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Biomedical subjects

J Abrams

Publications and source records attributed to J Abrams.

At least 37 records · Page 2Linked to original sources
PubMed1991

Clinical aspects of nitrate tolerance.

Tolerance to the organic nitrates is a vexing problem. Tolerance is clearly avoidable with the employment of appropriate and well-designed dosing regimes, utilizing fewer doses and/or a nitrate-free interval. The emerging story of thiol donors and ACE inhibition to prevent tolerance is as yet incomplete. Hopefully, future research will provide the clinician with additional modalities to eliminate the threat of nitrate attenuation. The organic nitrates are superb drugs whose potential usefulness in cardiovascular medicine is clearly limited by nitrate tolerance. While the mechanisms involved in producing vascular smooth muscle attenuation are complex and multiple, it appears that we will be able to resolve this problem in the future, increasing the remarkable benefits of these drugs for patients around the world.

Cardiovascular Diseases↗
PubMed1991

Production of granulocyte/macrophage-colony-stimulating factor by human natural killer cells. Modulation by the p75 subunit of the interleukin 2 receptor and by the CD2 receptor.

Resting natural killer (NK) cells express the p75 chain of the IL-2 receptor (IL-2R beta) and most NK cells express the CD2 (erythrocyte rosette) receptor. The cell adhesion molecule, LFA-3, is a natural co-ligand for CD2. Tac antigen (IL-2R alpha), a p55 IL-2R subunit, can be expressed after NK activation and may play a role in IL-2-induced NK proliferation. Little is known of the molecular mechanisms underlying cytokine production in NK cells. We investigated the roles of IL-2R alpha, IL-2R beta, and CD2/LFA-3 in the molecular regulation of NK cell granulocyte/macrophage-colony-stimulating factor (GM-CSF) production. Enriched populations of peripheral blood NK cells were separated into CD16-positive and CD16-negative fractions by flow cytometry; positively selected cells were greater than 97% positive for CD16 (the FcIII receptor for IgG which is present on almost all NK cells), less than 1% positive for the T cell antigen CD3, and did not demonstrate rearrangement of the T cell receptor beta chain gene by Southern blot. NK cell supernatants were harvested after 3-4 d of incubation with 0-100 U/ml IL-2, or after incubation with anti-CD2 (T11(3] MAb and sheep red blood cells (SRBC are a homologue for LFA-3). Parallel cell aliquots were harvested at 3-16 h for transcriptional run-on assays, S1 nuclease assays, and actinomycin D mRNA t1/2 determinations. IL-2-activated NK supernatants contained large amounts of GM-CSF (178 +/- 35 pg/ml) by ELISA as did supernatants from CD2-activated NK cells (T11(3) MAb + SRBC: 212 +/- 42) vs. less than 20 pg/ml for NK cells incubated alone or with either SRBC or T11(3) MAb alone. Sepharose-linked anti-CD3 MAb did not induce GM-CSF release from NK cells. By S1 analysis, both IL-2 and CD2 stimulation markedly augmented GM-CSF mRNA expression but with very different latencies of onset. IL-2R beta MAb inhibited greater than 85% of GM-CSF release from IL-2-activated NK cells and markedly suppressed IL-2-induced GM-CSF mRNA expression, whereas IL-2R alpha MAb even at 2,000-fold molar excess of IL-2 had little effect (less than 10%) on either GM-CSF release or mRNA expression. Run-on assays showed that GM-CSF is constitutively transcribed in NK cells and that IL-2 and CD2-activated cells had a three- to fourfold increased rate of GM-CSF transcription compared to nonstimulated cells. The t1/2 of GM-CSF mRNA in IL-2-activated NK cells was identical to that of unstimulated NK cells (15 min), whereas GM-CSF mRNA t1/2 in CD2-activated NK cells was increased 2.5-fold. We conclude that GM-CSF production in NK cells is regulated by both the IL-2Rbeta and the CD2 receptor but not by IL-2Ralpha, that both transcriptional and posttranscriptional signals act together to modulate the level of GM-CSF mRNA in NK cells, and that the molecular mechanisms underlying NK cell GM-CSF production are dependent in part on differential surface receptor activation.

Adult↗
PubMed1991

Recipient race does not influence waiting time for a cadaveric renal transplant--one organ procurement organization's experience.

There was no statistical significance to the differences in waiting time for cadaveric renal transplant by race. Whether for first transplant or second or greater, any differences in waiting time could not be accounted for by the recipient's race. CAUC made up 58% of the waiting list, 65% of the recipients, and 87% of the donors. The corresponding numbers for AA are: 38%, 29%, and 10%, respectively. More regional serum-sharing trays may be needed in order to expose recipients with high PRA to as many donors as possible in order to lessen their waiting time. It should be noted that fewer HLA mismatches occurred when donor and recipient race were identical. In light of this data, more study is needed to determine the relationship between donor and recipient race, corresponding HLA mismatches, and graft survival. If antigen-matching is found to increase graft survival, then an increase in minority donations will be required. Until that time, under the current allocation system and with the predominance of Caucasian donors, it is likely that Afro-Americans will continue to receive kidneys that have more HLA antigen mismatches than if Afro-Americans donated in numbers equivalent to their percentage of the waiting list.

Adult↗
PubMed1991

Estrogen replacement for the 1990s.

The benefits of ERT outweigh the potential disadvantages and risks for the majority of menopausal and postmenopausal women. The preventive measures described for premenopausal women should benefit their cardiovascular and skeletal systems.

Estrogen Replacement Therapy↗
PubMed1990

Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia.

The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

Base Sequence↗
PubMed1990

Host-reactive CD4+ and CD8+ T cell clones isolated from a human chimera produce IL-5, IL-2, IFN-gamma and granulocyte/macrophage-colony-stimulating factor but not IL-4.

In the present study, we investigated the lymphokine production patterns in a series of CD4+ and CD8+ host-reactive T cell clones isolated from PBL of a SCID patient, who was immunologically reconstituted by two allogeneic fetal liver and thymus transplantations 13 years ago. We demonstrate that these donor-derived T cell clones, specifically reacting with the MHC Ag expressed on the recipient cells, do not produce IL-4 and do not express IL-4 mRNA upon Ag or polyclonal stimulations. In contrast, CD4+ tetanus toxin-specific T cell clones isolated from the same patient and having the same HLA phenotype produced normal amounts of IL-4 upon activation. These data suggest that the failure to produce IL-4 is a specific characteristic of these host-reactive clones and is not due to a genetic defect of the transplanted cells. Furthermore, different modes of activation resulted in simultaneous production of IL-5, IL-2, IFN-gamma, granulocyte/macrophage-CSF, and transcription of the TNF-beta gene by the host-reactive clones, indicating that the lack of IL-4 production is not related to the mode of activation. The finding that some of these clones produce significant levels of IL-5 but no IL-4 indicates that the IL-4 and IL-5 genes are not always coexpressed in activated human T cells.

Antigens, CD↗
PubMed1990

APACHE II score does not predict multiple organ failure or mortality in postoperative surgical patients.

A clinical study was undertaken to evaluate the ability of the APACHE (acute physiology and chronic health care) II system to predict the development of multiple organ failure syndrome and subsequent mortality. The study was conducted in a university general surgery intensive care unit using the admission APACHE II score. Over a 1-year period, 92 patients qualified for the study, 24 of whom survived, 69 of whom suffered multiple organ failure syndrome, and 68 of whom died. The APACHE II score did not predict the development of multiple organ failure syndrome or mortality with clinical utility and significantly underestimated the potential for the development of multiple organ failure syndrome. Factors that did predict the development of multiple organ failure syndrome and mortality were the time-dependent changes in the PaO2-to-fraction of inspired oxygen ratio and serum lactate, creatinine, and bilirubin levels. Better markers of cell injury are needed for use in decision making and quality assurance analysis in surgical patients.

Humans↗
PubMed1990

Decreased activity of Reiter's syndrome after urethrectomy.

Reiter's syndrome is a chronic rheumatic disease that develops after infective urethritis or gastroenteritis and has a strong association with the HLA-B27 antigen. How these factors interact remains unclear. We present a patient with Reiter's syndrome who exhibited 2 novel features: unusually severe urethritis that produced strictures requiring surgery, and dramatic regression of his rheumatic manifestations following a urethrectomy.

Adult↗
PubMed1990

New insights into the management of myocardial ischemia. Overview.

Because of their vasodilatory and coronary effects, nitrates are valuable in the treatment of congestive heart failure, acute ischemic syndromes, and stable and unstable angina. Nitrates may also have antiplatelet and antithrombotic effects, and they may prevent adverse remodeling after an acute myocardial infarction.

Blood Circulation↗
PubMed1990

Management of myocardial ischemia: role of intermittent nitrate therapy.

Tolerance to long-term nitrate therapy has now been documented in a large number of clinical studies. These trials have demonstrated attenuation of effect over time but a return of responsiveness with the start of nitrate-free intervals. Intermittent therapy prevents attenuation or tolerance when used as the initial treatment regimen. This strategy is appropriate for use with isosorbide dinitrate, as well as intravenous or transdermal nitroglycerin. Transmucosal nitroglycerin has not been associated with tolerance; the lack of such an effect may be a result of rapid increases and decreases in drug levels. In the future, sulfhydryl donors may also prove useful in prevention or reversal of nitrate tolerance.

Coronary Disease↗
PubMed1990

Role of endogenously produced interleukin-6 as a second signal in murine thymocyte proliferation induced by multiple cytokines: regulatory effects of transforming growth factor-beta.

Previous studies have demonstrated that murine thymocytes proliferate in the presence of submitogenic concentrations of phytohemagglutinin-P (PHA-P) and various cytokines such as interleukin-1 (IL-1), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). We report that C3H/HeJ thymocytes stimulated with PHA-P and IL-1, IL-4, or TNF-alpha secrete significant levels of IL-6 as determined on B9 hybridoma cells. The possibility that thymocyte proliferation induced by these cytokines was mediated through IL-6 was investigated utilizing a neutralizing monoclonal antibody against murine IL-6, MP5 20F3.1. The results demonstrate that MP5 20F3.1 inhibited the proliferative response of thymocytes and B9 hybridoma cells to recombinant MuIL-6 (but not HuIL-6) and neutralized the endogenous IL-6 produced in the thymocyte cultures, but did not have any measurable effects on the proliferative responses induced by IL-1, IL-4, or TNF-alpha. Although the level of endogeneously produced IL-6 did not play a measurable role in the proliferative response induced by TNF-alpha, the addition of higher concentrations of IL-6 augmented the proliferation of murine thymocytes induced by rMu TNF-alpha. In addition, recombinant human transforming growth factor-beta 1 (rHu TGF-beta 1) significantly inhibited thymocyte proliferation induced by HuIL-1, rMuIL-4, rMuIL-6, and rMuTNF-alpha. The studies suggest that IL-1, IL-4, or TNF-alpha mediate a proliferative signal on murine thymocytes independent of IL-6 and that the proliferative signals provided by these cytokines as well as IL-6 are inhibitable by rHu TGF-beta 1.

Animals↗
PubMed1990

[Differential diagnosis of malignant ulcer of the mouth mucosa--the Sutton aphthae (periadenitis mucosa necrotica recurrens)].

Sutton's ulcer is one of the recurrent oral ulcers. It normally occurs on the nonkeratinized oral mucosa and heals by scar formation. The cause is assumed to be an immunologic response to oral epithelium or the antigen of a microorganism. Therapy is unspecific or topical use of antibiotics and cortisone is recommended. The exclusion of a local or systemic malignant disease seems to be the most important feature of a differential diagnosis.

Carcinoma, Squamous Cell↗
PubMed1990

Lysine vasopressin in the treatment of refractory hemodialysis-induced hypotension.

The etiology of hemodialysis-induced hypotension is multifactorial. We assessed the efficacy of intranasal lysine vasopressin (LV) in 6 patients with refractory hemodialysis-induced hypotension. Autonomic testing was abnormal in all. Intranasal LV and placebo were assessed in a double-blind crossover fashion. With LV, the mean number of hypotensive episodes was less (0.9 +/- 0.8 vs. 1.5 +/- 1; t = 3.95, p less than 0.05), as was the total volume of intravenous fluid administered because of hypotension (155 +/- 57 vs. 280 +/- 123 cm3; t = 2.98, p less than 0.05). Systolic, diastolic, and mean arterial blood pressures were significantly greater at 90 min of the dialysis session. Measured baseline epinephrine, norepinephrine, and antidiuretic hormone levels were elevated above normal levels and fell with hypotension despite the use of LV. The results from this study demonstrate the utility of LV in the treatment of refractory hemodialysis-induced hypotension.

Administration, Intranasal↗