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Biomedical subjects

S Levy

Publications and source records attributed to S Levy.

At least 55 records · Page 3Linked to original sources
PubMed2001

High prevalence and impact of subnormal serum vitamin B12 levels in Israeli elders admitted to a geriatric hospital.

BACKGROUND: The elderly are known to have higher rates of low and subnormal vitamin B12 levels than younger persons. Vitamin B12 deficiency has been extensively studied in the elderly, but primarily in outpatient settings. There is a paucity of data regarding the prevalence of low and low-normal B12 in frail, hospitalized, elderly patients, and its implications. Additionally, there is little information regarding vitamin B12 status in Israeli elders. OBJECTIVES: The objectives of the study were to estimate the prevalence of low and borderline vitamin B12 levels among frail, hospitalized, elderly patients, and their clinical implications. METHODS: We conducted a chart review, using a retrospective cohort design. The participants were 895 patients admitted to Harzfeld Medical Center in Gedera, Israel. Records were abstracted for vitamin B12 and Folic Acid levels, gastric disease, and outcomes including death, cognitive impairment and neurologic disease. RESULTS: Six hundred and forty patients were eligible for the study. In 15% of the patients, vitamin B12 level was in the low range (<150pmol/L) and in 25% in the low-normal range (150-250pmol/L). Gastric disease and antacid use were not associated with the vitamin B12 status. Mortality was higher in the high vitamin B12 group (p=0.02), perhaps reflecting a selection toward higher acuity in this group. Cerebrovascular disease was more common in patients with lower vitamin B12 levels (p=0.046). CONCLUSIONS: Forty percent of hospitalized elderly patients have low or borderline serum levels of vitamin B12, which may contribute to cerebrovascular disease and cognitive decline.

Aged↗
PubMed2001

Biomedical image skeletonization: a novel method applied to fibrin network structures.

To understand the rheological behavior of fibrin clots, we must obtain quantitative measurements of morphometric parameters of the networks formed under various conditions. The networks are so complex that researchers must currently manually segment the images of network samples and estimate the parameters from them. Skeletonization is a promising tool for automating this task. We here propose a method that rapidly constructs a coarse representation of a skeleton graph and, using the snake model, deforms the graph to obtain smooth skeletons. Unlike many existing approaches, our method does not involve explicit object boundary information or high order derivatives. Since our method processes a given image as a whole, the presence of multiple objects in an image is automatically detected and the skeletons of these objects are computed simultaneously.

Algorithms↗
PubMed2000

Allergen-induced airway hyperreactivity is diminished in CD81-deficient mice.

We demonstrated previously that CD81(-/-) mice have an impaired Th2 response. To determine whether this impairment affected allergen-induced airway hyperreactivity (AHR), CD81(-/-) BALB/c mice and CD81(+/+) littermates were sensitized i.p. and challenged intranasally with OVA. Although wild type developed severe AHR, CD81(-/-) mice showed normal airway reactivity and reduced airway inflammation. Nevertheless, OVA-specific T cell proliferation was similar in both groups of mice. Analysis of cytokines secreted by the responding CD81(-/-) T cells, particularly those derived from peribronchial draining lymph nodes, revealed a dramatic reduction in IL-4, IL-5, and IL-13 synthesis. The decrease in cytokine production was not due to an intrinsic T cell deficiency because naive CD81(-/-) T cells responded to polyclonal Th1 and Th2 stimulation with normal proliferation and cytokine production. Moreover, there was an increase in T cells and a decrease in B cells in peribronchial lymph nodes and in spleens of immunized CD81(-/-) mice compared with wild-type animals. Interestingly, OVA-specific Ig levels, including IgE, were similar in CD81(-/-) and CD81(+/+) mice. Thus, CD81 plays a role in the development of AHR not by influencing Ag-specific IgE production but by regulating local cytokine production.

Administration, Intranasal↗
PubMed2000

Syntheses and antifungal activity of pseudomycin side-chain analogues. Part 1.

We have described herein the syntheses of three novel series of aromatic ring containing pseudomycin side-chain analogues. Preliminary biological evaluations of these analogues clearly indicate that it is possible to synthesize rigid pseudomycin side-chain analogues without compromising in vitro antifungal activity.

Antifungal Agents↗
PubMed2000

Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo.

Drosophila transient receptor potential (TRP) is a prototypical member of a novel family of channel proteins underlying phosphoinositide-mediated Ca(2+) entry. Although the initial stages of this signaling cascade are well known, downstream events leading to the opening of the TRP channels are still obscure. In the present study we applied patch-clamp whole-cell recordings and measurements of Ca(2+) concentration by ion-selective microelectrodes in eyes of normal and mutant Drosophila to isolate the TRP and TRP-like (TRPL)-dependent currents. We report that anoxia rapidly and reversibly depolarizes the photoreceptors and induces Ca(2+) influx into these cells in the dark. We further show that openings of the light-sensitive channels, which mediate these effects, can be obtained by mitochondrial uncouplers or by depletion of ATP in photoreceptor cells, whereas the effects of illumination and all forms of metabolic stress were additive. Effects similar to those found in wild-type flies were also found in mutants with strong defects in rhodopsin, Gq-protein, or phospholipase C, thus indicating that the metabolic stress operates at a late stage of the phototransduction cascade. Genetic elimination of both TRP and TRPL channels prevented the effects of anoxia, mitochondrial uncouplers, and depletion of ATP, thus demonstrating that the TRP and TRPL channels are specific targets of metabolic stress. These results shed new light on the properties of the TRP and TRPL channels by showing that a constitutive ATP-dependent process is required to keep these channels closed in the dark, a requirement that would make them sensitive to metabolic stress.

2,4-Dinitrophenol↗
PubMed2000

The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.

PURPOSE: Unresectable squamous cell carcinomas of the head and neck (SCCHN) continue to pose a significant therapeutic challenge. This report defines the toxicities, efficacy, and prognostic factors associated with the combination of carboplatin (CBDCA), paclitaxel, and once-daily radiation for patients with locally advanced disease. Additionally, the pharmacokinetics of paclitaxel were investigated. METHODS AND MATERIALS: From 1993-1998, 62 patients with Stage III-IV SCCHN were treated with 70.2 Gy of RT at 1.8 Gy/fraction/day to the primary site. Weekly chemotherapy was given during RT consisting of paclitaxel (45 mg/m(2)/wk) and CBDCA (100 mg/m(2)/wk). All patients presented with locally advanced disease; 77% had T4 disease and 21% had T3 disease. Fifty-eight percent had N2b-N3 disease. RESULTS: Sixty patients were evaluable for response and survival with a median follow-up of 30 months (range 7-70). Ninety-eight percent of patients completed prescribed therapy. One patient died after refusing medical management for pseudomembranous colitis and is scored as a Grade 5 toxicity. Two patients suffered Grade 4 leukopenia. Median number of break days was two. A clinical complete response (CR) at the primary site was obtained in 82%, with a total (primary site and neck) CR rate of 75%. The median survival for the entire cohort is 33 months. Response to therapy and status of the neck at presentation were the only prognostic factors found to influence survival. The median survival for patients who attained a CR is 49 months versus 9 months in those who did not attain a CR (p < 0.0001). The 2- and 3-year overall survival for complete responders are 79% and 61%. Plasma paclitaxel concentrations in the range shown to be radiosensitizing were achieved. CONCLUSIONS: Weekly carboplatin and paclitaxel given concurrently with definitive once-daily external beam radiation therapy is well tolerated with over 90% of patients completing prescribed therapy. An ultimate CR rate of greater than 70% was obtained, which translated directly into improved survival. With 48% 3-year overall survival for the entire group, this regimen is an excellent option for this group of patients with a historically poor prognosis.

Adult↗
PubMed2000

The relation of perceived neighborhood danger to childhood aggression: a test of mediating mechanisms.

In the current study, two mediational mechanisms, parenting practices and children's beliefs about aggression, were hypothesized to account for the relationship between perceived neighborhood danger and childhood aggression. Using structural equation modeling, data were analyzed from an inner-city school-based sample of 732 predominantly African American 5th graders. Results suggested that perceived neighborhood danger was associated with strong positive beliefs about aggression, which in turn was associated high levels of aggression. The hypothesized mediating role of parenting practices (restrictive discipline, parental monitoring, and parental involvement) on the relation between perceived neighborhood danger and child aggression was not supported. However, the current findings suggest that children's positive beliefs about aggression mediated the relationship between restrictive discipline and aggression. Directions for future research are discussed.

Adult↗
PubMed2000

Parotid salivary gland dysfunction in chronic graft-versus-host disease (cGVHD): a longitudinal study in a mouse model.

Chronic graft-versus-host disease (cGVHD) is an autoimmune-like phenomenon resulting in morbidity and mortality following allogeneic bone marrow transplantation (BMT). Major salivary gland dysfunction and hyposalivation is one of the prevalent manifestations of cGVHD. We have used the B10.D2 to Balb/C cGVHD mice model in order to assess major salivary gland function in cGVHD, evaluating sialometric, sialochemical and histopathological parameters for almost 3 months. As cGVHD is a chronic debilitating disease it is of vast importance to evaluate these parameters on a prolonged longitudinal basis. We observed significant reduction in parotid salivary flow rate and disturbance in the salivary dynamic function in cGVHD mice in comparison to the normal and syngeneic transplanted controls. On days 18, 25, 46, 56 and 88 the mean flow rates of the cGVHD group were 37.4 +/- 4.4 microl/30 min, 40.5 +/- 4.6 microl/30 min, 32.5 +/- 2.3 microl/30 min, 22.2 +/- 3.2 microl/30 min and 14.8 +/- 3.8 microl/30 min, respectively, values which were lower than those of the syngeneic transplanted controls group by 42% (P < 0.04), 32% (P < 0.03), 44% (P < 0.01), 49% (P < 0.01) and 64% (P < 0.01), respectively. These changes in flow rates were paralleled by changes in the biochemical composition of the saliva. Moreover, the reduction in flow rates correlated with the degree of salivary gland destruction observed in the pathological slides. An inverse correlation was observed between the mean parotid salivary flow rate and the degree of fibrosis observed in the histopathological evaluation of the cGVHD mice (P < 0.01). Maximal flow rate 34.8 +/- 4.6 microl/30 min was observed when no fibrosis was observed while in mice with maximal fibrosis flow rates were minimal. This may point to the pathological mechanism leading to the major salivary gland dysfunction and hyposalivation observed in cGVHD. Thus, it may broaden our knowledge and provide the scientific background for designing better therapeutic strategies for this complication. Bone Marrow Transplantation (2000).

Animals↗
PubMed2000

Effects of percutaneous transluminal coronary angioplasty on coronary adenosine concentrations in humans.

BACKGROUND: Even minimal amounts of adenosine is released during myocardial ischemia. Its role in coronary blood flow has been extensively studied, but little is known about its behaviour during percutaneous transluminal angioplasty (PTCA) in man. MATERIAL AND METHODS: Using in situ samples the aim of this study was to evaluate adenosine plasma concentration before and after PTCA. Ten patients (8 men and 2 women, mean age 65 +/- 9 years) with a single stenosis of the left anterior descending coronary artery (LAD) of at least 70% and 10 healthy volunteers (4 men and 6 women, mean age 55 +/- 9 years) were included in the study. RESULTS AND DISCUSSION: We found that there is a close relationship between the degree of the stenosis and the adenosine concentrations in the great cardiac vein and in the LAD, and that after PTCA there is a drop in adenosine concentration downstream from the stenosis. This study confirms the crucial role of adenosine in coronary blood flow control.

Adenosine↗
PubMed2000

Leukocyte adhesiveness/aggregation test (LAAT) to discriminate between viral and bacterial infections in children.

OBJECTIVES: We previously noted that white blood cells (WBC) have increased adhesive properties during bacterial infections. Here, we aim to explore the possibility of using the different adhesive properties of WBC as a means of differentiating between viral and bacterial infections, a common problem in paediatrics. METHODS: The adhesive properties of WBC in the peripheral blood of 25 children with documented bacterial infections, 15 with documented viral infections and 36 with probable viral infections, were studied by means of a leukocyte adhesiveness/aggregation slide test (LAAT). The results of the LAAT were compared with those of the other acute phase reactants, namely WBC, differential count and erythrocyte sedimentation rate (ESR), which were taken in the same blood sample in each patient. RESULTS: The sensitivity, specificity and positive predictive value were 92%, 96%, and 92%, respectively for the LAAT; 83%, 87% and 80% for the ESR; 56%, 78% and 56% for the white blood cell count; and 54%, 74% and 50% for the differential count. CONCLUSIONS: The presence of bacterial infections in children can be tested using a simple slide test to reveal the increased state of leukocyte adhesiveness/aggregation in the peripheral blood. The LAAT is a reliable, rapid and inexpensive test, and it can be a useful laboratory tool for the paediatrician treating a child with acute febrile illness.

Bacterial Infections↗
PubMed2000

Differential expression of murine CD81 highlighted by new anti-mouse CD81 monoclonal antibodies.

We describe the use of a soluble CD81-Fc fusion protein to screen for novel monoclonal antibody (MAb) reactive with the extracellular loops of murine CD81 (TAPA-1). Two such MAbs, Eat1 and Eat2 (for Extracellular Anti-TAPA1), were used to assess the expression and function of CD81 on murine lymphocytes. Although CD81 is expressed uniformly on all human lymphocytes, murine CD81 was found to be expressed at much higher levels on resting B cells than on resting T cells. This was particularly evident when staining with the new MAbs, Eat1 and Eat2. The molecule is also functionally active on B cells, as Eat1 and Eat2 induce homotypic adhesion of B lymphocytes. Stimulated B cells undergo early apoptotic events in the presence of Eat2, as shown by binding of Annexin V-fluorescein isothiocyanate (FITC). Polyclonal activation of murine T cells also induces higher level CD81 expression, and many immortalized murine T-cell lines express high levels of the protein. In contrast to human CD81, which is expressed equally on all thymocytes, murine CD81 is induced during thymic development, being expressed at high levels on CD4+CD8+ thymocytes, in contrast to other subsets of thymocytes. Finally, murine dendritic cells, splenic macrophages, and non-killer (NK) cells all express high levels of CD81. We conclude that CD81 is differentially expressed in the murine immune system, and is involved in regulating the adhesion and activation of murine B cells.

Animals↗
PubMed2000

Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate with species permissiveness to infection.

Hepatitis C virus (HCV) glycoprotein E2 binds to human cells by interacting with the CD81 molecule, which has been proposed to be the viral receptor. A correlation between binding to CD81 and species permissiveness to HCV infection has also been reported. We have determined the sequence of CD81 from the tamarin, a primate species known to be refractory to HCV infection. Tamarin CD81 (t-CD81) differs from the human molecule at 5 amino acid positions (155, 163, 169, 180, and 196) within the large extracellular loop (LEL), where the binding site for E2 has been located. Soluble recombinant forms of human CD81 (h-CD81), t-CD81, and African green monkey CD81 (agm-CD81) LEL molecules were analyzed by enzyme-linked immunosorbent assay for binding to E2 glycoprotein. Both h-CD81 and t-CD81 molecules were able to bind E2. Competition experiments showed that the two receptors cross-compete and that the t-CD81 binds with stronger affinity than the human molecule. Recently, h-CD81 residue 186 has been characterized as the critical residue involved in the interaction with E2. Recombinant CD81 mutant proteins were expressed to test whether human and tamarin receptors interacted with E2 in a comparable manner. Mutation of residue 186 (F186L) dramatically reduced the binding capability of t-CD81, a result that has already been demonstrated for the human receptor, whereas the opposite mutation (L186F) in agm-CD81 resulted in a neat gain of binding activity. Finally, the in vitro data were confirmed by detection of E2 binding to cotton-top tamarin (Saguinus oedipus) cell line B95-8 expressing endogenous CD81. These results indicate that the binding of E2 to CD81 is not predictive of an infection-producing interaction between HCV and host cells.

Amino Acid Sequence↗
PubMed2000

Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes.

The intrinsic variability of hepatitis C virus (HCV) envelope proteins E1 and E2 complicates the identification of protective antibodies. In an attempt to identify antibodies to E2 proteins from divergent HCV isolates, we produced HCV E2 recombinant proteins from individuals infected with HCV genotypes 1a, 1b, 2a, and 2b. These proteins were then used to characterize 10 human monoclonal antibodies (HMAbs) produced from peripheral B cells isolated from an individual infected with HCV genotype 1b. Nine of the antibodies recognize conformational epitopes within HCV E2. Six HMAbs identify epitopes shared among HCV genotypes 1a, 1b, 2a, and 2b. Six, including five broadly reactive HMAbs, could inhibit binding of HCV E2 of genotypes 1a, 1b, 2a, and 2b to human CD81 when E2 and the antibody were simultaneously exposed to CD81. Surprisingly, all of the antibodies that inhibited the binding of E2 to CD81 retained the ability to recognize preformed CD81-E2 complexes generated with some of the same recombinant E2 proteins. Two antibodies that did not recognize preformed complexes of HCV 1a E2 and CD81 also inhibited binding of HCV 1a virions to CD81. Thus, HCV-infected individuals can produce antibodies that recognize conserved conformational epitopes and inhibit the binding of HCV to CD81. The inhibition is mediated via antibody binding to epitopes outside of the CD81 binding site in E2, possibly by preventing conformational changes in E2 that are required for CD81 binding.

Amino Acid Sequence↗
PubMed2000

Identification of amino acid residues in CD81 critical for interaction with hepatitis C virus envelope glycoprotein E2.

Human CD81 has been previously identified as the putative receptor for the hepatitis C virus envelope glycoprotein E2. The large extracellular loop (LEL) of human CD81 differs in four amino acid residues from that of the African green monkey (AGM), which does not bind E2. We mutated each of the four positions in human CD81 to the corresponding AGM residues and expressed them as soluble fusion LEL proteins in bacteria or as complete membrane proteins in mammalian cells. We found human amino acid 186 to be critical for the interaction with the viral envelope glycoprotein. This residue was also important for binding of certain anti-CD81 monoclonal antibodies. Mutating residues 188 and 196 did not affect E2 or antibody binding. Interestingly, mutation of residue 163 increased both E2 and antibody binding, suggesting that this amino acid contributes to the tertiary structure of CD81 and its ligand-binding ability. These observations have implications for the design of soluble high-affinity molecules that could target the CD81-E2 interaction site(s).

Amino Acid Sequence↗
PubMed2000

Fatal poisoning from Nicotiana glauca leaves: identification of anabasine by gas-chromatography/mass spectrometry.

Death of a worker occurred after ingestion of unknown amounts of Nicotiana glauca G leaves. The leaves were cooked after having been mistakenly considered to be spices of a type which grow in Thailand. After ingestion, two Thai workers collapsed, one with asystolia. Resuscitation efforts were successful only for one of the victims. A GC/MS method was used for the identification of anabasine as the main constituent in the leaves, food extract, blood, and the urine of the deceased. Lacking a standard, it was necessary to interpret the GC/MS spectrum to identify anabasine and establish its presence.

Anabasine↗