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Biomedical subjects

A Salamon

Publications and source records attributed to A Salamon.

At least 19 recordsLinked to original sources
PubMed2003

Characterisation of cellobiose dehydrogenases from the white-rot fungi Trametes pubescens and Trametes villosa.

Cellobiose dehydrogenase (CDH) is an extracellular haemoflavoenzyme that is produced by a number of wood-degrading and phytopathogenic fungi and it has a proposed role in the early events of lignocellulose degradation and wood colonisation. In the presence of a suitable electron acceptor, e.g. 2,6-dichloro-indophenol, cytochrome c, or metal ions, CDH oxidises cellobiose to cellobionolactone. When screening 11 different Trametes spp. for the formation of CDH activity, all the strains investigated were found to secrete significant amounts of CDH when cultivated on a cellulose-containing medium. Amongst others, Trametes pubescens and Trametes villosa were identified as excellent, not-yet-described, producer strains of this enzyme activity that has various potential applications in biotechnology. CDH from both strains was purified to apparent homogeneity and subsequently characterised. Both monomeric enzymes have a molecular mass of approximately 90 kDa (gel filtration) and a pI value of 4.2-4.4. The best substrates are cellobiose and cellooligosaccharides; additionally, lactose, thiocellobiose, and xylobiose are efficiently oxidised. Glucose and maltose are poor substrates. The preferred substrate is cellobiose with a Km value of 0.21 mM and a kcat value of 22 s(-1) for CDH from T. pubescens; the corresponding values for the T. villosa enzyme are 0.21 mM and 24 s(-1), respectively. Both enzymes showed very high activity with one-electron acceptors such as ferricenium, ferricyanide, or the azino-bis-(3-ethyl-benzthiazolin-6-sulfonic acid) cation radical.

2,6-Dichloroindophenol↗
PubMed2001

Metabolism and disposition of the novel antileukaemic drug, benzamide riboside, in the isolated perfused rat liver.

Benzamide riboside (BR) is a novel anticancer agent exhibiting pronounced activity against several human tumor cells, however, little is known about its biotransformation. To analyze for BR and its metabolites, livers of Wistar and mutant TR- rats were perfused with BR in a single pass system. In bile, native BR and its deamination product, benzene carboxylic acid riboside (BR-COOH) was quantified by HPLC. Total excretion of BR and BR-COOH into bile of Wistar rats was low (< 0.2%) whereas cumulative efflux of BR and its metabolite BR-COOH was high, representing 79% and 1.6% of infused BR, respectively. Biliary excretion of BR and BR-COOH in TR- rats, deficient in canalicular multispecific organic anion transporter, a membrane protein identical to MRP2 in tumor cells, was only slightly lower than in Wistar rats, indicating that BR and BR-COOH are non-substrates of MRP2. Experiments using rat hepatocytes incubated with BR did show a linear uptake of BR and a subsequent metabolism to BR-COOH that was largely excreted into the cellular supernatant. Examination of the cytotoxic activity against the human HL60 and K562 leukemia cells in a clonogenic assay demonstrated an IC50 of 619 microM and 1013 microM for BR-COOH compared to the IC50 of 0.21 microM and 0.46 microM for BR, suggesting the inertness of the metabolite. In summary, we found that deamination of BR to BR-COOH is the main metabolic pathway in rat liver. BR-COOH formation should also be considered in human liver during cancer therapy.

Animals↗
PubMed2001

Differential expression of cytokines and cytokine receptors in renal cell carcinoma.

Modulation of immunomechanisms by tumor cells can be caused by secretion of cytokines. In vitro data are usually gained in culture systems. It is debatable whether these systems are representative of the conditions inside the respective tumor tissues. Immunohistochemical studies of tumor tissue cryostats were compared with those in matched primary renal cell carcinoma tumor cell cultures. Results were correlated with histopathological characteristics and the in vitro cytotoxic effect of autologous tumor infiltrating lymphocytes (TILs). Expression of all studied cytokines and cytokine receptors could be shown in cryostats and cell cultures, but the detection pattern varied individually. The immunohistochemical results in cryostats were in good accordance with those in cell cultures. Expression of TGFbeta1 both in cryostats and cell cultures significantly correlated with the lack of cytotoxic activity of autologous TILs. Representative data can be obtained in tumor culture systems of primary renal cell carcinoma. TGFbeta1 secretion could play an important role in the interactions between tumor and cytotoxic cells.

Carcinoma, Renal Cell↗
PubMed2001

In vitro glucuronidation of the cyclin-dependent kinase inhibitor flavopiridol by rat and human liver microsomes: involvement of UDP-glucuronosyltransferases 1A1 and 1A9.

The metabolism of flavopiridol (FLAP), a novel anticancer drug currently undergoing clinical development, was investigated in rat and human liver microsomes. In the presence of uridine 5'-diphosphoglucuronic acid, two biotransformation products (M1 and M2) could be detected. Formation of metabolite M1 and M2 in terms of enzymatic efficacy (Vmax/K(M)) was about 50- and 5-fold higher in rat (1.58 +/- 2.23 and 7.22 +/- 1.17 microl/min/mg) as compared with human liver microsomes (0.032 +/- 0.016 and 1.52 +/- 0.93 microl/min/mg), indicating species-related differences in FLAP glucuronidation. Incubation in the presence of human recombinant UDP-glucuronosyltransferases (UGTs) demonstrated that M1 is almost exclusively catalyzed by UGT1A1, whereas M2 is formed by UGT1A9 and only to a minor extent by UGT1A1 and UGT1A10. Chemical inhibition experiments further prove the involvement of UGT1A1 and UGT1A9 in the formation of M1 and M2, as the UGT1A1 substrate bilirubin preferably inhibited M1 over M2 (K(i): 36 and 258 microM, respectively), whereas the UGT1A9 substrate propofol showed a more pronounced decrease in M2 but not in M1 formation (K(i): 47 and 142 microM, respectively). Both conjugates were purified from rat liver microsomes and analyzed by mass spectrometry, NMR, and UV experiments. On the basis of these results, M1 was identified as 5-O-beta-glucopyranuronosyl-flavopiridol and M2 as 7-O-beta-glucopyranuronosyl-flavopiridol. In conclusion, our results elucidate the enzymatic pathways of FLAP in rat and human liver, which must be considered during cancer therapy of patients.

Animals↗
PubMed2000

Spike-driven synaptic plasticity: theory, simulation, VLSI implementation.

We present a model for spike-driven dynamics of a plastic synapse, suited for aVLSI implementation. The synaptic device behaves as a capacitor on short timescales and preserves the memory of two stable states (efficacies) on long timescales. The transitions (LTP/LTD) are stochastic because both the number and the distribution of neural spikes in any finite (stimulation) interval fluctuate, even at fixed pre- and postsynaptic spike rates. The dynamics of the single synapse is studied analytically by extending the solution to a classic problem in queuing theory (Takacs process). The model of the synapse is implemented in aVLSI and consists of only 18 transistors. It is also directly simulated. The simulations indicate that LTP/LTD probabilities versus rates are robust to fluctuations of the electronic parameters in a wide range of rates. The solutions for these probabilities are in very good agreement with both the simulations and measurements. Moreover, the probabilities are readily manipulable by variations of the chip's parameters, even in ranges where they are very small. The tests of the electronic device cover the range from spontaneous activity (3-4 Hz) to stimulus-driven rates (50 Hz). Low transition probabilities can be maintained in all ranges, even though the intrinsic time constants of the device are short (approximately 100 ms). Synaptic transitions are triggered by elevated presynaptic rates: for low presynaptic rates, there are essentially no transitions. The synaptic device can preserve its memory for years in the absence of stimulation. Stochasticity of learning is a result of the variability of interspike intervals; noise is a feature of the distributed dynamics of the network. The fact that the synapse is binary on long timescales solves the stability problem of synaptic efficacies in the absence of stimulation. Yet stochastic learning theory ensures that it does not affect the collective behavior of the network, if the transition probabilities are low and LTP is balanced against LTD.

Action Potentials↗
PubMed1999

[The rate of acetylsalicylic acid non-respondents among patients hospitalized for acute coronary disease, previously undergoing secondary salicylic acid prophylaxis].

The authors determined the rate of acetylsalicylic acid (ASA) non-responders among patients receiving secondary prevention due to cardiovascular diseases at the appearance of acute coronary events. The non-responders were defined as: patients who have been treated with ASA because of acute coronary syndrome, but the subsequently performed platelet aggregation study did not confirmed an appropriate platelet inhibition. Among the 75 patients being investigated (44 male, 31 female, average age: 61.3 ys) 21 were hospitalized due to acute myocardial infarction and 54 for unstable angina, respectively. The daily doses of ASA were 200-325 mg. The aggregation of platelets was measured within 24 h after the admission. The investigations were performed with different amounts of 4 different inducers (ADP, arachidonic acid, epinephrine and collagen) taking dose-response curves. The antiaggregatory treatment with ASA was considered to be ineffective if the typical aggregation curves were obtained above the following final concentrations of the inducers: ADP: > 5 microM, epinephrine: > 5 microM, arachidonic acid: > 250 microM, collagen: > 2 micrograms/ml. These upper-threshold concentrations of the inducers were determined with the help of the data of healthy drug free volunteers. Twenty-six of the 75 patients (34%) were found to be non-responder to ASA, whereas the antiaggregatory effect of ASA was proven in 49 cases. No differences were found in gender. The compliance was proven with the HPLC-determination of urinary metabolites of ASA performed immediately after the upon admission. Seven patients (10.9%) showed a non-compliance, not showing any traces of ASA-metabolites in their urine. The authors emphasizing the importance of the laboratory control even of the prophylactic ASA treatment in order to continue the effective antiaggregatory therapy with other effective drugs.

Acute Disease↗
PubMed1997

Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat.

Rat liver cells express the multispecific organic anion transporter (cmoat, cmrp, mrp2) and P-glycoprotein (Pgp) in their canalicular membranes, proteins that are homologous to the multidrug-resistance related protein (MRP) and multidrug resistance (MDR) gene products in multidrug resistant tumor cells. We tested whether genistein, a modulator of drug resistance in tumor cells, affects biliary secretion of substrates of canalicular multispecific organic anion transporter (cmoat) (glucuronides of bilirubin and rhodamine, glutathione conjugate of bromsulphthalein) and of P-glycoprotein (Pgp) (rhodamine), respectively. Using the isolated perfused rat liver of control Wistar rats (TR+) and of a mutant strain (TR-) that expresses Pgp but not cmoat, we show that genistein effectively inhibits the secretion of anionic substrates of cmoat in Wistar rats but stimulates secretion of cationic rhodamine in TR- rats. Genistein is subject to glucuronidation and sulfatation and secretion of genistein and its metabolites stimulates bile flow in Wistar rats, but secretion is nearly absent in TR- rats. Because genistein and its metabolites are substrates for cmoat, inhibition of anion secretion by genistein is partially explained by competition for this transporter. Genistein is also a substrate of uridindiphosphate (UDP)-glucuronyltransferase isoenzyme(s). Inhibition of glucuronidation reduces the availability of bilirubin and rhodamine glucuronates for transport via cmoat, but unconjugated cationic rhodamine becomes available for transport via Pgp at an increased cellular concentration. Daidzein, a genistein analogue with no effect on protein tyrosine kinase (PTK) shows Similar effects on secretion of organic anions and cations supporting the conclusion that genistein affects transport in liver mainly through competition with other substrates at the sites of glucuronidation and transport via cmoat.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

The acute response of left ventricular filling dynamics to intravenous verapamil predicts the changes in exercise tolerance after oral verapamil therapy in patients with hypertrophic cardiomyopathy.

We studied the correlation between changes in left ventricular filling dynamics induced by acute intravenous administration of verapamil and the changes in exercise tolerance induced by oral administration of the agent in 30 patients with hypertrophic cardiomyopathy. Diastolic cardiac function was measured by means of a nuclear stethoscope before and 10 min after intravenous administration of verapamil, 0.15 mg.kg-1 over 2 min. Treadmill exercise tests using a modified Bruce protocol were performed before the initiation of oral verapamil treatment and after 4 weeks of oral therapy at a dose of 320-360 mg.day-1 (mean +/- SD 332 +/- 17 mg.day-1). Peak filling rate (PFR) increased in 21 patients, 18 of whom (86%) also had an increase in exercise duration, PFR showed no increase in nine patients, eight of whom (89%) had no change in exercise duration (sensitivity 95%, specificity 73%, predictive value of the positive result 86%, predictive value of the negative result 89%). Acute changes in time from the beginning of rapid filling to PFR (t-PFR) and in left ventricular end-diastolic volume (EDV) were less useful in predicting improvement in exercise tolerance. In 19 patients the changes in PFR and EDV paralleled. Twelve of the 13 patients (92%) with an increase in both parameters also had an increase in exercise duration, whereas all six in whom these parameters were reduced showed no increase in exercise duration (sensitivity 100%, specificity 86%, predictive value of positive results 92%, and predictive value of negative results 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

[Questions concerning two-stage reconstruction of injured flexor tendons. III. Ultrastructure of the tenosynovium in the pseudo-tendon sheath created by using a silicone rod].

Authors have investigated the ultrastructure of the pseudo tendon sheath, formed with silicon rod and man. They have observed a superficial structure, resembling the normal tendon sheath in scanning electron microscopic examination. With transmission electron microscopy phagocyte "A" type and secretion "B" type synovial cells were found. Authors state that the newly formed tenosynovium has an important role in the nutrition of the tendon graft and the prevention of adhesions.

Animals↗
PubMed1993

[Epidemiology of hand injuries in Vas County based on a survey].

Authors have found in a 1 year survey in the county Vas 7580 hand injuries. The major proportion of young men and adolescents in the material was conspicuous. The types of accidents were investigated together with the place of the accident and types of the injury. The material shows that in contrary to the work accidents in the recent past the number of the accidents at home has increased--and so their prophylaxis became the main point.

Accident Prevention↗
PubMed1992

[Abdominal injuries in polytraumatised patients].

Authors have observed in 1978-1984 in 87 of 214 polytrauma cases injuries of the abdominal organs. The data concerning children in whom the high ratio of injuries of the abdominal organs and the low mortality are conspicuous are shown separately. The necessity of urgent diagnosis to which especially the abdominal irrigation has given great help is stressed. After a review of the literature and a control of their own material the problem is considered as actual, as in polytraumas the abdominal injuries are frequent, the valuation of the abdomen in the patient, generally in shock or unconscious is problematic, the many times simultaneous therapy of the abdominal and joined injuries is difficult, the mortality high.

Abdominal Injuries↗
PubMed1991

[Incidence of fractures of the proximal femur and the distal end of the forearm (results of a Vas County survey compared to international data)].

Authors analysing the one year material of injured in one county, state the age and sex specific incidence in the two types of fractures. Compared with other European data they found difference in male/female distribution: the values concerning women are substantially lower in the county Vas, those of men are on the other side equal. To clear the difference and the tendency further examinations are thought to be necessary, especially regarding the increasing importance of femoral fractures of the hip region in public health and national economy.

Europe↗
PubMed1990

[Classification of polytraumatized patients, experience with the ISS system].

Authors assessed the process of healing of 161 polytraumatized patients from 1976- to 1987, treated intersively, using the ISS system. Mortality was 27 per cent. Independently from the ISS system the concomittant shock foretold invariably a bad prognosis, although this was also joined generally to a big point number. The ISS system is simple and characterized the degree of the injury well. Through it, it will be possible to measure the gravity of the injury, to estimate statistically the prognosis and to compare the different materials. The number of points in the ISS system shows a good correlation with the survival (death) and the length of the intensive treatment. No patient was lost below 28 points whereas over 49 only 2 have survived. The point value may give information only up to the level of statistical probability concerning the prognosis (or the activity of the treatment) of the single patients. Because of its simplicity, its wide spreading and good practical use the general introduction of the ISS point system, as basic system, is thought to be advisable. For a more accurate judging a further making better and completing of the system (age, conjoined diseases, factors influencing each other mutually) further of the use, if necessary, of the scores applied in accident surgery and intensive therapy seems to be suggested.

Critical Care↗
PubMed1989

Assessment of the intracardiac left to right shunts with a single scintillation probe.

In order to assess the accuracy of pulmonary time-activity curves obtained at bedside with a single scintillation probe and Technetium-99m-labelled erythrocytes, pulmonary to systemic flow ratio (Qp:Qs) was calculated for radionuclide and hemodynamic investigations in 104 patients with suspected intracardiac left to right shunts. Cardiac catheterization confirmed the presence of shunts in 76 patients. Pulmonary time-activity curve was 100% sensitive, 88% specific, and 96% accurate in detecting the shunt. Correlation between the radionuclide and hemodynamic Qp:Qs was excellent (r = 0.93). Results were classified in four quantitative categories according to the Qp:Qs values. In 76 patients (73%) radionuclide and hemodynamic data fell in the same category. We conclude that radionuclide pulmonary time-activity curves generated with a scintillation probe is a reliable method in quantitative assessment of intracardiac left to right shunts.

Adolescent↗
PubMed1989

Independent evaluation of a multidisciplinary rehabilitation program for chronic low back pain.

Severe chronic low back pain was diagnosed in 236 patients by one physician and they were referred to the University of Miami Comprehensive Pain and Rehabilitation Center (UMCPRC) over a 5-year period for an intensive 4-week inpatient treatment program. Of these 143 (61%) were able to be contacted by telephone and given a structured interview designed for the study. The average time elapsed at follow-up from referral for all patients was 22.5 months. Outcome was measured in the following terms: current levels of pain, percent decrease in pain, subsequent health care utilization, activities of daily living, and attitudes toward treatment. After completion of the interview, the McGill Pain Questionnaire and the Oswestry Low Back Pain Disability Questionnaire were sent to the patients. The patients fell into five groupings: Group 1--participants in the UMCPRC program (n = 39); Group 2--those whose participation was not approved by insurance (n = 30); Group 3--those who declined participation (n = 46); Group 4--participants in other programs (n = 14); Group 5--dropouts (n = 14). The five groups were not meaningfully different with regard to prereferral demographics. Interestingly, Group 1 patients exhibited significantly greater prereferral pain and unemployment levels. Despite this, at follow-up significantly more Group 1 members were employed and they exhibited a greater percent decrease in pain as compared to the nonparticipant groups. Returned McGill and Oswestry Questionnaires mirrored these findings. Group 1 members also demonstrated significantly lower rates of subsequent health care utilization, i.e., physician visits, hospitalizations, and surgery than the nonparticipant groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Immunohistochemical and immunologic changes in aponeurosis in Dupuytren's disease].

Authors examined the aponeurosis of 23 patients with Dupuytren's contracture and of 5, formerly healthy persons, who died in consequence of accidents. It was found that the IgA and IgM content of the palmar aponeurosis is significantly elevated in Dupuytren's disease. The distribution of the immunglobulin containing cells and the fibronection localisation of the aponeurosis was also examined. On the basis of their examinations they think that the autoimmun mechanism may have a role in the development of Dupuytren's disease.

Dupuytren Contracture↗