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Biomedical subjects

S Horowitz

Publications and source records attributed to S Horowitz.

At least 127 records · Page 7Linked to original sources
PubMed1986

Estimating mortality in skeletal populations: influence of the growth rate on the interpretation of levels and trends during the transition to agriculture.

Traditional paleodemographic methods of estimating mortality have been based on unrealistic assumptions about the prevalence of closed and stationary populations. When a living closed population was growing, the mean age at death of its skeletal survivors will be shifted below its true life expectancy. For declining populations, the mean age at death will be higher than true underlying life expectancy at birth. The faster the rate of growth, the larger and more curvilinear is the displacement. Mortality estimates can only be extracted from skeletal populations via an independent estimate of the growth rate. Fertility levels, however, can be estimated directly. The empirical importance of growth rate-dependent mortality estimates is demonstrated by reinterpreting mean-age-at-death data from several populations before and after the agricultural revolution; with detailed consideration given to the Old World populations of Acsadi and Nemeskeri and a New World population from central Illinois.

Agriculture↗
PubMed1986

Stage and species specificity of antigens encoded by two geographic strains of Schistosoma mansoni mRNA.

Proteins translated in vitro from Schistosoma mansoni adult worm mRNA were assessed for their antigenic specificities compared to different stages, strains and species of the parasite. RNA was extracted from both Puerto Rican and Brazilian parasites and directed the synthesis of high molecular weight proteins. Preabsorption of immune human serum with schistosomula was used to determine whether the in vitro translated proteins contained antigens shared between the adult and this immature stage. Three antigens (Mr 36,000, 29,000, 18,000) were observed to be present in both stages. When adult worm mRNA from 2 different geographic strains of S. mansoni (Puerto Rican and Brazilian) were compared, certain antigenic differences were found in their in vitro translation products (proteins at Mr 78,000, 26,000, 24,000, 22,000, 15,500), suggesting that different antigenic pools may exist in nature. The species specificity of the in vitro proteins was assessed using individual sera from humans whose species of schistosome infection and egg counts were known. Immunoprecipitation with these sera demonstrated that a large number of immunologically cross-reactive proteins were shared between S. mansoni and Schistosoma haematobium but not Schistosoma japonicum. Antigens or antigen complexes at Mr 47,000 and 37,000 were detected only in the immunoprecipitations using anti-S. mansoni sera, whereas an antigen of Mr 39,000 was precipitated only by anti-S. haematobium sera. The recognition of any 1 antigen or group of antigens, however, did not distinguish between intensities of infection.

Animals↗
PubMed1985

In vivo protection against S. mansoni infection by monoclonal antibodies.

A monoclonal antibody of the IgG1 class (27.21), that was previously shown to be cytotoxic in vitro to the schistosomula, conferred partial protection in vivo against challenge infection with S. mansoni. Monoclonal antibodies of the IgE class (54.10) were not effective in these experiments, but were capable of causing specific degranulation of basophilic cells upon contact with the young larva (3-6 h). The relevance of the IgE antibodies to protection observed in immunized mice is discussed.

Animals↗
PubMed1985

Identification of Schistosoma mansoni antigens by means of biologically active monoclonal antibodies.

Two monoclonal antibodies of the IgE class (54.10) and of the IgG1 class (27.21), that were shown previously to possess biological activity against Schistosoma mansoni larvae, were used for identification of surface antigens of the cercariae and schistosomula. This was performed by immunoprecipitation, immunoaffinity chromatography and immunoblotting. The epitope reactive with 27.21 mcIgG1 is present on four polypeptides (60, 50, 27 and 19 kDa) derived from the parasite. The 60 kDa is specific to cercariae, whereas the 50 kDa is a glycoprotein shared both by cercariae and schistosomula. The antigen reactive with the 54.10 mcIgE was isolated by affinity chromatography on 54.10 column, and contained three major peptides of 125, 94 and 30 kDa. The 125 and 94 kDa band probably originate from the same protein, since they yield almost identical peptide maps. The isolated antigen retained its biological activity as demonstrated in the basophils degranulation assay.

Animals↗
PubMed1985

An unusual genetic code in nuclear genes of Tetrahymena.

We have cloned and partially sequenced two histone H3 genes of Tetrahymena thermophila. The DNA sequences strongly suggest that both genes are active in the vegetatively growing cell. Comparison of the derived amino acid sequences of these two genes with the actual sequence of Tetrahymena histone H3 results in the surprising conclusion that TAA codes for glutamine. This represents the first demonstration of a coding function for this termination codon of the "universal" code. This observation has important implications for the evolution of ciliates and of the genetic code.

Amino Acid Sequence↗
PubMed1985

A Doppler echocardiographic method for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies.

In this study we tested a two-dimensional Doppler echocardiographic method for measuring volume flow across the tricuspid valve. Five anesthetized, open-chest dogs had a calibrated electromagnetic flow probe placed on the ascending aorta. Volume flow across the tricuspid valve was controlled by creating a variable femoral-to-pulmonary arterial shunt. Since no standard plane provided a direct view of the tricuspid valve orifice, tricuspid flow area was estimated by calculating a fixed circular flow orifice from the maximal late diastolic diameter of the tricuspid anulus in a four-chamber view. Doppler-determined velocities across the tricuspid valve and tricuspid anulus images in the four-chamber view were obtained in inspiration and expiration. For 24 cardiac outputs (0.6 to 4.0 liters/min), inspiratory tricuspid flow determined by the Doppler method correlated minimally better (r = .90, SEE = 0.30 liter/min) than did expiratory measurements (r = .89, SEE = 0.35 liter/min) with the time-averaged systemic flow determined electromagnetically. Doppler-determined tricuspid volume flows in four-chamber and short-axis two-dimensional echocardiographic views from 10 children were then compared with values determined simultaneously by thermodilution during cardiac catheterization. In the children, Doppler-determined flows in short-axis and four-chamber views, both in inspiration and expiration, were similar; when results for the two views were averaged in inspiration and expiration, the tricuspid flows predicted by the Doppler method were highly correlated (r = .98, SEE = 0.48 liter/min) with the results of thermodilution. The two-dimensional Doppler echocardiographic method provides a means of estimating volume flow across the tricuspid valve noninvasively.

Adolescent↗
PubMed1985

Enhanced incidence of isoproterenol-induced ventricular fibrillation in the magnesium-deficient rat.

The electrocardiogram was recorded and serum and bulk myocardial electrolytes were determined in male Sprague Dawley rats, subjected to dietary magnesium deficiency for various periods, to assess the time course of development and cessation of the enhanced arrhythmogenic action of isoproterenol (150 micrograms/kg, subcutaneously) and to establish possible relationships between electrolyte changes and severe ventricular dysrhythmias. Ventricular fibrillation occurred within 60 min following isoproterenol injection in 25, 25, 62.5, 50, and 62.5% of rats on magnesium deficient diet for 4, 7, 11, 15, and 19 days (N = 8), respectively, and resulted in death in most animals (83%). Reintroduction of normal chow following a 30-day period on magnesium-deficient diet normalized serum magnesium (from 1.42 +/- 0.23 to 1.90 +/- 0.08 mEq/liter, mean +/- SD) but did not significantly reduce the incidence of ventricular fibrillation. Magnesium deficiency did not produce statistically significant alterations in bulk myocardial content of sodium, potassium, magnesium, and calcium. However, sodium was elevated and potassium diminished in hearts from rats that died in ventricular fibrillation, but not in those that had recovered. Magnesium-deficient rats sacrificed 30 min after isoproterenol injection, that is before the occurrence of ventricular fibrillation, exhibited hypomagnesemia and hypokalemia as well as elevated sodium and diminished potassium and magnesium in the myocardium. In contrast, rats on Purina Chow exhibited hypermagnesemia, but also showed hypokalemia and diminished cardiac potassium. The results indicate that magnesium deficiency enhances the arrhythmogenic propensity of isoproterenol and that the development of ventricular fibrillation is preceded by serum and myocardial electrolyte alterations.

Animals↗
PubMed1985

Protective monoclonal antibody against Schistosoma mansoni: antigen isolation, characterization, and suitability for active immunization.

Monoclonal antibodies that bind to the surface of developing schistosomula were generated from the spleens of chronically infected mice that were boosted with cercarial glycoproteins. The two most reactive monoclonal antibodies, denoted 152-66-9B and 152-66-1C, were used for identification of surface antigens. The antigen detected by these monoclonal antibodies persisted on the surface of the developing larva for 72 hr posttransformation. This monoclonal antibody effected complement-mediated killing of schistosomula in vitro as efficiently as infected mouse sera. It was also very efficient in inhibiting the infectivity of both cercariae and schistosomula. The antigen reactive with the 152-66-9B monoclonal antibody contains two major polypeptides (45 and 30 KD). These polypeptide chains might have originated from the same protein, because they have the same isoelectric point in two-dimensional gel electrophoresis. Moreover, the affinity-purified antigen migrated as only one protein band of approximately 200 KD in SDS-PAGE in nonreducing conditions. The 9B antigen was isolated, purified, and used for immunization, resulting in an antigen dose-dependent partial protection against S. mansoni infection.

Animals↗
PubMed1984

Effects of intracoronary streptokinase and intracoronary nitroglycerin infusion on coronary angiographic patterns and mortality in patients with acute myocardial infarction.

We randomly assigned patients with a clinical diagnosis of acute myocardial infarction to one of four treatment groups: intracoronary streptokinase, intracoronary nitroglycerin, intracoronary streptokinase and intracoronary nitroglycerin, or conventional therapy without initial angiography. Of 124 patients 122 sustained acute myocardial infarction. Initial angiography revealed total occlusion of the coronary artery responsible for infarction in 67 per cent (61 of 91). Acute recanalization occurred in 74 per cent (32 of 43) of patients receiving streptokinase but in only 6 per cent (1 of 18) of patients treated with nitroglycerin alone (P less than 0.01). At angiography of all four groups on Day 10 to 14 the vessel responsible for acute myocardial infarction was patent in 77 per cent (71 of 92) of patients; there was no difference among groups, indicating gradual, endogenous thrombolysis in patients not treated with streptokinase. Patients with subtotal obstruction initially had significant improvement in left ventricular function, significantly lower peak creatine kinase levels, and a trend toward lower mortality than patients with total occlusion initially. Mortality at six months in patients receiving streptokinase (21 per cent, 13 of 62) did not differ significantly from that in patients not treated with streptokinase (10 per cent, 6 of 61). Additional studies will be necessary to assess treatment effects in the angiographic subsets identified by this trial.

Angiography↗
PubMed1984

Mapping of N6-methyladenosine residues in bovine prolactin mRNA.

N6-Methyladenosine (m6A) residues, which are found internally in viral and cellular mRNA populations at the sequences Apm6ApC and Gpm6ApC, have been proposed to play a role in mRNA processing and transport. We have developed a sensitive approach to analyze the level and location of m6A in specific purified cellular mRNAs in an attempt to correlate m6A location with function. Polyadenylylated mRNA is hybridized to cDNA clones representing the full size mRNA under study or fragments of it, and the protected RNA is digested and labeled with polynucleotide kinase in vitro. After enrichment for m6A with anti-m6A antibody, the [32P]-pm6A is separated on TLC plates, and compared with the total amount of radiolabeled nucleotides. Using this combination of in vitro RNA labeling and antibody selection, we were able to detect m6A in purified stable mRNAs that cannot be readily labeled in cells with greater sensitivity than was possible by previous techniques. We applied this technique to bovine prolactin mRNA and showed that this mRNA contains m6A. Moreover, all of the m6A residues in this message are found within the 3' two-thirds of the molecule and are highly concentrated (61%) within a sequence of 108 nucleotides at the 3' noncoding region of the message. The nonrandom distribution of m6A in a specific cellular mRNA, as demonstrated for bovine prolactin, will have to be taken into account when designing a model for m6A function.

Adenosine↗
PubMed1984

A pulsed Doppler echocardiographic method for calculating pulmonary and systemic blood flow in atrial level shunts: validation studies in animals and initial human experience.

The purpose of this study was to assess the accuracy of a quantitative two-dimensional range-gated Doppler echocardiographic method for estimating systemic and pulmonary flows in an open-chest canine preparation with a variable-sized atrial level shunt mimicking an atrial septal defect. In addition, we also report our initial experience with 10 children who had isolated atrial septal defects and who had pulmonary and systemic flow rations (QP:QS) determined by Doppler echocardiography simultaneously with green dye-shunt calculations in the cardiac catheterization laboratory. Ten mongrel dogs weighing 20 to 30 kg were anesthetized, intubated, and mechanically ventilated. Previously calibrated electromagnetic flow probes were placed around the ascending aorta and main pulmonary artery, and an atrial level shunt was created by inserting one-half inch diameter cannulae into the left and right atrial appendages and connecting both cannulae to 3/4 inch tubing that passed through a previously calibrated extracorporeal mechanical roller pump. This permitted quantitation as well as regulation of shunt size and direction. With each step-by-step variation in shunt magnitude, systemic and pulmonary flows were estimated by Doppler echocardiography and were matched to the simultaneous electromagnetic flowmeter recordings. Doppler-estimated systemic blood flow was obtained by imaging and recording Doppler flow velocities in the ascending aorta with the transducer positioned directly over the vessel. Doppler pulmonary flow was obtained by imaging the main pulmonary artery on the short-axis view and by determining flow velocity with the sample volume placed distal to the pulmonic valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Validation of a Doppler echocardiographic method for calculating severity of discrete stenotic obstructions in a canine preparation with a pulmonary arterial band.

The purpose of this study was to develop an open-chest animal preparation to validate the accuracy of a two-dimensional Doppler echocardiographic method for estimating pressure drops across discrete stenotic obstructions. Six mongrel dogs underwent median sternotomy and catheters were placed in the right ventricle, distal main pulmonary artery, and aorta of each. A 1/8 inch umbilical tape was sewn to the posterior rim of the pulmonary artery just above the anulus and was progressively tightened to vary the degree of stenosis. Ultrasound and Doppler studies were performed with a 2.5 MHz phased-array unit with capabilities for pulsed or continuous-mode Doppler and real-time imaging. Peak systolic main pulmonary arterial flow velocities were recorded by Doppler echocardiography within the jet distal to the band from an oblique parasternal short-axis echocardiographic view and corrected for angle of incidence between the direction of Doppler sampling and the presumed direction of flow. Doppler velocities were converted to gradients with a simplification of the Bernoulli equation (gradient = 4 X maximal Doppler flow velocity2 ). Maximal Doppler-determined systolic pulmonary arterial velocities showed a good linear correlation with the 63 measured pressure drops (r = .95, SEE +/- 36.3 cm/sec). An excellent correlation was also found between Doppler-calculated and actual pressure gradients (r = .96, SEE +/- 7.26 mm Hg). Our results suggest that this Doppler method for measuring gradients across discrete stenotic obstructions may be quite accurate in clinical applications.

Animals↗
PubMed1983

Anti-schistosome monoclonal antibodies of different isotypes--correlation with cytotoxicity.

Five monoclonal antibodies specific towards Schistosoma mansoni antigens were prepared by fusion of spleen cells of infected and immunized mouse with the murine myeloma NS-1 cells. Three of the five antibodies belonged to the IgG1 class, one was an IgM and the fifth one was an IgE. The IgE monoclonal antibody designated 54.10, induced antigen-specific degranulation of rat basophilic cell line, a property which served as the basis for the screening assay. Its biological function was demonstrated by a specific macrophage activation that led to killing of schistosomula; no such killing was obtained with anti-schistosome antibodies of other classes or with IgE of different antigenic specificity. The second monoclonal antibody of biological significance was an IgG1, designated 27.21 which is reactive in the immunofluorescence staining of surface antigens on intact schistosomula. All three monoclonal antibodies that belonged to the IgG1 class were effective in mediating killing of schistosomula by complement, with the highest effect exerted by 27.21. It is thus apparent that the 27.21 monoclonal antibody is directed against a densely distributed surface antigen on the schistosomula membrane which is possibly involved in the protective immunity. Preliminary data showed that immunoprecipitation with the 27.21 antibodies results in the isolation of three major protein bands, of 60 kd, 50 kd, 19 kd, respectively.

Animals↗
PubMed1983

The effect of variations of pulsed Doppler sampling site on calculation of cardiac output: an experimental study in open-chest dogs.

We measured aortic flow by two-dimensional Doppler echocardiography in an open-chest dog model to examine how variations in Doppler sample volume length and position influence aortic hemodynamic flow calculations. Fourteen dogs underwent right-heart bypass, in which venous return from the venae cavae drained by gravity to a reservoir. A variable-speed roller pump returned the blood to the pulmonary artery, fixing left-sided cardiac input and output. Echo Doppler measurements were performed using a 3.5 MHz transducer placed directly on the aortic arch to determine internal aortic cross-sectional area. The transducer was then directed to image the aortic arch for Doppler velocity measurements and the various sampling sites were investigated. Doppler cardiac output could then be determined for each of the various sample volumes over a range of known roller pump settings. Doppler velocity was analyzed using fast Fourier transform spectral analysis. Mean velocity over the cardiac cycle was obtained by planimetry of the area under the Doppler velocity curve with a minicomputer. Doppler-derived determinations of cardiac output achieved a correlation of r = 0.98-0.99 to values obtained by the roller pump over a range of cardiac outputs from 0.75-5 l/min. The standard error of the estimate was 0.21/min. In this laminar flow model, there was no difference between the predictive accuracy of any of the sampling sites over the range of roller pump flows. Our study shows that Doppler velocity measurements can be used to quantify aortic flow over a clinically useful range and that variations of sample length and position did not produce significant differences in calculated flows.

Animals↗