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M Halperin

Publications and source records attributed to M Halperin.

At least 19 recordsLinked to original sources
PubMed2000

Deregulated expression of homeobox-containing genes, HOXB6, B8, C8, C9, and Cdx-1, in human colon cancer cell lines.

Previously we have demonstrated a reciprocal deregulation of various homeobox genes (HOXB6, B8, C8 and C9 vs Cdx-1) in human colorectal cancer (CRC). In the present study, using RT-PCR, we have investigated the expression pattern of these homeobox genes in various human colon cell lines, representing various stages of colon cancer progression and differentiation. Thus, we have tested polyposis coli Pc/AA adenoma cells, Caco-2, HT-29 and LS174T adenocarcinoma cell lines. All cell lines, except LS174T, demonstrated a pattern of deregulated homeobox gene expression which resembled that of CRC. In contrast, the pattern of expression of these genes in the highly oncogenic LS174T cells, as well as in Caco-2 cells transfected with activated Ha-ras or Polyoma middle T oncogene, resembled that of the normal mucosa. The reciprocal deregulation of HOX and Cdx-1 genes in CRC and in CRC-derived cell lines suggests a possible role in human CRC development.

Adenocarcinoma↗
PubMed1996

Can a severe degree of ketoacidosis develop overnight?

Insulin-dependent diabetes mellitus in poor control, alcohol intake associated with extracellular fluid volume contraction, or hypoglycemia may each lead to an increased rate of production of ketoacids. Generally, several days of illness are required before ketoacidosis becomes severe. Two clinical examples are presented to suggest that a severe degree of ketoacidosis may develop over a short period of time, literally overnight. In both examples, there was the ingestion of a modest amount of ethanol. From a quantitative analysis of factors that may influence the rate of production and removal of ketoacids, the following were deduced. Contributing factors to the very rapid development of maximal ketoacidosis could include the absence of a lag period for the conversion of ethanol to acetyl-coenzyme A in the liver and an impaired ability of the brain and kidneys to oxidize ketoacids, especially if these ketoacids are produced very rapidly and/or if less metabolic work is performed by these organs. In special settings, ketoacidosis may develop more rapidly than is generally appreciated.

Adult↗
PubMed1996

Acute necrotizing pancreatitis, lactic acidosis and prolonged hypoglycemia in a hemodialysed patient--a logical but unfortunately fatal combination.

A hemodialysed patient with abdominal pain, severe lactic acidosis and prolonged hypoglycemia is described. The diagnosis of acute necrotizing pancreatitis was delayed and the patient died from both systemic and peripancreatic complications of the acute pancreatitis. The article deals with the problem of diagnosing acute pancreatitis in an end-stage renal failure (ESRF) patient; on the possible surgical options open to the physician in the management of acute pancreatitis and on a pathophysiological explanation behind both the lactic acidosis and hypoglycemia in this patient.

Acidosis, Lactic↗
PubMed1995

Adenocarcinoma at ureterosigmoidostomy junction in a renal transplant recipient 15 years after conversion to ileal conduit.

In recent years, adenocarcinoma of the colon mucosa has become a recognized complication of ureterosigmoidostomy and in most cases the tumor arises at the site of ureterocolonic anastomosis. We report a case of a 29-year-old renal transplant recipient who developed two colonic carcinomas at the site of ureterosigmoidostomy 25 years after the urinary diversion and 15 years after conversion to an ileal conduit. This case emphasizes the need for a careful life-long follow-up of all patients who undergo ureterosigmoidostomy.

Adenocarcinoma↗
PubMed1994

Chronic myelomonocytic leukemia associated with primary amyloidosis.

A case of chronic myelomonocytic leukemia (CMML) associated with primary amyloidosis (AL) is presented. Hepatosplenomegaly, macroglossia, and xanthelasma were the major physical findings. Laboratory tests showed macrocytic anemia, thrombocytopenia, monocytosis and a bi-clonal gammopathy. Early monocytes and monoblasts were noted in the bone marrow aspiration biopsy. Cytogenetic evaluation showed a clonal deletion of chromosome 21 long arm (21q-). Amyloid was present in the liver, tongue and xanthelasma. In addition, the patient was noted to have osteosclerosis of the lower extremities. Treatment with prednisone and colchicine resulted in a subjective response. The unusual association of CMML, and primary amyloidosis is discussed.

Adult↗
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↗