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Biomedical subjects

A Rubinstein

Publications and source records attributed to A Rubinstein.

At least 127 records · Page 7Linked to original sources
PubMed1992

Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus neoformans.

Patients with AIDS who become infected with Cryptococcus neoformans have a poor prognosis. We speculated that the presence of cryptococcal capsular polysaccharide may enhance HIV-1 infection. In an in-vitro study, the presence of cryptococcal polysaccharide significantly increased (p less than 0.05) production of p24 antigen after infection of H9 cells with HIV-1-infected H9 cells. We also found similar results when lymphocytes from an HIV-1-infected patient were co-cultured with mononuclear cells from an uninfected individual. Our findings suggest a new pathogenic role for the capsular polysaccharide--namely, the capacity to enhance HIV-1 infectivity.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Maternofetal transmission of AIDS: frequency of human immunodeficiency virus type 1 nucleic acid sequences in human fetal DNA.

Pediatric AIDS is increasing in frequency due to a rise in the number of human immunodeficiency virus type 1 (HIV-1)-infected women of childbearing age. Because outcome studies reveal that most children infected peripartum manifest HIV-1-related disease in the first year of life, intrauterine infection has been suspected. Fetal tissues from 23 second-trimester abortuses were examined. The presence of HIV-1 nucleic acid sequences was determined by the polymerase chain reaction and used to define infection of the fetus. By analysis of available tissues, 7 of 23 fetuses were infected, while control fetal tissue was negative. In situ hybridization for HIV-1 DNA showed that only 1 of 8 infected abortuses was positive, while all samples of noninfected tissues revealed no HIV-1 DNA. These studies indicate that maternofetal transmission of HIV-1 may occur in 30% of pregnancies (7/23) by the end of the second trimester.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Design of polymerase chain reaction primers for the selective amplification of HIV-1 RNA in the presence of HIV-1 DNA.

OBJECTIVE: To develop a sensitive method for the specific detection of HIV-1 RNA. DESIGN: Following reverse transcription, the presence of HIV-1 RNA can be detected by polymerase chain reaction (PCR) amplification. Since specific detection of HIV-1 RNA may be complicated by contamination with minute quantities of HIV-1 DNA, samples are treated with deoxyribonuclease (DNase) prior to analysis. This additional step increases the possibility of RNA degradation and sample contamination. METHODS: A primer, HG141, was designed to hybridize to the poly(A) tract present in HIV-1 genomic and all HIV-1 messenger (m) RNA with its 5' end and to the region upstream of the poly(A) tract with its 3' end. The increased stability of the HG141 primer/HIV-1 RNA or complementary (c) DNA complex, enabled PCR amplification to be performed with HG141 and the return primer HG62 at an annealing temperature above the melting temperature (Tm) of the primer-HIV-1 DNA complex. RESULTS: After reverse transcription of samples obtained from HIV-1-infected H9 cells, HG62/141-primed PCR amplification specifically detected HIV-1 RNA sequences without the need for DNAase pre-treatment. This technique was more sensitive for the detection of HIV-1 RNA than SK38/39-primed PCR amplification of DNase-treated samples. CONCLUSIONS: Since the presence of HIV-1 RNA is indicative of HIV-1 replication for the presence of HIV-1 virions, the RNA-specific primer described should facilitate the assessment of HIV-1 replication and the plasma HIV-1 viral load in HIV-1-infected individuals. This should prove useful in the evaluation of the effects of therapeutic interventions on HIV-1 infection.

Base Sequence↗
PubMed1992

Tumor necrosis factor-alpha in pediatric HIV-1 infection.

OBJECTIVE: To evaluate the diagnostic and prognostic value of serum tumor necrosis factor-alpha (TNF-alpha) levels in HIV-1-infected children. DESIGN: Serum levels of TNF-alpha were evaluated in 57 HIV-1-infected symptomatic children aged between 7 months and 8 years. METHODS: TNF-alpha levels were determined by enzyme immunoassay. The sensitivity of the assay was 10 pg/ml. RESULTS: TNF-alpha levels (mean +/- s.d.) were significantly elevated in HIV-1-infected patients (285 +/- 390 pg/ml), compared with HIV-1-uninfected age-matched controls (22.7 +/- 4.9 pg/ml). Among HIV-1-infected children the highest levels of TNF-alpha were noted in those with Mycobacterium avium intracellulare (MAI) infection and those with interstitial lymphoid pneumonitis (LIP). In contrast, patients with Pneumocystis carinii pneumonia, progressive encephalopathy or cachexia did not have markedly elevated TNF-alpha levels. CONCLUSIONS: Serum TNF-alpha is increased in symptomatic HIV-1-infected children, with higher levels in children with LIP or MAI. Serum TNF-alpha levels are not diagnostic for cachexia or progressive encephalopathy.

AIDS Dementia Complex↗
PubMed1992

Half-mustache--a clue to peptic ulcer?

In this article, we quantify a clinical observation that non-Ashkenazi Jews having a half-mustache on the lower part of their upper lip have a high frequency of peptic ulcer and dyspepsia. The prevalence rate for peptic ulcer and dyspepsia was 33.6% and 44.9%, respectively, in the study group, compared with 11.2% and 24.3% in the control group. Although psychological examination was not conducted, we hypothesize that subjects who trim their mustache in this manner have obsessive and perfectionist characteristics and show features of extroverted personality. We speculate that these traits may be contributory to the development of peptic ulcer and dyspepsia.

Adolescent↗
PubMed1992

Neopterin concentrations in pediatric human immunodeficiency virus infection as predictor of disease activity.

Neopterin concentrations in 50 children with human immunodeficiency virus infection were correlated with disease course. The neopterin concentrations ranged from 4 to 70 nM with a mean of 34.7 +/- 25.1 (SD) nM compared with a mean of 6.1 +/- 1.6 nM in the human immunodeficiency virus-negative control group. Elevated neopterin concentrations above the upper range of the control group were detected as early as 5 months of age. Nineteen of 20 patients (95%) with neopterin concentrations above 20 nM either died or have severe clinical disease. Increasing neopterin concentrations were also associated with poor prognosis even though the first value was below 20 nM. Conversely neopterin concentrations less than 20 nM or declining concentrations were associated with a stable clinical course, except in terminal illness. With stepwise logistic regression analysis neopterin concentrations were predictive for disease progression. This predictive value was further improved by the addition of CD4 cell counts.

Biopterins↗
PubMed1992

Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1.

The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.

Adult↗
PubMed1992

Vitamin A loading--an indicator of post-prandial lipoprotein clearance in healthy and hypertriglyceridemic subjects.

To study post-prandial lipoprotein metabolism in normolipidemic and hypertriglyceridemic subjects, a vitamin A fat loading test was used. This method specifically labels dietary fat particles with retinyl palmitate (RP). Following RP concentrations, metabolic behavior of chylomicrons and chylomicron remnants were studied. In normal subjects, post-prandial lipoproteins were present for more than 10 h. Total RP increased rapidly between 1 and 4 h, peaked at 6 h and declined rapidly between 6 and 10 h. The chylomicron and chylomicron remnant fractions behaved differently, showing precursor product relationship. The hypertriglyceridemic patients demonstrated a very severe defect in chylomicron clearance. This fraction was 2.8-fold higher than in normal subjects, which was 7,260 vs. 2,600 micrograms/l, respectively. The large magnitude and long duration of post-prandial lipemia in normal and hypertriglyceridemic patients support the hypothesis that these atherogenic particles may play a role in the development of coronary heart disease.

Adult↗
PubMed1992

Adhesion of bacteria on pectin casted films.

Pectin and non-pectin degrading bacteria were tested for their ability to adhere to a film casted of low methoxylated pectin (polygalacturonic acid). Klebsiella oxytoca and a newly isolated strain of Escherichia coli adhered to the film, whereas only K. oxytoca was able to utilize pectin as a sole carbon source. Other E. coli strains, containing plasmids with pectinolytic enzymes, did not adhere to the solid pectin film. Therefore, the ability of the bacteria to adhere to the films was not correlated with their ability to degrade pectin. When the solubilization (dissolution) of pectin matrices (tablets) was analysed with and without K. oxytoca, a significant retardation in the dissolution rate was observed in the presence of K. oxytoca, suggesting the formation of a biofilm on the matrix or sedimentation of insoluble pectin salts.

Bacterial Adhesion↗
PubMed1992

HIV-1 infection of human fetal thymocytes.

Some neonates with congenital human immunodeficiency virus type 1 (HIV-1) infection exhibit immune dysregulation. This suggests that fetal CD4+ cells, possibly thymocytes, may be infected during gestation. If thymocytes are infected, this may result in a disruption of T-cell differentiation. To examine this hypothesis, normal human fetal thymocytes were established in tissue culture, characterized, and then exposed to HIV-1. On initial isolation, fetal thymocytes were analyzed for phenotypic markers by flow cytometry and assessed for T-cell function by mitogen-stimulated thymidine incorporation. The thymocytes comprised greater than 70% double positive (CD4+, CD8+) cells and responded to T- but not to B-cell mitogens. Thereafter, thymocytes were incubated in either tissue culture medium containing infectious HIV-1 or in control (HIV-free) medium. Infection of fetal thymocytes was determined by light and electron microscopy in combination with immunocytochemistry, molecular hybridization, and an infectious cell center (ICC) assay. After 1 week in culture, the thymocytes exposed to HIV-1 were positive by immunocytochemistry for the HIV-1-associated protein gp41. In addition, the presence of HIV-1 DNA was detected by molecular hybridization confirming infection of these cells. The ICC assay demonstrated the production of infectious HIV-1 particles and budding of mature virions was observed by electron microscopy. These studies demonstrate that human fetal thymocytes can be infected with HIV-1 in vitro and that this infection results in production of infectious virions. These results support the hypothesis that vertical transmission of HIV-1 in vivo may result in the infection of fetal thymocytes, which may contribute to postnatal HIV-1-associated pathologic conditions.

Cells, Cultured↗
PubMed1991

Clinical utility of HIV-IgA immunoblot assay in the early diagnosis of perinatal HIV infection.

OBJECTIVE: To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. DESIGN: Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. SETTING: Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. PATIENTS: Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. MAIN OUTCOME MEASURE: Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. RESULTS: The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%--no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. CONCLUSION: The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms.

Female↗
PubMed1991

Cholesterol-lowering effects of a 10 mg daily dose of lovastatin in patients with initial total cholesterol levels 200 to 240 mg/dl (5.18 to 6.21 mmol/liter).

Subjects with plasma cholesterol levels greater than 240 mg/dl (6.21 mmol/liter) and those with greater than 200 mg/dl (5.18 mmol/liter) who have coronary artery disease, or those with 2 risk factors for ischemic heart disease who do not respond to a hypocholesterolemic diet should all be treated. Lovastatin, which is an inhibitor of hydroxymethygluteryl coenzyme A reductase, is a new agent for treating hypercholesterolemia and is administered in a dose of 20 to 80 mg/day. A study was conducted in which only 10 mg of lovastatin was given to 28 subjects with plasma cholesterol of 200 to 240 mg/dl (5.18 to 6.21 mmol/liter). Cholesterol plasma levels decreased in 19% and low-density lipoprotein cholesterol decreased by 24% from baseline levels after 20 weeks of treatment. All 28 patients decreased their cholesterol values to less than 200 mg% (5.18 mmol/liter), and only 1 had a low-density lipoprotein level greater than 130 mg% (3.36 mmol/liter) at termination of the study. Achievement of desirable values of cholesterol with 10 mg of lovastatin was accompanied by less adverse effects and with significant financial saving. The calculated saving for lovastatin consumers in the USA could be an amount of $60,000,000. Thus, it is recommended that this drug be manufactured in 10 mg tablets.

Cholesterol↗
PubMed1991

Endocrine function in children with human immunodeficiency virus infection.

We sought to determine if failure to thrive in pediatric patients with the human immunodeficiency virus could be explained based on endocrine dysfunction. Fourteen human immunodeficiency virus-infected pediatric patients, all of whom had adequate nutritional status, underwent endocrine evaluation. Growth hormone and cortisol responses to glucagon stimulation were adequate. Despite this, eight of the 12 subjects had low somatomedin C levels. Although all patients were clinically and biochemically euthyroid, 36% (5/14) demonstrated elevated baseline and peak thyrotropin levels in response to thyroid releasing hormone, suggesting a state of compensated hypothyroidism. Although the importance of these findings is unclear, it is possible that subtle alterations of thyroid regulation may contribute to failure to thrive in some pediatric patients infected with human immunodeficiency virus and may represent a potentially correctable defect.

Child↗
PubMed1991

In vitro release and intestinal absorption of physostigmine salicylate from submicron emulsions.

The in vitro release of physostigmine salicylate (PS) from a submicron emulsion and an aqueous solution was studied using the dialysis bag method. These formulations were then perfused to various locations along the rat small intestine (proximal, mid, and distal jejunum), and two lengths (10 and 55 cm). The disappearance of PS from the luminal compartment and its appearance in the blood compartment was monitored. In the in vitro drug release from emulsion experiments, a biphasic appearance of PS in the sink solution was observed, suggesting a possible sustained release from the emulsion. However, absorption data from perfusion studies did not correlate with this in vitro observation. No significant difference was found in absorption from emulsion versus solution in the mid jejunum where PS absorption was maximal. The difference between the two liquid formulations was observed only in those intestinal segments where the absorption was relatively low [absorption rate values of 4.6 +/- 0.86 and 9.98 +/- 2.04 (log%/min) x 10(-3) in the proximal and distal parts of the small intestine, respectively, as compared with 14.0 +/- 1.2-14.8 +/- 1.1 (log%/min) x 10(-3) in the mid jejunum]. In the distal part of the rat small intestine, PS was absorbed significantly better from solution than from the submicron emulsion. Cholinesterase activity in blood samples collected after intestinal perfusion with emulsion or solution revealed lower enzyme activity following emulsion administration.

Acetylcholinesterase↗
PubMed1991

Treatment of septic thrombocytopenia with immune globulin.

Thrombocytopenia frequently complicates systemic infection and results from multiple possible mechanisms. We and others have demonstrated that platelet-associated IgG (PAIgG) levels are elevated in the majority of patients with septic thrombocytopenia. Corticosteroids may be undesirable as a treatment for thrombocytopenia for patients with severe infection because of their potential for suppressing the immune response. We hypothesized that septic thrombocytopenia is, in most cases, an immune disorder analogous to idiopathic thrombocytopenic purpura (ITP) which might respond to intravenous gamma-globulin as a treatment for increasing the platelet count in this disorder. Intravenous immune globulin (IVIG), 400 mg/kg daily for 3 days, was administered in a randomized double-blind placebo-controlled trial. Twenty-nine patients who developed thrombocytopenia during a documented, septic episode were studied. Patients with disseminated intravascular coagulation (DIC), hypersplenism, or drugs known to cause thrombocytopenia were excluded. Elevated PAIgG levels were documented in 52% of evaluable patients. Mean platelet counts in the IVIG group rose from 43K at study entry to 178K (411% rise) by Day 9. In the placebo group platelets rose from 51K to 125K (261% rise; P = 0.02). Seventy-seven percent of the IVIG group had a minimum peak rise of 35K, vs 56% of the placebo group. Three patients in the placebo group had a serious bleeding episode, vs one in the IVIG group. The use of IVIG to treat septic thrombocytopenia not associated with DIC leads to a more rapid, more sustained, and greater increase in platelet count than placebo. Its use is recommended in the septic patient who is bleeding or is likely to need invasive or surgical procedures.

Blood Platelets↗
PubMed1991

Defective activation of the alternative pathway of complement in patients with homozygous C2 deficiency: studies in two unrelated families.

Selective homozygous deficiency of the second component of complement, C2, with increased susceptibility to infection was detected in five children of two unrelated families. Because the haemolytic activity of the alternative complement pathway (AP) was in the low normal range, we evaluated the AP activation pattern. Serum levels of factor B measured immunochemically and the haemolytic function of factor B were low normal. Levels of C3d were not increased. Activation products of factor B were undetectable indicating the absence of in vivo activation of AP. Activation of C3 in vitro by activators of the AP (zymosan A and lipopolysaccharide) was profoundly deficient in homozygous C2 deficiency while heterozygous carriers exhibited intermediate values. There was no correlation between serum levels of factor B and in vitro C3 activation. We conclude that defective AP activation may contribute to increased susceptibility to bacterial infections in some patients with homozygous C2 deficiency.

Child↗
PubMed1991

Cellular and antibody responses directed against the HIV-1 principal neutralizing domain in HIV-1-infected children.

The principal neutralizing domain (PND) for antibody response is located within the V3 variable region of gp120 and can also stimulate T-cell responses. In some adults infected with human immunodeficiency virus (HIV) an HIV-1-specific T-cell response can be detected by demonstrating in vitro proliferation to HIV-1 proteins and peptides. In other HIV-1 infected adults an HIV-1-specific T-cell response can involve interleukin 2 (IL-2) secretion in the absence of T-cell proliferation. To elucidate the T-cell responses to PND in children, we examined the proliferative and the IL-2 secretory responses of peripheral blood lymphocytes from 19 HIV-1-infected children toward a peptide which contained a highly conserved sequence of the principal neutralizing domain of HIVMN (PND-MN). Stimulation with PND-MN induced proliferation of lymphocytes from 2 of the children and IL-2 secretion by lymphocytes from 5 of the children. In a 3-month-old infant, the in vitro cellular response to the PND-MN indicated HIV-1 infection prior to the detection p24 antigen in her serum. Although antibodies directed against PND-MN were detected in all but one of the children examined, the presence of high-affinity/avidity antibodies to the PND-MN correlated with the presence of a cellular response to PND-MN. Thus, in HIV-1-infected children an HIV-1 specific T-cell response in the absence of a proliferative response can be assessed by determination of the IL-2 secretory response and correlates with the generation of high-affinity/avidity antibodies.

Amino Acid Sequence↗