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Biomedical subjects

A Barzilai

Publications and source records attributed to A Barzilai.

At least 19 recordsLinked to original sources

[Immediate breast reconstruction with transverse abdominal myocutaneous flap].

Mastectomy in 16 consecutive patients with carcinoma of the breast was immediately followed by reconstruction with a transverse abdominal, myocutaneous flap. Surgery was performed simultaneously by a team of general surgeons and a team of plastic surgeons. The final cosmetic result was considered very good by most patients. Complications were only minor and were treated conservatively. We consider breast reconstruction by this method, after mastectomy for breast carcinoma, to be the method of choice.

Breast Neoplasms

Necrobiotic xanthogranuloma with paraproteinemia.

Necrobiotic xanthogranuloma (NXG) is a rare skin disease mimicking necrobiosis lipoidica diabeticorum clinically and histologically. However, its association with paraproteinemia, and the evolution of hematologic malignancies in some cases, established NXG as a separate clinicopathologic entity. A typical case with indolent course is described.

Aged

Dopamine-induced programmed cell death in mouse thymocytes.

Exposure of mouse thymocytes to dopamine caused apoptosis (programmed cell death). This was manifested by cellular condensation and membrane damage shown by flow cytometry measurements and scanning electron microscopic study. Dopamine also affected thymocytic nuclei and their genomic DNA integrity. Most of the DNA molecules accumulated in a subdiploid peak in flow cytometry analysis, indicating DNA fragmentation to small particles. DNA analysis showed the typical pattern of 'DNA ladder' caused by internucleosomal DNA cleavage. X-ray microanalysis of the cellular elements of dopamine-treated cells showed elevation of sodium (Na), chloride (Cl) and calcium (Ca) peaks, accompanied by reduction in phosphate (P) concentrations. Comparison of the potassium (K) and P concentrations showed significant differences between the two major death processes: necrosis (induced by exposure to sodium azide (NaN3)) and apoptosis (induced by dopamine). High concentrations of K indicated cell viability while reductions in P and elevations in Ca levels were found to be typical of apoptotic cell death. The antioxidant dithiothreitol (DTT) suppressed dopamine-induced apoptosis in thymocytes, suggesting that its toxicity may be mediated via generation of reactive oxygen radicals. Our study suggests that under certain circumstances, dopamine and/or its metabolites, may induce a process of apoptotic cell death of the dopamine-producing cells in the substantia nigra. Increased accessibility of dopamine to the nigral cell nucleus or inability to scavenge excess free radicals generated from dopamine oxidation triggering programmed cell death, may cause the progressive nigral degeneration in Parkinson's disease.

Animals

Hepatitis E virus infection in hemophiliacs.

Israel is endemic for hepatitis E virus (HEV), the causative agent of enteric non-A, non-B hepatitis. Transmission is via the feco-oral route but the possibility of transmission through blood transfusion has been raised. This question was addressed by examining sera from 188 hemophilic patients in Israel, screening was performed with an enzyme immunoassay (EIA) for antibody against hepatitis E virus (anti-HEV) and confirmed with a neutralization test. Sixteen patients (9%) were seropositive for anti-HEV. A statistically significant difference was not found between the seroprevalence in this group and that of a healthy Israeli control population, matched for sex and age. The anti-HEV-seropositive hemophiliacs had the same seroprevalence of antibodies to hepatitis B and C virus and to HIV and the same number of cases with chronic hepatitis as among the anti-HEV-seronegative patients. The seroprevalence of antibodies to hepatitis A virus (anti-HAV) was, on the other hand, higher in the anti-HEV-seropositive group. This study indicates that HEV is not transmitted by cryoprecipitate or lyophilized factor concentrates. High prevalence of coinfection with hepatitis A supports our conclusion that HEV infection in Israeli hemophiliacs was due mainly to feco-oral transmission.

Adolescent

Necrotizing fasciitis: an indication for hyperbaric oxygenation therapy?

BACKGROUND: The accepted treatment protocol for necrotizing fasciitis (NF) consists of extensive surgery and wide spectrum antibiotics. Hyperbaric oxygenation (HBO) has been recommended as adjuvant therapy for NF, improving patient mortality and outcome. However, the beneficial effect of HBO for NF remains controversial. METHODS: A retrospective evaluation of treatment outcome in 37 patients treated for NF between 1984 and 1993 was carried out. The mortality rate, morbidity criteria, and risk factors for grave prognosis were compared between a group of 25 patients who received HBO as part of their treatment protocol and a group of the remaining 12 patients treated by surgical excision and antibiotics alone. RESULTS: The two groups were found to be similar with regard to age, gender, the incidence of individual risk factors for ominous prognosis, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score for disease's severity on presentation. The mortality rate among the HBO-treated patients was 36%, as opposed to 25% in the non-HBO group. The mean number of surgical débridements required per patient was significantly higher in the HBO group: 3.3 compared with 1.5 in the non-HBO-treated patients. Although the average length of hospitalization for survivors was shorter for the HBO group, the difference between the groups did not reach statistical significance. CONCLUSIONS: The results of this study cast doubt on the suggested advantage of HBO in reducing patient mortality and morbidity when used as adjuvant therapy for NF.

Adolescent

A controlled trial of intravenous immune globulin for the prevention of serious bacterial infections in children receiving zidovudine for advanced human immunodeficiency virus infection. Pediatric AIDS Clinical Trials Group.

BACKGROUND: Serious bacterial infections are common in children infected with the human immunodeficiency virus (HIV). Studies performed before zidovudine became standard therapy found that intravenous immune globulin decreases the number of serious bacterial infections in these children. We designed a multicenter study to evaluate the efficacy of intravenous immune globulin in children with advanced HIV infection who were receiving zidovudine. METHODS: In a double-blind trial 255 children between 3 months and 12 years of age who had the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) (n = 129) or placebo (0.1 percent albumin) (n = 126) every 28 days. All children received 180 mg of zidovudine per square meter of body-surface area orally four times daily. Treatment assignment was stratified according to whether the patients had a history of one or more serious bacterial infections, had previously been treated with zidovudine, or were currently receiving prophylaxis with trimethoprim-sulfamethoxazole. The median length of follow-up was 30.6 months. RESULTS: The estimated two-year rates of serious bacterial infections with confirmed pathogens were 16.9 percent for the immune globulin group and 24.3 percent for the placebo group (relative risk, 0.60; 95 percent confidence interval, 0.35 to 1.04; P = 0.07). The treatment effect was seen primarily among the 174 children who were not receiving trimethoprim-sulfamethoxazole prophylaxis at entry; the estimated two-year rates of infection were 11.3 percent for the immune globulin group and 26.8 percent for the placebo group (relative risk, 0.45; 95 percent confidence interval, 0.22 to 0.91; P = 0.03). For the 81 children who were receiving trimethoprim-sulfamethoxazole prophylaxis initially, the rates were 27.7 percent in the immune globulin group and 17.7 percent in the placebo group (relative risk, 1.26; 95 percent confidence interval, 0.44 to 3.66; P = 0.67). The two-year survival was similar in the two groups: 79.2 percent among immune globulin recipients and 75.4 percent among placebo recipients (P = 0.41). CONCLUSIONS: In children with advanced HIV disease who are receiving zidovudine, intravenous immune globulin decreases the risk of serious bacterial infections. However, this benefit is apparent only in children who are not receiving trimethoprim-sulfamethoxazole as prophylaxis.

AIDS-Related Complex

Dopamine induces apoptosis-like cell death in cultured chick sympathetic neurons--a possible novel pathogenetic mechanism in Parkinson's disease.

We report that exposure of cultured, postmitotic chick-embryo sympathetic neurons, to physiological concentrations of dopamine (0.1-1 mM) for 24 h initiates a cellular death process characteristic of apoptosis (= programmed-cell-death, PCD). Dopamine caused marked morphological alterations, mainly axonal disintegration and severe shrinkage and condensation of cell bodies. Flow-cytometric analysis of propidium-iodide-stained cell nuclei revealed the characteristic apoptotic nuclear fragmentation: increase in nuclear granularity and emergence of a large, distinct population of nuclei with reduced DNA content (subdiploid, apoptotic peak). These alterations were similar to changes induced by nerve growth factor (NGF) deprivation, a model of sympathetic neuronal PCD. Alterations were inhibited by the anti-oxidative agent DTT. Inappropriate, dopamine-induced activation of PCD might have a role in nigral neuronal degeneration in Parkinson's disease.

Animals

Distinctly phosphorylated neurofilaments in different classes of neurons.

Recent immunohistochemical experiments revealed that specific anti-neurofilament monoclonal antibodies yield distinct patterns in different types of neurons. This led to the suggestion that neurofilaments are a family of heterogeneous molecules whose occurrence and distribution are a function of cell type. In the present study we examined the hypothesis that this heterogeneity is due to differences in the extent of phosphorylation of neurofilament proteins in distinct types of neurons. In view of the large number of potential phosphorylation sites on the heavy neurofilament protein (NF-H), we focused on this protein and examined its extent of phosphorylation in different types of neurons. This was performed using neurofilaments isolated from axons of the cholinergic bovine ventral root motor neurons and of the chemically heterogeneous bovine dorsal root neurons. Two-dimensional gel electrophoresis revealed that the isoelectric point of ventral root NF-H (pl 5.10) was approximately 0.2 pl units more acidic than that of dorsal root NH-F. This difference was abolished by treating the neurofilaments with alkaline phosphatase, suggesting that the excess negative charge of ventral root NF-H is due to increased levels of phosphorylation. Amino acid analysis confirmed that the phosphoserine content of ventral root NF-H (27.2 +/- 2.5% of the serines) is markedly higher than that of dorsal root NF-H (15.5 +/- 6.2% of the serines). These findings provide a novel system for studying the biochemistry and function of distinctly phosphorylated neurofilaments in different types of neurones.

Animals

High versus ultra-high purity factor VIII concentrate therapy: prospective evaluation of immunological and clinical parameters in HIV seronegative and seropositive hemophiliacs.

This study aimed at evaluation of the immunological status and the clinical course of both HIV seronegative and seropositive hemophiliacs treated with either an ultra-pure factor VIII product (UP-F VIII), or a high-purity F VIII (HP-F VIII) concentrate. Eighteen HIV seronegative patients were divided into two groups of therapy and their immune status was followed for 2 years. During the second year of the study 8 patients of the HP-F VIII and 6 from the UP-F VIII therapy groups were switched to the alternative F VIII concentrates. Eighteen asymptomatic HIV seropositive patients were also divided into therapy groups and their immune status and any development of HIV-related symptoms were followed for 4 years. Evaluation of the HIV seronegative patients during the first year did not reveal any differences between the groups in the CD4 or CD8 cell counts, in natural killer cell (NK) activity, or in the mitogenic responses of T lymphocytes to Phytohemagglutinin (PHA), and of B lymphocytes to Pokeweed mitogen (PWM). The switch of 8 patients from the HP-F VIII and 6 from the UP-F VIII groups to the alternative concentrate did not yield any changes in their immune profile during the second year of the study. The HIV seropositive groups differed in the initial CD4 count, with a lower CD4 count (193 +/- 126 vs 437 +/- 142) and a higher F VIII consumption (63,000 +/- 17,000 vs 26,000 +/- 10,000) in the UP-F VIII group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

5-HT and cAMP induce the formation of coated pits and vesicles and increase the expression of clathrin light chain in sensory neurons of aplysia.

In the course of studying proteins involved in long-term facilitation in Aplysia, we found that 5-HT and cAMP, a second messenger activated by 5-HT, lead to the removal of a set of N-CAM-related cell adhesion molecules (apCAMs) from the surface membrane of sensory neurons by means of receptor-mediated endocytosis. Here we describe that, as part of this coordinated program for endocytosis, 5-HT and cAMP also induce in the sensory neurons an increase in the density of coated pits and coated vesicles and an increase in the expression of the light chain of Aplysia clathrin (apClathrin). The clathrin-related endocytosis seems designed to internalize and redistribute apCAMs and other surface membrane proteins in the sensory neurons, and thus it appears to constitute one of the initial steps in the growth of new synaptic connections that accompanies long-term facilitation.

1-Methyl-3-isobutylxanthine

[Nonsurgical treatment of gallstones].

Lately, nonoperative treatment is being used in high risk patients with gallbladder or bile duct stones. Procedures include oral dissolution, extracorporeal shock wave lithotripsy, mechanical lithotripsy, contact dissolution or extraction after papillotomy or via a T-tube tract. We review nonsurgical treatment of gallstones and present our experience in the treatment of 9 patients using combinations of the above-mentioned modalities.

Cholelithiasis

Modulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia.

A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation.

Amino Acid Sequence

Long-term sensitization training in Aplysia leads to an increase in calreticulin, a major presynaptic calcium-binding protein.

Long-term memory for sensitization in Aplysia requires new protein and RNA synthesis. Here, we identify a late protein as calreticulin, the major Ca(2+)-binding protein of the lumen of the endoplasmic reticulum. An antiserum against Aplysia calreticulin reveals an enrichment of calreticulin immunoreactivity in presynaptic varicosities. Quantitative S1 nuclease analysis indicates that the steady-state level of calreticulin mRNA in Aplysia sensory neurons increases during the maintenance phase of long-term sensitization. The finding that this mRNA increases in expression late, some time after training, is consistent with the idea that long-term neuromodulatory changes underlying sensitization may depend on a cascade of gene expression in which the induction of early regulatory genes leads to the expression of late effector genes.

Amino Acid Sequence

Long-term sensitization training in Aplysia leads to an increase in the expression of BiP, the major protein chaperon of the ER.

Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in Aplysia californica requires RNA and protein synthesis. These long-term behavioral changes are accompanied by long-term facilitation of the synaptic connections between the gill and siphon sensory and motor neurons, which are similarly dependent on transcription and translation. In addition to showing an increase in over-all protein synthesis, long-term facilitation is associated with changes in the expression of specific early, intermediate, and late proteins, and with the growth of new synaptic connections between the sensory and motor neurons of the reflex. We previously focused on early proteins and have identified four proteins as members of the immunoglobulin family of cell adhesion molecules related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER resident protein involved in the folding and assembly of secretory and membrane proteins. Behavioral training increases the steady-state level of BiP mRNA in the sensory neurons. The increase in the synthesis of BiP protein is first detected 3 h after the onset of facilitation, when the increase in overall protein synthesis reaches its peak and the formation of new synaptic terminals becomes apparent. These findings suggest that the chaperon function of BiP might serve to fold proteins and assemble protein complexes necessary for the structural changes characteristic of long-term memory.

Amino Acid Sequence