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Biomedical subjects

B S Edwards

Publications and source records attributed to B S Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1994

Diagnosis of coronary artery atheroembolism by right ventricular endomyocardial biopsy.

A case of coronary artery atheroembolism in a 54-year-old man, presenting as worsening congestive heart failure 2 months after mitral valve repair, left ventricular aneurysmectomy, and coronary artery bypass grafting, is reported. The diagnosis was made by right ventricular endomyocardial biopsy. The authors believe this to be the first such account in the literature.

Arterioles↗
PubMed1993

Calcium mobilization-associated and independent cytosolic acidification elicited in tandem with Na+/H+ exchanger activation in target cell-adherent human NK cells.

Flow cytometry was used to identify mechanisms by which human NK cells regulate intracellular pH (pHi) and to investigate the relationship between NK cell pHi and cytolytic function. Temporally resolved determinations of pHi were simultaneously made in NK cells that formed conjugates with target cells (NKC) and unconjugated NK cells (NKU) on the basis of the red/orange fluorescence emission ratio of the pH indicator seminapthylrhodafluor-1. Two pHi regulatory mechanisms were identified in NK cells: 1) a HCO3-/Cl- antiport that promoted pHi changes in response to variation of extracellular HCO3- and Cl- but not Na+ ion concentrations, was sensitive to stilbene derivatives 4,4'-diisothiocyanatostilbene sulfonic acid and 4-acetamido-4'-isothyocyanotostilbene-2-2'-disulfonic acid, and exhibited similar activity in NKC and NKU, and 2) a Na+/H+ exchanger that promoted pHi changes in response to extracellular Na+ ion concentration changes and was sensitive to dimethylamiloride (DMA), permeable to Na+ and Li+ but not K+ or N-methyl-D-glucamine, and quiescent in NKU but activated in target cell-adherent NKC. When Na+/H+ exchange was blocked with 10 microM DMA, the pHi of NKC bound to NK-sensitive K562 target cells progressively decreased for 3 to 4 min, then stabilized at 0.1 to 0.15 pH units below the pHi of NKU. A significant temporal decline in NKC pHi also occurred in the nominal absence of extracellular Ca2+ (0.07 +/- 0.02 pH units) and when NKC formed conjugates with NK-resistant B lymphoblastoid target cells that failed to mobilize NK cell Ca2+ (0.07 +/- 0.01 pH units) (mean +/- SD). However, the magnitude of the NKC cytosolic acidification response was consistently reduced (42 +/- 4 and 44 +/- 6%, respectively) under these Ca2+ flux response-limiting conditions. Thus, adhesion to target cells triggered two pHi-related responses in NK cells: 1) a decline in pHi which exhibited both Ca2+ mobilization-dependent and -independent components, and 2) Na+/H+ exchanger activation by which acid production was neutralized. Manipulations of HCO3- and DMA that clamped NKC pHi at values ranging from 6.8 to 7.2 failed to significantly influence NK cell cytolytic function. By contrast, isosmotic replacement of extracellular Na+ with NMDG resulted in a 57 +/- 22% inhibition of NK cell-mediated cytolysis (n = 8, p < 0.01). NKC pHi declined to 6.8 to 6.9 under these conditions, but this was not the apparent basis of impaired cytolysis because sustained elevation of NKC pHi by addition of dimethylamine failed to significantly reverse inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1993

The synergistic effects of cyclosporine and endothelin--demonstration of an important cardiodepressor action.

Cyclosporine represents the foundation for current immunosuppressive therapy following solid organ transplantation. CsA use is associated with renal insufficiency and systemic hypertension. We hypothesized that CsA would enhance the vascular actions of endothelin (ET). Three groups of anesthesized dogs (n = 15) were studied. Group 1 received CsA alone (1 mg/kg), group 2 received ET alone (1 ng/kg/min), and group 3 received combined CsA (1 mg/kg) and ET (1 ng/kg/min). The hemodynamic and renal effects were evaluated after 30 min. Combined treatment resulted in a profound reduction in mean arterial pressure (-62 +/- 14 mmHg (P < .05) and cardiac output (-2.2 +/- 0.4.1/min (P < .05). The reduction in mean arterial pressure and cardiac output were significantly greater than that observed with CsA or ET alone. Systemic vascular resistance was not significantly changed. Combined CsA and ET resulted in a significant reduction in renal blood flow (195 +/- 18 to 101 +/- 11 ml/mm P < .05) but without evidence of active renal vasoconstriction. The decline in GFR (31.8 +/- 5.6 ml/min to being unmeasurable) was of greater magnitude than the change in renal blood flow, suggesting enhanced afferent anteriolar vasoconstriction or an alteration in the ultrafiltration coefficient. These studies demonstrate an important and synergistic cardiodepressor effect when CsA and ET are combined.

Animals↗
PubMed1992

Resolution of adhesion- and activation-associated components of monoclonal antibody-dependent human NK cell-mediated cytotoxicity.

Flow cytometry was used to investigate two functional parameters of human natural-killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC): (i) the frequency of NK cells which formed conjugates (NKC) with autologous monoclonal antibody (mAb)-coated lymphocyte target cells, a measure of the avidity of CD16-dependent cell-cell adhesion, and (ii) the rise in the intracellular concentration of ionized calcium ([Ca2+]i) elicited in NKC by contact with target cells, a measure of CD16-dependent NK cell activation. For each of four rat IgG2b mAb directed against target cell antigens CDw52, CD5, CD45, and class I HLA, there existed quantitatively similar relationships between ADCC and rise in NKC[Ca2+]i but significant inter-mAb differences with respect to the ADCC vs the NKC frequency relationship. Cytolytic efficiencies of mAb appeared to be determined at the level of the NK cell, dependent upon CD16 and LFA-1, but restricted with respect to quantitative levels of NKC[Ca2+]i. In concert with this notion, targets coated with an IgG1 isotype-switch variant alpha CDw52 mAb promoted significant conjugate formation but failed to elicit a rise in NKC[Ca2+]i or ADCC. Thus, Fc regions of antibodies make contacts with NK cell CD16 which may strengthen cell-cell adhesion without eliciting an activation stimulus, a finding which supports a complexity of CD16 functional regulation of probable significance in the clinical consequences of antibody responses or therapeutic mAb manipulations.

Antibodies, Monoclonal↗
PubMed1992

Cell cycle progression in denV-transfected murine fibroblasts exposed to ultraviolet radiation.

Repair-proficient murine fibroblasts transfected with the denV gene of bacteriophage T4 repaired 70-80% of pyrimidine dimers within 24 h after exposure to 150 J/m2 ultraviolet radiation (UVR) from an FS-40 sunlamp. Under the same conditions, control cells repaired only about 20% of UVR-induced pyrimidine dimers. After UVR exposure, both control and denV-transfected cells exhibited some degree of DNA-synthesis inhibition, as determined by flow cytometric analysis of cell-cycle kinetics in propidium iodide-stained cells. DenV-transfected cells had a longer and more profound S phase arrest than control cells, but both control and denV-transfected cells had largely recovered from UVR effects on cell-cycle kinetics by 48 h after UVR exposure. Inhibition of DNA synthesis by UVR was also measured by determining post-UVR incorporation of bromodeoxyuridine (BrdU). The amount of BrdU incorporated was quantitated by determining with flow cytometry the quenching of Hoechst dye 33342 by BrdU incorporated in cellular DNA. DenV-transfected cells showed more marked inhibition of BrdU incorporation after low fluences of UVR than control cells. Differences between denV-transfected and control cells in cell-cycle kinetics following UVR exposure may be related to differences in mechanisms of repair when excision repair of pyrimidine dimers is initiated by endonuclease V instead of cellular repair enzymes.

Animals↗
PubMed1992

Prognostic features in patients with congestive heart failure and selection criteria for cardiac transplantation.

Cardiac transplantation can be a highly successful therapeutic option for patients with end-stage congestive heart failure. Successful results, however, depend on the appropriate selection of patients for the procedure. Patients whose survival or quality of life would be compromised without cardiac transplantation and who are likely to benefit from this intensive type of treatment are potential candidates. Each patient should undergo a thorough assessment to identify any medical or psychologic contraindications to cardiac transplantation. In this review, we discuss the important predictors of survival in patients with congestive heart failure: the cause of heart failure, the patient's symptomatic and functional status, the hemodynamic and pathologic findings, the evaluation of neurohumoral activity, and the presence of cardiac arrhythmias. Once a patient with congestive heart failure has been identified as having a limited life expectancy and severely impaired quality of life, cardiac transplantation should be considered.

Activities of Daily Living↗
PubMed1992

Total lymphoid irradiation: a novel and successful therapy for resistant cardiac allograft rejection.

Total lymphoid irradiation (TLI) is a novel type of adjuvant immunosuppression for patients who undergo cardiac transplantation and have refractory allograft rejection during standard immunosuppressive therapy. TLI consists of 6 to 10 fractions of 80 cGy (1 cGy = 1 rad) of irradiation to lymphatic tissues with use of the standard mantle and inverted Y fields. We have used TLI in six patients with biopsy-proven rejection that was refractory to standard treatments, including cyclosporine, azathioprine, antilymphocyte antibodies, and corticosteroids. In five patients, recalcitrant rejection was resolved after completion of TLI, and resolution persisted during long-term follow-up (17 to 30 months; mean, 22.2 months). In each patient, a substantial increase in the CD8 (suppressor T-lymphocyte) subset and elimination of B lymphocytes were demonstrated, findings that also persisted. Side effects were mild and primarily limited to transient leukopenia. In four patients, a readily treated cytomegalovirus reactivation was noted during TLI; thus, a causal relationship was suggested. In recipients of cardiac allografts who have refractory rejection, TLI provides long-lasting amelioration of the rejection profile. This result may be attributable to a relative enhancement of the suppressor T-cell subset and elimination of the B-lymphocyte line. Side effects are minimal, but monitoring for cytomegalovirus activation or reactivation is recommended.

Adult↗
PubMed1992

The sodium retaining effects of cyclosporine.

The effect of chronic cyclosporine administration on volume regulation was studied in mongrel dogs. Dogs received either cyclosporine (20 mg/kg/day p.o.; N = 7) or vehicle (N = 6) while being maintained on a constant sodium diet. Dogs had measurement of baseline vasoactive hormones. Daily sodium excretion was determined. Following eight days of drug administration, dogs were anesthetized, pre-volume expansion data was collected, and dogs underwent a one hour, 10% body weight 0.9% saline volume expansion. Daily sodium balance was +8.6 +/- 2.2 mEq in the cyclosporine group versus 0.4 +/- 1.8 mEq (P less than 0.05) in the control group after 8 days. Prior to acute volume expansion, aldosterone was 22.5 +/- 7.1 ng% in the cyclosporine group versus 4.7 +/- 0.7 ng% in controls (P less than 0.05). ANF was suppressed in the animals receiving cyclosporine. In response to volume expansion, the cyclosporine group demonstrated an attenuation of maximum urine flow by 56%, fractional excretion of sodium by 52%, and electrolyte free water clearance by 75% when compared to controls (P less than 0.05). We demonstrate that chronic cyclosporine administration activates the renin-angiotensin-aldosterone system, suppresses circulating ANF, and results in chronic sodium retention. Additionally, cyclosporine attenuates the natriuretic and diuretic response to acute volume expansion.

Animals↗
PubMed1992

Cardiac atrial natriuretic factor during evolution of congestive heart failure.

Congestive heart failure (CHF) is a pathophysiological condition associated with increased plasma levels of atrial natriuretic factor (ANF), a peptide hormone of cardiac origin that participates in the homeostatic control of intravascular volume and vascular tone. Atrial myocytes serve as the principal source of ANF under physiological conditions, although recent studies have demonstrated that ventricular myocardium may also synthesize ANF in models of CHF associated with ventricular hypertrophy. The current study was designed to investigate the roles of atrial and ventricular myocardium to synthesize, store, and release ANF during the evolution of tachycardia-induced CHF in the dog. The present study demonstrates a persistent elevation of plasma ANF during the evolution of CHF. In acute CHF (3 h), plasma ANF increased independent of cardiac ANF synthesis. In chronic CHF (15 and 30 days), plasma ANF is maintained by an increase in atrial synthesis and release of the peptide, without recruitment of ventricular ANF synthesis. The present study demonstrates that in acute CHF the increase in plasma ANF is regulated by release of stored peptide, and in chronic CHF the persistent elevation of plasma ANF is maintained by an increase in atrial synthesis of ANF.

Animals↗
PubMed1992

Role of renal Na+,K(+)-ATPase in the regulation of sodium excretion under normal conditions and in acute congestive heart failure.

BACKGROUND: Cardiac glycosides have traditionally been used as inotropic agents in the treatment of congestive heart failure (CHF). The renal actions of cardiac glycosides independent of inotropic effects are not characterized. The presence of endogenous digitalis-like factors (EDLFs) with characteristic Na+,K(+)-ATPase activity has been postulated in volume-expanded states such as CHF, and recent studies have demonstrated that at least one EDLF shares structural homology with ouabain. This study was undertaken to evaluate the renal actions of ouabain in normal dogs and those with CHF. METHODS AND RESULTS: After surgical preparation, normal dogs (n = 6) and dogs in pacing-induced CHF (n = 6) received intrarenal ouabain in sequential doses of 0.167 micrograms/kg/min, 0.334 micrograms/kg/min, and 0.668 micrograms/kg/min. Hemodynamics and renal function were evaluated during the infusion. There was no change in heart rate or mean arterial pressure during the infusion compared with baseline in both groups. Sodium excretion and urine volume significantly increased in both groups. Plasma renin activity, activated by the onset of pacing in the CHF group, was inhibited by the administration of intrarenal ouabain in this group only. CONCLUSIONS: These studies demonstrate that ouabain has diuretic and natriuretic actions independent of cardiac hemodynamics that are preserved in CHF. Furthermore, intrarenal ouabain suppresses activation of renin in CHF.

Acute Disease↗
PubMed1991

Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis.

BACKGROUND: Atherosclerosis is characterized by endothelial injury and the proliferation of arterial smooth-muscle cells. The latter may be a result of the release of growth factors from the vessel wall; such growth factors may include an endothelium-derived vasoconstrictor for peptide with mitogenic properties. We tested the hypothesis that plasma endothelin concentrations are elevated in persons with symptomatic atherosclerosis, independently of age. METHODS: We measured plasma endothelin levels in 100 normal subjects and in 40 patients with atherosclerosis predominantly of the following types: aortic and peripheral vascular disease (14 patients), renovascular disease (9 patients) coronary artery disease (9 patients), and carotid disease (8 patients). We also performed immunohistochemical staining for endothelin in the walls of atherosclerotic vessels. RESULTS: In the normal subjects, the mean (+/- SD) plasma endothelin concentration was 1.4 +/- 0.2 pmol per liter, with no correlation between age and plasma endothelin concentration (r = 0.13, P = 0.2). In the patients with symptomatic atherosclerosis, the mean plasma endothelin concentration was 3.2 +/- 1.2 pmol per liter (P less than 0.001), and there was a significant correlation between plasma endothelin and the number of sites of disease involvement (r = 0.89, P less than 0.001). In the immunohistochemical studies, endothelin-1-like immunoreactivity was observed in vascular smooth muscle as well as in endothelial cells. CONCLUSIONS: Endothelin may be a marker for arterial vascular disease. Whether it participates in the atherogenic process or is merely released from damaged endothelial cells is unclear.

Adolescent↗