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T Fekete

Publications and source records attributed to T Fekete.

At least 19 recordsLinked to original sources
PubMed2000

Photoreceptor distribution in the retinas of subprimate mammals.

Relevant data on the distribution of color cones are summarized, with special emphasis on the marked dorsoventral asymmetries observed in a number of mammalian species. In addition, an overview is given of studies that demonstrate the coexistence of two visual pigments within the same cone cell. The biological significance of these phenomena is discussed in conjunction with comparative immunocytochemical analyses of subprimate retinas. Based on various cone distribution patterns and temporal and spatial visual pigment coexpression, two models of cone photoreceptor differentiation are suggested.

Animals↗
PubMed2000

Cone differentiation with no photopigment coexpression.

PURPOSE: To decide whether the transitory coexpression of cone visual pigments described in the developing rat and gerbil retina is a universal feature of dichromatic mammalian species. METHODS: The rabbit, a species widely used in eye research, was selected for the study and a search made for the presence of cones that bound more than one cone antibody during the first postnatal week. To plot the densities of individual cone types and to colocalize the two visual pigments, immunocytochemistry on retinal wholemounts and consecutive tangential sections, respectively, were used. RESULTS: The sequence in which the visual pigments began to be expressed was the same as that observed in other mammals: first, rhodopsin; second, blue pigment; and last, green pigment. The striking increase in blue cone density numbers observed in the rat, however, did not occur in the rabbit. Instead, some days after the first blue cones appeared, the green cones also started to express their visual pigment, and this cone type soon outnumbered the blue cones. Within the limits of the immunocytochemical method, it was established that unlike the developing rat, the presence of double-labeled cones was not a character of the rabbit retina. CONCLUSIONS: Visual pigment coexpression is an interesting phenomenon of retinal development, however, it is not the exclusive scenario of photoreceptor differentiation. Each species must be carefully studied before deciding whether its retinal cones synthesize both pigments during retinal development.

Animals↗
PubMed1999

Human pancreatic leiomyosarcoma (PZX-7) growing as a serially transplantable xenograft in immunosuppressed mice.

BACKGROUND: Several human leiomyosarcoma xenografts have been established, but pancreatic smooth muscle sarcomas have never been serially transplanted and investigated. METHOD: Immunosuppression of CBA/CA mice was achieved by thymectomy, whole-body irradiation, and bone marrow reconstruction. Tumor fragments were subcutaneously implanted from a Grade III pancreatic leiomyosarcoma and serially passaged for more than 24 mo. The xenografted tumors were characterized by morphological, morphometrical, biochemical, and flow cytometric methods. RESULTS: The tumor has retained its characteristic morphology and no further differentiation occurred. The mitotic counts and the amount of the connective tissue all remained constant. The calculated volume doubling time was 11.3 d. Immunohistochemically, the tumor proved to be p53-negative, but the strong expression of the bcl-2 remained as a constant feature throughout successive transplantations. The DNA index and the proliferation indices did not change significantly with the time (mean DI: 1.65, range: 1.561-1.70; mean PI: 17.9%, range: 15.3-20.7%). Lactose dehydrogenase (LDH) isoenzyme electrophoresis evidenced a retained human pattern of the tumor even after 32 mo of transplantations. CONCLUSION: The first human pancreatic leiomyosarcoma xenograft (PZX-7) growing in immuno-suppressed mice is described and characterized.

Animals↗
PubMed1998

Position- and base pair-specific comparison of p53 mutation spectra in human tumors: elucidation of relationships between organs for cancer etiology.

A new approach to analyze the p53 mutation database of the European Molecular Biology Laboratory for a comparison of mutation spectra is described, with the aim of investigating organ specificity of etiological factors and putative organ-to-organ relationships in cancer pathogenesis. The number of entries of each nucleotide- and base-pair substitution-specific mutation was divided by the total number of tumors analyzed. For each organ pair, the difference of the mutation-specific frequency differences was calculated. Resulting values could range from 0 (full concordance) to 2 (full discordance). Skin, lung, and urinary bladder showed highly independent mutation spectra (maximum discordance value = 1.48 for skin versus brain), in agreement with the presence of specific factors responsible for a large number of the respective tumors (UV light, smoking, aromatic amines). The three organs with the smallest sum of discordance values were mammary gland (breast), colon and esophagus. The minimum organ-to-organ discordance value was 0.95, for stomach versus colon. For these organs, common, possibly also endogenous, cancer risk factors could be postulated as contributing to the observed mutation spectrum. The remaining cancers (ovary, sarcoma, leukemia/lymphoma, brain, head and neck, and stomach, in order or increasing discordance) were of intermediate range and showed a mix of values. Reasons for close relationship to some of the other organs and marked differences to others are discussed. Exclusion of the "hot-spot" mutations did not markedly alter the observed relationships, indicating that a putative selective growth advantage does not cover up the etiological basis for the observed mutation spectrum. It is expected that much more insight into carcinogenesis and cancer could be gained by further exploratory analyses of mutation databases.

Base Composition↗
PubMed1998

Effects of fibrates on the glycine conjugation of benzoic acid in rats.

In the course of glycine conjugation, benzoic acid is successively converted into benzoyl-CoA and benzoylglycine by mitochondrial enzymes (i.e. benzoyl-CoA synthetase and benzoyl-CoA/glycine N-acyltransferase, respectively), utilizing ATP, CoA, and glycine. Large doses of benzoate deplete CoA from the liver, suggesting that the supply of CoA may limit the capacity for glycine conjugation. Because fibrates are known to increase hepatic CoA synthesis, we examined whether treatment with fenofibrate or bezafibrate enhanced the capacity of rats to conjugate benzoic acid with glycine. Dietary administration of fenofibrate or bezafibrate (2.5 mmol/kg of feed, for 10 days) increased hepatic CoA levels 8-10-fold, while not affecting hepatic ATP levels; only fenofibrate elevated, albeit moderately, the concentration of glycine in liver. Hepatic mitochondria isolated from fibrate-fed rats, compared with those from controls, exhibited unchanged benzoyl-CoA synthetase activity but higher benzoyl-CoA hydrolase and lower benzoyl-CoA/glycine N-acyltransferase activities. Feeding with either fibrate increased liver mass by 50-60%. Control and fibrate-fed rats were administered benzoate at different doses, one to produce a large demand for CoA (i.e. 2 mmol/kg, iv) and two others to produce smaller demands for CoA (i.e. 1 mmol/kg or 2 mmol/kg plus glycine, iv). Fenofibrate-fed rats, and to a lesser extent bezafibrate-fed animals, exhibited increased glycine conjugation capacity, as indicated by faster disappearance of benzoate from the blood and appearance of benzoylglycine in the blood and urine, compared with controls; however, fibrates were not more effective in rats receiving the benzoate dose that produced the greatest demand for CoA. In contrast, benzoylglycine formation from benzoate (0.1-1 mM) was not enhanced in liver slices from fibrate-fed rats; moreover, it was lower than control levels in slices from bezafibrate-fed animals. Bezafibrate, but not fenofibrate, given to rats in a single dose (0.5 mmol/kg, ip) decreased the elimination and glycine conjugation of benzoate, indicating that bezafibrate is a direct inhibitor of glycine conjugation. In summary, fibrates influence glycine conjugation in a complex manner. Some fibrate-induced alterations (i.e. increased benzoyl-CoA hydrolase and decreased glycine transferase activities and direct inhibition by bezafibrate) can potentially hinder conjugation of benzoate with glycine, thus precluding conclusions regarding whether increased CoA availability enhances glycine conjugation. Fibrate-induced hepatomegaly appears to significantly contribute to the increased glycine conjugation capacity of rats treated with fenofibrate or bezafibrate.

Animal Feed↗
PubMed1996

Comparative susceptibilities of Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa to 11 antimicrobial agents in a tertiary-care university hospital.

The in vitro activity of cefepime was compared versus that of 10 antimicrobial agents commonly used in the treatment of serious infections caused by common aerobic gram-negative bacteria: aztreonam, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, ticarcillin-clavulanic acid, and tobramycin. We tested 30 clinical isolates representing a cross section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa collected at our tertiary-care university hospital. The most potent beta-lactams were imipenem and cefepime, which demonstrated significant activity against the majority of strains in all 3 genera of bacteria tested, as did ciprofloxacin and tobramycin. Ceftazidime was active against Pseudomonas aeruginosa but was less potent against Klebsiella and Enterobacter spp. Cefoperazone and ceftriaxone were less active than ceftazidime against Pseudomonas aeruginosa. Cefepime was found to be highly active against many resistant organisms that traditionally have been difficult to treat.

Anti-Bacterial Agents↗
PubMed1996

Dose-time response in mouse skin tumor induction by 7, 12-dimethylbenz[a]anthracene and 12-O-tetradecanoyl-phorbol-13-acetate.

The question was addressed whether the dose-response relationship derived from a carcinogenicity study can be used for mechanistic interpretation and to what extent the shape of the curve is dependent on the duration of the bioassay and the time of analysis. The mouse skin tumor model was used. It allows recording of the time of tumor appearance without interim sacrifice. Groups of 16 female NMRI mice were treated twice weekly by dermal administration with combinations of (a) 2.5 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) plus 0, 0.3, 1, 3, or 10 nmol 7,12-dimethylbenz[a]anthracene (DMBA) or with (b) 2.5 nmol DMBA plus 0, 0.1, 0.3, 1, 3, or 10 nmol TPA. The appearance of the first papilloma was recorded for each animal and the cumulative incidence data were analyzed in two ways: (i) With the usual dose-prevalence representation at a fixed time point, the dose response for TPA was sigmoidal, while it was linear-superlinear for DMBA. This was observed at all time points, indicating that the dose-response information may be used for a distinction between DNA-reactive and tumor-promoting mechanisms of action. (ii) When time-to-tumor and loss of tumor-free lifetime was analyzed as a function of dose, there was again a marked difference between DMBA and TPA. The tumor-free lifetime increased with each step of dose reduction but the slope was about four times larger for TPA compared with that for DMBA. Further reduction of the TPA dose could result in a situation in which the natural life span sets a limit to an observable effect. Under the conditions of this bioassay for mouse skin papilloma induction by a combination treatment with DMBA plus TPA, the findings support the idea of a no-effect low-dose threshold for the tumor-promoting agent.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Endogenous and exogenous factors in carcinogenesis: limits to cancer prevention.

Organ-specific cancer incidence rates can vary dramatically between low- and high-incidence areas. Such differences are due to (1) heritable susceptibility determinants, (2) risk factors associated with the environmental and local living conditions (e.g., viruses, pollution), and (3) personal life-style factors. For organs showing large differences between cancer registries, exogenous factors might be most important, while for organs showing only small differences, endogenous and unavoidable factors are expected to be more important. In this paper, a working hypothesis based on descriptive cancer epidemiology is presented to estimate, in a quantitative manner, the unavoidable contribution to the process of carcinogenesis and to discuss limitations to individual cancer prevention. Cumulative cancer incidence rates for a 75-year period of life (CR74, in percent) were taken from IARC Scientific Publication No. 120 (1992). For each organ, values were ranked in ascending order, and the ratio between high-rate and low-rate registries (90th percentile/10th percentile) was determined. This measure of variability among registries differed strongly between organs. Largest ratios were seen for organs with well-known exogenous risk factors, such as pharynx, lip, tongue, mouth, liver, esophagus, and melanoma in males, and lung, esophagus, gallbladder, liver, and bladder in females. Small ratios were seen for rectum, brain, colon, and Hodgkin's disease in males, and breast, rectum, ovary, brain, and colon in females. It is concluded that the process of carcinogenesis in the latter organs has a stronger endogenous/unavoidable component, for some tissues possibly of hormonal type. A fictitious population was composed where, for each organ, the minimum reported cancer rate was taken. When based on all cancer registries world-wide, CR74 sums over all sites of 2.0% and 2.3% resulted in males and females, respectively. When only Central/Western European countries were included in the analysis in order to reduce differences in risk factors nos. 1 and 2, the sum of the minimum values was 10.4% and 8.7%. After correction of the data for smoking, 'minimum' cancer incidence rates in males and females were estimated to be 7.6% and 6.8%. Based on a median cancer incidence rate for nonsmoking males in Europe of about 21%, therefore, individual preventive measures taken by a nonsmoker can reduce the cancer risk, on average, 'only' by a factor of about 3. A considerable fraction of cases thus appears to be hardly avoidable.

DNA Damage↗
PubMed1996

Lipoic acid impairs glycine conjugation of benzoic acid and renal excretion of benzoylglycine.

Glycine conjugation of benzoic acid is catalyzed by the mitochondrial enzymes benzoyl-coenzyme A(CoA) synthetase and benzoyl-CoA: glycine N-acyltransferase and requires ATP, CoA, and glycine as cosubstrates. Lipoic acid (LA), an important endogenous and also therapeutic compound, depletes hepatic CoA; therefore, it may interfere with glycine conjugation. To test this hypothesis, LA (0.5-1.5 mmol/kg ip) was given to anesthetized, glycine-loaded rats 1 hr before administration of benzoic acid (1 mmol/kg iv). LA inhibited glycine conjugation of benzoic acid in a dose-dependent manner as indicated by: 1) reduced clearance of benzoic acid from blood; 2) delayed appearance of benzoylglycine in blood; and 3) decreased excretion of benzoylglycine in urine. LA also decreased urinary excretion of injected benzoylglycine, indicating that reduced excretion of this metabolite after benzoic acid injection is caused by diminished formation and impaired renal transport of benzoylglycine. Urine formation was decreased by LA in a dose-dependent fashion, and acute renal failure was evident in rats receiving the highest dose. LA depleted hepatic CoA, carnitine, and glutathione, but not ATP, whereas it increased the hepatic concentration of glycine. In isolated and solubilized rat liver mitochondria, LA inhibited both benzoyl-CoA synthetase (IC50 approximately 1.5 mM) and benzoyl-CoA:glycine N-acyltransferase (IC50 approximately 0.3 mM). Thus, depletion of CoA and inhibition of the pertinent enzymes seem responsible for impairment of glycine conjugation of benzoic acid by LA. LA may also impair renal tubular cell function, compromising the tubular secretion of benzoylglycine and causing acute renal failure.

Acyltransferases↗
PubMed1996

Does hepatic ATP depletion impair glycine conjugation in vivo?

Conjugation with glycine, a reaction important in the elimination of carboxylic acids (e.g. benzoic and salicylic acids), takes place in hepatic mitochondria and uses ATP, coenzyme A, and glycine. Although normal ATP supply does not limit glycine conjugation in vivo (Gregus, Z., et al., Drug Metab. Dispos. 20, 234, 1992), ATP deficiency may impair it. This hypothesis was tested by examining the effect of ATP depletors (oligomycin, fructose, and ethionine) on glycine conjugation and elimination of benzoic acid in rats. Pretreatment with the mitochondrial ATP synthesis inhibitor oligomycin (0.5-2 mg/kg, intraportally) decreased glycine conjugation of benzoic acid markedly and in a dose-dependent manner, as indicated by the delayed elimination of benzoate and delayed appearance of benzoylglycine in blood. Oligomycin also dramatically diminished urinary excretion of benzoylglycine, because it inhibited not only formation of benzoylglycine from benzoate, but also the renal transport of benzoylglycine. Treatment with fructose (a consumer of both cytosolic and mitochondrial ATP) or ethionine (a consumer of cytosolic ATP) depleted hepatic ATP from approximately 2.5 micromol/g to levels comparable with those observed after administration of 1 mg/kg oligomycin (approximately 1.2 micromol/g). Despite this, elimination of benzoate and formation of benzoylglycine were decreased less by fructose than by oligomycin and only negligibly by ethionine. ATP depletors did not influence hepatic glycine levels, and only oligomycin lowered coenzyme A levels in liver. However, the oligomycin-induced decline of hepatic coenzyme A levels was delayed, contrary to impairment of glycine conjugation, which was almost immediate. In summary, impairment of benzoylglycine formation by ATP depletors apparently correlates with their capacity to diminish ATP levels in hepatic mitochondria (i.e. at the site of glycine conjugation). These observations suggest that limited availability of mitochondrial (but not cytosolic) ATP reduces glycine conjugation capacity. Therefore, mitochondrium toxic agents and pathological mitochondrial injuries acting in liver may compromise glycine conjugation by decreasing ATP supply.

Adenosine Triphosphate↗
PubMed1994

A comparison of serial plate agar dilution, Bauer-Kirby disk diffusion, and the Vitek AutoMicrobic system for the determination of susceptibilities of Klebsiella spp., Enterobacter spp., and Pseudomonas aeruginosa to ten antimicrobial agents.

The use of rapid, automated technologies for assessment of antimicrobial susceptibility and determination of minimum inhibitory concentrations has been evolving for over a decade. We compared the Vitek AutoMicrobic system and Bauer-Kirby disk diffusion with the National Committee for Clinical Laboratory Standards methods of serial plate agar dilution for qualitative and quantitative susceptibilities of 301 hospital isolates of Klebsiella spp., Enterobacter spp., and Pseudomonas aeruginosa. Antibiotics tested were aztreonam, cefoperazone, ceftazidime, ceftriaxone, ciprofloxacin, gentamicin, imipenem, piperacillin, ticarcillin-clavulanic acid, and tobramycin. Agar dilution and Bauer-Kirby results were more strongly correlated for all three genera than were the results for agar dilution and Vitek. If agar dilution is presumed to be the "gold standard," Bauer-Kirby disk diffusion had only half the number of false susceptibles as did the Vitek. Thus, the Vitek AutoMicrobic system seems to be somewhat less reliable for both qualitative and quantitative measurement of susceptibility and resistance than is Bauer-Kirby disk diffusion.

Agar↗
PubMed1994

Investigation of a pseudo-outbreak of orthopedic infections caused by Pseudomonas aeruginosa.

OBJECTIVE: To report a pseudoepidemic of Pseudomonas aeruginosa infections discovered during an investigation of postoperative joint infections. DESIGN: A retrospective review of case patients' hospital charts, operative reports, and laboratory data, as well as environmental culturing, polymerase chain reaction (PCR) ribotyping of outbreak isolates, and in vitro analysis of P aeruginosa growth characteristics. SETTING: A 510-bed, university-affiliated adult tertiary care hospital. RESULTS: Between October 1 and December 1, 1992, seven postsurgical joint infections were diagnosed, including four caused by P aeruginosa. A bottle of "sterile" saline used to process tissue specimens was found to be contaminated with P aeruginosa. Further investigation revealed that P aeruginosa had grown from seven additional tissue cultures, all of which had been processed with the contaminated saline. PCR ribotypes of the contaminant matched those of the clinical isolates. In vitro, P aeruginosa strains were viable in commercial nonbacteriostatic saline, but never caused visible turbidity. Six patients received antibiotics for their presumed infections; four patients had peripherally inserted central catheters placed, and one experienced severe anaphylactic reactions to several antibiotics. CONCLUSIONS: Pseudoepidemics due to common organisms are often difficult to detect, and delayed recognition can result in substantial morbidity. This outbreak investigation illustrates the potential for contamination of diluents in the microbiology laboratory and emphasizes the need for meticulous quality control.

Adolescent↗
PubMed1993

Antimicrobial susceptibility testing of Neisseria gonorrhoeae and implications for epidemiology and therapy.

Antimicrobial susceptibility testing (AST) of Neisseria gonorrhoeae has been under development since the early days of antimicrobial agents. However, it is rarely applied to clinical isolates today. The history of the various in vitro tests to determine the susceptibility of N. gonorrhoeae to antibiotics is rich with evidence that these results predict response to therapy for almost all agents tested. Further, AST is a useful and important aspect of strain characterization and disease epidemiology in conjunction with the more specific but laborious techniques of auxotyping, serotyping, and plasmid analysis. Current technology has overcome many of the objections to AST for N. gonorrhoeae with standardization of test media and the development of an accurate disk diffusion AST method that is suited to most clinical laboratories regardless of volume or level of technical expertise. Ironically, the very low level of resistance to the current primary treatment strategy in the United States, ceftriaxone or another potent cephalosporin, makes the use of AST somewhat superfluous.

Anti-Bacterial Agents↗