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N Cohen

Publications and source records attributed to N Cohen.

At least 55 records · Page 3Linked to original sources
PubMed2000

Immune deviation following stress odor exposure: role of endogenous opioids.

Olfactory cues can alter immune function. BALB/c mice exposed to odors produced by footshock stressed donor mice have increased antibody responses and increased splenic interleukin (IL)-4 production following immunization relative to recipients of odors from unstressed animals. Here we document that exposure to stress odors results in analgesia that is blocked by the non-selective opioid receptor antagonist naltrexone. The stress odor-induced increase in antigen-driven IL-4 and antibody is also blocked by oral administration of naltrexone. Thus, we provide evidence that immune deviation can occur following a psychosocial stressor, and that the deviation appears to be mediated by endogenous opioid production.

Administration, Oral↗
PubMed2000

The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families.

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder with a triad of symptoms: megaloblastic anemia, deafness, and non-type 1 diabetes mellitus. Occasionally, cardiac abnormalities and abnormalities of the optic nerve and retina occur as well. Patients with TRMA often respond to treatment with pharmacological doses of thiamine. Recently, mutations were found in patients with TRMA in a thiamine transporter gene (SLC19A2). We here describe the mutations found in eight additional families. We found four novel mutations and three that were previously described. Of the novel ones, one is a nonsense mutation in exon 1 (E65X), two are missense mutations in exon 2 (S142F, D93H), and another is a mutation in the splicing donor site at the 5' end of intron 4 (C1223+1G>A). We also summarize the state of knowledge on all mutations found to date in TRMA patients. SLC19A2 is the first thiamine transporter gene to be described in humans. Reviewing the location and effect of the disease causing mutations can shed light on the way the protein functions and suggest ways to continue its investigation.

Alleles↗
PubMed2000

Metabolic and clinical effects of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure.

BACKGROUND: Magnesium depletion and hypomagnesemia are common among furosemide-treated patients with chronic congestive heart failure. HYPOTHESIS: This investigation evaluated clinical and metabolic effects of oral magnesium supplementation. METHODS: Ten patients with severe congestive heart failure maintained on high dose furosemide (> or = 80 mg/day) received a supplement of oral magnesium citrate 300 mg/daily for 30 days. Clinical parameters were followed, and peripheral blood mononuclear cell magnesium and zinc content, serum and urine magnesium, potassium, zinc, calcium, phosphorus, and creatinine were assessed. RESULTS: Peripheral blood mononuclear cell magnesium content and serum potassium rose significantly at the end of the study (2.09 +/- 1.89 to 3.99 +/- 2.26 micrograms/mg cell protein, p < 0.05, and 4.17 +/- 0.38 to 4.39 +/- 0.27 mEq/l, p < 0.05, respectively), while the other parameters remained unchanged. CONCLUSION: In some of these patients, oral magnesium supplementation is effective in achieving substantial increments in intracellular magnesium and serum potassium which, in turn, may have cardioprotective effects.

Administration, Oral↗
PubMed2000

Keratoconus and mitral valve prolapse.

PURPOSE: To investigate the prevalence of keratoconus in patients with mitral valve prolapse (MVP). METHODS: Videokeratography was performed in 36 patients (72 eyes) with an echocardiographic diagnosis of MVP, and were compared with 25 controls. All participants underwent slit-lamp examination and completed a medical questionnaire about joint hypermobility, arthralgia, asthma, and allergic reactions. RESULTS: Keratoconus was found in eight eyes (11. 1%) (P =.056) of eight patients (22.2%) (P =.049) in the MVP group and in one eye (2%) of one patient (4%) in the control group. The keratoconus was unilateral and asymptomatic in all cases. Conjunctival papillae were statistical significant higher in the MVP group (P =.015). A statistically significant intergroup difference existed in the presence of an allergic reaction (P =.001), but not in arthralgia, hypermobility of joints, or asthma. CONCLUSION: A borderline important association of MVP with keratoconus and with allergy exists. Patients with mitral valve prolapse complaining of poor vision should be suspected of having keratoconus.

Adult↗
PubMed2000

Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device.

OBJECTIVES: Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. METHODS: Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAG's); and (c) proteoglycan content as assessed by alcian blue staining intensity. RESULTS: A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. CONCLUSIONS: Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future application may be a long-term preservation of chondral grafts, without freezing. Avoidance of freezing of cartilage grafts, might prevent the cartilage degeneration often observed in frozen osteochondral grafts.

Aged↗
PubMed2000

Standardization criteria for the detection of BCR/ABL fusion in interphase nuclei of chronic myelogenous leukemia patients by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH), as a new clinical test, is not presently standardized. For practical reasons, each laboratory must build its own criteria. In this work, we present our standardization criteria for clinical practice, which include not only the methods for cell fixation, specimen preparation, and hybridization conditions, but mainly the definition of false-positive range and the scoring criteria of microscopic analysis. These include signal assessment, difference between individual microscopists, evaluation of specimen homogeneity, and the minimum number of scored nuclei required for a clinically reliable result. For this purpose, we analyzed by FISH 24 healthy volunteer donors, 31 patients affected by non-chronic myelogenous leukemia (CML) hematological malignancies, 47 CML patients at diagnosis, and 82 CML patients during treatment for the BCR/ABL fusion. In this article, we present several quality control and assurance methods that can be useful in providing standardization of the FISH technique.

Cell Nucleus↗
PubMed2000

High-dose chemotherapy (CTM) for breast cancer.

We designed and implemented a new mitoxantrone-based high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninety-one breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m2), thiotepa (600 mg/m2), and mitoxantrone (24-60 mg/m2)) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 +/- 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 +/- 19%; for stage IV patients at 5 years was 17 +/- 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Fatal haemoptysis induced by invasive pulmonary aspergillosis in patients with acute leukaemia during bone marrow and clinical remission: report of two cases and review of the literature.

We describe two patients with acute leukaemia who died of massive haemoptysis caused by invasive pulmonary aspergillosis (IPA). The fatal event occurred during the period of bone marrow remission which followed chemotherapy-induced neutropenia. This is a rare complication. We were able to find additional 17 similar cases in the English literature, which we review. Clinically, the picture consisted of unremitting fever with profound and prolonged neutropenia, cough and dyspnoea. Both our patients were treated with broad-spectrum antibiotics, fluconazole and amphotericin B. An upper lobe infiltrate in one case, and a progressive pleural effusion in the other, were late findings on chest radiographs during the period of bone marrow recovery. Both patients succumbed to sudden massive haemoptysis during the period of bone marrow and clinical improvement. In conclusion, patients with acute non-lymphoid leukaemia are at significant risk for IPA-induced fatal haemoptysis during bone marrow and clinical remission. A high index of suspicion should be sustained throughout the entire clinical course. In view of the potential fatal outcome, aggressive diagnostic and treatment efforts are mandatory.

Acute Disease↗
PubMed2000

Reduced NO accumulation in arthrotic cartilage by exposure to methylene blue.

Nitric oxide (NO) appears to be a final common inflammation mediator of cartilage degradation. Halting the pathological formation of excessive NO, by suppressing the inducible NO synthase (iNOS) activity, may help to preserve cartilage integrity. We used fresh ex-vivo human articular cartilage explants from normal and arthrotic joints for assessment of NO levels, as determined by its nitrite degradation products and nitric oxide synthase expression. We measured matrix proteoglycan content, assessed by image analysis of alcian blue staining, and proteoglycan synthesis, assessed by sulfate incorporation into proteoglycans. The effect of methylene blue, a nitric oxide synthase inhibitor, on matrix preservation was evaluated. Cartilage discs in vitro, derived from normal appearing joints, secreted about one tenth as much NO compared to discs derived from arthrotic cartilage. Cartilage explants showed a time-dependent reduction in the amount of aggrecan within the cartilaginous matrix. Addition of methylene blue to the growth medium lowered nitric oxide accumulation and prevented matrix degradation in the cultured cartilage discs. The cartilage matrix preservation effect was mediated through downregulation of all three isoforms of NOS, i.e., the neuronal NOS, endothelial NOS and inducible NOS and upregulation of TGF beta receptor in the chondrocytes. Our findings indicate that inhibition of NOS activity preserves cartilage matrix in vitro.

Cartilage, Articular↗
PubMed2000

Warfarin for stroke prevention still underused in atrial fibrillation: patterns of omission.

BACKGROUND AND PURPOSE: The value of warfarin in preventing stroke in patients with chronic atrial fibrillation is well established. However, the prevalence of such treatment generally lags behind actual requirements. The aim of this study was to evaluate doctor- and/or patient-related demographic, clinical, and echocardiographic factors that influence decision for warfarin treatment. METHODS: Between 1990 and 1998, 1027 patients were discharged with chronic or persistent atrial fibrillation. This population was composed of (1) patients with cardiac prosthetic valves (n=48), (2) those with increased bleeding risks (n=152), (3) physically or mentally handicapped patients (n=317), and (4) the remaining 510 patients, the main study group who were subjected to thorough statistical analysis for determining factors influencing warfarin use. RESULTS: The respective rates of warfarin use on discharge in the 4 groups were 93.7%, 30.9%, 17.03%, and 59.4% (P=0.001); of the latter, an additional 28.7% were discharged on aspirin. In the main study group, warfarin treatment rates increased with each consecutive triennial period (29.7%, 53.6%, and 77.1%, respectively; P=0.001). Age >80 years, poor command of Hebrew, and being hospitalized in a given medical department emerged as independent variables negatively influencing warfarin use: P=0.0001, OR 0.30 (95% CI 0.17 to 0.55); P=0.02, OR 0.59 (95% CI 0.36 to 0.94); and P=0.0002, OR 0.26 (95% CI 0.12 to 0.52), respectively. In contrast, past history of stroke and availability of echocardiographic information, regardless of the findings, each increased warfarin use (P=0.03, OR 1.95 [95% CI 1.04 to 3.68], and P=0.0001, OR 3.52 [95% CI 2.16 to 5.72], respectively). CONCLUSIONS: Old age, language difficulties, insufficient doctor alertness to warfarin benefit, and patient disability produced reluctance to treat. Warfarin use still lags behind requirements.

Age Factors↗
PubMed2000

Prenatal diagnosis and carrier detection for molybdenum cofactor deficiency type A in northern Israel using polymorphic DNA markers.

Molybdenum cofactor deficiency (MoCoD) is an autosomal recessive, fatal neurological disorder, characterized by the combined deficiency of sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase. We have recently reported an excessive occurrence of this fatal disorder among segments of the Arab population in Northern Israel suggesting that the true incidence of MoCoD is probably underestimated in this highly inbred population. This lethal disease can be diagnosed prenatally by assay of sulphite oxidase activity in chorionic villus samples in pregnancies of couples who have had previously affected children (obligatory carriers). However, to date, there is no biochemical assay for carrier detection among the population at risk. Recently we demonstrated the linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3 in two consanguineous Israeli-Arab unrelated kindreds. The description of the MOCS1 gene that maps to the same region and which carries multiple mutations in MoCoD type A followed this finding. We describe here one additional kindred of Arab-Israeli origin, which is also linked to the MOCS1 locus, and demonstrate the feasibility of prenatal diagnosis and carrier detection using microsatellite markers in selected families when mutations are unknown. A complete correlation between the biochemical and DNA assays was found in a total of six samples (five chorionic villus and one amniocyte culture sample) obtained from the three MoCoD families.

Chorionic Villi↗
PubMed2000

[Epidemiological information obtained from anti-hepatitis C virus screening in blood donors and candidates for autologous transfusion from 1992 to 1996 in the Alpes-Maritimes region].

OBJECTIVES: To determine the evolution of the frequency of anti-hepatitis C virus antibodies from 1992 to 1996 in blood donors and in candidates for autologous transfusion in the Alpes-Maritimes region and to assess risk factors. METHODS: Anti-hepatitis C virus antibodies were assessed by second generation ELISA in 1992 and in the first quarter of 1993, and then by third generation ELISA; in all cases, anti-hepatitis C virus antibodies were confirmed by RIBA test. RESULTS: Since 1992 (when the second generation ELISA test became available), the prevalence of anti-hepatitis C virus antibodies in blood donors in the Alpes-Maritimes region (0.54% in 1992 to 0.20% in 1996) has decreased. Positive ELISA anti-hepatitis C virus was confirmed by RIBA in 53 to 68% of anti-hepatitis C virus blood donations. The percentage of anti-hepatitis C virus donors with ALT above the upper limit (donation exclusion threshold) was between 28 and 56%.The most frequent age interval for new anti-hepatitis C virus positive donors was between 30 and 40 years. Since 1992, a third of the anti-hepatitis C virus blood donors agreed to participate in a medical history questionnaire. One or several risk factors were found in almost all donors. The most frequent source of infection was nosocomial (50%). During the 5 years of the study, the number of candidates for autologous transfusion increased: 717 in 1992 to 1 528 in 1996. The prevalence of anti-hepatitis C virus in this older population (mean age: 64 years) decreased progressively (2.9% in 1992 to 1.1% in 1996, P<0, 01) since the prevalence of anti-HBc remained stable, near 12%. Among the 96 subjects found to be anti-hepatitis C virus positive before an autologous transfusion, 49 were transfused before 1990 and 40 had a history of surgery. CONCLUSION: The prevalence of anti-hepatitis C virus has decreased since 1992 in blood donors and in candidates for autologous transfusion which may suggest that there is better screening in the general population and presenting the spread of hepatitis C virus infection.

Adult↗
PubMed2000

Poison exposure in children before Passover.

BACKGROUND: Extensive cleaning of homes in Israel before Passover may result in increased exposure of children to cleaning substances. OBJECTIVES: To evaluate the potential danger of Passover cleaning to children, and to study the risk factors in order to identify areas for prevention. METHODS: All cases of poison exposure in Jewish and Arab children under the age of 15 years reported to the Israel Poison Information Center during 1990-95 (n = 5,583) were analyzed for the 6 weeks before and 6 weeks after Passover. Poison exposures in Jewish children < 15 years old were studied in seven pediatric emergency rooms for the 2 weeks before and 6 weeks after Passover (n = 123). RESULTS: The IPIC data showed a highly significant 38% increase in the average weekly poison exposure rate for the 2 weeks before Passover compared with the remaining 10 weeks. Data recorded by the pediatric emergency rooms showed a twofold increase in cleaning substance poisoning during the 2 weeks before Passover compared with the following 6 weeks. The rise in exposures to cleaning substances was observed among children from secular, religious and ultra-orthodox families. In these exposures, the substance was found in open containers in 70% of cases. CONCLUSIONS: The extensive cleaning of homes among Jewish families in preparation for Passover poses the danger to young children of cleaning substance poisoning. Increasing public awareness, closer observation of children, and keeping these substances in closed containers should increase children's safety during this annual cleaning.

Adolescent↗
PubMed2000

Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene.

BACKGROUND: Androgenetic alopecia is considered to be genetically determined. Recently, a rare autosomal recessive form of hereditary alopecia, termed atrichia with papular lesions (APL), was found to result from mutations in the human hairless gene. OBJECTIVE: Our aim was to assess the pattern of androgenetic alopecia in heterozygous carriers of a deleterious mutation in the human hairless gene. METHODS: Healthy male second-degree relatives (n = 31) of patients affected with APL and belonging to a large consanguineous kindred were interviewed and given a Hamilton score of baldness. DNA was obtained from each subject and analyzed for the presence of a mutation in the human hairless gene known to affect this family. The age at onset and extent of baldness were compared in healthy homozygotes and heterozygous carriers of the mutation. RESULTS: Statistical analysis of the results revealed no differences in age at onset and extent of androgenetic alopecia between the two groups of subjects. CONCLUSION: The present study reports the first attempt to characterize the phenotype of heterozygous carriers of a mutation in the human hairless gene. It indicates that the presence of a deleterious mutation in one allele of the hairless gene does not affect the pattern of androgenetic hair loss.

Adult↗
PubMed1999

Structure and function of the mammalian egg zona pellucida.

The zona pellucida is a thick extracellular coat that surrounds all mammalian eggs and preimplantation embryos. The zona pellucida supports communication between oocytes and follicle cells during oogenesis; protects oocytes, eggs, and embryos during development, and regulates interactions between ovulated eggs and free-swimming sperm during and following fertilization. Mutant females that produce eggs that lack a zona pellucida are infertile. The functions of the zona pellucida during fertilization now can be ascribed to certain of its glycoproteins. Here we describe some aspects of zona pellucida structure and function as they relate to mammalian fertilization. J. Exp. Zool. (Mol. Dev. Evol.) 285:251-258, 1999.

Animals↗
PubMed1999

Cell surface expression of the endoplasmic reticular heat shock protein gp96 is phylogenetically conserved.

In mammals, the heat shock protein gp96 complexed to antigenic peptides elicits T cell adaptive immunity. By itself, however, gp96 can evoke responses that are characteristic of innate immunity. Interestingly, this protein, which resides in the endoplasmic reticulum, is expressed on the surface of certain mouse tumor cells. Given that heat shock proteins are highly conserved, we investigated whether the cell surface expression of gp96 is also evolutionarily conserved. Our data reveal that gp96, most likely containing the endoplasmic reticulum retention motif (KDEL), is expressed on the surface of three different Xenopus lymphoid tumor cell lines, each derived from a different spontaneously arising thymic tumor. Levels of expression differ among the tumor lines tested, with more immunogenic tumors expressing greater amounts of surface gp96. Moreover, a high level of gp96 surface expression is detectable on a subset of Xenopus normal nontransformed splenic lymphocytes (mainly surface IgM+ B cells) but not on other normal cells, including macrophages and nucleated erythrocytes. Surface expression of a gp96 protein homologue occurs also on some, but not all, T and B cell clones derived from peripheral blood cells of the channel catfish, as well as on lymphocyte-like cells, but not on erythrocytes from the hagfish, a primitive agnathan vertebrate lacking markers of an adaptive immune system. gp96 is actively directed to and retained on the plasma membrane of Xenopus lymphocytes and tumor cells and hagfish lymphocyte-like cells by a process that requires vesicular transport. This selective surface expression of gp96 on some immune cells from different vertebrate classes is consistent with an ancestral immunological role of gp96 as danger-signaling molecule.

Animals↗