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Biomedical subjects

M Rabinowitz

Publications and source records attributed to M Rabinowitz.

At least 19 recordsLinked to original sources

Weight gain and maturity in fetuses exposed to low levels of lead.

The relationship between prenatal low-level lead exposure and fetal growth was evaluated in a sample of 4354 pregnancies in which the mean umbilical cord blood lead level was 7.0 micrograms/dl (SD = 3.3; 10th percentile, 3.4 micrograms/dl, 90th percentile, 10.9 micrograms/dl). Higher cord blood lead levels were significantly associated with gestations of slightly longer duration. Comparing infants with cord blood lead levels greater than or equal to 15 micrograms/dl to those with levels less than 5 micrograms/dl, adjusted risk ratios of 1.5 to 2.5 were observed for low birth weight (less than 2500 g) and for fetal growth indices that express birth weight as a function of length of gestation (e.g., small-for-gestational age, intrauterine growth retardation). The 95% confidence intervals of these risk ratios included 1, however, precluding rejection of the null hypothesis of no association. We conclude that the risk of adverse fetal growth is not increased at cord blood lead levels less than 15 micrograms/dl but that modest increases in risk may be associated with levels greater than or equal to 15 micrograms/dl.

Body Weight

Low-level lead exposure and children's cognitive function in the preschool years.

In a cohort of 170 middle and upper-middle class children participating in a prospective study of child development and low-level lead exposure, higher blood lead levels at age 24 months were associated with lower scores at age 57 months on the McCarthy Scales of Children's Abilities. The mean blood lead level at age 24 months was 6.8 micrograms/dL (SD = 6.3; 75th, 90th, and 99th percentiles: 8.8, 13.7, 23.6, respectively) and for all but 1 child was less than 25 micrograms/dL, the current definition of an "elevated" level. After adjustment for confounding, scores on the General Cognitive Index decreased approximately 3 points (SE = 1.4) for each natural log unit increase in 24-month blood lead level. The inverse association between lead level and performance was especially prominent for visual-spatial and visual-motor integration skills. Higher prenatal exposures were not associated with lower scores at 57 months except in the subgroup of children with "high" concurrent blood lead levels (ie, greater than or equal to 10 micrograms/dL). The concentration of lead in the dentine of shed deciduous teeth was not significantly associated with children's performance after adjustment for confounding.

Age Factors

Avoiding blood transfusion. A report of two cases.

It is prudent to avoid blood transfusion whenever possible. Recent reports question the standards previously considered acceptable for blood transfusion. Acute hemorrhage followed by hypovolemia, tachycardia and orthostatic hypotension with dizziness are still considered acceptable criteria for automatic blood transfusion in most patients. We report two cases in which hypovolemia, tachycardia and orthostatic hypotension with dizziness were present. Transfusion was avoided. Hypovolemia, tachycardia and orthostatic hypotension with dizziness do not require transfusion in a few carefully selected and well-monitored patients.

Adult

Alzheimer's dementia and binding to alpha 2 adrenoreceptors in platelets.

Seventy-five patients with probable Alzheimer's disease were screened for binding of alpha 2 receptors (A2R) to their platelet membranes; the results were compared with 51 age- and sex-matched controls. Receptor binding assays were performed using [3H] Yohimbine as the radioligand. The results showed a higher binding capacity in the demented population as compared to the control group (2.18 +/- 0.15 fmol/mg protein, as compared to 1.73 +/- 0.13, P less than 0.03). This increased binding to platelets in the demented patients was more prominent in demented females: 34% higher binding as compared with female controls (2.06 +/- 0.5 vs 1.54 +/- 0.04). The difference between demented and normal males was less (2.34 +/- 0.05 vs 1.88 +/- 0.05). The results indicate an involvement of the A2R system, either primarily or secondarily, in the disease process. Since there is an overlap between results from the patients with Alzheimer's disease and the normal subjects, A2R may serve as only a supportive marker for Alzheimer's disease.

Aged

Lead and pregnancy.

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Abnormalities, Drug-Induced

Sexually transmitted cytomegalovirus proctitis in a woman.

A heterosexual woman with cytomegalovirus (CMV) proctitis after anal intercourse is presented. Whereas CMV infection typically occurs in immunosuppressed patients, including patients with acquired immune deficiency syndrome (AIDS), this patient has no evidence of immunodeficiency, and is human immunodeficiency virus (HIV) negative during 8 months of follow-up since onset of proctitis. A review of the literature reveals no other report of sexually transmitted CMV proctitis in an immunocompetent woman after anal intercourse.

Adult

Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development.

In a prospective cohort study of 249 children from birth to two years of age, we assessed the relation between prenatal and postnatal lead exposure and early cognitive development. On the basis of lead levels in umbilical-cord blood, children were assigned to one of three prenatal-exposure groups: low (less than 3 micrograms per deciliter), medium (6 to 7 micrograms per deciliter), or high (greater than or equal to 10 micrograms per deciliter). Development was assessed semiannually, beginning at the age of six months, with use of the Mental Development Index of the Bayley Scales of Infant Development (mean +/- SD, 100 +/- 16). Capillary-blood samples obtained at the same times provided measures of postnatal lead exposure. Regression methods for longitudinal data were used to evaluate the association between infants' lead levels and their development scores after adjustment for potential confounders. At all ages, infants in the high-prenatal-exposure group scored lower than infants in the other two groups. The estimated difference between the overall performance of the low-exposure and high-exposure groups was 4.8 points (95 percent confidence interval, 2.3 to 7.3). Between the medium- and high-exposure groups, the estimated difference was 3.8 points (95 percent confidence interval, 1.3 to 6.3). Scores were not related to infants' postnatal blood lead levels. It appears that the fetus may be adversely affected at blood lead concentrations well below 25 micrograms per deciliter, the level currently defined by the Centers for Disease Control as the highest acceptable level for young children.

Child Development

Temperature sensitive pet mutants in yeast Saccharomyces cerevisiae that lose mitochondrial RNA.

This is a description of a new class of temperature sensitive pet mutants in Saccharomyces cereviase that lose all or part of their mitochondrial RNA at the restrictive temperature. These mutants fall into 8 different complementation groups, mna1 to mna8, and 2 different classes based on their phenotype. Class I mutations, mna1-1 through mna5-1, cause complete or partial loss of mitochondrial RNA at the restrictive temperature. The mutation, mna1-1, is especially interesting since it causes a loss of both mitochondrial DNA and RNA when the mutant is grown on a fermentable carbon source at the restrictive temperature. However, when this mutant is grown at the permissive temperature on a non-fermentable carbon source then shifted to the restrictive temperature, only the mitochondrial RNA is lost. This indicates that the primary cause for the pet phenotype is due to the loss of mitochondrial RNA and not DNA. Class II mutations, mna6-1 through mna8-1, cause complete loss of the 14S rRNA after growth at the restrictive temperature in a fermentable carbon source. This loss appears to be specific for the 14S rRNA, since all other transcripts probed by Northern analysis are normal.

DNA, Mitochondrial

A modified, solid phase radioimmunoassay for the differential diagnosis of acute and convalescent phases of hepatitis A infection.

The commercial assays for diagnosing the presence of hepatitis A antibodies (HAVAB; Abbott Laboratories, North Chicago, IL) or the presence of IgM class anti-hepatitis A virus antibodies (HAVAB-M; Abbott) do not provide precise information as to the timing of the acute infection. IgM class antibodies are detected as late as six months after the acute infection. In this study the authors describe a modified HAVAB test that inactivates the IgM class antibodies. It thus measures the proportion of IgG antibodies out of the total anti-hepatitis A virus antibodies. In a study of 139 patients with impaired liver function, the available and modified tests showed good agreement except for the convalescent phase of hepatitis A. During serial testing for three months after the acute infection, the commercial tests continuously detected IgM class antibodies. The modified test detected predominantly IgG class antibodies from four weeks on. By six weeks, 85% of the patients had predominantly IgG class antibodies. The modified test thus provides information on the timing of recent hepatitis A infection.

Acute Disease

Pregnancy hypertension, blood pressure during labor, and blood lead levels.

Pregnancy hypertension, blood pressure during labor, and the umbilical cord blood lead concentration were assessed in 3851 women for whom additional demographic, medical, and personal information was available. Lead levels correlated with both systolic (Pearson r = 0.081, p = 0.0001) and diastolic (r = 0.051, p = 0.002) blood pressures during labor. The incidence of pregnancy hypertension increased with lead level. Multivariate models of pregnancy hypertension and systolic blood pressure as a function of maternal age, parity, hematocrit, ponderal index, race, and diabetes were improved by including lead as a predictor variable. At these observed levels of exposure (mean blood lead, 6.9 +/- 3.3 [SD] micrograms/dl), lead appears to have a small but demonstrable association with pregnancy hypertension and blood pressure at the time of delivery, but not with preeclampsia.

Adult

Correlates of low-level lead exposure in urban children at 2 years of age.

The blood lead levels of a large number of US preschool children approach the value regarded as the upper limit of normal. To reduce the number of children whose levels increase into the range thought to be toxic, the antecedents and correlates of levels in the 0- to 25-micrograms/dL range must be identified. In a large longitudinal study of middle and upper-middle class children living in metropolitan Boston, we evaluated how well five sets of variables predicted children's blood lead levels at 2 years of age: environmental lead sources, mouthing activity, home environment/care giving, prior developmental status, and sociodemographic characteristics. A series of bivariate and multivariate analyses indicated that only environmental lead sources and, to a lesser extent, mouthing activity accounted for significant portions of the variance in blood lead levels. Environmental lead sources were not significantly related to the home environment/care-giving variables or to sociodemographic characteristics. The most promising approach for achieving community-wide reductions in children's blood lead levels is reduction in the amount of lead in the proximate environment.

Analysis of Variance

Expression of myosin heavy chains during thyroid hormone-induced cardiac growth.

The expression of mRNAs for two cardiac myosins has been studied in the ventricles of hypo- and hyperthyroid rabbits by using cloned cDNA sequences corresponding to the mRNAs of the alpha- and beta-myosin heavy chains (HCs). The temporal change in relative levels of the alpha and beta HC mRNAs after triiodothyronine (T3) treatment of hypothyroid rabbits was determined by nuclease S1 mapping. In the hypothyroid state, only NC beta-mRNA was expressed in the ventricles. The HC alpha-mRNA was first detectable 4 h after administration of T3 (200 micrograms/kg) to hypothyroid animals. By 12, 24, and 72 h, HC alpha-mRNA represented 20, 50, and 90% of total myosin mRNA. The relationship between the relative mRNA levels and relative synthesis rates of myosin HCs was evaluated in 5- to 6-wk-old normal and thyrotoxic rabbits. Myosin synthesis rates were determined by labeling of protein in vivo with [2H]leucine. The V1 (HC alpha) and V3 (HC beta) isomyosins were separated by immune affinity chromatography and the HCs were isolated electrophoretically. In a normal euthyroid group of animals and in animals 12 and 24 h after administration of 200 micrograms of thyroxine, the relative mRNA levels and relative synthesis rates of the alpha and beta HCs were not significantly different. Our results show that, first, thyroid hormone causes a rapid accumulation of HC alpha-mRNA and loss of HC alpha-mRNA, and second, in normal and thyrotoxic rabbits, the relative synthesis rates of HC alpha and HC beta reflect the relative abundance of their respective mRNAs. These data are consistent with the thyroid hormones regulating synthesis of ventricular myosin at steps that precede translation of its message.

Animals

Environmental correlates of infant blood lead levels in Boston.

From a blood lead survey of 11,837 births, 249 newborns were enrolled in a 2-year, longitudinal study. Their blood leads (PbB) were measured semiannually, and their homes were visited for repeated collections of dust, soil, indoor air, tap water, and paint. Recent refinishing activity and the sizes of nearby streets were recorded. Overall mean PbB was 7.2 micrograms/dl (SD = 5.3) at birth. PbB did not vary systematically with age. Each subject's average postnatal PbB correlated highly with the amount of lead in dust (r = 0.4, P less than 0.0001) and soil (r = 0.3, P less than 0.001), and with the lead in paint (r = 0.2, P less than 0.01). Dust, soil and air lead levels correlated with one another. Refinishing activity in the presence of lead paint was associated with elevations of PbB. Water lead, proximate traffic, weight of recovered dust, race, maternal age and education, and sex were not predictive of PbB. Multivariate models of PbB were constructed that become increasingly predictive with age (r2 = 20 to 37%). Indoor dust lead, lead in soil, refinishing activity, and season were the independent variables.

Air Pollutants

Characterization of a yeast mitochondrial promoter by deletion mutagenesis.

We have generated collections of mutants of the promoter for the small rRNA gene from the mitochondria of yeast deleted from either the 3' or 5' end. Plasmids containing the partially deleted promoter were assayed for their ability to direct correct transcriptional initiation in a homologous in vitro system. We find that the region required for high-efficiency promoter function lies between positions -10 and +2. Our methods detected no effect of flanking sequences on the strength of this promoter.

Base Sequence

Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth in the rat.

Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth were examined in 29 to 46 day old rats. DNA synthesis was examined in vitro using isolated nuclei from rat heart and adult X. laevis spleen. Cytoplasmic extract (CE) was obtained from a 105 000 g supernatant of rat heart and fetal liver homogenates. To measure DNA synthesis we utilised DNA within the isolated quiescent nucleus as the template and measured the effect of CE on the incorporation of 3H-TTP into an acid precipitable product. In a homologous system of rat heart nuclei from weanling rats and CE from cardiac muscle undergoing induced growth, no stimulation of 3H-TTP incorporation was observed. Cardiac muscle CE however, did possess stimulatory factor(s) since quiescent X. laevis nuclei could be stimulated with the rat heart CE. Furthermore, CE from hearts undergoing induced growth had greater activity than extract from control hearts. While cardiac muscle nuclei were not stimulated by heart CE, they showed substantial stimulation by CE from fetal rat liver, which contains a large population of proliferating cells. Stimulation by fetal rat liver was greater with nuclei obtained from hearts undergoing induced growth than from control hearts. Stimulatory factor(s) in CE was distinct from DNA polymerase-alpha activity, as shown by separation of the two activities on a 5 to 15% glycerol gradient.

Animals