PubMed Health⌕ Search

Biomedical subjects

A Hage

Publications and source records attributed to A Hage.

At least 19 recordsLinked to original sources
PubMed2001

Determination of the toxicity of several aromatic carbonylic compounds and their reduced derivatives on Phanerochaete chrysosporium using a Pseudomonas putida test system.

We tested four aromatic carbonylic compounds and their corresponding reduced derivatives, possible substrates, and products of a biotransformation for toxicity against the white-rot fungus Phanerochaete chrysosporium. The bacterium Pseudomonas putida, which has been proven to be a good test organism for investigating toxic effects, was used as a primary screen. For both P. chrysosporium and P. putida, all ketones showed a higher toxicity than their corresponding alcohol derivatives. Within one chemical group a direct correlation between the hydrophobicity (logP values) of the compounds and their toxicity could be observed. Furthermore, all tested compounds also caused an isomerization of cis to trans unsaturated fatty acids in P. putida, a mechanism of this bacterium to adapt its membrane to toxic environmental influences. Toxicity of aromatic carbonylic compounds in an established biotransformation system with P. chrysosporium can be estimated by calculating the corresponding logP values of the substrates and potential products. P. putida can be used to test the toxicity of aromatic ketones to the basic diomycete P. chrysosporium.

Alcohols↗
PubMed2001

Optimization of stereoselective ketone reduction by the white-rot fungus Merulius tremellosus ono991.

A recently isolated white-rot fungal strain, Merulius tremellosus ono991, displays high stereoselectivity during the reduction of arylketones. In order to increase the productivity and specific yield of the optically active alcohols, the culture conditions for the reduction of the model ketone compound 1'-acetonaphtone to alpha-methyl-1-naphtalenemethanol were optimized with respect to oxygen supply, choice of primary substrate and arylketone concentration. Alternative electron acceptors were also used to elucidate the role of reduction equivalents in the reduction process. The optimal yields of alpha-methyl-1-naphtalenemethanol were obtained in N2-flushed incubations with glycerol as primary substrate. The specific yield was increased from 57% to 98% compared to incubations under air with glucose. Most of the yield increase was due to N2-flushing and could be attributed to two factors. First, an increased stability of the product, alpha-methyl-1-naphtalenemethanol, in anaerobic compared to aerobic atmosphere was demonstrated. Second, fermentative metabolism increased reduced enzyme cofactors available for the reduction. Diverting reducing equivalents away from fermentation with alternative electron acceptors correlated with a decreased yield of alpha-methyl-1-naphtalenemethanol. Furthermore, the dependency of ketone reductase for common occurring metabolic reducing equivalents, NAD(P)H, was demonstrated by the reduction of 1'-acetonaphtone in cell extracts of M. tremellosus ono991.

Basidiomycota↗
PubMed2001

Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure.

In heart failure (HF) patients, reflex renal vasoconstriction during exercise is exaggerated. We hypothesized that muscle mechanoreceptor control of renal vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls were enrolled in two exercise protocols: 1) low-level rhythmic handgrip (mechanoreceptors and central command) and 2) involuntary biceps contractions (mechanoreceptors). Renal cortical blood flow was measured by positron emission tomography, and renal cortical vascular resistance (RCVR) was calculated. During rhythmic handgrip, peak RCVR was greater in HF patients compared with controls (37 +/- 1 vs. 27 +/- 1 units; P < 0.01). Change in (Delta) RCVR tended to be greater as well but did not reach statistical significance (10 +/- 1 vs. 7 +/- 0.9 units; P = 0.13). RCVR was returned to baseline at 2-3 min postexercise in controls but remained significantly elevated in HF patients. During involuntary muscle contractions, peak RCVR was greater in HF patients compared with controls (36 +/- 0.7 vs. 24 +/- 0.5 units; P < 0.0001). The Delta RCVR was also significantly greater in HF patients compared with controls (6 +/- 1 vs. 4 +/- 0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients. Given that the exaggerated response was elicited in both the presence and absence of central command, it is clear that intact muscle mechanoreceptor sensitivity contributes to this augmented reflex renal vasoconstriction.

Adult↗
PubMed2000

Exaggerated renal vasoconstriction during exercise in heart failure patients.

BACKGROUND: During static exercise in normal healthy humans, reflex renal cortical vasoconstriction occurs. Muscle metaboreceptors contribute importantly to this reflex renal vasoconstriction. In patients with heart failure, in whom renal vascular tone is already increased at rest, it is unknown whether there is further reflex renal vasoconstriction during exercise. METHODS AND RESULTS: Thirty-nine heart failure patients (NYHA functional class III and IV) and 38 age-matched control subjects (controls) were studied. Renal blood flow was measured by dynamic positron emission tomography. Graded handgrip exercise and post-handgrip ischemic arrest were used to clarify the reflex mechanisms involved. During sustained handgrip (30% maximum voluntary contraction), peak renal vasoconstriction was significantly increased in heart failure patients compared with controls (70+/-13 versus 42+/-1 U, P=0.02). Renal vasoconstriction returned to baseline in normal humans by 2 to 5 minutes but remained significantly increased in heart failure patients at 2 to 5 minutes and had returned to baseline at 20 minutes. In contrast, during post-handgrip circulatory arrest, which isolates muscle metaboreceptors, peak renal vasoconstriction was not greater in heart failure patients than in normal controls. In fact, the increase in renal vasoconstriction was blunted in heart failure patients compared with controls (20+/-5 versus 30+/-2 U, P=0.05). CONCLUSIONS: During sustained handgrip exercise in heart failure, both the magnitude and duration of reflex renal vasoconstriction are exaggerated in heart failure patients compared with normal healthy humans. The contribution of the muscle metaboreceptors to reflex renal vasoconstriction is blunted in heart failure patients compared with normal controls.

Adult↗
PubMed2000

Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure.

The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.

Acetylcholine↗
PubMed1999

Reduction of aryl acids by white-rot fungi for the biocatalytic production of aryl aldehydes and alcohols.

Ligninolytic basidiomycetes were screened for their ability to reduce aryl acids to the corresponding aldehydes and alcohols. Seven fungal strains converted p-anisic acid in high molar yields to the reduced products. The white-rot fungus Bjerkandera sp. strain BOS55 was one of the best reducing strains and was highly tolerant towards high concentrations of different aromatic acids. It was tested for the reduction of p-anisic, veratric, 3-chloro-4-methoxybenzoic, 3,5-dichloro-4-methoxybenzoic, 3,4-dichlorobenzoic, 4-fluorobenzoic, and 3-nitrobenzoic acids. All of these compounds were reduced to their corresponding aldehydes and alcohols.

Alcohols↗
PubMed1998

Safety and hemodynamic effects of intravenous triiodothyronine in advanced congestive heart failure.

Most patients with advanced congestive heart failure have altered thyroid hormone metabolism. A low triiodothyronine level is associated with impaired hemodynamics and is an independent predictor of poor survival. This study sought to evaluate safety and hemodynamic effects of short-term intravenous administration of triiodothyronine in patients with advanced heart failure. An intravenous bolus dose of triiodothyronine, with or without a 6- to 12-hour infusion (cumulative dose 0. 1 5 to 2.7 microg/kg), was administered to 23 patients with advanced heart failure (mean left ventricular ejection fraction 0.22 +/- 0.01). Cardiac rhythm and hemodynamic status were monitored for 12 hours, and basal metabolic rate by indirect calorimetry, echocardiographic parameters of systolic function and valvular regurgitation, thyroid hormone, and catecholamine levels were measured at baseline and at 4 to 6 hours. Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect. Acute intravenous administration of triiodothyronine is well tolerated in patients with advanced heart failure, establishing the basis for further investigation into the safety and potential hemodynamic benefits of longer infusions, combined infusion with inotropic agents, oral triiodothyronine replacement therapy, and new triiodothyronine analogs.

Female↗
PubMed1998

Polycyclic aromatic hydrocarbon oxidation by the white-rot fungus Bjerkandera sp. strain BOS55 in the presence of nonionic surfactants.

The effect of nonionic surfactants on the polycyclic aromatic hydrocarbon (PAH) oxidation rates by the extracellular ligninolytic enzyme system of the white-rot fungus Bjerkandera sp. strain BOS55 was investigated. Various surfactants increased the rate of anthracene, pyrene, and benzo[a]pyrene oxidation by two to fivefold. The stimulating effect of surfactants was found to be solely due to the increased bioavailability of PAH, indicating that the oxidation of PAH by the extracellular ligninolytic enzymes is limited by low compound bioavailability. The surfactants were shown to improve PAH dissolution rates by increasing their aqueous solubility and by decreasing the PAH precipitate particle size. The surfactant Tween 80 was mineralized by Bjerkandera sp. strain BOS55; as a result both the PAH solubilizing activity of Tween 80 and its stimulatory effect on anthracene and pyrene oxidation rates were lost within 24 h after addition to 6-day-old cultures. It was observed that the surfactant dispersed anthracene precipitates recrystallized into larger particles after Tween 80 was metabolized. However, benzo[a]pyrene precipitates remained dispersed, accounting for a prolonged enhancement of the benzo[a]pyrene oxidation rates. Because the endogenous production of H2O2 is also known to be rate limiting for PAH oxidation, the combined effect of adding surfactants and glucose oxidase was studied. The combined treatment resulted in anthracene and benzo[a]pyrene oxidation rates as high as 1450 and 450 mg L-1 d-1, respectively, by the extracellular fluid of 6-day-old fungal cultures.

Biodegradation, Environmental↗
PubMed1998

A novel complication of peritoneovenous shunt: cardiac tamponade.

For the last two decades, peritoneovenous shunts (PVS) have commonly been used in the management of refractory ascites. However, these devices are associated with a wide variety of complications. We report a case of cardiac tamponade due to ventricular perforation by a PVS. Given the substantial morbidity associated with PVS, other therapeutic options should be considered before proceeding with PVS placement.

Ascites↗
PubMed1998

The University of California at Los Angeles experience in heart transplantation.

In the last decade, the number of patients undergoing heart transplant has steadily increased as a result of expanding indications for this procedure. The limitation on the number of transplants performed has been the number of donor organs available. At UCLA, 900 heart transplant procedures have been performed from 1984-1998. Since 1991, the percent of patients free from rejection and infection in the first year after transplant was 70% and 73%, respectively. Actuarial one-, 3-, and 5-year survival rates are 84%, 76%, and 72%, respectively. Survival of patients aged 60 years and over (n = 105) was comparable to that of patients under age 60. We have been pursuing corticosteroid-free immunosuppression, which has led to a decrease in infection complications. Our work with pravastatin early after transplantation has led to a decrease in clinically severe rejection episodes, which has translated into improved survival. Pravastatin also appears to decrease the development of transplant coronary artery disease and appears to have an adjunct immunosuppressive effect in our heart transplant patients on CsA-based immunosuppression. We have also demonstrated benefit of cardiac rehabilitation early after transplant which should therefore be considered as standard postoperative care. Finally, we have participated and led the multicenter mycophenolate study in demonstrating this drug's effectiveness in improved outcomes in primary heart transplant recipients. Future studies include the use of Rapamycin and interleukin-2 receptor blockers which have been demonstrated in kidney transplantation to significantly reduce rejection. Our program is committed to seek better ways to improve outcome and the quality of life of our heart transplant patients.

Adult↗
PubMed1997

Impact of acute mental stress on sympathetic nerve activity and regional blood flow in advanced heart failure: implications for 'triggering' adverse cardiac events.

BACKGROUND: Evidence is accumulating that specific "triggers," such as intense psychological stress, may precipitate myocardial infarction and sudden death. Patients with advanced heart failure have increased resting sympathoexcitation, which has been directly related to increased mortality. The impact of triggers on sympathetic nerve activity and regional blood flow in heart failure has not been examined in patients with heart failure. METHODS AND RESULTS: Twenty-seven patients with heart failure (NYHA functional class III or IV) and 26 age-matched normal control subjects were studied. Muscle sympathetic nerve activity, heart rate, mean arterial pressure, forearm blood flow, and renal blood flow were measured during mental stress testing with mental arithmetic and Stroop color word test. Patients with heart failure had elevated levels of resting muscle sympathetic nerve activity and heart rate. Mental stress significantly increased muscle sympathetic nerve activity and heart rate in both patients with heart failure and control subjects, although the magnitude of increases tended to be blunted in patients with heart failure. Nevertheless, absolute levels of sympathetic activity in patients with heart failure remained significantly higher than levels in control subjects during mental stress. The decrease in renal blood flow in patients with heart failure was similar to that of control subjects, despite greater resting renal vasoconstriction. The increase in forearm blood flow during mental stress testing in patients with heart failure was blunted compared with that of control subjects. CONCLUSIONS: Patients with heart failure do not have augmented muscle sympathetic nerve activity responses to mental stress, despite elevated resting levels of sympathetic activity, but they do have markedly higher absolute levels of sympathetic nerve activity during mental stress as well as at rest.

Adult↗
PubMed1996

Pretransplant panel reactive-antibody screens. Are they truly a marker for poor outcome after cardiac transplantation?

BACKGROUND: The effect of pretransplant sensitization on outcome after cardiac transplant has been controversial. Sensitization, defined as a positive panel-reactive antibody (PRA) screen in patients awaiting transplant, represents circulating antibodies to a random panel of donor lymphocytes (usually T lymphocytes). The significance of pretransplant circulating antibodies to B lymphocytes has not been reported, and many centers disregard its use. METHODS AND RESULTS: We retrospectively reviewed the pretransplant PRA screens for 311 patients who underwent cardiac transplant at our institution. The PRA screen was performed by use of the lymphocytotoxic technique treated with dithiothreitol to remove IgM autoantibodies. Patients with PRA > or = 11% against T or B lymphocytes had significantly lower 3-year survival (T lymphocytes, 39%; B lymphocytes, 56%) than those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 76% and 78%; B lymphocytes, 78% and 74%, respectively) (P < .001). For this high-risk group, the rejection episode tended to occur earlier than in those patients with PRA = 0% and PRA = 1% to 10% (T lymphocytes, 2.3 versus 4.0 and 3.8 months; B lymphocytes, 2.1 versus 4.1 and 3.4 months, respectively), and there were more clinically severe rejections that required OKT3 therapy. CONCLUSIONS: Cardiac transplant patients with pretransplant T- and/or B-lymphocyte PRA > or = 11% despite negative donor-specific crossmatch at the time of transplant appear to have earlier and more severe rejection with significantly lower survival after transplant surgery. Modification of immunosuppression in these high-risk patients may be warranted.

Adult↗
PubMed1996

Dynamics of muscle sympathetic nerve activity in advanced heart failure patients.

Muscle sympathetic nerve activity (MSNA) is increased in patients with heart failure compared with healthy subjects. We applied spectral and correlation techniques to determine if qualitative as well as quantitative differences in MSNA differentiate heart failure patients from healthy subjects. We recorded MSNA, heart rate, and respiration in 11 heart failure patients and 10 healthy humans. Our results are as follows. 1) Statistically significant low-frequency modulation of MSNA at 0.029 +/- 0.002 Hz (mean +/- SE; range 0.026-0.038 Hz) was found in 10 of 11 heart failure patients but in only 2 of 10 healthy controls (differences between groups, P < 0.01; chi 2 test). 2) Heart rate and respiration also demonstrated significant low-frequency modulation in a similar range. 3) Spectral and correlation techniques revealed that low-frequency modulation of MSNA was highly correlated with low-frequency modulation of respiration in heart failure patients, but not in healthy subjects. In contrast, low-frequency modulation of MSNA did not correlate well with low-frequency modulation of heart rate. In summary, low-frequency modulation of respiration is coupled to low-frequency modulation of MSNA in heart failure patients, but not in normal subjects. We speculate that this low-frequency modulation of respiration may represent subclinical Cheyne-Stokes breathing, which has marked qualitative effects on MSNA in patients with heart failure.

Adolescent↗
PubMed1995

Evidence for preserved cardiopulmonary baroreflex control of renal cortical blood flow in humans with advanced heart failure. A positron emission tomography study.

BACKGROUND: The effect of cardiopulmonary baroreflexes on the renal circulation in healthy humans and patients with heart failure is unknown because of the technical limitations of studying the renal circulation. Positron emission tomography (PET) imaging is a new method to measure renal cortical blood flow in humans that is precise, rapid, reproducible, and noninvasive. The purpose of this study was to compare the effect of acute cardiopulmonary baroreceptor unloading by phlebotomy on regional blood flow in healthy humans and humans with advanced heart failure. METHODS AND RESULTS: We compared renal cortical blood flow and forearm blood flow in 10 healthy volunteers and 8 patients with heart failure (left ventricular ejection fraction, 0.24 +/- 0.02) during cardiopulmonary baroreceptor unloading with phlebotomy (450 mL). The major findings of this study are: (1) At rest, renal cortical blood flow is markedly diminished in humans with heart failure compared with healthy humans (heart failure, 2.4 +/- 0.1 versus healthy, 4.3 +/- 0.2 mL.min-1.g-1, P < .001). (2) In healthy humans, during phlebotomy, forearm blood flow decreased substantially (basal, 3.3 +/- 0.4 versus phlebotomy, 2.6 +/- 0.3 mL.min-1.100 mL-1, P = .02) and renal cortical blood flow decreased slightly but significantly (basal, 4.3 +/- 0.2 versus phlebotomy, 4.0 +/- 0.3 mL.min-1.g-1, P = .01). (3) The small magnitude of reflex renal vasoconstriction is not explained by the inability of the renal circulation to vasoconstrict, since the cold pressor stimulus induced substantial decreases in renal cortical blood flow in healthy subjects (basal, 4.4 +/- 0.1 versus cold pressor, 3.7 +/- 0.1 mL.min-1.g-1, P = .003). (4) In humans with heart failure, during phlebotomy, forearm blood flow did not change (basal, 2.6 +/- 0.3 versus phlebotomy, 2.7 +/- 0.2 mL.min-1.100 mL-1, P = NS), but renal cortical blood flow decreased slightly but significantly (basal, 2.4 +/- 0.1 versus phlebotomy, 2.1 +/- 0.1 mL.min-1.g-1, P = .01). (5) The cold pressor stimulus induced substantial decreases in renal cortical blood flow in patients with heart failure (basal, 2.9 +/- 0.1 versus cold pressor, 2.3 +/- 0.1 mL.min-1.g-1, P = .008). Thus, in patients with heart failure, there is an abnormality in cardiopulmonary baroreflex control of the forearm circulation but not the renal circulation. CONCLUSIONS: This study demonstrates the power of PET imaging to study normal physiological and pathophysiological reflex control of the renal circulation in humans and describes the novel finding of selective dysfunction of cardiopulmonary baroreflex control of one vascular region but its preservation in another in patients with heart failure.

Adult↗
PubMed1995

1H nuclear-magnetic-resonance investigation of oxidized Fe4S4 ferredoxin from Thermotoga maritima. Hyperfine-shifted resonances, sequence-specific assignments and secondary structure.

The oxidized Fe4S4 ferredoxin from the hyperthermophilic bacterium Thermotoga maritima has been investigated by one- and two-dimensional NMR in order to characterize its hyperfine-shifted resonances originating from the cysteinyl cluster ligands and to assign its resonances in the diamagnetic shift range. The chemical shift and relaxation time pattern of the hyperfine-shifted signals is very similar to other oxidized Fe4S4 ferredoxins. A tentative sequence-specific assignment of these resonances according to a general pattern of chemical shift of cysteine protons versus sequence position of cluster ligand is presented. Furthermore, sequence-specific assignments for 85% of the amino acid residues that were obtained without any guidance by known X-ray structures of ferredoxins are given. They reveal the formation of at least two elements of secondary structure by the polypeptide chain of T. maritima ferredoxin: an alpha-helix comprising residues C43-D49 and a double-stranded antiparallel beta-sheet consisting of the N- and C-terminal parts of the protein. This folding pattern is very similar to that of the crystallographically characterized ferredoxin from the mesophile Desulfovibrio gigas [Kissinger, C.R., Sieker, L.C., Adman E.T. & Jensen, L.H. (1991) J. Mol. Biol. 219, 693-715] and therefore suggesting different mechanisms of stabilization for T. maritima ferredoxin and the ferredoxin from the hyperthermophilic archaeon Pyrococcus furiosus that was recently investigated by NMR [Teng, Q., Zhou, Z.H., Smith, E.T., Busse, S. C., Howard, J.B., Adams M.W.W. & La Mar, G.N. (1994) Biochemistry 33, 6316-6326].

Amino Acid Sequence↗
PubMed1995

The University of California at Los Angeles experience in heart transplantation.

In the last decade, the number of patients undergoing heart transplantation has steadily increased as a result of expanding indications for cardiac transplantation. The limitation on the number of transplants performed has been the number of donor organs available. At UCLA, 511 heart transplant procedures were performed from 1984-1994. The mean number of rejection episodes and infections per patient in the first year after transplant was 1.1+/-1.3 and 1.0+/-1.2, respectively. Actuarial one-, 3-, and 5-year survival rates were 84%, 77% and 73%, respectively. Survival of patients age 60 years and over (n=105) was comparable to that of patients under age 60. Despite transplanting more critically ill patients (Status 1) and having longer cold ischemic times, outcomes have been improving. We have been pursuing corticosteroid-free immunosuppression, which no doubt has led to the decrease in infection complications. Furthermore, our work with pravastatin early after transplantation has led to a decrease in clinically severe rejection episodes which has translated into improved survival. Pravastatin also appeared to decrease the development of transplant coronary artery disease and appeared to have an adjunct immunosuppressive effect in our heart transplant patients on CsA-based immunosuppression. Future studies will include the use of mycophenolate mofetil which has properties against B-lymphocytes in addition to T-lymphocytes to block both humoral and cellular rejection. Our program continues to seek better ways to improve survival and the quality of life of our patient population.

Academic Medical Centers↗