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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 127 records · Page 7Linked to original sources
PubMed1997

The early socialization of aggressive victims of bullying.

This study reports the first prospective investigation of the early family experiences of boys who later emerged as both aggressive and bullied (i.e., aggressive victims) during their middle childhood years. It was hypothesized that a history of violent victimization by adults leads to emotion dysregulation that results in a dual pattern of aggressive behavior and victimization by peers. Interviews with mothers of 198 5-year-old boys assessed preschool home environments. Four to 5 years later, aggressive behavior and peer victimization were assessed in the school classroom. The early experiences of 16 aggressive victims were contrasted with those of 21 passive (nonaggressive) victims, 33 nonvictimized aggressors, and 128 normative boys. Analyses indicated that the aggressive victim group had experienced more punitive, hostile, and abusive family treatment than the other groups. In contrast, the nonvictimized aggressive group had a history of greater exposure to adult aggression and conflict, but not victimization by adults, than did the normative group, whereas the passive victim group did not differ from the normative group on any home environment variable.

Adult↗
PubMed1996

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina. A multicenter trial.

BACKGROUND: Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. METHODS AND RESULTS: Patients were randomized to one of two doses of heparin (n = 50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n = 113) (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg.kg-1.h-1 r-hirudin regimens were significantly lower than with 0.05 mg.kg-1.h-1 r-hirudin; levels with 0.1- to 0.2-mg.kg-1.h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg.kg-1.h-1 hirudin. At 24 hours, they were higher with the 0.05-mg.kg-1.h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. CONCLUSIONS: Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.

Angina, Unstable↗
PubMed1996

The role of p53 in the induction of polyploidity of myelomonocytic leukemic M1/2 cells.

p53 was shown to play a central role in the maintenance of genomic integrity. The present experiments suggest that p53 is involved in the control of cell ploidity. Using a p53 non-producer cell line, M1/2, that was reconstituted to express either wild type or mutant p53 protein, by infection with the temperature sensitive (Ts) p53Val135 virus, it was found that both loss of wild type p53 or overexpression of mutant p53, may be associated with the generation of cell polyploidity. Overexpression of mutant p53 protein enhanced the appearance of giant cells that further accumulated following gamma-irradiation. Expression of wild type p53 reduced the level of giant cells which accumulated in the parental M1/2 p53 non-producer cells following gamma-irradiation. This activity of the wild type p53 seems to be mediated by either the reduction in the rate of giant cell generation, as observed in M1/2 derived cell lines expressing low levels of wild type p53 protein or by facilitating their apoptosis, as observed in wild type p53 high-producer cells. The latter conclusion is further supported by the observation that isolated giant cells are directly induced to undergo apoptosis following wild type p53 expression.

Animals↗
PubMed1996

HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.

In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.

B-Lymphocytes↗
PubMed1996

Human erythrocytes bearing electroinserted CD4 neutralize infection in vitro by primary isolates of human immunodeficiency virus type 1.

Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Prediction of renal impairment in elderly patients with congestive heart failure treated with captopril.

This study assessed the usefulness of the oral captopril test in the prediction of renal impairment among elderly patients with congestive heart failure (CHF). Forty-seven patients aged > or = 65 years with CHF (EF < 40%) participated in a prospective nonrandomized series. Blood samples for plasma renin activity (PRA) were drawn before and 60 minutes after 50 mg of oral captopril. Twenty-four hours later, captopril was administered (up to 75 mg/day over a 4 day period), and renal laboratory and clinical assessment were performed at baseline and for a 9 day period. In 7 of 47 patients (14.9%), deterioration of renal function was observed. During the captopril test, the PRA increased significantly after 1 hour in almost all patients and the mean blood pressure decreased from 99.2 +/- 14.6 mmHg to 92.2 +/- 13.7 mmHg (p < 0.001). All patients whose baseline PRA level was < 1.9 ng/ml/hr and whose stimulated PRA was < 3.2 ng/ml/hr maintained a stable renal function throughout the study period. Significant statistical correlation (p < 0.05) was found between the initial PRA, the changes in PRA or mean blood pressure during the captopril test, and the change in plasma creatinine and creatinine clearance in the entire group, and was even more evident in a subgroup of patients with an ejection fraction > or = 30%. All these correlations were not statistically significant in the patients with an ejection fraction < 30%. It is thus concluded that measurement of pretreatment PRA levels might be a useful laboratory tool for predicting the renal safety of captopril use in patients with CHF whose EF > or = 30%.

Administration, Oral↗
PubMed1996

Intestinal bypass of the esophagus.

Esophageal replacement by a segment of isoperistaltic ileum with cecum or by transverse or left colon will allow near-normal swallowing for many years. The authors reviewed the course of 59 children who had bypass of their entire esophagus and of four whose distal esophagus was resected and replaced. The follow-up period ranges from 1 to 37 years; in 36 cases, it exceeds 5 years. Thirty children had caustic strictures and 25 had either isolated esophageal atresia or atresia with fistula. Two children with esophageal injury caused by foreign body ingestion and two with congenital strictures also required complete bypass. Four patients required resection and replacement of the distal esophagus only; two had acquired strictures from gastroesophageal reflux, one had varices, and one had a teratoma involving the esophagus. A retrosternal isoperistaltic ileocolic segment is our preference for complete esophageal replacement. Forty-eight patients underwent esophageal reconstruction with this procedure. The esophagus damaged by caustic ingestion was left in place in all patients, without any subsequent problem. The authors have not used the distal esophagus for anastomosis in patients with atresia, because this segment may be abnormal; and, in any case, an isoperistaltic cologastric anastomosis does not reflux. The right or left colon or jejunum was used in the other cases. Three children lost an interposed intestinal segment from necrosis even though the bowel appeared to be well vascularized at the end of the operation. Each patient had successful reconstruction using another type of interposition. An intrathoracic leak occurred in one infant. A cervical anastomotic leak developed in 11 children, and a stricture in 13. Strictures were more common in patients who had caustic burns. Three patients required surgery for adhesive intestinal obstruction. A redundant colon transplant with ulceration, and the herniation of an ileal segment into the pleural cavity with obstruction prompted reoperation in two other patients. There were two deaths early in the series, one of which was secondary to postoperative respiratory arrest. The other death occurred in a child who had a caustic pharyngeal burn and chronic aspiration. All patients were seen in our office recently, or they or their parents were interviewed by phone. All of them are taking all of their nutrition by mouth. Forty-three of the 61 survivors have had no difficulty with swallowing. One required reoperation to enlarge the thoracic inlet. Seventeen other have mild dysphagia that does not require treatment. The patients with esophageal atresia or atresia and fistula consistently have not grown as well as those who required replacement for an acquired condition or injury.

Burns, Chemical↗
PubMed1996

Long-term dual perfusion of isolated human placental lobules with improved oxygenation for infectious diseases research.

An improved method for long-term perfusion of the isolated human term placental lobule has been developed to investigate the maternofetal transfer of infectious agents, in particular the human immunodeficiency virus (HIV). The purpose of this paper is to describe those modifications that allow for substantially prolonged perfusions in in a biohazard environment. The method described has been adapted from previous models. The perfusion apparatus has been modified for use within a biohazard hood, and, intravenous bags contain the medium for circulation of perfusates in closed circuits. A Mera Silox-S 0.3 membrane oxygenator delivers more oxygen to the tissue, and, Electromedic Cardioplegia heat exchangers warm the perfusate prior to oxygenation. Viability criteria (glucose consumption, lactate production, de novo production of human placental lactogen (hPL), volume loss, flow, temperature, pressure, oxygen transfer, carbon dioxide production, absence of IgM transfer and light and electron microscopy) demonstrate that the placental tissue remains in a functional state throughout the perfusion. Oxygen and glucose consumption are both stable over time; lactate levels remain constant; and hPL continues to be produced. These significant modifications of the perfusion system have permitted the investigators to increase the duration of perfusion to 48 h while preserving normal metabolic function of ultrastructurally intact tissue as demonstrated by ultra structural observations. This perfusion model device provides biohazard precautions and may be applied to other studies of placental physiology.

Carbon Dioxide↗
PubMed1996

Invasive ability of C. jejuni/coli isolates from children with diarrhea and the effect of iron-regulated proteins.

The invasive ability of C. jejuni/coli strains isolated from children with diarrhea was studied using an in vitro HEp-2 cell invasion assay. The ratio between the number of intracellular bacteria and the number of bacteria in the inoculum was determined (invasion index). It was found that under anaerobic conditions, there was a significant decrease in the invasion index as compared to standard conditions (5% CO2). Of 11 strains tested, seven were determined as invasive on the basis of invasion indexes within the range of 0.0002-0.01. In a previous study [D. Schwartz et al., Zbl. Bakt. 280, 338-347 (1994)], it was found, that most of the C. jejuni/coli isolates tested produced an outer membrane protein when grown under conditions of iron depletion (IRP). The IRP were detected in eight of the nine strains tested in the present study (five invasive and three non-invasive strains). In one non-invasive strain, IRP was not detected. When kept under conditions of iron depletion, one of the invasive strains exhibited a significant increase in invasive capacity. The results suggest that iron depletion seems to stimulate the invasion capacity of C. jejuni/coli in vitro.

Bacterial Adhesion↗
PubMed1996

Induction of apoptosis and p53 expression in immature thymocytes by direct interaction with thymic epithelial cells.

Apoptosis of normal thymocytes was shown to be triggered by several mechanisms (e.g. glucocorticoids, gamma-irradiation). In the present study the authors report on thymocyte apoptosis that is induced by thymic epithelial cells. The thymocytes undergo a massive apoptotic death within 24 h of cocultivation with thymic epithelial cell monolayers derived from primary cultures (PTEC) or from a thymic epithelial cell line (TEC). Non-thymic monolayers were inactive. Apoptosis induction in this experimental model requires direct contact between the thymocytes and the thymic epithelial monolayer and can be blocked by anti-CD2 and anti-LFA-1 antibodies. The immature CD3-/+dull CD4+CD8+ thymocytes were the cells which undergo apoptosis. The fact that the authors are dealing with a massive apoptotic process of immature cells in the absence of exogenous antigen suggests that it involves the nonselected thymocytes. The apoptotic pathway selected by thymocytes following their culturing on TEC involves p53 expression. Indeed it was found that TEC-induced apoptosis, led to the accumulation of p53 protein that preceded the step of DNA fragmentation in freshly isolated thymocytes as well as in a glucocorticoid resistant thymoma cell line. Since glucocorticoid-induced thymocyte apoptosis is p53-independent, glucocorticoids are conceivably not involved in TEC-induced thymocyte death. The in vitro experimental model presented here may reflect the physiological sequence of events leading to thymocyte death in the thymus.

Animals↗
PubMed1996

The peptide synthetase gene phsA from Streptomyces viridochromogenes is not juxtaposed with other genes involved in nonribosomal biosynthesis of peptides.

By complementation of a previously described non-phosphinothricin tripeptide (PTT)-producing mutant, NTG1, which is blocked in nonribosomal synthesis of the peptide, a DNA fragment including the putative peptide synthetase gene phsA was isolated (W. Wohlleben, R. Alijah, J. Dorendorf, D. Hillemann, B. Nussbaumer, and S. Pelzer, Gene 115:127-132, 1992). Sequence analysis of phsA revealed that it encodes a protein of 622 amino acids with regions which are highly similar to core motifs characteristic for peptide synthetases. PhsA represents one functional domain of a peptide synthetase which is necessary for activation and condensation of one amino acid, probably N-acetyl-demethyl-phosphinothricin. With regard to the arrangement of the flanking genes, phsA is the first peptide synthetase gene which is not in the direct neighborhood of additional peptide synthetase genes involved in the formation of peptide antibiotics. Gene disruption mutants with internal fragments of phsA subcloned in temperature-sensitive pGM vectors were generated. Integration occurred either into the chromosomal copy of phsA or into a gene outside the known phsA locus, resulting in two classes of non-PTT-producing mutants. In cofeeding experiments the former phsA mutants showed the same phenotype as did NTG1, which confirmed participation of phsA in nonribosomal synthesis of PTT. A truncated phsA gene was overexpressed in Escherichia coli, and the resulting protein of 593 amino acids was purified for raising antibodies. By performing immunoblotting experiments, the expression of phsA could be detected in Streptomyces viridochromogenes Tü494 in the stationary-growth phase after 4 days of incubation.

Amino Acid Sequence↗
PubMed1996

Proliferating arterial smooth muscle cells after balloon injury express TNF-alpha but not interleukin-1 or basic fibroblast growth factor.

We have recently reported that balloon withdrawal injury to rabbit abdominal aortas induces sustained activation indicated by the expression of certain adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in regenerating endothelial cells and/or proliferating smooth muscle cells (SMCs). Local cytokine signaling may contribute to ongoing modulation of cellular functions and proliferation of intimal SMCs after acute vascular injury. We therefore studied the expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), proinflammatory and SMC growth-promoting cytokines, and basic fibroblast growth factor (bFGF) in SMCs of rabbit aorta at 2 (n = 4), 5 (n = 4), and 10 days (n = 6) after balloon injury. All animals were given bromodeoxyuridine (BrdU, 10 mg/kg per day) continuously to label proliferating SMCs. Frozen cross sections of injured vessels at each time point after balloon injury were examined by immunoperoxidase staining with monoclonal antibodies. As early as 2 days after injury, before intimal thickening begins, foci of medial SMCs expressed TNF-alpha, but not all TNF-alpha-positive medial SMCs had incorporated BrdU, suggesting that TNF-alpha expression by medial SMCs may precede their proliferation. At 5 days, TNF-alpha-bearing and BrdU-labeled medial SMCs increased in number. At 10 days after injury, when uniform intimal thickening occurred, almost all neointimal SMCs and foci of medial SMCs labeled with BrdU. Most of the BrdU-positive (proliferating) SMCs expressed immunoreactive TNF-alpha. Reverse transcription polymerase chain reaction showed increased TNF-alpha mRNA at 10 days after ballooning in the injured portion of the aorta. In contrast, regions of SMC proliferation showed inconsistent IL-1 beta expression, and bFGF, abundant in normal rabbit arteries, was not detected in areas of SMC replication. These data indicate that replication of arterial SMCs after balloon injury occurs in regions of TNF-alpha but not IL-1 beta expression and correlates inversely with the presence of bFGF. These results indicate that SMC-derived TNF-alpha serves as a marker of modulated SMC phenotype after acute vascular injury and may contribute to local cellular activation and proliferation of SMCs at sites of arterial injury.

Animals↗
PubMed1996

24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study.

Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

Induction of HL-60 cells to undergo apoptosis is determined by high levels of wild-type p53 protein whereas differentiation of the cells is mediated by lower p53 levels.

The observation that wild-type p53 may induce cells to undergo either apoptosis or differentiation raises the question of whether these two events share similar p53-dependent pathways. To evaluate the interrelationship between these two p53-dependent processes, our study focused on the human HL-60, a promyelocytic p53 nonproducer cell line in which p53 expression was introduced and the induction of apoptosis and differentiation was followed under controlled conditions. p53 expression was induced in the HL-60 cell line by infection with the recombinant wild-type p53 (p53WT) vaccinia virus. Viral infection gave rise to cells expressing various levels of wild-type p53 protein. High levels of p53 protein induced cells to undergo rapid apoptosis, whereas lower levels of p53 protein induced cells to undergo cell differentiation at a more moderate rate of kinetics. These results suggest that p53 protein levels may determine whether a given cell should prefer one pathway over the other to exit the cell cycle. Accordingly, we propose that the p53 vaccinia virus may be used as a potential vector for cell therapy leading toward the exit of p53 null human primary hematopoetic tumors from the malignant state in vivo via the apoptotic or cell differentiation pathways.

Apoptosis↗
PubMed1996

[Aortopulmonary window: influence of associated cardiovascular lesions on surgical management].

Aortopulmonary (AP) window is an uncommon cardiac anomaly which is frequently associated with other cardiac anomalies. Concomitant repair of all intra- and extracardiac anomalies is usually recommended. Between October 1993 and July 1994, 4 patients aged 37 days, 4 weeks, 3.5 and 1.5 years, respectively, underwent repair of AP window and associated malformations. The associated anomalies consisted of interrupted aortic arch (IAA), and atrial and ventricular septal defects in the 1st patient, patent ductus arteriosus in the 2nd, inlet ventricular septal defect in the 3rd and congenital narrowing of the right pulmonary artery and a patent foramen ovale in the 4th. Extreme metabolic acidosis after repair of IAA in the 1st, dictated ligation of the AP window before repair of the intracardiac anomalies at 2 months of age. In the 2nd and 3rd, repair of the window and associated anomalies was performed in a single stage. In the 4th, left pulmonary artery banding preceded complete repair. All patients are doing well at 18, 13, 12 and 11 months, respectively, of follow-up after their last operation. Surgical management of AP window may have to be staged according to the physiological influence of the associated anomalies in each patient, to minimize the cumulative risk of complete repair.

Abnormalities, Multiple↗