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J Blum

Publications and source records attributed to J Blum.

At least 109 records · Page 6Linked to original sources
PubMed1988

Synthesis, effectiveness and metabolic fate in cows of the caesium complexing compound ammonium ferric hexacyanoferrate labelled with 14C.

Adding ammonium ferric hexacyanoferrate (AFCF) to cows' fodder produced after the Chernobyl nuclear accident prevented milk contamination by increasing the faecal elimination of 137Cs. Synthesis of ammonium ferric hexa[14C]-cyanoferrate (AF14CF) and its purification were performed for the study of the metabolic fate of this complex, and the evaluation of the possible release of cyanide. The stability of this colloidal product, tested by anaerobic incubation in rumen juice in vitro, showed no release of free cyanide from AF14CF, but hexacyanoferrate was identified in the rumen juice and 0.13% of the added radioactivity was converted to labelled CO2. AF14CF administered per os to two cows showed a nearly quantitative excretion of radioactivity in faeces during the first 3 d (91-95%). A very low but significant level of radioactivity appeared in plasma, blood cells, expired CO2 and was detected in organs taken 9 d after administration. Total cumulative radioactivity in urine and milk amounted to 0.19-0.47% and 0.068-0.071% respectively for the two cows. Labelled hexacyanoferrate and thiocyanate were identified in the urine and also in faeces. In spite of this relative instability of AFCF in the rumen of cows, the poor absorption of AF14CF degradation products showed that AFCF constitutes an efficient and safe food additive to prevent the absorption of radioactive caesium from ruminant feed and its secretion in milk.

Accidents↗
PubMed1986

Mutagenicity of N-substituted phenanthrene 9,10-imines in Salmonella typhimurium and Chinese hamster V79 cells.

We previously showed that some (nonsubstituted) aziridines derived from polycyclic aromatic hydrocarbons (arene imines) elicit various mutagenic and genotoxic effects in bacteria and mammalian cells and that these arene imines are active at much lower concentrations than the corresponding epoxide analogues. In the present study, N-substituted derivatives of phenanthrene 9,10-imine were investigated. All 10 derivatives studied showed direct mutagenicity in Salmonella typhimurium TA100. Some of the compounds additionally exhibited weak effects in the strains TA98 and TA1537. Most N-substituted derivatives were weaker mutagens than unsubstituted phenanthrene 9,10-imine but stronger mutagens than phenanthrene 9,10-oxide. Bulky substituents reduced the mutagenicity more than did small substituents. In addition, the derivatives with electron-withdrawing substituents (with the exception of N-chlorophenanthrene 9,10-imine) were weaker mutagens than those with electron-donating substituents. Phenanthrene 9,10-imine and five N-substituted derivatives were investigated to determine whether they induce gene mutations at the hgprt locus in V79 cells. Four compounds, including the parent aziridine, were positive in the V79 test. The other two compounds were negative. The mutagenic potencies in the V79 cell system did not correlate well with those obtained with the Salmonella system. Overall, the study shows that in addition to unsubstituted arene imines, N-substituted derivatives are mutagenic. This finding is of interest, as metabolic pathways leading from aromatic compounds to N-substituted arene imines are conceivable.

Animals↗
PubMed1986

Structure-activity relationships in the mutagenicity of N-substituted derivatives of phenanthrene-9,10-imine.

A series of K-region, N-substituted phenanthrene imines were tested for mutagenicity in Salmonella typhimurium TA100. All chemicals were mutagenic in the absence of an exogenous metabolic activation system. The apparent decay times of the mutagenic species in diffusion plates and their alkylating activities were also measured. The unsubstituted phenanthrene-9,10-imine was approximately 70-fold more mutagenic than the corresponding phenanthrene-9,10-oxide. N-substitution with electron-releasing groups resulted in chemicals that were more mutagenic than those substituted with electron-withdrawing groups. The mutagenic activity of the latter group of chemicals was comparable with that of phenanthrene-9,10-oxide. Except for N-chlorophenanthrene imine, both alkylation of p-nitrothiophenol and apparent decay times in diffusion plates were inversely correlated with mutagenicity. It is hypothesized that reactivity towards p-nitrothiophenol (alkylating activity) and mutagenicity reflect different reactions, in contrast to other chemical mutagens. The results suggest that the high potency of phenanthrene imines as mutagens is possibly due to DNA binding via an aziridinium ion rather than a carbonium ion.

Alkylating Agents↗
PubMed1985

Inactivation of glutathione peroxidase by superoxide radical.

The selenium-containing glutathione peroxidase, when in its active reduced form, was inactivated during exposure to the xanthine oxidase reaction. Superoxide dismutase completely prevented this inactivation, whereas catalase, hydroxyl radical scavengers, or chelators did not, indicating that O2 was the responsible agent. Conversion of GSH peroxidase to its oxidized form, by exposure to hydroperoxides, rendered it insensitive toward O2. The oxidized enzyme regained susceptibility toward inactivation by O2 when reduced with GSH. The inactivation by O2 could be reversed by GSH; however, sequential exposure to O2 and then hydroperoxides caused irreversible inactivation. Reactivity toward CN- has been used as a measure of the oxidized form of GSH peroxidase, whereas reactivity toward iodoacetate has been taken as an indicator of the reduced form. By these criteria both O2 and hydroperoxides convert the reduced form to oxidized forms. A mechanism involving oxidation of the selenocysteine residue at the active site has been proposed to account for these observations.

Animals↗
PubMed1985

[Hemodynamic testing at rest and during exertion after mitral valve replacement with a St. Jude Medical prosthesis].

177 mitral valve replacements with the St Jude Medical prosthesis (SJM) were carried out from March 1979 to December 1983. 45 of these patients (22 men and 23 women) underwent right heart catheterisation 6 or 8 months after surgery. These patients were operated for pure mitral stenosis in 24 cases, mitral regurgitation in 10 cases and mixed mitral disease in 24 cases. There was associated aortic valve disease in 26 patients and valve replacement with a Björk prosthesis was carried out in 19 cases. Tricuspid valvuloplasty was performed in 6 patients. 37 patients were at Stage III or IV of the NYHA classification before surgery; one year later, only 1 patient remained at Stage III, 4 patients were at Stage II and 38 at Stage I. 2 patients died in the first postoperative year of extracardiac causes. Resting pulmonary capillary pressure (Pw) fell from 18 +/- 7 mmHg to 9 +/- 4 mmHg after surgery (p less than 0.001); cardiac index rose from 2.21 +/- 0.45 to 2.59 +/- 0.49 1/min/m2 (p less than 0.001). A capillary arteriolar obstruction observed in 16 patients before surgery was only found in 9 of these patients after surgery. The changes in pulmonary pressures and cardiac output during exercise were studied in 22 patients. Pw rose from 7.6 +/- 1.5 mmHg to 20 +/- 4 mmHg; cardiac index increased from 2.62 +/- 0.19 to 5.46 +/- 0.72 1/min/m2. When compared with theoretical results in a normal subject, pulmonary artery pressures were abnormally high in 13 subjects (59 p. 100), reflecting a stenosing effect of the prosthesis, unmasked by exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Arene imines, a new class of exceptionally potent mutagens in bacterial and mammalian cells.

K-region aziridines of polycyclic aromatic hydrocarbons reverted Salmonella typhimurium his- (TA100, TA98) and Escherichia coli trp- strains (WP2 uvrA), without requiring activation by mammalian enzymes. The number of revertants induced per nmol in S. typhimurium TA 100, the most responsive strain, variea from 6 to 10,000 for the seven monoaziridines and the two bisaziridines tested. Interestingly, the mutagenic potencies (y) of the monoaziridines were closely related (r = 0.984) with those of the corresponding epoxide analogues (x) by the equation y = 19.6 X0.97, i.e., the aziridines were about 20-fold stronger mutagens than were the epoxides. One of the aziridines, benzo(a)pyrene (BP)-4,5-imine, was investigated in several additional mutagenicity test systems: toxicity in DNA repair-deficient (rec-) and -proficient (rec+) Bacillus subtilis strains; induction of 6-thioguanine resistance in V79 Chinese hamster cells; and induction of sister chromatid exchanges in cultured human fibroblasts. In all systems, BP-4,5-imine was much more active than the epoxide analogue, BP-4,5-oxide. The difference in activity was particularly large in the two test systems with mammalian target cells in which several hundredfold higher concentrations of the epoxide had to be used in order to elicit equipotent effects. Even r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-BP, which is one of the most potent mutagens known for V79 cells, was less active in the mammalian cells than was BP-4,5-imine. One reason that arene imines are such potent mutagens may be that they are poorly detoxified. Addition of highly purified microsomal epoxide hydrolase, which strongly reduced the mutagenicity of BP-4,5-oxide and benz(a)anthracene-5,6-oxide in S. typhimurium, had no effect on the mutagenicity of the corresponding aziridines. Furthermore, while benz(a)anthracene-5,6-oxide was inactivated by highly purified cytosolic epoxide hydrolase, benz(a)anthracene-5,6-imine was not inactivated. It is noteworthy that the arene imines are isomeric with and structurally closely related to aromatic amines. Some aziridines derived from nonaromatic structures (ethylene imines) have been reported as metabolites of xenobiotics; others are used as chemotherapeutics. At present, however, the results are mainly of theoretical interest in that a new type of arene derivatives with exceptionally potent, probably ultimate, mutagenicity was discovered and may be exploited for the study of mechanisms of chemical carcinogenesis.

Animals↗
PubMed1984

A hybrid superoxide dismutase containing both functional iron and manganese.

A hybrid superoxide dismutase containing functional Mn and Fe has been isolated from Escherichia coli. Streptomycin, which binds tightly to both the Mn- and the Fe-containing superoxide dismutases, had the expected effect on the electrophoretic and chromatographic behavior of the hybrid. Treatment of the hybrid with H2O2, which selectively inactivates the Fe-containing enzyme, resulted in partial inactivation accompanied by a resegregation of subunits, with the formation of active Mn-enzyme and inactive Fe-enzyme. A similar resegregation of subunits was observed when the hybrid was exposed to 2.5 M guanidinium chloride. Hybrids containing Mn or Fe could be generated in vitro by mixing the Mn-enzyme with the Fe-enzyme, removing metals with 8-hydroxyquinoline in the presence of 2.5 M guanidinium chloride, and then dialyzing against Mn(II) or Fe(II) salts. Ten per cent of the activity of the Fe-superoxide dismutases is resistant to H2O2, which correlates with its content of Mn. Since the activity remaining after exhaustive treatment with H2O2 exhibited the electrophoretic mobility of the Fe-enzyme, we concluded that some of the active sites of the Fe-enzyme were actually occupied by Mn. It should be noted, however, that for purposes of metal reconstitution experiments, a definite specificity was demonstrated. The Mn-enzyme was reconstituted with Mn(II), whereas the Fe-enzyme activity was recovered using only Fe(II). We propose that the Fe-superoxide dismutase may be heterogeneous and that 10% of its activity is actually due to a Mn-containing variant with the same electrophoretic mobility. Only the apohybrid enzyme regained enzymatic activity using both Mn(II) and Fe(II).

Escherichia coli↗
PubMed1984

Enzymatic defenses against oxygen toxicity in the hydrothermal vent animals Riftia pachyptila and Calyptogena magnifica.

Two deep-sea hydrothermal vent organisms, the tube worm Riftia pachyptila and the clam Calyptogena magnifica, contain superoxide dismutase, dianisidine peroxidase, and glutathione peroxidase. The tube worm trophosome exhibits an iron-containing superoxide dismutase, ordinarily associated with prokaryotes and not previously seen in an animal tissue, in accord with the presence of symbiotic bacteria in this tissue. The enzymes which provide a defense against oxygen toxicity are thus present in these animals.

Animals↗
PubMed1984

[Hemodynamic data during muscular exercise after myocardial infarction. Correlations with coronaro-ventriculographic data].

Forty six patients aged 25 to 67 years (average : 52 years) underwent measurement of pulmonary arterial pressure (PAP), systemic pressure and cardiac output (Fick) at rest and during exercise in the recumbent position 12 +/- 3 weeks after uncomplicated myocardial infarction; the results were then compared with those of coronary angiography and right anterior oblique monoplane left ventriculography. The site of infarction was anterior in 18 cases and postero-diaphragmatic in 28 cases; it was non-transmural in 4 cases. Twenty patients (43%) had multivessel disease; this was equally common in anterior and inferior wall infarction. Regional wall abnormalities of 3 or more segments were observed in 14 cases. Mean PAP increased from 12,3 +/- 4,6 Torr at rest to 27,8 +/- 10,5 Torr on exercise. In 17 patients (Group A) PAP was normal at rest and during exercise (10 +/- 2 Torr and 18 +/- 3 Torr respectively); 25 patients (Group B) had normal resting PAP (12 +/- 3 Torr) but an abnormal rise on exercise (32 +/- 8 Torr); in 4 patients (Group C) PAP was abnormal at rest (24 +/- 4 Torr) and on exercise (44 +/- 7 Torr). The increase in PAP on exercise was inversely correlated to the ejection fraction (p less than 0.001) and related to the extent of left ventricular hypokinesia (p less than 0.001). Patients in Group A had higher ejection fractions (p less than 0.05), dp/dt/p index (p less than 0.01) and left ventricular compliance (p less than 0.01), lower resting (p less than 0.01) and exercise (p less than 0.05) systemic pressures and small regional wall abnormalities (p less than 0.01) than patients in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Superoxide, hydrogen peroxide, and oxygen toxicity in two free-living nematode species.

Two species of free-living nematodes, Turbatrix aceti and Caenorhabditis elegans, exhibited a marked sensitivity to 3 atm of 100% O2. Environmental changes in pH and temperature, which altered nematode respiration, resulted in alterations in the survival of these organisms under high pO2. Levels of defensive enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and dianisidine peroxidase were measured in the two species. No changes in the level of superoxide dismutase or catalase activity were induced by exposure of the nematodes to high pO2. Manipulation of these two enzymes was however achieved using the inhibitors 3-amino-1,2,4-triazole and diethyldithiocarbamate. 3-Amino-1,2,4-triazole (20 mM) eliminated greater than or equal to 80% of the catalase activity in vivo and diethyldithiocarbamate (5 mM) decreased the level of CuZn superoxide dismutase by greater than or equal to 70%. Both of these compounds increased the sensitivity of C. elegans to high pO2 toxicity. Compounds capable of intracellular redox-cycling with O2- -production, such as plumbagin, increased CN- -resistant respiration in the nematodes and imposed an O2-dependent toxicity. These experiments demonstrate the toxicity of intracellular O2- and H2O2 in nematodes and the importance of superoxide dismutase and catalase in providing a defense against these toxic molecules in vivo.

Animals↗
PubMed1983

Renal graft irradiation in acute rejection.

To evaluate the effect of graft irradiation in the treatment of acute rejection of renal transplants, a randomized study was conducted from 1978 to 1981. Patients with acute rejection were given standard medical management in the form of intravenous methylprednisolone, and were chosen randomly to receive either graft irradiation (175 rads every other day, to a total of 525 rads) or simulated (sham) irradiation. Eighty-three rejections occurring in 64 grafts were randomized to the protocol. Rejection reversal was recorded in 84.5% of control grafts and 75% of the irradiated grafts. Recurrent rejections were more frequent and graft survival was significantly lower in the irradiated group (22%) than in the control group (54%). Graft irradiation does not appear to be beneficial in the treatment of acute rejection of renal transplants when used in conjunction with high-dose steroids.

Female↗
PubMed1982

Decreased incidence of antiarrhythmic drug efficacy at electrophysiologic study associated with the use of a third extrastimulus.

Drug trials during electrophysiologic study were performed in 166 patients with sustained ventricular tachycardia (VT) or ventricular fibrillation. In the first 21 patients (group I), a maximum of two extrastimuli was used. In 145 subsequent patients (group II), drug efficacy was assessed using three extrastimuli if one or two failed to induce VT. The incidence of acute drug efficacy was 15 of 21 (71%) in group I, but only 44 of 145 (30%) in group II (p less than 0.01). To assess the influence of the third extrastimulus on the differing incidence of acute drug efficacy, we examined the 69 group II patients whose VT was initially induced by one or two extrastimuli. Acutely effective agents were identified for 19 of these 69 patients using up to three extrastimuli to define efficacy. In 24 of te 50 patients for whom no effective drug could be found, VT was induced with one or two extrastimuli during all drug trials. In the remaining 26 patients VT could be induced after drug administration only with use of three extrastimuli. If efficacy had been defined using a maximum of two extrastimuli, these 26 patients would have been considered responsive to drug testing. Overall, 45 to 69 (65%) rather than 19 of 69 (28%) would have had a favorable response (p less than 0.001). Fourteen group I patients and 17 group II patients in whom VT was initially induced by one or two extrastimuli received chronic therapy with agents predicted effective during acute drug trials. At 18 months, the cumulative percent of patients free of arrhythmia recurrence by actuarial analysis was 79 +/- 14% in group I and 80 +/- 14% in group II (NS). Use of three extrastimuli during drug trials is associated with a lower incidence of acute drug efficacy. Limited data suggest that prophylaxis against VT induction by three, rather than two, extrastimuli may not be a stronger predictor of chronic efficacy in patients whose VT is initially induced by one or two extrastimuli. Further study is needed to identify optimal pacing methods for antiarrhythmic drug assessment.

Anti-Arrhythmia Agents↗
PubMed1982

Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study.

A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eight-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steroids.

Adolescent↗
PubMed1982

Hospice criteria.

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Hospices↗