Isolation and characterization of ribonucleoprotein particles from heart muscle.
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Biomedical subjects
Publications and source records attributed to M Rabinowitz.
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Mitochondrial proliferation was studied in mature female rats following aortic constriction. Mitochondrial DNA (mtDNA) was assayed by a fluorometric method. The conditions for removal of nuclear DNA were developed and verified by assessment of molecular conformation of DNA. The mtDNA concentration in mitochondria increased 2,4, and 7 days post-operatively by 11, 72 and 117% respectively. Comparison with the rates of accumulation of cytochrome c, b, and aa3 indicates that during the first 24 hours of cardiac enlargement the inner mitochondrial components accumulate faster then mtDNA, but during the six subsequent days the rate of mtDNA increment far outstrips that of the cytochromes. These data indicate that the amount of available mtDNA templates is not the only factor regulating the transcriptional and translational processes in the enlarging myocardium. The analysis of population of replicative intermediates of mtDNA have shown dramatic decrease in the frequency of D-loops in preparations obtained from hypertrophied hearts. This observation indicates that the increase in replicative flux of mtDNA is associated with the removal of a block in the conversion of D-loops to other intermediates.
A prospective cohort study was conducted to assess the association between early development and low-level prenatal and postnatal lead exposure. Infants' performance between 6 and 24 months on the Mental Development Index of the Bayley Scales of Infant Development declined with increasing concentration of lead in blood, but the decline varied with children's age at exposure, level of exposure, and socioeconomic status. Within the second year of life, the performance of children in lower socioeconomic strata was adversely affected at lower levels of prenatal exposure (blood lead levels of 6 to 7 micrograms/dl) than was the performance of children in higher socioeconomic strata. However, even the performance of these advantaged infants was lower when cord blood lead level exceeded 10 micrograms/dl, well below the figure currently regarded as the maximum permissable level for young children. Exploratory analyses suggested that early postnatal blood lead levels between 10 and 25 micrograms/dl were also associated with lower Mental Development Index scores, but only among children in lower socioeconomic strata.
Three adult men were fed 204 Pb - a rare, stable isotope of lead - daily for about 100 days. Simultaneous blood and facial hair measurements of this tracer and of total lead concentrations were made by mass spectrometric isotope dilution analysis. Although the blood showed an immediate response to the intake of the tracer, the facial hair showed a more gradual response and a delay of approximately 35 days. Since the pattern of appearance of lead in hair does not appear to represent a simple time delay of blood lead concentration, the existence of a physiological pool of lead fed by the blood and giving rise to the content in hair is suggested. Hair lead values should, therefore, be interpreted as the integral of the blood lead values over the mean life of this intermediate pool - about 100 days.
As part of a study of early childhood development, more than 200 children had their blood lead concentrations (PbB) determined semiannually during the first 2 yr of life. These children were selected from 11,837 consecutive births surveyed for umbilical cord PbB at Boston Lying-In Hospital. Candidate subjects were drawn from the highest, lowest, and middle deciles of PbB. The mean PbB was 7.2 +/- 5.3 (standard deviation) micrograms/dl at birth and did not change appreciably with age. However, the average change in an individual's PbB every 6 months was 4 micrograms/dl, which was several fold in excess of the analytical reproducibility. Only 25% of the children in the highest category at birth were in the highest category at 2 yr of age. Approximately 40% of the children remained in their immediately previous PbB tertile category. A stochastic description of these patterns of change fits the data. Our results should caution investigators who might wish to rely on a single determination to categorize children with PbB.
A strong statistical correlation was found among the monthly averages of lead concentrations in umbilical cord blood (about 500 births/month), indoor air (12 sites/month), and gasoline lead sales between March, 1980 and April, 1981 in Boston. Tap water lead (24/month) variations did not correlate with blood lead in this population.
As part of a longitudinal study of the sources and developmental effects of current urban lead exposure, lead was measured in tap water from the homes of 249 infants, in 100 breast milk samples, and in 73 samples of the infant formula used by non-nursing mothers. Also, the blood lead levels of the infants who received these fluids were determined at birth and at 6 months of age. Among the infants who were breast fed, the lead content of their milks correlated very well with their 6-month blood lead levels (r = .42, P = .0003). The mean lead content of infant formulas and breast milk were not significantly different, nor was the blood lead of children fed one or the other. Lead levels in maternal milk correlated poorly with umbilical cord blood lead (r = .18, P = .10). Tap water and infant blood lead levels correlated minimally (r = .11, P = .10). Since milk represents much of the diet of young infants and because breast milk lead levels are stable, it is possible to relate blood lead and daily dosage in this population.
Thinking-aloud protocols provided by Joseph and Patel were reanalyzed to determine the extent to which their conclusions could be replicated by independently developed coding schemes. The data set consisted of protocols from four cardiologists (low domain knowledge = LDK) and four endocrinologists (high domain knowledge = HDK), individually working on a diagnostic problem in endocrinology. The two analyses agree that the HDK physicians related data to potential diagnoses more than did the LDK group and were more focused on the correct diagnostic components. However, the reanalysis found no meaningful difference between the groups in diagnostic accuracy, speed of diagnosis, or the breadth of the search space used to seek a solution. In the reanalysis, the HDK physicians employed more single-cue inference and less multiple-cue inference. The generalizability of results of protocol-analysis studies can be assessed by using several complementary coding schemes.
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The half-life of cardiac myosin heavy chains (HC) was determined, with leucyl-tRNA as precursor, to be 5.4 days. Myosin HC are labeled more rapidly than actin; myosin light chains (LC1 and LC2) are labeled more slowly than HC. The observed differences are attributable to heterogeneity in the half-lives, e.g., actin, and to the effect of dilution by the existing macromolecular precursor pool (LC1 and LC2). Cardiac and skeletal muscle contain a population of filaments that can be released from myofibrils by ATP-relaxing solution. The easily released filaments (ERF) are devoid of alpha-actinin and M-protein. Labeling of ERF is more rapid than that of residual myofibrils. Cardiac and skeletal muscle contains calcium-activated neutral protease, which selectively removes alpha-actinin when incubated with isolated myofibrils. During development of pressure-induced cardiac hypertrophy, the labeling of LC2 is increased. In regressing cardiac hypertrophy the activities of free and total cathepsin D and of acidic RNase are unaltered.
Four hundred and fifty-five exfoliated primary incisors were obtained from children whose mothers provided information about a wide range of pre-, peri-, and postnatal characteristics of both the mother and child. These teeth then were examined for the presence of hypoplastic enamel defects (HED). The basic form of the null hypothesis tested was that children who had HED of a primary incisor did not differ from those who did not have such a defect. Of the primary incisors examined, 18.5% had HED (25.0% maxillary and 10.1% mandibular). The following items were found to be associated most strongly (P less than 0.003) with an increase in a child's risk of developing HED; 1) maternal antenatal history of smoking, higher prepregnancy weight, and failure to obtain prenatal care during the first trimester; 2) prematurity, low birth-weight and their associated correlates; and 3) postnatal measles infection. Left-handedness, maternal tea and Tylenol (McNeil Consumer Products Co., Fort Washington, PA) consumption, and failure to screen for undue lead burden were associated less prominently (P less than 0.05) with HED prevalence. Season of birth and serum and dentin lead levels were not related to the prevalence of HED. Many of these risk factors are also covariates of low socioeconomic status such as suboptimal nutrition and increased risk of infection. Additional investigation is needed to delineate the associations between specific pre- and perinatal nutritional and infectious factors, socioeconomic status, and HED development.
The developmental impact of prenatal and early postnatal low-level lead exposure was assessed in a prospective study of 249 middle and upper-middle class infants with umbilical cord blood lead levels in the range currently considered "normal." Infants were classified into three exposure groups: "low" (less than 3 micrograms/dl), "mid" (6 to 7 micrograms/dl), and "high" (greater than or equal to 10 micrograms/dl). At 6 and 12 months, the lead concentration of capillary blood was measured, and the Bayley Scales of Infant Development administered. At both ages, Mental Development Index scores, adjusted for confounding, were inversely related to infants' umbilical cord blood lead levels. The difference between the mean adjusted scores of the infants in the low and high cord blood lead groups was 5.8 points at 6 months and 7.3 points at 12 months. At neither age were scores significantly related to postnatal blood lead levels. Prenatal exposure to lead levels relatively common among urban populations appear to be associated with less favorable development through the first year of life.
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