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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 145 records · Page 8Linked to original sources

Characterization of IgG and IgG subclass antibodies present in paired maternal and fetal serum which are directed against HIV-1 proteins.

Passive immunity is conferred to the fetus by maternal antibodies, the majority of which are transported across the placenta during the third trimester of pregnancy. To determine the placental transport of anti-HIV-1 antibodies, serum from 5 women infected with human immunodeficiency virus (HIV) and their abortuses were examined for anti-HIV-1 antibodies. The gestational age of the abortuses ranged from 18 to 24 weeks and following polymerase chain reaction amplification, HIV-1 gag DNA was detected in tissue from 2 of the abortuses. The concentration of total IgG antibodies present in cord blood ranged from 2.9% to 12.5% of maternal levels. Antibodies directed against the envelope proteins, gp160 and gp120, the reverse transcriptase protein, p66, and the capsular protein, p24, were present in fetal and maternal serum. Although IgG1 was the predominant subclass antibody generated in response to HIV-1 proteins, IgG2, IgG3, and IgG4 directed against HIV-1 proteins were also detected. There were large differences in the antigens recognized by the antibodies produced in the mothers, and the IgG subclasses of the antibodies produced. HIV-1 proteins recognized by antibodies present in cord blood were similar to those recognized by paired maternal serum and IgG1, IgG2, IgG3 recognizing HIV-1 proteins were detected in fetal serum. However, there was a dichotomy in placental transport of IgG subclass antibodies to HIV-1 proteins. The role of these antibodies in prevention of vertical transmission of HIV-1 has yet to be determined.

DNA, Viral↗

Inhibition of HIV-1 infection by alkylureas.

The risk of infection by HIV-1 through transfusion of contaminated blood products has been markedly decreased but not eliminated by serological screening of donors. Methods are required to further minimize or eliminate the risk of infection of blood product recipients. We therefore examined the capacity of alkylureas to inhibit infectivity of HIV-1. Incubation of free HIV-1 virions with alkylureas suppressed their infectivity, and the minimal inhibitory concentration of the alkylureas was related to the length of the alkyl chain. Butylurea, the most potent inhibitor of HIV-1, inhibited the infectivity of 10(5) median tissue culture infective dose (TCID)50 of HIV-1, chronically HIV-1-infected H9 cells and mononuclear cells from two HIV-1-infected patients. Size fractionation of HIV-1 following incubation with butylurea indicated that the structure of the virus was disrupted by butylurea. This study demonstrates that butylurea, at a concentration that has been shown not to affect red blood cell function, can inhibit infectivity of extracellular and intracellular HIV-1. Since the HIV-1 inhibitory capacity of the alkylureas increases with the length of the alkyl side chain, it is likely that hydrophobic interactions between the alkylureas and HIV-1 are responsible for the observed effect.

Cell Line↗

Correlation of serum antigen and antibody concentration with clinical features in HIV infection.

Serum antigen and antibody values were studied in 164 infants and children infected perinatally with HIV. HIV antigens p17, p24, gp41, and gp120 were determined in sera by immunoblot and antigen capture assays. Lymphocyte blast transformation, serum immunoglobulins, and circulating immune complexes were also evaluated. Altogether 50 patients had HIV antigens measured: 31 (62%) patients had p17 antigen in the serum and 29 (58%) had p24 antigen present. In 19 (38%) and nine (18%) patients, respectively, gp120 and gp41 were detected. All four HIV antigens were detected in seven (14%) patients. There was a positive correlation between the concentration of each HIV sequential specimens were outcome. When sequential specimens were analysed, 120 (73%) patients had p24 antigen present. Patients with stage P2B and P2D (Centers for Disease Control classification) had the highest concentrations of p24 antigen with a mean of approximately 200 pg/ml. Altogether 70% of patients with a p24 antigen concentration of greater than 30 pg/ml eventually died or had severe clinical disease within six to 24 months. Infants under 15 months of age with a p24 antigen concentration as low as 5 pg/ml also did poorly. Increased immunoglobulins and decreases in mitogenic responses and absolute CD4+ lymphocyte counts were more prevalent in patients with raised p24 antigen. Raised concentrations of circulating immune complexes were seen in the symptomatic phase of the disease whereas in the terminal stage of the disease raised serum antigen and a decrease in circulating immune complexes and absolute CD4+ lymphocyte count were evident. Loss of p24 and/or p17 antibody as well as a decreasing ELISA optical density for HIV antibody also signalled progression of the disease.

Antigen-Antibody Complex↗

The effect of prolonged intermittent exercise, combined with food deprivation, on plasma metabolite concentration.

To examine the effect of continuous fasting combined with prolonged, intermittent exercise on glucose homeostasis, 16 endurance-trained subjects, ranging in age from 18-21 years, were completely deprived of food during 81 h of field maneuvers. Water was supplied to avoid dehydration. Participants marched 10 h each night at an estimated intensity of 35-45% of mean VO2 max covering a total distance of 105 km, and had a relative rest during day time. Blood was sampled prior to the beginning of the march, at the end of 81 h, and after 24 h of recovery. Samples were analyzed for plasma glucose, insulin, alanine, free fatty acids (FFA), and 3-hydroxybutyrate (3-HB). Body weight decreased from a mean (+/- S.E.M.) of 73.0 +/- 0.6 kg at pre-march to 66.5 +/- 0.6 kg at 81 h of fasting (p less than 0.05), and remained unchanged at 24 h after march termination. Glucose, insulin, and alanine decreased, whereas FFA and 3-HB increased significantly at 81 h fast (p less than 0.05). Within 24 h of recovery all parameters changed significantly (p less than 0.05), approaching baseline values. The results indicate that in trained individuals under extreme survival conditions, as in the present study, blood glucose is maintained above hypoglycemic levels at the expense of fat and fat-derived substrates that become the main energy sources utilized.

Adult↗

Genetic affinities of Ethiopian Jews.

Three different types of genetic polymorphisms studied in Ethiopian Jews are reviewed and used in genetic distance analyses between them and several relevant populations. In classical markers Ethiopian Jews cluster with other Ethiopian tribes and occupy a central position on a principal component map between African and Asian populations. Analysis of mitochondrial DNA types and 5' beta-globin haplotypes portrays Ethiopian Jews in the same manner, and locates them between African and Caucasoid populations. Their genetic profile as mirrored through these genetic markers correlates with their geographic origin and reflects both Caucasoid and Negroid components in their gene pool.

Blood Grouping and Crossmatching↗

Prevalence of diabetes mellitus in Ethiopian immigrants.

The prevalence of diabetes mellitus among 445 new immigrant Ethiopian Jews was studied immediately after their arrival to Israel, and found to be 0.4%. This low prevalence could be attributed to their long trek accompanied by severe malnutrition which caused death to the old, weak and sick, leaving a selectively young and healthy population group.

Adolescent↗

Fatty acid composition of adipose tissue in Ethiopian immigrants: a prospective study during their first year in Israel.

We measured the subcutaneous adipose tissue fatty acid composition in 22 male Ethiopian Jews, aged 17-65, shortly after their immigration to Israel. These subjects showed a concentration of linoleic acid (17.8%), which was relatively low compared with Israeli levels, and a high concentration of palmitic acid (28.5%). The linoleic/saturated (P/S) ratio was 0.52. After 5 months, a repeat measurement indicated increases of the linoleic acid content and of the P/S ratio to 20.1% and 0.62, respectively (P less than 0.05). In another sample from the same immigrant group, levels after 1 year in Israel were 20.9% and 25.1% for linoleic and palmitic acid, respectively, and the P/S ratio was 0.67. These results differed significantly (P less than 0.02) from those obtained in the first sample after immigration. Apart from decreasing plasma triglyceride levels, no pattern of lipid changes was discernible in our limited samples. Changes in subcutaneous fatty acid composition reflect changes in diet over months, suggesting a decreased carbohydrate intake and in increased fat intake. It remains to be seen whether changing fatty acid composition in conjunction with changes in blood lipids or other factors, over a prolonged period of time, will affect the cardiovascular risk in the immigrants.

Adipose Tissue↗

Blood pressure in Ethiopian immigrants: relationship to age and anthropometric factors, and changes during their first year in Israel.

Blood pressure was measured in 483 Ethiopian immigrants during the first week following their arrival in Israel. Mean levels of diastolic (DBP) and systolic blood pressures (SBP) were very low compared with known levels in the Israeli population. BPs were elevated in men greater than 20 years old and in women greater than 40 years old. Quetelet index averaged below 2.00 g/cm2. Considerable weight gains were observed in 265 individuals examined after 1 year. Simultaneously, DBP increased by 4 mm Hg on average, whereas the changes in SBP were small. At the end of 1 year, the mean SBP ranged from 107 (age 5-9 and 10-14) to 124 mm Hg (age greater than or equal to 60) and mean DBP from 69 (age 10-14 and 15-19) to 78 mm Hg (age greater than or equal to 60), remaining nevertheless considerably lower than levels observed in diverse Israeli population groups. Covariance analysis revealed that initial BPs, gender, age, and weight gain significantly affected SBP and DBP at the end of the year.

Adaptation, Physiological↗

A clinical evaluation of nuclear estrogen receptors combined with cytosolic estrogen and progesterone receptors in breast cancer.

Breast cancer tissue from 95 women was simultaneously assayed for three receptors: cytosolic estrogen (CER), cytosolic progesterone (CPR), and nuclear estrogen (NER). The main objective was to determine whether the addition of NER assay to the currently accepted practice with only CER and CPR could improve the predictive capacity of receptors. Forty-two patients were studied for response to hormone therapy and 95 patients were studied for survival; the median follow-up period was 73 months (range, 8 to 300 months). The incidence of CER+, CPR+, and NER+ was 74%, 70%, and 52%, respectively. Each receptor appeared more frequently, although not significantly so, in higher age groups. Forty percent of tumors had all three receptors positive and 14% had all negative; the remaining tumors showed all possible combinations of receptors. Both the rate of response and survival curves among 70 patients with CER+ did not show any significant difference whether NER was positive or negative. Also, among 38 patients with CER+, CPR+, and NER+, there was no significant difference in the clinical outcome as compared to 17 patients with CER+, CPR+, and NER-. Among 25 patients with CER- the rare occurrence of NER+ in only three patients did not suggest any clinical implication. It is concluded, therefore, that on overall clinical grounds the current series does not support the addition of NER assay whenever data is available on both CER and CPR.

Age Factors↗

Solid-phase anti-CD3 antibody activation of murine tumor-infiltrating lymphocytes.

Seventeen consecutive s.c. murine tumors, derived from a sarcoma and a colon adenocarcinoma, were cultured in the presence of recombinant interleukin 2 (rIL-2) for growth of tumor-infiltrating lymphocytes (TIL). Identical cultures were activated by solid-phase monoclonal antibody directed against the murine CD3 epsilon-chain, in conjunction with rIL-2. Forty-eight h later, cells were replaced in rIL-2 alone. Proliferation of anti-CD3-stimulated cultures was 1- to 17-fold greater than those cultured with rIL-2 alone (P less than 0.05). Both culture conditions yielded TIL which stained greater than 80% Thy-1.2+/Lyt-2+ (P greater than 0.05), less than 7% Thy-1.2+/L3T4+ (P greater than 0.05). Regardless of culture condition, longitudinal studies of in vitro cytotoxicity generated from 10 TIL preparations revealed no significant differences between the ability of TIL to lyse the murine natural killer-sensitive line YAC or heterologous or autologous tumor (P greater than 0.05). In vivo antitumor activity of TIL was tested by the adoptive transfer of suboptimal doses of TIL plus systemic rIL-2 to mice with pulmonary micrometastatic disease. No difference in tumor regression was noted between the TIL cultured with anti-CD3 plus rIL-2 or with rIL-2 alone (P greater than 0.05). Anti-CD3 stimulation of murine TIL cultures significantly increases lymphocyte cell yield without alteration of their phenotype, in vitro tumoricidal activity, or in vivo therapeutic effect.

Animals↗

Immune complexes in pediatric human immunodeficiency virus infection.

Circulating immune complexes (CIC) were analyzed in a cohort of 30 children infected with the human immunodeficiency virus. Elevated CIC were detected by the C1q assay in 70% (21/30) of all patients and by the Raji cell assay in 93% (28/30) of all patients. While only less than one third of patients with elevated CIC had free serum antibodies to Epstein-Barr virus, 80% (16/20) of them had detectable antibodies to Epstein-Barr virus associated with CIC. Enriched CIC in human immunodeficiency virus-infected children contained low levels of complement. These findings document that, as an expression of the humoral immunodeficiency, CIC in human immunodeficiency virus-infected children are deficient in complement and can thus be underestimated if complement-precipitating methods are used for their detection.

Antigen-Antibody Complex↗

The effect of the aminosteroid U-78517G on peritumoural brain oedema.

U-78517G belongs to a novel group of compounds-aminosteroids (AS) which are potent inhibitors of central nervous system tissue lipid peroxidation and are devoid of classical glucocorticoid and mineralocorticoid activities. The AS have been found to possess cerebral protective properties against ischaemia, ischaemic oedema, trauma to the cerebrum and spinal cord and in sub-arachnoid hemorrhage. The possible efficacy of U-78517G in attenuating peritumoural oedema was examined in rats harbouring cerebral 9L gliosarcomas. 19 Sprague-Dawley rats were implanted intracranially with 9L gliosarcoma cells. On day 14 post implantation rats were randomized to control (no treatment n = 10) and AS treated animals (n = 9). On day 20 animals were sacrificed and six brain samples per rat were examined for the percentage of water content. Oedema was assessed with the wet/dry weight technique. The AS treated animals were found to have a significant increase in peritumoural oedema (+1.38%, P less than 0.001) possibly related to an increase in cerebral blood flow associated with AS treatment. Further studies are, however, underway to precisely clarify this unexpected observation.

Animals↗

Lipid profile in trained subjects undergoing complete food deprivation combined with prolonged intermittent exercise.

Sixteen male subjects [18-21 years, maximal oxygen consumption (VO2max) = 59.2 ml.kg-1.min-1 +/- SEM 5.6] participated in a study to evaluate the effect of prolonged, complete food deprivation combined with physical effort, on plasma lipoprotein concentrations. The subjects were deprived of food for 81 h but were supplied with water: they walked for 10 h a day at 40% of VO2max, covering a total of 105 km. During this period the subjects' average mass decreased significantly (P less than 0.05) reflecting a marked catabolic process. Plasma concentration of low density lipoprotein-cholesterol [( LDL-C]) and triglycerides were significantly lower (P less than 0.05) and total cholesterol, high-density lipoprotein-cholesterol [( HDL-C]), and free fatty acid levels were significantly higher (P less than 0.05) at the end of the experimental period compared to the start. The ratio between plasma [HDL-C] to plasma [LDL-C] increased from 0.51 to 0.89 at the end of the exercise period, reflecting a marked anti-atherogenic effect. All changes were transient and reversible within 12 days of recovery.

Adolescent↗

Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain.

Many, but not all, infants born to mothers infected with the human immunodeficiency virus (HIV) are infected in utero. We have now shown that mothers who have high-affinity/avidity antibodies directed toward the principal neutralizing domain (PND) of gp120 are less likely to transmit HIV to their children. An ELISA that preferentially measures the level of the biologically functioning, high-affinity/avidity antibodies against PND is described. In a retrospective study of 15 maternal/neonatal serum samples, the assay correctly identified the 4 uninfected and the 11 HIV-infected infants. Other clinical and laboratory parameters such as p24 antigen, phytohemagglutinin mitogenic index, and absolute surface antigen T4+ cell counts did not accurately predict HIV fetal transmission. In addition to introducing a promising diagnostic tool, this study provides the in vivo evidence that protective antibodies may prevent infection by HIV.

Amino Acid Sequence↗

Human immunodeficiency virus (HIV) circulating immune complexes in infected children.

Circulating immune complexes (CIC) were studied for the presence of human immunodeficiency virus (HIV) antigens (HIV-Ag) in 55 children infected by the human immunodeficiency virus type 1 (HIV-1). CIC were elevated in 85% of patients. In 33 of 55 patients CIC included at least one HIV-Ag (HIV-Ag-CIC). Sixty percent of patients had p17 antigen, 50% had p24 antigen, and 16% had gp120 associated with CIC. Levels of HIV-Ag-CIC did not correlate with free serum HIV antigens. Patients with high HIV-Ag-CIC had a more severe clinical course and 90% of those with markedly elevated HIV-Ag-CIC (greater than 3+) have died within 6 to 24 months. HIV-Ag-CIC were also present in some patients including neonates and young infants in whom free HIV-Ag was undetectable. Monitoring of HIV-Ag in isolated CIC may be of value for early detection of HIV infection and for monitoring of disease outcome.

Antigen-Antibody Complex↗