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R S Schwartz

Publications and source records attributed to R S Schwartz.

At least 19 recordsLinked to original sources
PubMed1995

Decreased content of protein 4.2 in ankyrin-deficient normoblastosis (nb/nb) mouse red blood cells: evidence for ankyrin enhancement of protein 4.2 membrane binding.

Homozygous normoblastosis (nb/nb) mice, whose red blood cell (RBC) membranes are nearly completely deficient in full-length 210-kD ankyrin, were used to study interactions between ankyrin and protein 4.2 (P4.2). Although it is unclear whether or not these proteins interact in the membrane, both ankyrin and P4.2 bind to the cytoplasmic domain of band 3 (cdb3). In addition to the complete deficiency of full-length ankyrin, nb/nb RBC membranes are also partially spectrin deficient, resulting in morphologically spherocytic and mechanically fragile cells. A new finding was that nb/nb RBC membranes are severely (approximately 73%) P4.2 deficient compared with wild type (+/+) or high reticulocyte mouse RBC membranes. Metabolic labeling of nb/nb reticulocytes showed active P4.2 synthesis at levels comparable with high reticulocyte controls suggesting that the nb/nb P4.2 deficiency was not the result of defective P4.2 synthesis. Reconstitution of nb/nb inside-out vesicles (IOVs) with human RBC ankyrin restored ankyrin levels to approximately 80% of +/+ IOV levels and increased binding of exogenously added human RBC P4.2 by approximately 60%. These results suggest that ankyrin is required for normal associations of P4.2 with the RBC membrane.

Animals↗
PubMed1995

Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study.

BACKGROUND: Coronary calcium identified by electron-beam computed tomography (EBCT) correlates poorly with luminal atherosclerotic narrowing, but calcium, an intimate part of coronary plaque, may be more directly related to atheromatous plaque area. METHODS AND RESULTS: Thirty-eight coronary arteries from 13 autopsy hearts were dissected, straightened, and scanned with EBCT in 3-mm contiguous increments. Coronary calcium area was defined as one or more pixels with a density > 130 Hounsfield units (0.18 mm2/pixel). Each artery was divided into corresponding 3-mm segments, representative histological sections were stained, and atherosclerotic plaque area per segment (mm2) was quantified. Coronary artery calcium and coronary artery plaque areas were correlated for the hearts as a whole, for individual coronary arteries, and for individual coronary artery segments. The sums of histological plaque areas versus the sums of calcium areas were highly correlated for each heart and for each coronary artery. However, coronary plaque area was on the order of five times greater than calcium area. Furthermore, minimal diffuse segmental coronary plaque could be present despite the absence of coronary calcium detectable by EBCT. CONCLUSIONS: This histopathologic study confirms an intimate relation between whole heart, coronary artery, and segmental coronary atherosclerotic plaque area and EBCT coronary calcium area but suggests that there is a threshold value for plaque area below which coronary calcium is either absent or not detectable by this methodology.

Adult↗
PubMed1995

Identification of a band-3 binding site near the N-terminus of erythrocyte membrane protein 4.2.

Protein 4.2 (P4.2) is a major component of the erythrocyte plasma membrane accounting for approx. 5% of total membrane protein. The major membrane binding site for P4.2 is contained within the cytoplasmic domain of band 3 (cdb3), although the precise location of the cdb3 binding site is not known. To identify the cdb3 binding site, we used synthetic P4.2 peptides (15-mers) that spanned the entire 721-amino-acid large isoform of P4.2, and determined the binding of these peptides to cdb3 in an in vitro binding assay. One peptide, P8 (L61FVRRGQPFTIILYF), bound strongly to cdb3 and four others bound less strongly (P22, L271LNKRRGSVPILRQW; P27, G346EGQRGRIWIFQTST; P41, L556WRKKLHLTLSANLE; P48, I661HRERSYRFRSVWPE). These peptides have in common a cluster of two or three basic amino acid residues (arginine or lysine), in a region without nearby acidic residues. Cdb3 bound saturably to P8 with a Kd of 0.16 microM and a capacity of 0.56 mol of cdb3 monomer/mol of P8. Use of overlapping synthetic peptides further defined the cdb3 site as being contained within V63RRGQPFTIILYF. Replacement of R64R with R64G, G64R or G64G almost completely abolished cdb3 binding, suggesting that R64R is essential for cdb3 binding. P8 competitively inhibited binding of purified human erythrocyte P4.2 to cdb3. In blot overlay assays, cdb3 bound to a 23 kDa N-terminal P4.2 tryptic peptide containing V63RRGQPFTIILYF but not to other P4.2 tryptic peptides lacking this site. The V63RRGQPFTIILYF site is highly conserved in mouse and human erythrocyte P4.2 as well as between P4.2 and transglutaminase proteins, which are evolutionarily related to P4.2.

Amino Acid Sequence↗
PubMed1995

A prospective study of treatment of acquired (autoimmune) factor VIII inhibitors with high-dose intravenous gammaglobulin.

A decrease in inhibitor titer has been reported in some patients with acquired factor VIII inhibitors treated with intravenous gammaglobulin (IGIV). We have conducted a prospective, multicenter study of high-dose IGIV in treatment of this disorder to determine efficacy. Nineteen patients received induction therapy with IGIV, 1,000 mg/kg x 2 consecutive days or 400 mg/kg x 5 consecutive days, followed by maintenance doses at intervals as clinically indicated. A > or = 25% reduction in inhibitor titer was observed in 8 of 16 assessable patients, six of whom met the criteria for response. A rapid decline in inhibitor titer over 3 to 4 days was observed in two patients, but in four additional responding patients--two of whom received repetitive maintenance doses of IGIV--the decline was more gradual, with final nadirs being reached several weeks to many months after treatment. The inhibitor disappeared in three patients with low-level inhibitors, less than 1 Bethesda unit (BU). Concomitant therapy with prednisone may have contributed to the response in two of the patients but was not a factor in four patients; the response rate is, therefore, estimated to be between 25% and 37.5%. These results confirm the beneficial effect of IGIV in treatment of some patients with acquired autoimmune factor VIII inhibitors.

Adult↗
PubMed1995

Jumping genes.

Explore the source record for details and available documents.

DNA Transposable Elements↗
PubMed1995

Quantification of coronary artery calcium by electron beam computed tomography for determination of severity of angiographic coronary artery disease in younger patients.

OBJECTIVES: This study attempted to 1) evaluate five quantitative measures of coronary artery calcium and determine which best agreed with coronary artery disease severity at angiography; and 2) determine optimal quantity cutpoints to distinguish among no, mild and significant disease. BACKGROUND: Coronary artery calcium identified noninvasively by electron beam computed tomography is a sensitive marker for atherosclerosis. Quantitative assessments of calcium could distinguish among patients with no, mild and significant disease in clinical, screening and research settings. METHODS: One hundred sixty patients, 23 to 59 years old, underwent coronary angiography and electron beam computed tomography. Coronary artery calcium was defined as dense (> 130 Hounsfield units) foci > or = 2 mm2 on the tomogram. Regression and receiver operating characteristic analyses were used to evaluate five quantitative measures of calcium as predictors of the largest stenosis in the coronary arteries and to identify optimal cutpoints for distinguishing among disease categories. No disease was defined as no stenosis, mild disease as 10% to 49% diameter stenosis in one or more major branches and significant disease as > or = 50% diameter stenosis in one or more major branches. RESULTS: All measures evaluated performed well. With calcific area as the quantitative measure, the best cutpoint for discriminating between patients with and without disease was the presence of calcium: sensitivity 81%, specificity 86% and overall accuracy 83%. The best cutpoint for discriminating between patients with and without significant disease was 18 mm2: sensitivity 86%, specificity 81% and accuracy 83%. CONCLUSIONS: Because the ranges of calcium quantity overlapped across disease categories, no cutpoints would distinguish among categories with absolute certainty. However, selected cutpoints could rule out disease in most healthy subjects and identify most patients with significant disease.

Adult↗
PubMed1995

Coronary calcium, as determined by electron beam computed tomography, and coronary disease on arteriogram. Effect of patient's sex on diagnosis.

BACKGROUND: Coronary artery calcium identified by electron beam computed tomography (EBCT) has potential for noninvasive localization of coronary atherosclerotic disease. However, the effect of a patient's sex on its diagnostic capability has not been examined in a clinical population. METHODS AND RESULTS: Fifty women and 89 men had EBCT scans done an average of 1 day after coronary arteriography. Maximum arteriographic percent luminal diameter stenosis of any artery was paired with the total EBCT coronary calcium score for each subject. The women (age, 56 +/- 11 years [mean +/- SD]) were older than the men (age, 47 +/- 7 years), but the subjects were matched for indications for arteriography and extent of disease as assessed by arteriography. Sensitivity, specificity, and positive and negative predictive values for coronary calcium were nearly identical for men and women, regardless of the degree of arteriographic disease. EBCT was highly sensitive to the presence of arteriographic disease (range, 94% to 100%), but had only moderate specificity (57% to 66%) for significant disease (> or = 50% stenosis) and low specificity (35% to 38%) for any arteriographic disease (> 0% stenosis). Negative predictive values in men and women ranged from 79% to 91% for any arteriographic disease and from 95% to 100% for significant disease, respectively. Numerical calcium scores were significantly different between subjects with normal arteriograms and those with significant disease; however, calcium score had limited power to separate trivial, moderate, and significant disease. Receiver operating characteristic curve areas, determined as an extension of the analyses of sensitivity and specificity, were high for EBCT-defined calcium scores for both any arteriographic disease and significant arteriographic disease, and were not different between the sexes. CONCLUSIONS: In a middle-aged population, noninvasive definition of coronary calcium by EBCT has similar predictive value for arteriographic coronary artery disease in men and women.

Calcinosis↗
PubMed1995

Trophic factor supplementation: effect on the age-associated changes in body composition.

Many of the changes in body composition associated with aging are similar to those found in states of growth hormone deficiency. Elderly people have also been found to have significant abnormalities in several trophic factor systems including growth hormone/insulin-like growth factors, and both male and female sex hormones. This has led to intense interest in the clinical effects of trophic factor supplementation in older individuals. This article reviews the age-related alterations in the growth hormone and sex steroid axes, as well as the effects of supplementation. In addition, important questions about the use of trophic factors in the elderly that must be addressed in future research are put forth.

Aged↗
PubMed1995

Involuntary weight loss in older outpatients: incidence and clinical significance.

OBJECTIVES: To describe the incidence, anthropometric parameters, and clinical significance of weight loss in older outpatients. DESIGN: Four-year prospective cohort study. SETTING: University-affiliated Veterans Affairs Medical Center. PATIENTS: Two hundred forty-seven community-dwelling male veterans 65 years of age or older. MEASUREMENTS: Anthropometrics (weight, height, skin-folds, and circumferences), health status measures (Sickness Impact Profile scores, health care utilization, self-reported ratings of health), and bloodwork (cholesterol, albumin, others) were obtained at baseline and followed annually for 2 years. Outcome measures (hospitalization, nursing home placement, and mortality rates) were followed for a minimum of 2 years after any identified weight change. MAIN RESULTS: The mean annual percentage weight change for the study population was -0.5% (SD: +/- 4.0%; range: -17% to +25%). Four percent annual weight loss was determined to be the optimal cutpoint for defining clinically important involuntary weight loss using ROC curve analysis. The annual incidence of this degree of involuntary weight loss was 13.1%. At baseline, involuntary weight losers were similar to nonweight losers in age (73.9 +/- 7.9 vs 73.3 +/- 6.7 years), body mass index (26.8 +/- 3.9 vs 26.9 +/- 4.1 kg/m2), and all other anthropometric, health status, and laboratory measures. Relative to nonweight losers, involuntary weight losers had significantly (P < or = .05) greater decrements in central skinfold and circumference measures (subscapular skinfolds, -2.9 vs -0.4 mm; suprailiac skinfolds, -4.2 vs -0.2 mm; and waist to hip ratio, -.01 vs + .00). Both groups had significant decreases in their triceps skinfolds (an estimate of peripheral subcutaneous fat), whereas arm muscle area and albumin levels did not decline significantly in either group. Over a 2-year follow-up period, mortality rates were substantially higher (RR = 2.43; 95% CI = 1.34-4.41) among involuntary weight losers (28%) than among nonweight losers (11%). Of interest, a similar increase in 2-year mortality (36%) was also observed among subjects with voluntary weight loss (by dieting). Survival analyses adjusting for differences between weight losers and nonweight losers in baseline age, BMI, tobacco use, and other health status and laboratory measures yielded similar results. CONCLUSIONS: These results indicate that involuntary weight loss occurred frequently (13.1% annual incidence) in this population of older veteran outpatients. When involuntary weight loss occurred, the predominant anthropometric changes were decrements in measures of centrally distributed fat (trunkal skinfolds and circumferences). Finally, involuntary weight loss greater than 4% of body weight appears to be clinically important as an independent predictor of increased mortality.

Age Factors↗
PubMed1995

Quantity of coronary artery calcium detected by electron beam computed tomography in asymptomatic subjects and angiographically studied patients.

OBJECTIVE: To determine the prevalence and quantity of coronary artery calcium (CAC) in asymptomatic subjects from the general population, to identify asymptomatic subjects without risk factors for coronary artery disease (CAD) with CAC scores in the top quartile of the distribution, and to compare CAC scores in patients who underwent angiography with percentiles in asymptomatic subjects of the same age and sex. DESIGN: We studied two samples from Rochester, Minnesota, which consisted of 772 asymptomatic subjects from the general population and 145 patients who underwent angiography, all of whom were 20 to 59 years of age. METHODS: Asymptomatic subjects were classified on the basis of their CAD risk profile. All subjects in both study samples underwent electron beam computed tomography. Age- and sex-specific calcium score percentiles were calculated in the asymptomatic sample. RESULTS: CAC prevalence in the asymptomatic subjects was lower in female than in male subjects and increased with advancing age. Of the asymptomatic sample, 8% had a low-risk profile with calcium scores in the top quartile of the distribution. More patients than expected in the angiography sample had calcium scores above the 50th through 95th score percentiles. CONCLUSION: The quantity of CAC was substantially increased in patients who underwent angiography. Subjects with large amounts of CAC but without known CAD risk factors may be a valuable subset of the population to investigate for previously unidentified CAD risk factors.

Adult↗
PubMed1994

Relation of coronary calcium determined by electron beam computed tomography and lumen narrowing determined by autopsy.

Coronary calcium determined by electron beam computed tomography (CT) has not been systematically evaluated regarding prediction of histopathologic atherosclerotic disease. Furthermore, gender specificity has not been examined. The 3 major epicardial arteries were dissected from 13 consecutive hearts (5 women and 8 men) after autopsy. Each artery was straightened and scanned using CT in contiguous 3 mm thick cross sections. After imaging, histologic sections were prepared at corresponding intervals and luminal area obstruction determined by planimetry. Electron beam CT scans were analyzed to determine coronary calcium area (i.e., tomographic area with CT density > 130 Hounsfield units). A total of 522 histologic specimens were examined and paired with corresponding CT scans (182 in women, 340 in men). Receiver-operating characteristic (ROC) analysis was used to define site specificity of calcium area for luminal area narrowing by atherosclerosis. ROC curve areas for segmental CT calcium and prediction of atherosclerosis representing mild, moderate, or severe disease were, respectively, 0.712, 0.843, and 0.857 for women and 0.732, 0.793, and 0.841 for men. Curves relating false-positive rate (1-specificity) to predefined degrees of atherosclerotic narrowing versus calcium area were curvilinear. In both women and men, calcium areas on the order of 1 mm2/coronary segment were necessary to predict at least mild atherosclerosis with a false-positive rate of 0% (i.e., 100% specificity), whereas a calcium area > 3 mm2 was necessary to predict the same result for severe disease. In conclusion, coronary artery calcium area as determined by electron beam CT has the potential to predict segmental histopathologic coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. The Kogenate Study Group.

Recent studies suggest that treatment of hemophiliacs with highly purified factor VIII concentrates may preserve immune function. To test this hypothesis, we prospectively studied 51 hemophilic patients (21 human immunodeficiency virus [HIV] seropositive and 30 seronegative) who were on home therapy exclusively with recombinant factor VIII (Kogenate, Miles Laboratory, Berkeley, CA) for 3.5 years. Patients, all of whom had been previously treated with plasma-derived factor VIII concentrates, were monitored every 6 months with T-lymphocyte subsets and beta 2-microglobulin levels. Mean rate of change in absolute CD4 cell counts, calculated from regression slopes for individual patients, showed a small but statistically significant decrease over the 3.5-year study period for HIV seropositive hemophiliacs. No decrease in CD4 cell counts was seen in HIV seronegative hemophiliacs when the data for children under age 6 years were excluded from the analysis. beta 2-microglobulin levels and CD8 cell counts remained unchanged. These data show stability of immunologic parameters in HIV seronegative hemophiliacs, and a small decrease in CD4 cell counts in HIV seropositive hemophiliacs treated with recombinant factor VIII.

CD4-Positive T-Lymphocytes↗
PubMed1994

Immunoglobulin V regions and the B cell.

There is now substantial evidence that a small group of V genes predominates in the Ig repertoire of preimmune B cells. This phenomenon of V gene restriction may reflect preferential accessibility of these genes to recombinase, homology-directed V gene rearrangement, promoters and enhances of V gene transcription, or positive and negative selection mediated by the anti-self binding properties of the B cells surface Ig. These mechanisms may operate alone or in combination to influence V gene rearrangement and populations of immature B cells. Although constraints on the pool of rearranged V genes may seem disadvantageous to the immune system, the mechanisms that generate the CDR3s of heavy and light chains ensure extensive diversity in the pre-B-cell population. In mature B cells, somatic mutation of V genes adds further diversity. CDR3 sequences and somatic mutations not only provide potentially useful clonal markers but also help to identify the normal counterparts of malignant B cells.

Animals↗