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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 325 records · Page 18Linked to original sources
PubMed1991

The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3.

The Marfan syndrome is a common autosomal dominant disorder of connective tissue. Despite many years of intensive investigation, the primary genetic defect has not yet been identified. Reverse genetic methods, targeted at mapping this disease gene, have resulted in an initial report of linkage of the genetic locus for the Marfan phenotype in Finnish families to two polymorphic markers on chromosome 15. We have investigated four large multiplex American families with classic Marfan syndrome using standard genetic linkage methods. Our data confirm the assignment of the Marfan syndrome gene to chromosome 15, but establish a more centromeric location (defined by markers D15S25 and D15S1) as the most probable site for the genetic defect (lod score = 12.1, theta = 0.00). These data should facilitate identification and characterization of the Marfan syndrome gene and, in selected families, have immediate application to diagnosis of equivocal cases or prenatal counseling.

Chromosome Mapping↗
PubMed1991

Particulate air pollution and daily mortality in Detroit.

Particulate air pollution has been associated with increased mortality during episodes of high pollution concentrations. The relationship at lower concentrations has been more controversial, as has the relative role of particles and sulfur dioxide. Replication has been difficult because suspended particle concentrations are usually measured only every sixth day in the U.S. This study used concurrent measurements of total suspended particulates (TSP) and airport visibility from every sixth day sampling for 10 years to fit a predictive model for TSP. Predicted daily TSP concentrations were then correlated with daily mortality counts in Poisson regression models controlling for season, weather, time trends, overdispersion, and serial correlation. A significant correlation (P less than 0.0001) was found between predicted TSP and daily mortality. This correlation was independent of sulfur dioxide, but not vice versa. The magnitude of the effect was very similar to results recently reported from Steubenville, Ohio (using actual TSP measurements), with each 100 micrograms/m3 increase in TSP resulting in a 6% increase in mortality. Graphical analysis indicated a dose-response relationship with no evidence of a threshold down to concentrations below half of the National Ambient Air Quality Standards for particulate matter.

Air Pollution↗
PubMed1991

Air pollution and acute respiratory illness in five German communities.

To assess the impact of short-term exposure to air pollution on respiratory illness in children we recruited pediatricians and hospitals in five German cities to report daily counts of children's visits for croup symptoms and obstructive bronchitis. Data were collected for at least 2 years in each location. These symptoms are predominantly found in very young children, with the croup reporting peaking at 2 years of age and obstructive bronchitis at 1 year. Attacks of croup and obstructive bronchitis were relatively rare events: the mean number of cases of croup per day in each city ranged from 0.5 to 3, and obstructive bronchitis was even less frequent. A total of 6330 cases of croup and 4755 cases of obstructive bronchitis were observed during the study. The distributions of these events were quite skewed and were modeled as a Poisson process. To focus the analysis on short-term correlations and avoid seasonal confounding, biannual, annual (seasonal), and six shorter term cycles were controlled for in the regression models. After controlling for short-term weather factors, total suspended particulate matter (TSP) and nitrogen dioxide (NO2) were associated with croup cases. An increase in TSP levels from 10 micrograms/m3 to 70 micrograms/m3 was associated with a 27% increase in cases of croup; the same increase in NO2 levels resulted in a 28% increase in cases. No pollutant was associated with daily cases of obstructive bronchitis.

Air Pollution↗
PubMed1991

The risk of lead toxicity in homes with lead paint hazard.

While lead paint has long been known to be a major source of lead poisoning, only a few small epidemiologic studies have attempted to assess directly the relative risk of lead poisoning due to the presence of lead paint. Using data from over 200,000 screening tests of children in the city of Chicago performed between 1976 and 1980, the relative risks can be quantified for children living in a major urban area. Lead paint was found to be a significant predictor of the probability of a child having lead toxicity. As expected, the reduction in leaded gasoline sales during the period reduced mean blood lead levels and increased the percentage of lead toxic children whose toxicity could be attributed to paint lead. Poisson regression models indicated that with the elimination of leaded gasoline, the relative risk of lead toxicity given lead paint exposure was 5.70 (95% CI, 4.13-7.86) during the winter and fall. The relative risk rose to 12.81 (95% CI, 7.33-22.4) in the spring and 15.8 (95% CI, 8.90-28.1) in the summer, probably due to increased exposure to window wells.

Bayes Theorem↗
PubMed1991

Comorbidity of psychiatric disorders and personality profiles of American World War II prisoners of war.

To characterize the effects of trauma sustained more than 40 years ago, prevalence of psychiatric disorders and personality dimensions were examined in a sample of 62 former World War II POWs. The negative effects of their experiences are reflected in their multiple lifetime diagnoses and in their current personality profiles. Fifty percent met DSM-III posttraumatic stress disorder (PTSD) criteria within 1 year of release; 18 (29%) continued to meet the criteria 40 years later at examination (chronic PTSD). A lifetime diagnosis of generalized anxiety disorder was found for over half the entire sample; in 42% of those who never had PTSD, 38% of those with recovery from PTSD, and 94% of those with chronic PTSD. Ten percent of those without a PTSD diagnosis had experienced a depressive disorder, as had 23% of those with recovery from PTSD and 61% of the POWs with chronic PTSD. The combination of depressive and anxiety disorders also was frequent in the total sample (61%). Current MMPIs of three groups with psychiatric diagnosis were compared with those of POWs who had no diagnoses and with a group of Minnesota normal men. Profile elevations for the groups, from highest to lowest, were: POWs with chronic PTSD, POWs with recovery from PTSD, POWs with other psychiatric diagnoses, POWs with no disorders, and Minnesota normal men. Symptoms of anxiety, depression, and somatic concerns combined with the personality styles of suppression and denial characterize the current adjustment of negatively affected POWs.

Adaptation, Psychological↗
PubMed1991

Effects of V2 receptor activity on the pressor response to vasopressin in the rat.

1. To determine the contribution of V1 and V2 receptor activity on the enhancement of reflex buffering of the pressor response to arginine-vasopressin (AVP), mean arterial pressure (MAP) and heart rate (HR) changes were examined in response to graded injections of phenylephrine, AVP, or Phe2Orn8OT, a potent, selective V1-receptor agonist in the absence and presence of Val4DArg8VP, a potent, selective V2-receptor agonist. 2. There were no significant differences in MAP responses to the V1 agonist in the absence and presence of the V2 agonist in either conscious intact or autonomic-blocked rats. 3. Autonomic blockade with methscopolamine and hexamethonium increased the pressor sensitivity to phenylephrine threefold. In contrast, the pressor sensitivities to AVP and Phe2Orn8OT were increased 14-fold and 11-fold, respectively, by autonomic blockade. 4. V2-receptor activity does not have any inherent vasocative action or synergistic vasoactive action with V1-receptor activity. 5. V2 receptors do not play a role in enhancing reflex buffering of the pressor response to AVP; V1 receptors are suggested to play the role.

Animals↗
PubMed1991

Candida albicans pacemaker site infection.

A 69-year-old man with a history of diabetes and episodic lymphocytopenia underwent pacemaker implantation for complete heart block. Despite prophylactic antibiotics, pocket irrigation, and strict sterile technique, a fungal (Candida albicans) pacemaker site infection developed that required pacemaker explanation and systemic amphotericin B therapy. After 3 days of temporary pacing, a second pulse generator was implanted on the opposite side. At 2-year follow-up, he has had no recurrence of pacemaker infection. This report underscores the predilection of diabetics for infections, and in particular, their susceptibility to Candida albicans.

Aged↗
PubMed1991

Regulation of ACTH secretory pathways in cultured pituitary cells.

Although chloroquine, an agent that disrupts regulated protein secretion, has previously been shown to decrease the adrenocorticotropic hormone (ACTH) secretory response to adenosine 3',5'-cyclic monophosphate or corticotropin-releasing factor (CRF) in AtT-20 and rat anterior pituitary cells, respectively, it has no effect on the response to vasopressin. The present study extended experiments with chloroquine to cultured sheep anterior pituitary cells, which have a greater maximum response to vasopressin. Chloroquine (200 microM) had no effect on basal ACTH secretion or on stimulation by vasopressin. In contrast to the rat, the net response to CRF was tripled by chloroquine in ovine cells. The effect of chloroquine on the response to CRF was more effective by coexposure of cells to CRF and chloroquine than by pretreatment with chloroquine. Monensin or vinblastine did not increase the ACTH response to CRF. The results indicate ACTH release in response to vasopressin is chloroquine insensitive in this way, can be dissociated from the mechanism that responds to CRF, and would be consistent with the CRF response mechanism involving pathways that can alter the secretory pool of ACTH. When chloroquine acts to increase the response to CRF, it is likely not to act by stabilizing the CRF-receptor complex.

Adrenocorticotropic Hormone↗
PubMed1991

Effect of AVP on susceptibility of ovine pituitary cells to a cytotoxic analogue of CRF.

Although exposure to arginine vasopressin (AVP) has been reported to induce anterior pituitary corticotrophs to bind and become responsive to corticotropin-releasing factor (CRF), the identity of these inducible CRF target cells is unknown. Such cells may themselves be the AVP-responsive corticotrophs or other cells that become CRF targets secondary to a paracrine signal from AVP target cells. The present study used a cytotoxin (Cx), specific for CRF target cells, that eliminates responses of treated cells to a subsequent challenge with CRF but leaves responses to AVP intact. We hypothesized that, if AVP target corticotrophs themselves become CRF targets, then the addition of AVP during treatment with Cx should render these cells susceptible to the cytotoxin and should eliminate the response to subsequent AVP as well. Ovine pituitary cells were chosen for the study because they respond more robustly than rat cells to AVP. Pretreatment of ovine pituitary cells with Cx (400 pM) or Cx plus AVP (10 nM) eliminated the adrenocorticotropic hormone (ACTH) secretory response to CRF (10 nM), as assessed 3 days later. Cx alone also reduced the secretory response to AVP from 23.9 +/- 3.4 to 11.5 +/- 1.9 ng ACTH/3 h (P less than 0.05). However, pretreatment with AVP (10 nM) plus Cx caused no further reduction in the secretory response to AVP (10.1 +/- 2.6 ng ACTH/3 h). These data suggest that, if AVP induces erstwhile non-CRF target cells to become CRF targets, then these induced cells are not themselves initially AVP target corticotrophs.

Adrenocorticotropic Hormone↗
PubMed1991

A potent new synthetic analog of vasopressin with relative agonist specificity for the pituitary.

The biological activity of a new synthetic analog of vasopressin, deamino[D-3-(3'-pyridyl)-Ala2, Arg8] vasopressin, was assessed in a number of assays. Antidiuretic (V2) and vasoconstrictor (V1), agonist and antagonist activities were assessed in rats in vivo. Corticotropin-releasing activity was assessed with cultured dissociated ovine anterior pituitary cells in vitro and in sheep in vivo. Compared to vasopressin, the analog is a weak agonist at antidiuretic receptors (1/381 compared to AVP); it is a weak antagonist of the vasoconstrictor response (pA2 = 6.22). Nonetheless, the analog is a full, relatively potent agonist at pituitary corticotrope receptors (relative potency of 1/36). These data indicate that analogs of vasopressin can be synthesized which are relatively selective for agonist activity at pituitary vasopressin receptors, and in doing so, further support the contention that the pituitary receptor is quite distinct from the classical V1 receptor.

Adrenocorticotropic Hormone↗
PubMed1991

Short stature and decreased serum growth hormone-binding protein in the Mountain Ok people of Papua New Guinea.

Two circulating GH-binding proteins (GH-BP), one of which is related to the GH receptor, have been described. To assess their possible role in or link with determining statural growth, we measured their activity/level in the serum of 25 adult subjects from a short-statured population from the highlands of Papua New Guinea (Mountain Ok people, similar in stature to African pygmies) and in 25 normal-statured North American control subjects. The Mountain Ok people have normal levels of GH, insulin-like growth factor-I (IGF-I), IGF-II, and serum albumin and prealbumin in association with short stature, making them a unique study population. Levels of the high affinity (GH receptor-related) GH-BP were significantly lower in the Mountain Ok subjects than in the taller controls (5.2 +/- 3.0% vs. 10.6 +/- 3.9% GH bound/160 microL, respectively; mean +/- SD; P less than 0.001). In contrast, the low affinity GH-BP was comparable in Mountain Ok and control subjects. Because of the structural similarity between the GH receptor and GH-BP, these data suggest that a limitation in GH receptor/GH-BP endowment may be associated with short stature despite normal circulating IGF-I levels. Alternatively, it is possible that the GH-BP itself plays an important role in growth promotion. Thus, the GH receptor (and/or GH-BP) complement may be a determinant of the genetically programmed height achieved.

Adult↗
PubMed1991

ICI 181,037: a novel eukalemic diuretic with antiarrhythmic activity.

ICI 181,037, the most active compound from a series of 1,1-diarylcarbin-1-ol-2 amines, was evaluated for diuretic and cardiovascular activity. In saline-loaded rats, the magnitude of water diuresis and saluresis produced by ICI 181,037 (10 mg/kg, p.o.) was equal to that of hydrochlorothiazide. Water diuresis and saluresis produced by ICI 181,037 were enhanced with SKF 525A, ampicillin or neomycin plus lincomycin, suggesting that ICI 181,037 is an active diuretic. In conscious dogs, the saluretic activity of ICI d-181,037 (5 mg/kg, p.o.) was about 80% of the corresponding hydrochlorothiazide value, whereas the l-isomer demonstrated only minimum saluretic activity. In both rats and dogs, the concurrent kaliuresis after ICI 181,037 or its enantiomers was minimal as compared to hydrochlorothiazide. Following chronic dosing with diuretic doses, the basal levels of plasma potassium in dogs were not altered. In amphibian in vitro models for mimicking mammalian nephron, ICI 181,037 and its enantiomers demonstrated antinatriferic and antichloriferic activities, suggesting multiple renal sites of action for this agent. Racemic ICI 181,037 and its isomers reversed ouabain-induced arrhythmia in dogs and/or reduced the ouabain-induced mortality in mice after intravenous administration. It is concluded that ICI 181,037, particularly its d-isomer, is a novel eukalemic diuretic and possesses antiarrhythmic activity.

Acetamides↗
PubMed1991

Daily diaries of respiratory symptoms and air pollution: methodological issues and results.

Daily diaries of respiratory symptoms are a powerful technique for detecting acute effects of air pollution exposure. While conceptually simple, these diary studies can be difficult to analyze. The daily symptom rates are highly correlated, even after adjustment for covariates, and this lack of independence must be considered in the analysis. Possible approaches include the use of incidence instead of prevalence rates and autoregressive models. Heterogeneity among subjects also induces dependencies in the data. These can be addressed by stratification and by two-stage models such as those developed by Korn and Whittemore. These approaches have been applied to two data sets: a cohort of school children participating in the Harvard Six Cities Study and a cohort of student nurses in Los Angeles. Both data sets provide evidence of autocorrelation and heterogeneity. Controlling for autocorrelation corrects the precision estimates, and because diary data are usually positively autocorrelated, this leads to larger variance estimates. Controlling for heterogeneity among subjects appears to increase the effect sizes for air pollution exposure. Preliminary results indicate associations between sulfur dioxide and cough incidence in children and between nitrogen dioxide and phlegm incidence in student nurses.

Air Pollution↗
PubMed1991

Lead, blood pressure, and cardiovascular disease in men and women.

Lead has been shown to be associated with elevated blood pressure in males in the NHANES II survey and in numerous other studies. This study confirms the association in males aged 20 to 74 and documents a significant, although weaker, association in females as well. Prospective cardiovascular disease studies such as the Framingham study indicate that increases in blood pressure should be associated with increased risk of cardiovascular disease. Using electrocardiogram data from NHANES II, this study confirms the expected association of lead with left ventricular hypertrophy (p less than 0.01). Such an association with permanent cardiovascular changes adds weight to the blood pressure findings. The logistic risk coefficients from the Framingham study can be combined with the study's association between lead and blood pressure to examine its implication for more serious outcomes. The results suggest that a halving of the population mean blood lead level would reduce myocardial infarctions by approximately 24,000 events per year and incidence of all cardiovascular disease by over 100,000. These numbers suggest a small attributable risk compared to the vast incidence of cardiovascular disease in the U.S., but a large attributable risk compared to most environmental toxins. Several biological mechanisms have been identified, with different implications for the use of bone lead as an exposure measure.

Adult↗
PubMed1990

Differential regulation of two glucose transporters by chronic growth hormone treatment of cultured 3T3-F442A adipose cells.

New methods for the analysis of glucose transporters were used to analyze the molecular mechanisms involved in the insulin-antagonistic effects of growth hormone (GH), which is known as a diabetogenic hormone. The ability of GH to alter the number and mRNA levels of two different glucose transporters in cultured 3T3-F442A adipocytes was investigated using specific antibodies and cDNA probes. At concentrations of GH as low as 0.5 and 5 ng/ml and at incubation times as short as 4 h, GH decreased rates of 2-deoxyglucose uptake in 3T3-F442A adipocytes. 3-O-Methyl-D-glucose uptake was inhibited to an extent similar to that of 2-deoxyglucose uptake (60-80%) after a 24-h incubation with GH (500 ng/ml), indicating that GH inhibits glucose metabolism specifically at the step of glucose transport. To determine whether reduced rates of glucose transport might result from reduced numbers of glucose transporters, whole cell lysates were prepared from GH-treated cells and subjected to immunoblotting using antibodies that identify Glut 1 (HepG2/rat brain) and Glut 4 (muscle/adipose) transporters. GH caused a time- and dose-dependent decrease in the number of Glut 1 transporters in the cell. Northern and slot-blot analyses showed a GH-induced dose-dependent decrease in levels of Glut 1 mRNA. In contrast, levels of Glut 4 transporter and mRNA were unchanged by GH. These data suggest that GH regulates Glut 1 and Glut 4 transporters differentially and that it exerts its inhibitory effect on glucose uptake at least in part by decreasing the synthesis of Glut 1 transporters. These studies provide the first evidence that GH regulates a key gene in metabolic regulation and can interfere with gene expression.

Adipose Tissue↗
PubMed1990

Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo.

The Eta-1 gene specifies a secreted product of activated T cells and is associated with genetic resistance to infection by an obligate intracellular bacterium. Previous studies have suggested that eta-1 might affect the ability of macrophages to migrate to the site of bacterial infection and/or to inhibit intracellular bacterial growth. We therefore examined the interaction of eta-1 with macrophages in vitro and in vivo. We find that macrophages express approximately 10(4) eta-1 receptors/cell and each receptor has a Kd of approximately 5 x 10(-10) M. The subsequence of eta-1 containing an RGD motif is required for binding because a synthetic peptide containing the eta-1 RGD domain inhibited protein attachment to macrophages. We also found that subcutaneous inoculation of mice with eta-1 resulted in a cellular infiltrate comprised primarily of macrophages. We propose that the interaction between eta-1 and its receptor on macrophages results in a change in macrophage physiology resulting in accumulation of these cells at extravascular sites.

Amino Acid Sequence↗