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M Halperin

Publications and source records attributed to M Halperin.

At least 19 recordsLinked to original sources
PubMed1992

Chronic lactic acidosis in a patient with acquired immunodeficiency syndrome and mitochondrial myopathy: biochemical studies.

A 30-yr-old man with acquired immunodeficiency syndrome treated with zidovudine developed biopsy-proven mitochondrial myopathy. Chronic lactic acidosis (lactate, 10 +/- 1 mmol/L) persisted for more than 5 wk. Liver function tests were normal, but the concentration of lactose rose to 16.1 mmol/L when 500 mmol of ethanol was infused. The concentration of lactose rose by only 1.5 mmol/L with maximally tolerated exercise. If this mitochondrial lesion compromised flux through the electron transport system, increased turnover of ATP with exercise should have exacerbated the degree of lactic acidosis because of increased need to regenerate ATP via glycolysis. Two possible explanations will be discussed: first, there was both a rapid rate of production of lactic acid in affected muscles in conjunction and an equally rapid rate of removal by uninvolved organs. Second, there was a low net rate of production of lactic acid in involved muscles despite the exercise.

Acidosis, Lactic↗
PubMed1991

Moloney murine leukemia virus IN protein from disrupted virions binds and specifically cleaves its target sequence in vitro.

The integration of retroviral DNA plays an essential role in the viral life cycle. Previous studies of the Moloney murine leukemia virus (M-MuLV) have shown that viral integration is mediated by the integrase (IN) protein acting on the 13-bp inverted repeats that flank the linear viral DNA produced during reverse transcription. Prior studies have also shown that when the M-MuLV IN protein is produced in Escherichia coli it retains an ability to specifically associate with the viral inverted repeats (Krogstad and Champoux, 1990). In this study we present evidence that the IN protein present in detergent-disrupted virions is capable of specifically interacting with double-stranded oligonucleotides that correspond to the viral inverted repeats, and that this interaction may change after integration-related processing of the viral att sites. We further present evidence that, in vitro, detergent-disrupted virions are capable of specifically cleaving ds-IR oligonucleotides in an IN-dependent reaction that mimics the trimming step that precedes integration.

Animals↗
PubMed1991

Can oxygen consumption in blood in vitro be detected by a change in PCO2?

The PO2 measured in a sample of blood can be misleadingly low, owing to consumption of oxygen in vitro in patients with leukemia. The purpose of this study was to determine whether a rise in PCO2 in such blood could be a useful indication of consumption of oxygen in vitro. Because of the non-bocarbonate buffer capacity of blood and the carriage of CO2, mainly as bicarbonate, we reasoned that the rise in PCO2 would be too small to be helpful. Hence the quantitative relationship between the consumption of oxygen and the production of CO2 in blood was determined. Other reactions yielding CO2 (the titration of lactic acid) were monitored. Consumption of oxygen was stimulated in blood of normals in vitro by adding methylene blue (100 mumol/L); in addition, blood from four patients with leukemia was studied without additions. The rate of consumption of oxygen at 22 degrees C was linear over 60 min; the respiratory quotient was close to unity. The rise in PCO2 was small even when the fall in PO2 was 60 mmHg. We conclude that a rise in PCO2 is not a reliable way to diagnose consumption of oxygen in blood in vitro as patients may hyperventilate, making it very difficult to recognize a small rise in PCO2.

Adult↗
PubMed1990

Early methodological developments for clinical trials at the National Heart, Lung and Blood Institute.

The National Heart Institute, now known as the National Heart, Lung and Blood Institute (NHLBI), initiated its first multicentre randomized clinical trials of rheumatic fever and rheumatic heart disease in 1951. The modern era of multicentre trials began, however, when the Coronary Drug Project was initiated in the 1960s. This trial and subsequent NHLBI trials stimulated a wide variety of research on clinical trial methodology. This paper reviews early methodologic developments in four areas. First, an organizational structure for multicentre clinical trials was developed and codified in the 'Greenberg Report' in 1967. Second, design considerations related to patient risk, non-compliance, a lag in treatment effect, and changing risk were explored. The 'intention-to-treat' principle was implicit in these investigations. Thirdly, the concept of periodic review of accumulating data, recommended in the Greenberg report, stimulated research on methods for sequential analysis. Three statistical approaches were developed and investigation of their statistical properties continues today. These approaches are usually described as group sequential, stochastic curtailment, and Bayesian methods. Finally, comparison of treatments in longitudinal studies has been an increasing part of NHLBI research and methods have been developed for design and analysis of longitudinal studies.

Blood↗
PubMed1990

Enzyme-linked immunosorbent assay for distinguishing serological responses of lepromatous and tuberculoid leprosies to the 29/33-kilodalton doublet and 64-kilodalton antigens of Mycobacterium tuberculosis.

Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and of 28 tuberculoid leprosy patients reacted in a significant manner to 29/33-kilodalton (kDa) doublet and 64-kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed a significantly high immunoglobulin G antibody titer to the purified M. tuberculosis 29/33-kDa doublet and 64-kDa antigens in lepromatous and tuberculoid leprosy patients, respectively, as compared with normal subjects and tuberculosis patients. This enzyme-linked immunosorbent assay serology may be useful for distinguishing two polar types of leprosy and for diagnosing leprosy in general.

Antibodies, Bacterial↗
PubMed1989

Identification of mycobacterial antigens for "ELISA" serology in the diagnosis of leprosy and tuberculosis.

Using an immunoblotting assay (ImBA), several immuno-crossreactive antigenic components (ImCRAC-myc) have been identified in the whole sonicates of M. bovis-BCG, and M. tuberculosis (Mtb) and M. leprae (ML) whereby the sera of 100% lepromatous leprosy (L-Lep) reacted to 29/33 KD doublet and that of 100% tuberculoid leprosy (T-Lep) reacted to 64 KD bands. The antigens upon purification from Mtb Sonicates were used in a direct ELISA to measure antibody isotypes in the sera from L-Lep, T-Lep, healthy Lep. contacts (Lep. c), normal Dutch controls (N) and tuberculosis (TB) patients. A significantly high IgG titre to the doublet 29/33 KD and to 64 KD were observed among L-Lep and T-Lep patients respectively in comparison to sera from other groups of individuals. In certain cases of L-Lep patients, raised IgM titre to either or both to 29/33 KD doublet and 64 KD were also found. On the other hand, consistantly but significant high IgA-antibody titre to cell wall (CW), cytosol (cyt) and P90 fractions of Mtb distinguished clearly the TB patients from Lep groups, normals (NN) and Lep-c. It appeared that such antibody reactivity of TB sera might be directed to the groups of 58-60, 38-40, 18-20 and 14 KD antigens of mycobacteria e.g. Mtb. On the basis of the present observations we conclude that the measurement of class specific antibody response to the panel of these antigens could diagnose differentially between Lep, TB and NN/Lep-c among the population at large in an endemic area.

Antibodies, Bacterial↗
PubMed1989

Distribution-free confidence intervals for a parameter of Wilcoxon-Mann-Whitney type for ordered categories and progressive censoring.

Halperin, Gilbert, and Lachin (1987, Biometrics 43, 71-80) obtain confidence intervals for Pr(X less than Y) based on the two-sample Wilcoxon statistic for continuous data. Their approach is applied here to ordered categorical data and right-censored continuous data, using the generalization zeta = Pr(X less than Y) + 1/2Pr(X = Y) to account for ties. Deviations from nominal coverage probability for various sample sizes and values of zeta are obtained via simulation of either three or six ordered categories based on underlying Poisson or exponential distributions. The simulation results indicate that the proposed method performs quite well, and it is apparently superior to the approach of Hochberg (1981, Communications in Statistics--Theory and Methods A10, 1719-1732) for values of zeta far from 1/2.

Biometry↗
PubMed1987

Stochastic curtailing for comparison of slopes in longitudinal studies.

In some clinical trials, rate of change of a physiological function is used as a surrogate for a more serious outcome. We assume an expected change linear in time for each study participant with variation in slopes and intercepts from individual to individual and repeated measures over time for each individual. We also assume that deviations of response for an individual from expected response have zero mean, constant variance, and are uncorrelated. Under these assumptions we describe ways in which stochastic curtailing as defined by Lan, Simon, and Halperin (Commun Stat Seq Anal 1:207-219, 1982) can be implemented in a two-treatment trial for one-sided comparison of slopes in the two groups. Staggered entry is taken into account, as is the possibility that some of an individual's responses are not available; this is assumed to be random. The analysis assumes the number of participants in each group is large and that most individuals have at least two measurements (including baseline value). The possibility that rate of change is not constant and its consequences are discussed.

Clinical Trials as Topic↗
PubMed1986

Interleukin 1 inhibitory activity secreted by a human myelomonocytic cell line (M20).

Culture supernatants from a myelomonocytic cell line (M20) were found to inhibit interleukin 1 (IL 1) activity in vitro. The factor, isolated from these supernatants, inhibited augmentation of phytohemagglutinin response of mouse thymus cells induced by IL 1 derived from several established cell lines. Various IL 1-dependent activities such as lymphocyte and fibroblast proliferation in vitro were also inhibited by the factor. The factor did not inhibit IL 2-induced or other proliferative responses not related to IL 1. Preliminary biochemical characterization of the factor indicated that the activity resides in a protein with a molecular mass of 52 kDa.

Cell Division↗
PubMed1986

In vitro differentiation and establishment of cell lines derived from human myelomonocytic leukemia cells.

Primary cultures of cells derived from 13 patients with acute myelomonocytic leukemia (AMML) were studied with particular emphasis on in vitro proliferation, cell differentiation and the mode for establishment of cell lines. Using irradiated human macrophage monolayers to assist cell growth, we obtained four new cell lines of myelomonocytic origin. All the cell lines were characterized for cytochemical markers and response to phorbol esters (TPA), a differentiation inducing agent. In the absence of any inducing agent, spontaneous differentiation of blast cells into mature macrophages-like cells occurred in 8 out of the 13 primary cultures. Thus, maturation induction by agents such as TPA is not always required in order to obtain leukemic cell differentiation in vitro. The regulation of cell proliferation and differentiation by cellular interactions and by extrinsic soluble products is discussed in detail, in the light of these findings.

Cell Differentiation↗
PubMed1986

The orthogonal electrocardiogram as risk indicator for the prediction of myocardial infarction and/or cardiac death.

In a prospective study on Coronary Heart Disease (CHD) orthogonal electrocardiograms (Frank) were recorded annually for ten years from 1,444 asymptomatic, middle-aged males with a mean age of 57.4 +/- 10.6 years. Cases with overt or suspected CHD were excluded. The purpose of the study was to identify risk indicators in electrocardiograms and to compare them with other known risk factors used for prediction of acute CHD events such as myocardial infarction (MI) and/or cardiac death (CD). Such acute events occurred in 88 cases. Pre-event ECGs of these acute events were compared with all others without events, using logistic regression analysis. Identified ECG risk indicators were then compared with other known risk factors such as smoking, blood pressure, cholesterol, age, weight, etc. The predictive power of the ECG, derived mainly from the ST-T complex, exceeded all others by a wide margin. The amplitude of the first 1/8 of the ST-T complex in lead x (similar to V5-V6) together with relative body weight proved best when one pre-event record was available. Prediction improved when ECG changes between two pre-event recordings were included. Precision of measurements by computer appeared essential for improvements in CHD prediction.

Adult↗
PubMed1986

Regulation of glutamine metabolism in dog kidney in vivo.

In summary, we propose: that renal ammoniagenesis is regulated both by factors dependent and independent of the acid-base status, the net effect of the ammoniagenic process on the proton balance being directly related to the rate of urinary ammonium excretion; that the renal metabolism of glutamine should not be examined independently of the metabolism of other substrate physiologically taken up by the kidney; that different pathways for glutamine metabolism will change during acid-base disorders of organic or nonorganic origin; that, among the main glutamine utilizing pathways, only the GLDH pathway is influenced directly by the acid-base status; the ammoniagenic transamination pathways is regulated by substrate availability in the kidney; that the lowest ammoniagenic flux in the kidney coincides with the rate of alanine production since alanine appears to derive directly from glutamine. When this pathway is stimulated without concomitant acidosis, most of the ammonia produced is not excreted in urine but released in the renal venous blood: thus, no significant effect on the acid-base balance is produced; that glutamine is metabolized by proximal kidney tubules of acidotic dogs probably through net oxidation; that the quantitative analysis of the metabolic consequence of this process indicates that the rate of ATP turnover at this site may effectively place an upper limit to the rate of glutamine oxidation, and ammonia production by the kidney, and that this limit is nearly reached in chronically acidotic animals.

Acid-Base Equilibrium↗
PubMed1986

Detection of different interleukin-1 activities in human monocytes and monocytic cell lines.

Culture supernatants from normal human monocytes, monocyte hybrid cell lines, and myelomonoblastic cell lines were tested for human interleukin-1 (IL-1) activity. In the present study, we report the detection of IL-1 secreted by several cell lines of monocyte origin and compare their biological and biochemical characteristics. IL-1 activity was tested by the regular assay of phytohemagglutinin (PHA) response of mouse thymus cells. IL-1 was found to be constitutively secreted by U937 and the M20 cell lines, as well as by three of the monocyte hybrid cell lines. The activity was always augmented following dialysis and did not require the presence of serum for its secretion. We compared the IL-1 activity of the myelomonoblastic M20 and hybrid 1C4 cell lines to that of normal monocytes. We found differences in the kinetics of IL-1 secretion, the pattern of activity following dilution of concentrated supernatants, and augmentation of activity by various inducers. The differences described may be explained by concomitant secretion of IL-1 inhibitory factors, as well as the secretion of activities other than IL-1. Preliminary biochemical analysis showed that all three cell sources tested shared some species of molecules characterized by gel filtration and ion-exchange chromatography. However, some species of molecules expressing IL-1 activity were unique to the cell lines and were not found in normal monocytes.

Animals↗
PubMed1985

Mode of delivery in the low birth weight fetus. Delivery by cesarean section independent of fetal lie versus vaginal delivery in vertex presentation. A study with long-term follow-up.

In a paired controlled multicenter study of patients in preterm labor of unknown etiology without additional maternal or fetal complications, 59 low birth weight infants in vertex presentation born vaginally were compared with 59 infants delivered by cesarean section. In the early postpartum period, hypothermia and acidosis occurred more often in the vaginal delivery group. The rate of respiratory disorders and need for assisted ventilation did not differ between the groups. Persistent ductus arteriosus occurred in 19% in the vaginal delivery group and in 7% in the abdominal delivery group. At follow-up until 18-24 months of age the rate of cerebral palsy did not differ between the groups, whereas the rate of psychomotor retardation was significantly higher in the vaginal delivery group (p less than 0.05). The difference in percentage of total outcome, i.e. sum of mortality and neurodevelopmental sequelae, being 20.3% in the vaginal delivery group versus 8.5% in the cesarean section group, fails to reach a statistical significance, but the results suggest that for the low birth weight infants, vaginal delivery may be more hazardous than abdominal delivery.

Adult↗