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Biomedical subjects

D Schwartz

Publications and source records attributed to D Schwartz.

At least 109 records · Page 6Linked to original sources
PubMed1998

Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group.

A safety and immunogenicity trial was conducted in vaccinia-immune and vaccinia-naive human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive 10(6) or 10(7) TCID50 of canarypox (ALVAC) vector expressing HIV-1MN gp160 or 10(5.5) TCID50 of ALVAC-rabies virus glycoprotein control at 0 and 1 or 2 months and ALVAC-gp160 or 50 microg of HIV-1SF2 recombinant (r) gp120 in microfluidized emulsion at 9 and 12 months; others received rgp120 at 0, 1, 6, and 12 months. All vaccines were well-tolerated. Neither vaccinia-immune status before vaccination nor ALVAC dose affected HIV immune responses. HIV-1MN and HIV-1SF2 neutralizing antibodies were detected more often (100%) in ALVAC-gp160/rgp120 recipients than in recipients of ALVAC-gp160 (<65%) or rgp120 (89%) alone. ALVAC-gp160/rgp120 also elicited more frequent HIV V3-specific and fusion-inhibition antibodies, antibody-dependent cellular cytotoxicity, lymphoproliferation, and cytotoxic CD8+ T cell activity than did either vaccine alone. Trials with ALVAC expressing additional HIV components and rgp120 are underway.

AIDS Vaccines↗
PubMed1998

Amiodarone induced pulmonary fibrosis in infancy.

We report a case of pulmonary fibrosis in an infant receiving amiodarone for treatment of intractable atrioventricular reentrant tachycardia secondary to Wolff-Parkinson-White syndrome. At 9 months, a screening chest radiograph showed a diffuse interstitial infiltrate in an asymptomatic, thriving infant. Amiodarone was discontinued and the pulmonary fibrosis resolved gradually over 6 months. This case documents the first report of amiodarone induced pulmonary fibrosis in the pediatric age group. We speculate that as amiodarone is used more frequently to manage pediatric arrhythmias, pulmonary fibrosis, a known complication of this antiarrhythmia in adults may be seen with increasing frequency in children.

Adrenergic beta-Antagonists↗
PubMed1998

Diagnosis of pulmonary tuberculosis using PCR assays on sputum collected within 24 hours of hospital admission.

There have been few studies evaluating the efficacy of polymerase chain reaction (PCR) testing in front-line clinical practice. We assessed the diagnostic yield of PCR prospectively in a blinded study of patients admitted to rule out tuberculosis and compared PCR results to a culture and clinical diagnosis of tuberculosis. Specimens were sent for routine smear, culture, and PCR analysis. Sputum sediments were submitted for PCR amplification of IS6110 sequences by an in-house assay and also the Roche Amplicor PCR assay targeting 16s ribosomal RNA genes. Eighty-five patients were enrolled: 27 patients had cultures positive for tuberculosis; 12 were smear-positive. PCR by both assays on the first specimen picked up all patients smear-positive on any specimen. A positive PCR on at least one of two specimens collected in the first 24 h was 85 and 74% sensitive and 88 and 93% specific for tuberculosis by the in-house and Roche techniques, respectively. Sensitivity in smear-negative patients was 73 and 53%, respectively. The in-house PCR detected 100% and Roche detected 95% of patients with more than paucibacillary (greater than 20 colonies) tuberculosis. We conclude that PCR may be a useful tool to evaluate patients for tuberculosis within the first hospital day.

Female↗
PubMed1998

Bayer Immuno 1 PSA Assay: an automated, ultrasensitive method to quantitate total PSA in serum.

The Bayer Immuno 1 PSA Assay measures total PSA in human serum and demonstrates excellent performance with an interassay CV < or = 3.4% and a biological detection limit of 0.03 microgram/L. No significant interference from common hormonal and chemotherapeutic drugs, kallikrein, prostatic acid phosphatase, and trypsin, or elevated levels of total bilirubin, hemoglobin, triglycerides, and IgG was observed. The 95th percentile values for healthy individuals increased with age from 3.0 micrograms/L for males 50-59 years and 3.3 micrograms/L for males 60-69 years, to 4.6 micrograms/L for males > or = 70 years. Clinical studies with retrospective samples demonstrated correspondence between serial measurements of PSA and clinical outcome for 98% of 159 prostate cancer patients. Clinical sensitivity for patients with clinical evidence of disease, untreated at the time of specimen draw, increased with increasing stage from 77.5-100%. Specificity of 60-70% for BPH and other benign urogenital diseases was consistent with previous findings. Bayer Immuno 1 PSA Assay values for 2131 specimens from healthy subjects and patients with prostate cancer, BPH, and other malignant and nonmalignant diseases correlated well with the Abbott IMx PSA Assay over the range 0.0-6,238 micrograms/L (Y = 1.10 x + 0.02). The Bayer Immuno 1 PSA Assay provides automated ultrasensitive, precise, and equimolar measurement of total PSA in human serum.

Aged↗
PubMed1998

Alternatively spliced mRNA transcripts encoding the extracellular domain of the FSH receptor gene. Expression in the mouse ovary during the ovulatory cycle.

OBJECTIVE: To evaluate regulation of follicle-stimulating hormone (FSH) receptor expression in the mouse ovary during different stages of an artificially induced ovulatory cycle. STUDY DESIGN: Follicular maturation was achieved in pubertal female mice by pregnant mares' serum gonadotropin (PMSG). Ovulation was induced 48 hours later by human chorionic gonadotropin (hCG). Ovaries were harvested before treatment, at 24 and 48 hours after PMSG and at 3, 9 and 12 hours after hCG. RNA was extracted using a single-step isolation method and used for reverse transcription. The cDNA was amplified by polymerase chain reaction (PCR) using primers designed to amplify a 512-basepair product corresponding to the extracellular fragment of the FSH receptor. RESULTS: PCR products, resolved by electrophoresis on agarose gels, showed four bands corresponding to four discrete, alternatively spliced forms of the FSH receptor. Expression of the various transcripts varied at different stages of the ovulatory cycle such that the larger transcripts increased up to 48 hours following PMSG and began to decrease thereafter, reaching a trough 12 hours following hCG administration. Conversely, a smaller transcript reached a peak 9 hours following hCG administration and decreased thereafter. CONCLUSION: The various transcripts represent different FSH receptor mRNA splicing and may mediate changes in receptor function. Since these alternative spliced forms encode different portions of the extracellular domain, it is possible that they have altered hormone-binding affinity serving a regulatory purpose, such as decreasing hormone binding affinity.

Alternative Splicing↗
PubMed1997

Role of wild type p53 in the G2 phase: regulation of the gamma-irradiation-induced delay and DNA repair.

Upregulation of the p53 protein was shown to induce cell cycle arrest at the G1/S border and in some cases at the G2/M border. Furthermore, it was suggested that p53 is associated with the induction of the various DNA repair pathways. Previously, we demonstrated that cells co-expressing endogenous wild type p53 protein, together with dominant negative mutant p53, exhibit deregulation of apoptosis, G1 arrest and delay in G2 following gamma-irradiation. In the present study, we investigated the role of p53 protein in the DNA damage response at the G2 phase. Using p53-null, wild type p53 and mutant p53-producer cell lines, we found that the two C-terminally spliced p53 forms could prevent gamma-irradiation induced mutagenesis prior to mitosis, at the G2/M checkpoint. We found that at the G2 phase, p53 may facilitate repair of DNA breaks giving rise to micronuclei, and regulate the exit from the G2 checkpoint. At the G1 phase, only the regularly spliced form of p53 caused growth arrest. In contrast, both the regularly and the alternatively spliced p53 forms directed postmitotic micronucleated cells towards apoptosis. These results provide a functional explanation for the cell cycle-independent expression of p53 in normal cycling cells, as well as in cells where p53 is up-regulated, following DNA damage.

Animals↗
PubMed1997

Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats.

Excess NO generation plays a major role in the hypotension and systemic vasodilatation characteristic of sepsis. Yet the kidney response to sepsis is characterized by vasoconstriction resulting in renal dysfunction. We have examined the roles of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the renal effects of lipopolysaccharide administration by comparing the effects of specific iNOS inhibition, -N6-(1-iminoethyl)lysine (L-NIL), and 2,4-diamino6-hydroxy-pyrimidine vs. nonspecific NOS inhibitors (nitro- -arginine-methylester). cGMP responses to carbamylcholine (CCh) (stimulated, basal) and sodium nitroprusside in isolated glomeruli were used as indices of eNOS and guanylate cyclase (GC) activity, respectively. LPS significantly decreased blood pressure and GFR (112+/-4 vs. 83+/-4 mmHg; 2.66+/-0.29 vs. 0. 96+/-0.22 ml/min, P < 0.05) and inhibited the cGMP response to CCh. GC activity was reciprocally increased. L-NIL and 2, 4-diamino-6-hydroxy-pyrimidine administration prevented the decrease in GFR (2.71+/-0.28 and 3.16+/-0.18 ml/min, respectively), restored the normal response to CCh, and GC activity was normalized. In vitro application of L-NIL also restored CCh responses in LPS glomeruli. Neuronal NOS inhibitors verified that CCh responses reflected eNOS activity. L-NAME, a nonspecific inhibitor, worsened GFR (0.41+/-0.15 ml/min), a reduction that was functional and not related to glomerular thrombosis, and eliminated the CCh response. No differences were observed in eNOS mRNA expression among the experimental groups. Selective iNOS inhibition prevents reductions in GFR, whereas nonselective inhibition of NOS further decreases GFR. These findings suggest that the decrease in GFR after LPS is due to local inhibition of eNOS by iNOS, possibly via NO autoinhibition.

Animals↗
PubMed1997

Arterial thrombosis induces early upregulation of intercellular adhesion molecule in the media.

PURPOSE: Thrombosed peripheral vessels that are pharmacologically or mechanically recanalized have diminished long-term patency rates compared with vessels that are repaired before occlusion. We hypothesized that thrombosis induces proinflammatory changes in the arterial media that may contribute to postthrombotic vascular remodeling. METHODS: We studied expression of intercellular adhesion molecule (ICAM), a mediator of leukocyte recruitment, in the arterial wall after thrombosis. Thrombosis was induced in rabbit superficial femoral arteries by embolizing polystyrene beads (Thr-emb) or by ligation (Thr-lig). Control vessels were dissected but not ligated (C-dis) or were subjected to bead embolization and immediate removal (C-emb). Arterial wall ICAM expression was measured by indirect immunohistochemical analysis at 6 hours, 24 hours, and 1 week. Staining intensity was graded from 0 (none) to 4 (intense) by observers who were blinded to the experimental conditions. RESULTS: No increase in ICAM expression by thrombosed vessels was present at 6 hours. After 24 hours, ICAM expression in the media of thrombosed vessels was increased (Thr-emb, 2.3 +/- 0.5; Thr-lig, 2.0 +/- 0) compared with control vessels (C-dis, 0 +/- 0; C-emb, 0.8 +/- 0.5; p < 0.004). This difference became more marked at 1 week. ICAM staining localized to actin-staining regions of the media. CONCLUSIONS: Arterial thrombosis, but not surgical injury, induces pronounced early and sustained upregulation of ICAM expression in smooth muscle-containing regions of the arterial media. Upregulation of ICAM is likely to promote recruitment of inflammatory cells or mediate vascular remodeling after luminal thrombosis.

Animals↗
PubMed1997

Nuclear antigen expressed by proliferating cells.

We describe a novel mouse monoclonal antibody (PRA-72) that recognizes a nuclear antigen associated with cell proliferation. The monoclonal antibody stained the nuclei of logarithmically growing cultured stromal cells. The nuclear staining disappeared when these cells entered Gzero phase of the cell cycle. Western blot analysis revealed a nuclear protein which appeared as a doublet at 35-40 KD, which was undetectable in extracts from confluent cells. Immunocytological study of purified cell populations from various cell cycle phases revealed peripheral nuclear staining in all stages except mitosis, when the chromosomes were observed enveloped with the antigen. In co-cultures of quiescent stromal cells and proliferating hemopoietic precursors, only the latter showed nuclear staining by PRA-72 monoclonal antibody. Further indications for selective expression of the antigen by proliferating cells were found by an immunohistochemical study of various tissues including newborn mouse bone marrow and its surrounding connective tissue, mouse tongue epithelium, and human carcinoma of the colon. This antibody may, therefore, prove useful in the evaluation of human tumors.

Adenocarcinoma↗
PubMed1997

The murine C'-terminally alternatively spliced form of p53 induces attenuated apoptosis in myeloid cells.

The onset of p53-dependent apoptosis results from the accumulation of damaged DNA. Recently, it was shown that the C' terminus of the p53 protein plays a central role in sensing damaged DNA. In our present study, we examined the role of the C' terminus in the induction of apoptosis. A temperature-sensitive (ts) mutant of the alternatively spliced form of p53 (p53AS-ts) and the ts mutant of the regularly spliced form (p53RS-ts) were used to generate series of stable clones with increasing amounts of p53 protein. Apoptotic patterns induced by either the regularly spliced p53 product (p53RS) or a C'-terminally alternatively spliced p53 product (p53AS) were compared. We found that although both forms of p53 induced apoptosis following expression of the wild-type protein conformation, the kinetics were different. Apoptosis induced by the p53AS protein was attenuated compared to that induced by p53RS. The delay in the manifestation of the apoptotic features following p53AS expression was in agreement with a delay in the regulation of the expression of apoptosis-related genes. The observation that p53 with an altered C' terminus is still capable of inducing apoptosis suggests that the actual onset of the apoptotic process most probably involves structural domains other than the C' terminus of the p53 molecule. However, the fact that the apoptotic activity mediated by the p53AS product was slower than that mediated by the p53RS product suggests that the C' terminus indeed exerts a certain control on the apoptotic activity of the p53 molecule.

Alternative Splicing↗
PubMed1997

Retinal detachment in AIDS: long-term results after repair with silicone oil.

AIMS: To study the long-term results of vitrectomy and silicone oil injection in AIDS patients with retinal detachment due to viral retinitis. METHODS: A consecutive series of 83 eyes in 75 AIDS patients who were treated with vitrectomy and silicone oil for retinal detachment due to viral retinitis was studied prospectively and followed until the last patient in the series had died. RESULTS: Median postoperative survival was 6 months, but 20% of patients survived 12 months or more. Whereas best corrected visual acuity was 20/100 or better in over half the patients 1-2 months after operation, there was a distressing decrease in acuity by 6 months, owing to a variety of factors. Patients operated on before macular detachment did not have significantly better postoperative vision than those operated within a week after macular detachment. Almost all patients who had already lost vision in the fellow eye and many who had cytomegalovirus retinitis in the fellow eye with retention of good vision had their quality of life improved by the surgery in that the operated eye eventually became the better seeing eye. In no patient whose fellow eye was normal and free of retinitis, however, did the operated eye ever become the better eye. CONCLUSIONS: Although the majority of patients recovered macular vision in the first 1-2 months after operation, there was a gradual decline in acuity thereafter, sometimes without obvious cause. The results of this series suggest that it may be reasonable to postpone surgery until the macula detaches and that patients whose fellow eye is free of retinitis with normal vision are unlikely to have their quality of life improved significantly by the surgery.

AIDS-Related Opportunistic Infections↗
PubMed1997

Agmatine affects glomerular filtration via a nitric oxide synthase-dependent mechanism.

Arginine decarboxylase is present in the kidney and metabolizes the amino acid, arginine, to agmatine. Agmatine increases filtration rate in single nephrons (J. J. Lortie, W. F. Novotny, O. W. Peterson, V. Vallon, K. Malvey, M. Mendonca, J. Satriano, P. Insel, S. C. Thomson, and R. C. Blantz. J. Clin. Invest. 97:413-420, 1996). Experiments were conducted to determine whether exogenously administered agmatine exerts these effects via interaction with nitric oxide synthase (NOS) and whether this interaction depends upon alpha 2-adrenergic receptors. Agmatine microperfused (1 microM) into the urinary space of surface glomeruli of the rat increased nephron filtration rate from 33 +/- 4 to 40 +/- 5 nl/min with complete recovery within 10 min. When NG-monomethyl-L-arginine (L-NMMA), a nonselective NOS inhibitor, was systemically infused, agmatine no longer increased single-nephron glomerular filtration rate (SNGFR). BHT-933, an alpha 2-adrenergic agonist, did not increase SNGFR and was unaffected by concurrent L-NMMA. In vitro incubation of freshly harvested glomeruli with agmatine resulted in significant increases in the generation of cGMP, effects similar to carbachol, and blocked by nitro-L-arginine methyl ester (L-NAME) but not yohimbine, an alpha 2-adrenergic antagonist. Agmatine exerts effects on glomerular ultrafiltration via a constitutive NOS-dependent mechanism, and this does not require the participation of alpha 2-adrenoreceptors.

Agmatine↗
PubMed1997

Differential expression of the regularly spliced wild-type p53 and its COOH-terminal alternatively spliced form during epidermal differentiation.

In the present study, we investigated the role of p53 in the differentiation of epidermal keratinocyte cells. The interrelationship between p53 expression and the various stages of epidermal differentiation and the role of the COOH terminus of the p53 molecule in this process were determined by comparing the expression of the regularly spliced p53 (RSp53) molecule and that of the COOH-terminal alternatively spliced (ASp53) form. p53 mRNA distribution was studied by in situ analysis of frozen skin sections and by reverse transcription-PCR analysis of the various wild-type p53 forms expressed in neonatal skin cell fractions separated by Percoll gradient. p53 protein levels were measured by fluorescence-activated cell sorting analysis and immunohistochemistry, using antibodies that recognize either the COOH terminus of RSp53 or ASp53. The results show that although less mature keratinocyte cells predominantly express the RSp53 form, the more mature cells preferentially express the ASp53 form. Therefore, it is possible that the two p53 forms are associated with different functions required at the various stages of keratinocyte differentiation. The results suggest that the COOH-terminal domain of the p53 molecule is important for its activity in the process of keratinocyte differentiation.

Alternative Splicing↗