Biomedical subjects
J Schwartz
Publications and source records attributed to J Schwartz.
Rectovaginal fistula associated with fecal impaction.
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Air pollution and respiratory symptoms in preschool children.
A diary study on a random sample of 625 Swiss children aged 0 to 5 yr was conducted in two cities in Switzerland to investigate the association between air pollution and respiratory symptoms. Total suspended particulates (TSP), SO2 and NO2 were measured by city monitor. In addition, passive samplers inside and outside the home measured NO2 concentration during the 6 wk each child was on the diary. Diaries were filled out by parents, and 20% were validated with the attending pediatrician's case notes. Incidence and duration of symptom episodes were examined separately. The study included any episode, episodes of coughing without runny nose, upper respiratory episodes, and episodes of breathing difficulty. In regressions using 6-wk average pollution that controlled for medical history, NO2 measured outdoors but not indoors was associated with the duration of any symptom. Total suspended particulates were a more significant predictor of duration of any symptom than NO2. The 6-wk average TSP was significantly associated with incidence of coughing episodes and marginally significant as a predictor of upper respiratory episodes. Previous day's TSP was a significant predictor of incidence of upper respiratory symptoms. Annual average of NO2 was associated with the duration of any episode and of upper respiratory episodes. We conclude that the incidence and duration of respiratory symptom episodes are likely associated with particulate concentrations and duration may be associated with NO2.
Increased mortality in Philadelphia associated with daily air pollution concentrations.
Cause-specific deaths by day for the years 1973 to 1980 in Philadelphia, Pennsylvania, were extracted from National Center for Health Statistics mortality tapes. Death from accidents (International Classification of Disease, Revision 9 greater than or equal to 800) and deaths outside of the city were excluded. Daily counts of deaths were regressed using Poisson regression on total suspended particulate (TSP) and/or SO2 on the same day and on the preceding day, controlling for year, season, temperature, and humidity. A significant positive association was found between total mortality (mean of 48 deaths/day) and both TSP (second highest daily mean, 222 micrograms/m3) and SO2 (second highest daily mean, 299 micrograms/m3). The strongest associations were found with the mean pollution of the current and the preceding days. Total mortality was estimated to increase by 7% (95% CI, 4 to 10%) with each 100-micrograms/m3 increase in TSP, and 5% (95% CI, 3 to 7%) with each 100-micrograms/m3 increase in SO2. When both pollutants were considered simultaneously, the SO2 association was no longer significant. Mortality increased monotonically with TSP. The effect of 100 micrograms/m3 TSP was stronger in subjects older than 65 yr of age (10% increase) compared with those younger than 65 yr of age (3% increase). Cause-specific mortality was also associated with a 100-micrograms/m3 increase in TSP: chronic obstructive pulmonary disease (ICD9 490-496), +19% (95% CI, 0 to 42%), pneumonia (ICD9 480-486 & 507), +11% (95% CI, -3 to +27%), and cardiovascular disease (ICD9 390-448), +10% (95% CI, 6 to 14%). These results are somewhat higher than previously reported associations, and they add to the body of evidence showing that particulate pollution is associated with increased daily mortality at current levels in the United States.
Cessation of recurrent bleeding from gastrointestinal angiodysplasia, after beta blocker treatment in a patient with hypertrophic subaortic stenosis--a case history.
The authors present the case of an elderly patient suffering from obstructive cardiomyopathy and bleeding colonic angiodysplasia. After treatment with propranolol, the bleeding stopped without recurrence.
Profuse diaphoresis as the presenting symptom of myocardial ischemia with normal appearance of coronary arteriogram--a case report.
The authors present a case of a patient suffering from profuse diaphoresis as the sole manifestation of myocardial ischemia (syndrome x or coronary vasospasm). The diagnosis was established by positive exercise thallium 201 imaging and normal-appearing coronary arteriogram.
Hypernatremic dehydration complicated by peripheral gangrene in elderly--case reports.
The authors describe the association of hypernatremic dehydration and peripheral gangrene in elderly patients. This association is known in infancy but hitherto has not been described in the elderly.
Holt-Oram syndrome in an elderly patient--a case history.
The authors present a typical case of Holt-Oram syndrome in an eighty-year-old woman. The patient had atrial-septal defect and phocomelia but was independent in the activities of daily living.
Intercellular communication within the anterior pituitary influencing the secretion of hypophysial hormones.
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Growth hormone induces c-fos and c-jun expression in cells with varying requirements for differentiation.
GH is one of the major factors required for the differentiation of 3T3-F442A preadipocyte fibroblasts into adipocytes. An early event following the addition of GH to 3T3-F442A preadipocytes is induction of the expression of c-fos and c-jun. Although c-fos and c-jun expression has been observed in conjunction with growth factor-stimulated differentiation in several cell types, it is not clear whether protooncogene expression and differentiation are necessarily related. In this study the relationship between the induction of these protooncogenes and differentiation was evaluated by taking advantage of several cell lines that are related to 3T3-F442A cells but have varying GH requirements for differentiation. Adipose differentiation in the adipogenic cell lines 3T3-L1 and 3T3-GI-16 is known to be GH independent, requiring insulin or insulin-like growth factor-I. In both 3T3-L1 and 3T3-GI-16 preadipocytes, GH, nevertheless, induced the expression of mRNA for both protooncogenes. GH (2.2 nM) was more effective than insulin (1 microM) in inducing c-fos expression in these two adipogenic cell lines, suggesting that induction of the protooncogenes is not sufficient to induce adipogenesis. 3T3-C2 fibroblasts do not differentiate in response to any of the stimuli that convert 3T3-F442A fibroblasts to adipocytes. However, GH (2.2 nM) as well as calf serum induced the expression of c-fos and c-jun in 3T3-C2 cells. NIH-3T3 fibroblasts, which do not undergo differentiation, also showed induction of c-fos by GH. Thus, GH-induced expression of c-fos and c-jun occurs in nondifferentiating cells. Furthermore, in differentiated 3T3-F442A adipocytes, GH stimulated the expression of c-fos and c-jun as it does in the preadipocytes. Since GH elicits a variety of metabolic responses in 3T3-F442A adipocytes, the present findings raise the possibility that induction of c-fos and c-jun expression might be associated with multiple events in GH-stimulated 3T3-F442A adipocytes. The lack of requirement for GH in GH-independent and nondifferentiating cells compared to 3T3-F442A cells does not appear to reflect the lack of GH receptors, since expression of mRNA for the GH receptor was evident in all of the cell types tested and, thus, corresponds with the ability of GH to induce protooncogene expression. Although GH-induced c-fos expression was relatively invariant, since it was evident in all of the cell types studied, this response could clearly be regulated, since it was attenuated by prior exposure to GH or serum in 3T3-F442A preadipocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Growth hormone synergizes with serum growth factors in inducing c-fos transcription in 3T3-F442A cells.
GH is a major regulator of growth and metabolism, but cellular effects of GH alone have been difficult to demonstrate. Accordingly, suggestions have arisen that GH works in conjunction with other agents in producing its characteristic long term biological effects. In 3T3-F442A cells, in addition to eliciting long term changes, GH rapidly increases the transcription of c-fos. The present study uses this rapid response to examine whether GH interacts with other factors early in its action, and whether such interactions lead to changes in gene expression. The induction of c-fos mRNA in response to the combination of GH (2.2 nM) and 10% calf serum or fetal calf serum was more than 3 times the additive effects of GH and either of the sera alone, indicating synergism between GH and serum. Insulin-like growth factor-I (IGF-I), which also induces c-fos, had an effect with GH that was greater than the additive responses to the two agents. Nuclear run-off experiments indicated that the synergism between GH and IGF-I occurred at the level of transcription of c-fos. However, synergism between GH and serum in inducing c-fos transcription was greater than synergism between GH and IGF-I, suggesting that factors in addition to IGF-I contribute to the interaction of GH with serum. Insulin and fibroblast growth factor also synergized with GH in inducing c-fos expression. Platelet-derived growth factor and epidermal growth factor appeared to induce c-fos additively with GH, suggesting that different types of interactions occur between GH and the various growth factors. In inducing c-jun, which works coordinately with c-fos in transcriptional regulation, the effect of GH was additive with that of IGF-I and synergistic with that of serum. These findings indicate that early in its action, GH interacts with other growth factors in inducing protooncogene expression in 3T3-F442A cells. Such interactions between GH and serum or specific growth factors result in synergistic induction of the expression of c-fos. These findings suggest a generalized mechanism in which a major contribution of GH to cellular growth regulation is to synergize with other growth-promoting signals early in transduction of such signals in targets cells, resulting in enhanced gene transcription.
Cytokines, muscle proteolysis, and the catabolic response to infection and inflammation.
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Host and environmental factors influencing the peripheral blood leukocyte count.
The peripheral leukocyte count is an important predictor of mortality. Hence, host and environmental factors influencing the peripheral leukocyte count are of interest. The authors studied 8,635 subjects, aged 30-74 years, who were seen as part of the National Health and Nutrition Examination Survey II in 1976-1980, and sought to assess the relation of age, sex, obesity (body mass index), alcohol use, and various parameters of cigarette smoking to the peripheral leukocyte count using multiple regression analysis. Various parameters of cigarette smoking were statistically significant independent predictors of the peripheral leukocyte count with higher leukocyte counts seen among current smokers, relative to former or never smokers. Among current smokers, a dose-response relation was seen for cigarettes/day and total pack-years smoked. A dose-response relation with pack-years and years since quitting was seen in former smokers. Other variables that were statistically significant independent predictors of a higher peripheral blood leukocyte count were younger age, male sex, increased body mass index, and decreased alcohol consumption. Although the specific cell or cells responsible for these relations are not defined by this analysis, the results support the suggestion that a number of host and environmental factors can influence cellular markers of inflammation.
Cognitive functioning in late Lyme borreliosis.
Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment. Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible.
Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome.
Six Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likelihood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.
Growth hormone alters lipolysis and hormone-sensitive lipase activity in 3T3-F442A adipocytes.
While growth hormone (GH) has long been known as a lipolytic hormone, it has been difficult to study the cellular mechanisms for this effect. Since cultured 3T3-F442A adipocytes have recently proven to be useful to study chronic effects of GH on adipocyte metabolism, we examined the effects of GH on lipolysis. In these cells, GH alone produced a dose-dependent increase in the release of glycerol after 24 to 48 hours. The maximum increase occurred with 10 ng/mL human GH. The effect of GH was similar in the presence and absence of dexamethasone. Under each condition, the stimulation of glycerol release was accompanied by a GH-induced increase in the activity of hormone-sensitive lipase (HSL), a key lipolytic enzyme. The increase in HSL required 24 hours with GH and lasted at least 48 hours. The increase in HSL activity by epinephrine, like glycerol release, was potentiated by GH. Although GH potently simulates the activity of the lipogenic enzyme glycerol phosphate dehydrogenase (GPD) in differentiating 3T3-F442A preadipocytes, GH had a negligible effect on GPD activity in the differentiated adipocytes with chronic or short-term incubation. However, in contrast to the chronic effect of GH, short-term (30-minute) incubation with GH inhibited epinephrine-stimulated glycerol release, a characteristic transient antilipolytic effect of GH. These studies indicate that chronic GH treatment is lipolytic in cultured 3T3-F442A adipocytes, and document that lipolytic responses to GH involve an increase in the activity of HSL.
Vmw65 phosphorothioate oligonucleotides inhibit HSV KOS replication and Vmw65 protein synthesis.
Phosphorothioate-modified oligomers have been shown to be more stable than natural oligomers to serum and cellular nucleases. For this reason we used these analogs to explore the utility of antisense molecules as potential antiviral agents. The oligomers we studied are complementary to the initiation region of the Vmw65 (alpha-TIF) gene of HSV-1 which is important both for its structural role and in the transactivation of the alpha genes of HSV. Our results demonstrate that Vmw65-specific oligomers inhibit HSV KOS replication in a dose-dependent manner from 25 micrograms/ml (4.3 microM) to 50 ng/ml (9 nM). Vmw65 protein synthesis is inhibited from 51 to 68% at 5 micrograms/ml (0.8 microM) using Vmw65-specific oligomers 293s and 432s respectively. A random AT-rich oligomer, 007s, inhibited HSV KOS replication in a non-dose-dependent manner. Inhibition was only observed at a concentration of 12.5 micrograms/ml (2.1 microM) or more, using an MOI (multiplicity of infection) of 0.05 PFU/cell and a 24-h post-infection harvest.
Cell-free expression of the coxsackievirus 3C protease using the translational initiation signal of an insect virus RNA and its characterization.
We have expressed the 3C protease of coxsackievirus B3 (CVB3) in a cell-free system. This expression system employs the translational initiation signal of an insect virus RNA, black beetle virus (BBV) RNA 1, to direct CVB3-specific protein synthesis. Using this expression system, we demonstrate that a biologically active 3C protease is synthesized which possesses both cis and trans processing capabilities. This in vitro-synthesized 3C protease is analogous to the native 3C, which was obtained from cytoplasmic extracts of CVB3-infected HeLa cells, in all biological parameters that were evaluated. In addition, antibody prepared against the 3C protease purified from extracts of CVB3-infected HeLa cells cross-reacts with the 3C protease produced in this cell-free system. Using the translational initiation signal from BBV RNA 1, we also have expressed the CVB3 capsid precursor and part of the P2 region in vitro, and have shown that the capsid precursor is cleaved between 1C (VP3) and 1D (VP1) by the proteolytic activity of in vitro-synthesized 3C in trans. Evidence also is presented to implicate the 2A protein of CVB3 as having proteolytic function.