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Biomedical subjects

J Weinberg

Publications and source records attributed to J Weinberg.

At least 55 records · Page 3Linked to original sources
PubMed1997

Identification of a synthetic peptide that mimics an HIV glycoprotein 120 envelope conformational determinant exposed following ligation of glycoprotein 120 by CD4.

CD4 ligation of HIV envelope gp120 results in conformational changes in gp120 that lead to exposure of the gp41 fusogenic domain and fusion with the host cell membrane. One determinant at or near the CD4-binding site exposed on gp120 subsequent to CD4 binding is defined by two human MAbs termed 17b and 48d. These MAbs do not block CD4 binding to gp120; rather, their binding to gp120 is upregulated following CD4 binding. To determine if synthetic peptide mimetopes could be found that reflect conformational determinants on the surface of gp120, synthetic gp120 peptides from 10 divergent HIV isolates were screened for their ability to bind to 17b and 48d in ELISAs. Although MAb 48d binds to HIV IIIB recombinant gp120 protein, in our studies 48d selectively bound only to the HIV Can0A V3 peptide and not to HIV IIIB V3 peptide, whereas MAb 17b bound none of the peptides tested. Monoclonal antibody 48d bound to the HIV Can0A V3 peptide both in solid-phase ELISA and in solution in a competitive ELISA, but could not bind to HIV Can0A V3 peptide bound to human T cells. The HIV Can0A V3 peptide induced anti-HIV antibodies in rhesus monkeys that neutralized the laboratory-adapted HIV MN strain but did not induce antibodies that neutralized HIV IIIB/LAI, HIV SF-2, or HIV RF isolates, or that neutralized HIV primary isolates. These data suggested that the primary sequence of the HIV Can0A V3 loop exists in a conformer that mimicks a non-V3 determinant of native gp120 exposed subsequent to CD4 binding on the surface of gp120 of laboratory-adapted HIV strains. Structural studies of the Can0A V3 peptide and/or the 48d MAb may provide important information regarding the nature of gp120 conformational changes that occur following gp120 ligation by CD4.

Amino Acid Sequence↗
PubMed1997

Effects of social housing condition on the response of the Shionogi mouse mammary carcinoma (SC115) to chemotherapy.

In the present study, we demonstrate that social housing conditions significantly alter the response of the transplantable androgen-responsive Shionogi mouse mammary tumor (SC115) to chemotherapy. Mice were reared either in groups (G) or as individuals (I). Immediately following tumor cell or vehicle injection, mice were rehoused from group to individual (GI) or from individual to group (IG) conditions. A combination of Adriamycin (4 mg/kg) and cyclophosphamide (61.5 mg/kg), in a series of three i.p. injections 7 days apart, was initiated when mean tumor weights of mice within a housing condition (GI or IG) reached 1 g. Survival probability was significantly greater in mice in the IG housing condition compared to those in the GI housing condition (47% versus 19%, respectively). Additionally, the median survival time following the initiation of chemotherapy was greater for mice in the IG than for mice in the GI condition (24.5 days versus 15.0 days, respectively). These findings suggest that a psychosocial stressor, social housing condition, can significantly influence chemotherapeutic efficacy.

Androgens↗
PubMed1997

Arachidonic acid products-mediated contraction induced by bradykinin in relaxed mesenteric arterial rings from Holtzman rats.

This study describes the contractile action of bradykinin on rat isolated mesenteric arterial rings and a possible mechanism responsible for this action. Bradykinin induced dose-dependent contraction of relaxed mesenteric arterial rings from Holtzman rats, but not from Wistar rats. A second bradykinin challenge in the same ring induced a very small effect or no effect at all. Destruction of the endothelium did not modify the response to bradykinin. des-Arg9-[Leu8]bradykinin failed to antagonize bradykinin's action. HOE 140 (D-Arg- [Hyp3, Thi5,D-Tic7,Oic8]bradykinin) reduced bradykinin-induced contractions. Indomethacin abolished the contractile response to bradykinin; prostaglandin F2 alpha induced a long-lasting contraction, dissimilar from that induced by bradykinin; L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]-2,2-dimethyl propanoic acid), an antagonist of the thromboxane receptor, inhibited bradykinin-induced contractions. These results suggest that bradykinin-induced contraction in mesenteric arterial rings is indirect, through activation of bradykinin B2 receptors, resulting in liberation of prostanoids from outside the endothelium. Thromboxane A2 is probably an intermediate in this response but we cannot exclude the participation of other prostanoids.

Animals↗
PubMed1997

An economic analysis of varicella vaccination for health care workers.

A simulation model was constructed to assess the relative costs and cost-effectiveness of different screening and vaccination strategies for dealing with hospital incidents of varicella exposure, compared with current policies, using data from published sources and a hospital survey. The mean number of incidents per hospital year was 3.9, and the mean annual cost of managing these incidents was pounds 5170. Vaccination of all staff would reduce annual incidents to 2.2 at a net cost of pounds 48,900 per incident averted. Screening all staff for previous varicella, testing those who are uncertain or report no previous varicella, and vaccinating those who test negative for VZV antibodies, reduces annual incidents to 2.3 and gives net savings of pounds 440 per incident averted. Sensitivity analyses do not greatly alter the ranking of the options. Some form of VZV vaccination strategy for health care workers may well prove a cost-effective use of health care resources.

Chickenpox↗
PubMed1997

Object-recognition and spatial learning and memory in rats prenatally exposed to ethanol.

Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities.

Animals↗
PubMed1997

The European Sero-Epidemiology Network.

The purpose of serological surveillance is to monitor levels of immunity to particular diseases within a population in order to enhance the quality of information on which public health measures, such as vaccination programmes, are based. Serological surv

Journal Article↗
PubMed1997

Thrombotic thrombocytopenic purpura associated with ticlopidine therapy.

A patient who developed thrombotic microangiopathy while on ticlopidine therapy is reported. Thrombotic microangiopathy resolved with discontinuation of the drug and treatment with plasma exchange and has not recurred during 10 months of follow-up. The emerging data on the risk of developing thrombotic microangiopathy while on Ticlopidine and the possible mechanisms underlying this association are reviewed. The need for careful monitoring of the platelet count and hematocrit in addition to the white cell count during the first 3 months of therapy with this drug is emphasized. It is important that nephrologists, who are frequently called upon to diagnose thrombotic microangiopathy, be aware of its association with ticlopidine. Other drug-induced syndromes of thrombotic microangiography are also considered and compared, with respect to possible mechanisms of disease in each case.

Fibrinolytic Agents↗
PubMed1997

Effect of surrogate fostering on splenic lymphocytes in fetal ethanol exposed rats.

This study evaluated the effects of surrogate fostering as a procedure to control for postnatal effects of ethanol on the maternal female that may indirectly affect the offspring. Effects of fostering on the development of splenic lymphocytes, as well as possible differential effects of fostering on female and male offspring were examined. Litters from prenatal ethanol exposed (E), pair-fed (PF), and ad libitum-fed control (C) conditions were fostered at birth to surrogate untreated dams who had given birth within the same 12-hr period, or were reared by their biological mothers. At 15 and 60 days of age, offspring from each of the conditions were sacrificed and splenic leukocytes were enumerated and analyzed for expression of differentiation antigens, using flow cytometry. At 15 days of age, fostering reduced the percentages of CD45RA+ and CD5+ cells in E compared with PF and in PF compared with C offspring, and reduced the percentage of CD4+ cells in E compared with C offspring. Fostering also had differential effects on E and C offspring, resulting in reduced percentages of CD45RA+ and CD5+ cells in fostered E compared with nonfostered E offspring, but increased percentages of CD45RA+, CD5+, and CD8+ cells in fostered C compared with nonfostered C offspring. Fostering also down-regulated CD5 antigen expression in E compared with C offspring and up-regulated CD4 antigen expression in C offspring compared with their nonfostered counterparts. At 60 days of age, E females overall had higher percentages of CD45RA+ cells compared with C females and higher percentages of CD4+ cells compared with PF and C females. Nonfostered E females had higher percentages of CD5+ cells than nonfostered C females. In contrast, E males overall had greater percentages of CD4+ cells compared with PF and C males. Among males, the percentage of CD5+ cells was increased in nonfostered E compared with nonfostered C, whereas the percentages of CD45RA+ and CD5+ cells were decreased in fostered E males compared with nonfostered E. For both females and males in the nonfostered condition there were no effects of prenatal ethanol treatment on differentiation antigen expression. However, after fostering, E females had higher CD45RA and CD5 antigen expression compared with PF and C females, whereas E males had increased CD4 antigen expression and C males had decreased CD5 antigen expression compared with their nonfostered counterparts. These data demonstrate that fostering at birth has differential effects on splenic lymphocyte populations in E, PF, and C offspring. Moreover, the effect of fostering varies with age and has differential long-term effects on female and male offspring. Thus, rather than serving as a control for indirect maternal effects of ethanol on offspring, fostering appears to be a treatment in itself and may actually confound the effects of prenatal ethanol exposure by differentially affecting E, PF, and C females and males.

Animals↗
PubMed1997

The effect of cold stress on lymphocyte proliferation in fetal ethanol-exposed rats.

Prenatal ethanol exposure and stress have each been shown to have significant effects on the immune system. This study examined the possible interactive effects of prenatal ethanol exposure and exposure to stress later in life on the immune system. Differential vulnerability to these challenges in female and male offspring was assessed. At 5 to 6 months of age, female and male offspring from prenatal ethanol-exposed (E), pair-red (PF), and ad libitum-fed control (C) conditions were exposed to 0, 1 or 3 days of cold (4 degrees C). At the end of the cold period, the proliferative response of splenic lymphocytes to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM) was assessed. The data demonstrate a significant interactive effect between prenatal ethanol exposure and cold stress in female offspring. After 1 day of cold stress, E females had significantly increased PWM-induced lymphocyte proliferation compared with PF and C females, and significantly increased Con A-induced lymphocyte proliferation compared with PF females. There were no differences in PWM or Con A-induced lymphocyte proliferation among E, PF, and C females after 0 or 3 days of cold stress, nor among E, PF, and C males on any test day. Regardless of prenatal treatment, females exposed to 1 or 3 days of cold had significantly greater basal plasma corticosterone levels than females not exposed to cold. In contrast, only E males exposed to 1 or 3 days of cold had significantly increased basal plasma corticosterone levels, compared with E males not exposed to cold; PF and C males showed no significant change in basal corticosterone after cold stress. These data demonstrate that, in response to the challenge of cold stress, changes in lymphocyte proliferation to PWM and Con A may occur selectively in E females. Moreover, the interactive effects of prenatal ethanol and cold stress may result in enhanced rather than suppressed immune responsiveness.

Acclimatization↗
PubMed1997

Effect of prenatal ethanol exposure on fetal calcium metabolism.

Alcohol consumption has adverse effects on both adult and developing bone. The mechanisms by which alcohol affects bone, however, are unknown. This study examined the possibility that maternal alcohol consumption may affect fetal bone development by altering fetal levels of parathyroid hormone (PTH), 1,25(OH)2D, or calcitonin (hormones that regulate calcium (Ca) and bone metabolism in the adult animal). Female Sprague-Dawley rats were bred and divided into three groups: 1 group was fed lab chow ad libitum (Control; C) and the other 2 groups received a liquid diet with (Ethanol; E) or without (Pair-fed; PF) ethanol. Blood from dams and fetuses was collected on day 21 of gestation, and selected fetuses were stained for determination of the degree of bone ossification. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups. Total Ca levels in fetal serum, however, showed a trend to be increased in E compared with PF and C fetuses, and no significant group differences were found in fetal serum levels of albumin, PTH, or calcitonin. Serum levels of 25-OH-D and 1,25(OH)2D were significantly decreased in E and PF, compared with C fetuses. Total Ca levels in maternal serum did not vary with the group; however, serum albumin levels were higher in E, compared with PF and C dams, suggesting that serum ionic Ca levels may have been reduced in the E dams. Serum levels of 25-OH-D were reduced in the E, compared with PF and C dams, whereas levels of 1,25(OH)2D were elevated. PTH levels did not vary among groups. Interestingly, serum calcitonin levels were elevated in the E, compared with PF and C, dams. These results indicate that the effects of ethanol on fetal bone development do not appear to be related to alterations in fetal serum levels of PTH, 1,25(OH)2D, or calcitonin. Maternal ethanol consumption, however, results in reduced appetite and a decrease in dietary Ca intake. Despite the reduced Ca intake, the ability of the dam to maintain Ca homeostasis appeared intact, although this may be dependent on the duration of ethanol consumption.

Alcohol Drinking↗
PubMed1996

Comparative fluorescence in situ hybridization mapping of primate chromosomes with Alu polymerase chain reaction generated probes from human/rodent somatic cell hybrids.

We have used Alu polymerase chain reaction generated probes from rearranged human/rodent somatic cell hybrids for fluorescence in situ hybridization and comparative mapping of some intrachromosomal changes in the karyotypes of great apes (Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus), a gibbon (Hylobates lar), and an Old World monkey (Macaca fuscata). Probes containing chromosomes 2 and 18 fragments confirmed inversions already suggested by the banding pattern of great ape homologues. However, a chromosome 3 fragment showed complex rearrangements in the gibbon and macaque karyotype which were previously not well defined from banding. 'Subchromosomal painting' will allow the identification of intrachromosomal changes on the basis of DNA homology and provides a powerful method to study karyological and genomic evolution.

Animals↗