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Biomedical subjects

J Krall

Publications and source records attributed to J Krall.

At least 37 records · Page 2Linked to original sources
PubMed1992

The prognostic significance of race and survival from prostate cancer based on patients irradiated on Radiation Therapy Oncology Group protocols (1976-1985).

A number of studies have identified race as a prognostic factor for survival from prostate cancer. To evaluate the prognostic significance of race in a controlled setting, we evaluated 1294 patients treated on three prospective randomized trials conducted by the Radiation Therapy Oncology Group between 1976 to 1985. One-hundred and twenty (9%) of the patients were coded as black, while 1077 (83%) of the patients were coded as white. Protocol 7506 included 607 patients with clinical Stage T3-T4Nx or T1b-T2N1-2. Protocol 7706 included 484 patients with clinical Stage T1b or T2 who were node negative. Protocol 8307 included 203 Stage T2b-T4 patients with no lymph node involvement beyond the pelvis. Univariate and multivariate analyses were used to assess the possible independent significance of race and other prognostic factors, including Gleason score, serum acid phosphatase, nodal status, and hormonal status. Protocols 7706 and 8307 revealed that race was not of prognostic significance for disease-free or overall survival by either univariate or multivariate analysis. Univariate analysis of Protocol 7506 revealed that the median survival for blacks was somewhat shorter (5.4 years vs. 7.1 years, p = 0.02). This difference persisted after a multivariate analysis. A higher percentage of blacks treated on 7506 had an abnormally elevated serum acid phosphatase compared to whites (p = 0.006), and the time to distant failure tended to be shorter (p = 0.07). These findings suggest that blacks treated on 7506 may have had more extensive disease at presentation. Based on these prospective randomized trials, it is most likely that the lower survival noted for black Americans with prostate cancer reflects the tendency for blacks to present with more advanced disease. Differences in access to care, the quality of care received, and the impact of co-morbid conditions may explain the lower survival reported for black Americans elsewhere in the literature.

Black or African American↗
PubMed1991

Paraquat-resistant HeLa cells: increased cellular content of glutathione peroxidase.

Paraquat-resistant HeLa cells were selected and characterized to determine the mechanism(s) of the toxic action of paraquat for cultured mammalian cells. From HeLa cells already selected for resistance to the toxicity of 40 microM paraquat more resistant cells were selected in 90 microM paraquat. In these more resistant cells (PQRHM90) one adaptation which occurred at the lesser concentration of paraquat, magnification of the cellular content of both the CuZn- and the Mn-containing superoxide dismutases, did not increase further. Instead, the cellular content of catalase and of glutathione peroxidase increased. The increased cellular content of glutathione peroxidase appeared more likely to have produced increased resistance to paraquat than did the augmented content of catalase because, after cultivation in the absence of paraquat, the cells retained both resistance to 90 microM paraquat and the increased content of glutathione peroxidase, while the content of catalase declined. The cellular content of reduced glutathione in the PQRHM90 cells grown in paraquat was diminished in comparison with that in the cells from which they derived. The data suggest that the PQRHM90 cells resisted the toxicity of paraquat by increasing the cellular activity of glutathione peroxidase as a means of detoxifying the H2O2 produced by paraquat.

Catalase↗
PubMed1991

Sarcoplasmic reticulum-associated cyclic adenosine 5'-monophosphate phosphodiesterase activity in normal and failing human hearts.

Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less than or equal to 1.0 microM, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (Ki = 0.031 +/- 0.008 microM) and the cilostamide derivative OPC 3911 (Ki = 0.018 +/- 0.004 microM), but was essentially insensitive to rolipram. Vmax and Km were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031 microM, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027 microM in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Identification and characterization of proteins in sarcoplasmic reticulum from normal and failing human left ventricles.

Monoclonal and polyclonal antibodies to the major sarcoplasmic reticulum proteins of rabbit skeletal and canine cardiac muscle have been used to identify and characterize the corresponding components of human cardiac sarcoplasmic reticulum. The Ca2(+)-transporting ATPase of human cardiac sarcoplasmic reticulum was identified as a 105,000-Da protein antigenically distinct from its rabbit skeletal muscle counterpart. Human cardiac sarcoplasmic reticulum also contained 53,000- 155,000- and 165,000-Da glycoproteins antigenically related to the low and high molecular weight glycoproteins of canine cardiac and rabbit skeletal muscle sarcoplasmic reticulum. The ryanodine-sensitive Ca2+ channel of human cardiac sarcoplasmic reticulum was identified as a 400,000-Da protein antigenically related to its counterparts in canine cardiac and rabbit skeletal muscle. Human cardiac calsequestrin was identified as a 52,000-Da protein. Human phospholamban was identified as a 29,000-Da substrate for phosphorylation by cAMP-dependent protein kinase. Immunoblots of sarcoplasmic reticulum from the normal left ventricles of four unmatched organ donors and the excised failing left ventricles of nine patients with idiopathic dilated cardiomyopathy were compared in search of qualitative differences in the protein patterns of the failing hearts. No such differences were found with respect to the Ca2+ ATPase, the 53,000-Da glycoprotein, the ryanodine-sensitive Ca2+ channel, calsequestrin or phospholamban. In contrast, the 165,000-Da glycoprotein band, present in all four preparations from nonfailing hearts, was absent from three of nine preparations from failing hearts, and staining of the 155,000-Da glycoprotein in these three preparations appeared to be relatively increased. The absence of the 165,000-Da glycoprotein band may identify or reflect a pathogenetic mechanism in a subset of patients with idiopathic dilated cardiomyopathy.

Animals↗
PubMed1990

Phospholamban-mediated stimulation of Ca2+ uptake in sarcoplasmic reticulum from normal and failing hearts.

Studies in animal models have suggested that alterations affecting phospholamban-mediated stimulation of Ca2+ uptake by sarcoplasmic reticulum are involved in the pathophysiology of heart disease. A monoclonal antibody that binds to phospholamban and stimulates Ca2+ uptake was used to characterize phospholamban-mediated effects in human cardiac sarcoplasmic reticulum and to compare these effects in tissue from normal and failing hearts. Stimulation of Ca2+ uptake by anti-phospholamban monoclonal antibody simulated the effect of phosphorylation of phospholamban by cAMP-dependent protein kinase. Binding of anti-phospholamban antibody reduced the K0.5 of the Ca2(+)-transporting ATPase from 0.53 microM [( Ca2+]) to 0.29 microM [( Ca2+]), without affecting Vmax or nHill. At 0.2 microM Ca2+, stimulation was 1.93-fold in sarcoplasmic reticulum prepared from normal human left ventricular myocardium and 1.94-fold in sarcoplasmic reticulum prepared from the left ventricular myocardium of patients with heart failure resulting from idiopathic dilated cardiomyopathy. Stimulation of Ca2+ uptake in canine cardiac sarcoplasmic reticulum under identical conditions was 1.89-fold. Phospholamban-mediated stimulation of Ca2+ uptake in human cardiac sarcoplasmic reticulum is thus comparable in magnitude to that observed in other species and results from an increase in the apparent affinity of the Ca2(+)-transporting ATPase for Ca2+. The pathogenesis of heart failure in idiopathic dilated cardiomyopathy does not, however, appear to involve intrinsic alterations of this mechanism.

Adenosine Triphosphatases↗
PubMed1989

Evaluation of neutron irradiation of pancreatic cancer. Results of a randomized Radiation Therapy Oncology Group clinical trial.

Between 1980-84, the Radiation Therapy Oncology Group conducted a trial in patients with untreated, unresectable localized carcinomas of the pancreas. Patients were randomly chosen to receive either 6,400 cGy with photons, the equivalent dose with a combination of photons and neutrons (mixed-beam irradiation), or neutrons alone. A total of 49 cases were evaluable, of which 23 were treated with photons, 11 with mixed-beam therapy, and 15 with neutrons alone. The median survival time was 5.6 months with neutrons, 7.8 months with mixed-beam radiation, and 8.3 months with photons. The median local control time was 6.7 months with neutrons, 6.5 months with mixed-beam radiation, and 2.6 months with photons. These differences are not statistically significant. Evidence of moderate-to-life-threatening gastrointestinal or hepatic injury was present in three patients treated with neutrons and one patient treated with photons. The causes of this apparent difference are discussed. This study demonstrates there is no evidence to suggest that neutron irradiation, either alone or in combination with photon irradiation, produces better local control or survival rates than photon irradiation.

Adenocarcinoma↗
PubMed1989

Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy.

We measured Ca2+ uptake by sarcoplasmic reticulum prepared from left ventricular myocardium obtained from six nonfailing human hearts and nine excised hearts from patients with class IV idiopathic dilated cardiomyopathy. Ca2+ uptake had a Vmax of 593 +/- 82 nmol/mg-min, a K0.5 of 0.68 +/- 0.07 microM, and an nHill of 1.7 +/- 0.1 in the nonfailing hearts. The corresponding values in the excised failing hearts were 593 +/- 36 nmol/mg-min, 0.63 +/- 0.03 microM, and 1.6 +/- 0.1. The beta-receptor density in crude sarcolemma prepared from left ventricular myocardium was 110.0 +/- 15.3 fmol/mg in the unmatched donors and 52.1 +/- 4.5 fmol/mg in the excised failing hearts. These results suggest that abnormal Ca2+ handling in idiopathic dilated cardiomyopathy in humans is not the result of any intrinsic alteration of Ca2+ uptake by sarcoplasmic reticulum.

Adult↗
PubMed1988

Superoxide mediates the toxicity of paraquat for cultured mammalian cells.

To establish some of the necessary steps in the toxic action of paraquat for cultured mammalian cells, we isolated paraquat-resistant HeLa cells after lethal increments in concentration of paraquat in the medium. The paraquat-resistant cells had increased the cellular content of both the Mn-containing and the CuZn-containing superoxide dismutases. The effect of paraquat on the consumption of oxygen by the wild-type and the resistance cells was similar; in both cases exposure to paraquat for 24 or more hours produced similar proportions of cyanide-resistant consumption of oxygen, suggesting that paraquat entered both cells, underwent reduction, and donated electrons to molecular oxygen. When cultivated for 5 months in the absence of paraquat the paraquat-resistant cells maintained the increased cellular content of superoxide dismutases and remained resistant to paraquat. This observation suggested that resistance to paraquat might be caused by enrichment for the two superoxide dismutases and, further, that the increased cellular content of the two enzymes was not a response to growth under stressful conditions. NIH/3T3 cells whose content of superoxide dismutase was increased by transcription of the transfected cDNA for the human CuZn superoxide dismutase were also resistant to paraquat, suggesting strongly that paraquat promotes the formation of O2- as a necessary part of its cytotoxic effects in two types of cultured mammalian cells.

Base Sequence↗
PubMed1986

Superoxide mediates the toxicity of paraquat for Chinese hamster ovary cells.

The roles of superoxide and H2O2 in the cytotoxicity of paraquat were assessed in Chinese hamster ovary cells. Neither catalase nor superoxide dismutase inhibited the loss of ability to form colonies when added to the medium. When introduced into the cells, superoxide dismutase but not catalase inhibited the toxicity of paraquat. That superoxide dismutase acted by its known catalytic action is shown by the loss of inhibition when the enzyme was inactivated by H2O2 before being introduced into the cells. The lack of inhibition by catalase, by dimethyl sulfoxide, and by desferoxamine suggests that the toxicity is not mediated by a reaction between H2O2 and superoxide to engender the hydroxyl radical. Exposure of Chinese hamster ovary cells to paraquat may be a suitable means to determine the effects of superoxide anion in cultured cells and the ways in which cells can resist this toxic action.

Animals↗
PubMed1984

Treatment-related morbidity in phase III RTOG studies of extended-field irradiation for carcinoma of the prostate.

The incidence, severity, time of onset, and clinical course of complications of treatment have been reviewed in the RTOG studies of extended field irradiation in carcinoma of the prostate. A total of 526 patients, entered between 1976 and 1980 and followed for a minimum of 18 months, comprised the study population. In most instances of treatment-related morbidity, the symptoms were recorded during the first several months to 1 year following completion of treatment. Late occurrences, however, were not uncommon in certain types of radiation-produced injuries, such as proctitis, hematuria, and urethral strictures. Resolution of symptoms has been observed in a large proportion of patients including those with late occurrences of treatment-related morbidity, although the probability and the pattern of resolution differed considerably from one type of morbidity to another. Symptoms of cystitis are more likely to abate than those of proctitis. In patients who develop symptoms of proctitis the probability of persistence of symptoms beyond the second year following occurrence has been estimated at 20%-30%. Hematuria and symptoms secondary to urethral strictures seem to be even more likely to recur or persist, while genital and leg edema remain chronic in the majority of patients.

Adenocarcinoma↗
PubMed1983

Catalase and superoxide dismutase in Escherichia coli.

We assessed the roles of intrabacterial catalase and superoxide dismutase in the resistance of Escherichia coli to killing by neutrophils. E. coli in which the synthesis of superoxide dismutase and catalase were induced by paraquat 10-fold and 5-fold, respectively, did not resist killing by neutrophils. When bacteria were allowed to recover from the toxicity of paraquat for 1 h on ice and for 30 min at 37 degrees C, they still failed to resist killing by neutrophils. Induction of the synthesis of catalase 9-fold by growth in the presence of phenazine methosulfate did not render E. coli resistant to killing by either neutrophils or by H2O2 itself. The lack of protection by intrabacterial catalase from killing by neutrophils could not be attributed to an impermeable bacterial membrane; the evolution of O2 from H2O2 was no less rapid in suspensions of E. coli than in lysates. The failure of intrabacterial catalase or superoxide dismutase to protect bacteria from killing by neutrophils might indicate either that the flux of O-2 and H2O2 in the phagosome is too great for the intrabacterial enzymes to alter or that the site of injury is at the bacterial surface.

Catalase↗
PubMed1982

Long-term survival with ventricular pacemaking: initial 15-year experience.

The records of all 380 adult patients receiving cardiac pacemakers at West Virginia University in the 15-year period ending January 1, 1977, were reviewed. The five-year survival rate was 58 per cent and the 10 year, 38 per cent with a median survival of 74 months. Life expectancy approached life-table curves if the mortality during the initial year was ignored. Although the younger patients lived the longest, their expected survival was reduced more than in the older patients. The need for a pacemaker in a young person implies serious life-shortening consequences. Unlike reports in the literature, patients with sinoatrial disease fared worse than those with A-V block.

Actuarial Analysis↗