal canal metastases.

Pituitary carcinoma with metastatic endocrine secreting tissue is rare. Eight cases of malignant, growth hormone-secreting tumours, all metastatic within the central nervous system have been previously described. Complete surgical resection was not possible and the patients died within 4 years of presentation with distant spread. Here we describe the first case of an apparent surgical cure of a somatotroph carcinoma metastatic to the cervical spine, documented by biochemical assessment and magnetic resonance and radioligand imaging. The possibility that intrathecal metastasis of somatotroph tumours may be responsible for some cases of treatment resistant acromegaly is discussed.

Acromegaly↗