PubMed Health⌕ Search

Biomedical subjects

M Halperin

Publications and source records attributed to M Halperin.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1985

A new myelomonoblastic cell line (M20): analysis of properties, differentiation, and comparison with other established lines of similar origin.

A new myelomonoblastic cell line (M20) was established from the peripheral blood of a ten-year-old child with acute myeloblastic leukemia, using an improved method for supporting the initial stages of cell proliferation. The addition of irradiated macrophage monolayers to the proliferating cells appeared to overcome the deterioration of the primary cultures and enable them to continue proliferating until they became independent of this environment. The cell line that developed consisted of myeloblasts and promyelocytes characterized by light and scanning electron microscopy, cytochemistry, and enzymatic activities. The cells expressed Fc receptors and WT1 antigens but did not exhibit HLA-DR, HMA1, Epstein-Barr virus nuclear antigen, and surface Ig. The M20 cells produced colonies when cultured in semisolid medium and secreted lysozyme, prostaglandin E2, and interleukin 1. An attempt was also made to analyse the position of the M20 cells in the scheme of differentiation of the myelomonocytic lineage using different approaches. Treatment of the cells with 12-O-tetradecanoyl phorbol 13-acetate induced their adherence to plastic surfaces and partial maturation to macrophages as judged by morphological criteria, cytochemistry, and enzyme activities. However, comparison of the M20 cells to other well-established myelomonoblastic cell lines did not reveal any pattern suggesting a possible relationship between surface markers, cell function, and differentiation pathway of the various cell lines tested. Establishment of additional cell lines and identification of new markers may assist in defining the mechanisms involved in normal differentiation and malignant transformation of this cell lineage. In addition, such cell lines may also provide a tool for the quantitative recovery of a variety of monokines.

Animals↗
PubMed1985

Studies on the "labile-bound" glucose compartment in erythrocytes: studies on Psammomys obesus (sand rat) and preliminary studies on human erythrocytes.

Enzymatic (glucose oxidase) measurement of glucose concentration in the fluid compartment of Psammomys erythrocytes (Gfe) and of its concentration in the fluid compartment of blood plasma (Gfp) gives the ratio (mean +/- SD): Gfe/Gfp = 1.50 +/- 0.43 (n = 12, 23 degrees C). However, when we added 3H-labeled glucose (G*) in vitro to the whole blood, the ratio after 2 min was G*fe/G*fp = 0.90 (SD 0.11) and after 5 min G*fe/G*fp = 0.97 (SD 0.12). These calculations were based on previous determination of the fractional volumes of the fluid and non-fluid compartments in Psammomys blood. The results suggest that there is more than one compartment of measurable glucose in Psammomys erythrocytes. Glucose undergoes a fast free transfer between the plasma and the erythrocyte fluids, and a much slower transmission to another measurable compartment in the erythrocyte, where it is loosely bound to other molecules. This loosely bound glucose does not participate in the fast kinetic transmission across the erythrocyte membrane, but it is measurable by the glucose-oxidase-based method. Preliminary studies on human erythrocytes lead to similar conclusions.

Animals↗
PubMed1985

Inhibition of natural killer cell-mediated cytotoxicity by lipids extracted from Mycobacterium bovis BCG.

Several studies have demonstrated an augmentation of natural killer (NK) cell-mediated cytotoxicity by various adjuvants including BCG. Inhibitory effects of BCG have also been reported, particularly for relatively high doses. Because the cell wall of Mycobacterium bovis BCG contains a high proportion of lipids, the possibility was considered that these lipids may modulate NK activity. A total lipid fraction was extracted from Mycobacterium bovis BCG and used for the lipid modulation of NK effector and target cells. Treatment of effector or target cells resulted in decreased membrane fluidity and decreased NK cell-mediated cytotoxicity in both cases. Pretreatment of target cells did not affect the binding between target and effector cells, as shown in the single cell assay, whereas pretreatment of effectors resulted in inhibition of conjugation. It was further demonstrated that treatment of target cells which were first programmed for lysis protected these cells from subsequent lysis during the killer cell independent lysis stage. The results of this study suggest that adverse effects of BCG treatment on immune functions may be mediated by BCG derived lipids.

Cell Line↗
PubMed1984

Cotton-thread tear test: an experimental study for testing drugs suspected of side effects on lacrimation.

We tested tear fluid production and lacrimal peroxidase secretion in rats without and with drug consumption with the cotton-thread tear test. Twelve frequently prescribed drugs in patients were given in recommended therapeutic and excessive doses to rats. Daily oral doses during five days of Sudafed Plus (chlorpheniramine/pseudoephedrine combination), promethazine, atropine, timolol, aspirin, diazepam and furosemide equivalent to the doses used for adult humans on a drug-to-body-weight basis or excessive doses, resulted in about 20-60% reduction of tearing. Changes in lacrimal peroxidase secretion were found after administration of atropine, aspirin, furosemide, indomethacine and pilocarpine. Generally, tear production and lacrimal peroxidase secretion returned to baseline levels after withdrawal of the drugs.

Animals↗
PubMed1983

The fine-thread method: lacrimation test for measuring ocular side-effects of drugs in the rat.

Tear production was measured by means of the fine-cotton-thread method in rats. Sedation with hypnorm had no pharmacological effect on normal tear production. Daily oral administration of atropine which was comparable with the dose used for human adults on a drug-to-weight basis, resulted in a 60-percent reduction of tearing. Tearing returned to base-line levels after withdrawal of atropine.

Animals↗
PubMed1983

The Coronary Drug Project. Role of the National Institutes of Health.

A clinical trials staff within an Institute is essential for adequate participation in and monitoring of any large cooperative clinical trial supported by that Institute. At minimum such a staff should consist of a medical scientist with professional interests and experience in clinical trials methodology; a biometrician with direct experience and interest in the design, large-scale data collection, data analysis, and quality control needs of such trials; a contract specialist; and additional consultants in the technical areas related to the clinical disease or intervention study, such as pharmacology, laboratory operations, computer science, or other areas. The continuity of professional development and experience of such a staff is essential to expand the capabilities for participation and advancement of this rapidly developing science of the design, organization, and conduct of cooperative clinical trials.

Biometry↗
PubMed1983

Influence of solutes in plasma on the total CO2 content determination: implications for clinical disorders.

The purpose of these experiments was to determine the effect of non-aqueous solids on the total CO2 content of plasma. Two major groups of compounds were explored; those which reduced the total CO2 content, such as saline, and those which did not, such as albumin. To assess the former, sufficient sodium chloride was added to a bicarbonate solution gassed with 5% CO2 to increase the total volume by 10%. The total CO2 content fell the predicted 10% from 27.2 to 24.5 mmol/L when sodium chloride was added. In contrast, when the aqueous volume of a bicarbonate solution gassed with 5% CO2 was decreased by isohydric albumin, the total CO2 content was not reduced. We hypothesize that carbamino-compounds were formed with albumin and this raised the volume of CO2 released by an excess of acid. Therefore, the calculated pK' for the bicarbonate buffer system, which is derived from solutions lacking proteins, is not solely determined by the concentrations of bicarbonate, dissolved CO2, carbonate and carbonic acid when albumin is present. The clinical implications of these results will be discussed.

Acid-Base Imbalance↗
PubMed1983

Importance of medullary events in ammonium excretion: studies in acute respiratory and acute metabolic acidosis.

The renal medulla can play an important role in acid excretion by modulating both hydrogen ion secretion in the medullary collecting duct and the medullary PNH3. The purpose of these experiments was to characterize the intrarenal events associated with ammonium excretion in acute acidosis. Cortical events were monitored in two ways: first, the rates of glutamine extraction and ammoniagenesis were assessed by measuring arteriovenous differences and the rate of renal blood flow; second, the biochemical response of the ammoniagenesis pathway was examined by measuring glutamate and 2-oxoglutarate, key renal cortical metabolites in this pathway. There were no significant differences noted in any of these cortical parameters between acute respiratory and metabolic acidosis. Despite a comparable twofold rise in ammonium excretion in both cases, the urine pH, PNH3, and the urine minus blood PCO2 difference (U-B PCO2) were lower during acute hypercapnia. In these experiments, the urine PCO2 was 34 mmHg (1 mmHg = 133.322 Pa) lower than that of the blood during acute respiratory acidosis while the U-B PCO2 was 5 +/- 3 mmHg in acute metabolic acidosis. Thus there were significant differences in medullary events during these two conditions. Although the urine pH is critical in determining ammonium excretion in certain circumstances, these results suggest that regional variations in the medullary PNH3 can modify this relationship.

Acidosis↗
PubMed1982

Grouping and linear regression.

With a large number of observations, the method of grouping is often employed to provide simpler graphs or tables. When one investigates the relationship between two variables, one usually groups based on the magnitude of the independent variable, and then plots the dependent variable averages against independent variable averages to get a clearer graph. If grouping is based on the magnitude of the dependent variable, the plot of group means as indicated above does not appropriately describe the relationship of the dependent variable to the independent variable. These results are demonstrated theoretically for the special case of bivariate normality (and thus linear regression), but would be expected to be similar for other distribution assumptions. An example is given from an epidemiological study.

Blood Pressure↗