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B Toth

Publications and source records attributed to B Toth.

At least 19 recordsLinked to original sources

C8-Arylguanine and C8-aryladenine formation in calf thymus DNA from arenediazonium ions.

Arylhydrazides, arylhydrazines, and N-alkyl-N-arylnitrosamines are metabolized to arenediazonium ions which yield C8-arylpurine adducts in calf thymus and cellular DNA. The mechanism of adduct formation has not been fully elucidated. C8-Arylguanine adducts likely form from direct aryl radical (Ar*) addition to the C8 position of guanine. However, the amounts of C8-aryladenine adducts measured here are inconsistent with direct radical attack at the C8 position of adenine. An intermediate product, an aryltriazene, is likely formed which then decomposes to the C8-aryladenine adduct. We have demonstrated that N1-aryl-N3-purinyltriazene adducts are formed from a variety of para-substituted arenediazonium ions with adenine. Decomposition of the N1-aryl-N3-purinyltriazene, at high pH and elevated temperatures, has been shown to give C8-aryladenine derivatives, and a free radical mechanism for this process has been proposed. Here we show that this process can occur under physiological conditions and that the C8-aryladenine adduct can be quantitated by HPLC. ESR studies, in which DMPO was used as a spin trap, have been used to demonstrate the intermediacy of aryl radicals during the decomposition of the N1-aryl-N3-purinyltriazenes and to demonstrate that this process also occurs in calf thymus (ct) DNA treated with arenediazonium ions. These results suggest the involvement of an aryl radical in the formation of the observed DNA adducts. Finally, we have found that the treatment of ct DNA with arenediazonium ions produces a significant amount of depurination. Both the formation of C8-arylguanine and C8-aryladenine adducts and the generation of apurinic sites may contribute to the genotoxicity of arylhydrazides, arylhydrazines, N-alkyl-N-arylnitrosamines, and arenediazonium ions.

Adenine↗

Increased blood vessel density in decidua parietalis is associated with spontaneous human first trimester abortion.

Spontaneous pregnancy loss affects 15-18% of couples, and a number of potential causes are being discussed. The purpose of the present study was to assess if angiogenic disorders in the decidua of early human pregnancy could be related to spontaneous abortions. First trimester human decidua from elective terminations of normally progressing pregnancies and from missed abortions were investigated immunohistochemically. We quantified vessel density in decidua from normal pregnancies and from abortions by von Willebrand factor (vWF), platelet endothelial cell adhesion molecule (PECAM-1) and CD34 staining. Decidual blood vessel expression of alphavbeta3 integrin was also investigated. Significant increase (P < 0.02) in vessel density was observed in decidua parietalis of abortions, compared to decidua basalis. This increase was detected on slides stained for vWF and CD34, but not for PECAM-1. We observed a 15% increase analysing with vWF and a 77% increase with CD34 staining. alphavbeta3 integrin expression was not significantly different, neither in decidua parietalis from abortion, nor parietalis from normal pregnancies. Our data suggest that the increased vascularization in decidua parietalis from abortions could reflect complex disorders, such as specific cytokine expressions and hypoxia phenomena during the development of the decidua.

Abortion, Induced↗

Immunophenotyping of acute lymphoblastic leukaemia in routinely processed bone marrow biopsy specimens.

AIMS: To assess the value of immunophenotyping of acute lymphoblastic leukaemia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and enable differentiation from acute myeloid leukaemia. METHODS: 45 routinely processed bone marrow biopsy specimens (formalin fixed, paraffin embedded and mildly decalcified in EDTA) reported to contain leukaemic infiltrates on the basis of cytomorphological and enzyme-cytochemical analysis of bone marrow smears (22 c-ALL, 11 T-ALL, 2 B-ALL, 10 u-ALL (unclassified)) were immunostained by the ABC method with a broad panel of 26 antibodies against various haemopoietic antigens. RESULTS: Staining with antibodies directed against myeloperoxidase and lysozyme showed that seven cases were either biphenotypic or mixed leukaemias (2), or of myelogenous origin (acute myeloid leukaemia (AML)-M1 (2); AML-M4 (2); AML-M5a (1)). Five of these seven cases had been diagnosed initially as u-ALL. Three further cases with no compact leukaemic infiltrates were excluded. ALL was confirmed in the remaining 35 cases. Because of revised diagnoses, the total numbers of ALL subtypes changed (23 c-ALL, 8 T-ALL, 2 B-ALL, 2 u-ALL). Immunostaining of more than 10% of blast cells in at least one case was found with 19 of the 26 antibodies. The most sensitive lineage specific antibodies for diagnosis were found to be anti-CD10 for c-ALL (22/23) and beta F1 for T-ALL (6/8). Expression of aberrant antigens was fairly common--for example, 7/23 cases of c-ALL stained with antibodies against T cell associated antigens. CONCLUSIONS: Immunohistochemical investigation of routinely processed bone marrow biopsy specimens enables reliable detection of ALL subtypes c-ALL and T-ALL. A minimum panel of antibodies, against TdT, CD34, myeloperoxidase, lysozyme, CD10, CD79a, and CD20, and the antibody beta F1, is proposed for the immunophenotyping of acute leukaemia.

Antigens, Neoplasm↗

The effect of extraction of third molars on late lower incisor crowding: a randomized controlled trial.

The problem of late mandibular incisor crowding is a well established phenomenon, the cause of which has been the substance of considerable debate over the years. A central issue is the possible role of the third molars though no definitive conclusions have been consistently drawn. This prospective study was designed to investigate the effects of randomly assigned early extraction of third molars on late crowding of the mandibular incisors. One-hundred-and-sixty-four patients entered the study from 1984 following completion of retention after orthodontic treatment. Seventy-seven patients (47%) returned for records up to a mean of 66 months later, and their start and finish study casts were digitized on a reflex microscope to determine Little's index of irregularity, intercanine width and arch length. Forty-four of the patients had been randomized to have third molars removed. There was no evidence of responder bias. Where third molars were extracted the mean increase in lower labial segment irregularity was reduced by 1.1 mm from a mean of 2.1 mm for the group where third molars were retained (P = 0.15, not statistically significant). This difference was also not considered to be clinically significant. The principal conclusion drawn from this randomized prospective study is that the removal of third molars to reduce or prevent late incisor crowding cannot be justified.

Adolescent↗

Subacute uremic and diabetic polyneuropathy.

We present 4 patients who had a subacute, predominantly motor polyneuropathy associated with diabetes mellitus and end-stage renal disease. Electrophysiological studies and muscle biopsy indicated a primary axonal degeneration of nerve with secondary segmental demyelination, and mild to moderate, acute and chronic denervation of muscle. A relative absence of denervation potentials on needle electromyography was an unusual feature. Three of our patients improved with a switch from conventional to high-flux hemodialysis. We speculate on possible mechanisms.

Aged↗

Aryl radical formation during the metabolism of arylhydrazines by microsomes.

Many arylhydrazines are genotoxins, although the mechanism of their genotoxicity is unknown. Previous studies have shown that arylhydrazines are metabolized to arenediazonium ions, which produce C8-arylguanine adducts in DNA suggesting the intermediacy of an aryl radical. Here we have looked for the formation of aryl radicals from arylhydrazines and microsomes by ESR spin trapping. Only hydroxyl radicals are trapped upon incubation of p-methylphenylhydrazine with rat liver microsomes and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). However, hydroxyl and aryl radicals were trapped upon incubation of p-(methoxymethyl)phenylhydrazine with rat liver microsomes. Evidence for hydroperoxyl radical formation was also obtained. In contrast, when either of these substrates was incubated with microsomes from C5O cells, aryl and hydroxyl radicals were trapped. The ESR signal intensity of the spin-trapped aryl radicals parallels the extent of C8-arylguanine formation in DNA, and therefore, the aryl radical is likely the intermediate responsible for C8-arylguanine adduct formation. Aryl radicals and C8-arylguanine adducts may be related to the genotoxicity of arylhydrazines and related compounds that are oxidatively metabolized to arenediazonium ions, the precursor to aryl radicals, including arylalkyl nitrosamines, arylazo compounds, and triazenes.

Animals↗

Outbreak of sporotrichosis among tree nursery workers.

In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was conducted to identify risk factors for sporotrichosis, and an environmental investigation was done. The risk of sporotrichosis increased significantly with the duration of working with sphagnum moss (P < .05), in particular with filling topiaries (P < .05), and with having less gardening experience (P < .05). Wearing gloves was protective (P < .005). Sporothrix schenckii was cultured from patients and sphagnum moss used in topiary production. Use of restriction fragment length polymorphism revealed an identical pattern for patient isolates that was different from the patterns of environmental isolates. Physicians should be aware of sporotrichosis in patients with ulcerative skin lesions who have a history of occupational or recreational exposure to sphagnum moss.

Adult↗

Did the introduction of general practice fundholding change patterns of emergency admission to hospital?

OBJECTIVES: To test the hypothesis that the introduction of general practice fundholding was associated with a change in the proportion of emergency admissions to hospital. METHODS: Before and after natural experiment with control group. The experimental group was first-wave fundholding general practices in the South Western Regional Health Authority, the control group was all practices that remained non-fundholding as of April 1993. Data were collected on episodes of care in hospitals in the South Western region involving cholecystectomy, hernia repair, intervertebral disc operation and prostatectomy. The additional impact of fundholding status on any underlying changes in proportions of emergency admissions was examined using multiple logistic regression. RESULTS: There was no evidence of an interaction between fundholding status and before/after time period. Odds ratios and confidence intervals for the interaction of general practice fundholding status and time were: prostatectomy 1.02 (0.77 to 1.34); hernia repair 0.94 (0.7 to 1.24); intervertebral disk operations 1.67 (0.8 to 3.47); prostatectomy 0.94 (0.69 to 1.27). CONCLUSIONS: The results provide no evidence that, in the first 2 years of the scheme, fundholding had an impact on the proportion of emergency admissions to hospital.

Budgets↗

8-Arylguanine adducts from arenediazonium ions and DNA.

Arenediazonium ions (ArN2+) are genotoxic though the source of their genotoxicity is unknown. The present studies were undertaken to determine if reductive decomposition of ArN2+ to aryl radicals (Ar) in the presence of calf thymus DNA (ctDNA) or in cells results in the formation of DNA adducts. We found that when arenediazonium ions of the general structure p-X-ArN2+ (X = CH3, CH2OCH3, CH2OH) are allowed to react with ctDNA or incubated with cells under conditions that produce p-X-Ar, DNA adducts are formed with guanine. The structure of the adduct is the C8-substitution product derived from guanine and p-X-Ar. Formation of p-X-Ar was determined by ESR spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The extent of C8-arylguanine adduction was measured by high performance liquid chromatography (HPLC) analysis of the DNA hydrosylate and comparison with authentic synthetic standards. The C8-arylguanine adducts observed to form may be important in regard to the genotoxicity of ArN2+, though other DNA adducts such as the N6-triazene of adenine or C8-aryladenine adducts can form. Finally, though the formation of C8-arylguanine adducts from arenediazonium ions has been proposed, this is the first report demonstrating their formation in DNA.

Animals↗

Meta-analysis.

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Bias↗

Agaricus bisporus: an assessment of its carcinogenic potency.

This assessment focuses on the concentrations of some chemicals present in the Agaricus bisporus mushroom, the cancer-inducing doses of these chemicals or mushroom used in the animal experiments, the total amounts of these chemicals or mushroom needed to induce cancer in these mice, and the estimated total amounts of these chemicals or mushroom needed to induce cancer in humans. By adding the estimated amounts of chemicals needed to induce cancer and by comparing it with the amount of raw mushroom needed to induce the same effect, it becomes obvious that we have accounted for less than 2% of the carcinogenic components of the Agaricus bisporus mushroom. Since some unavailable data handicapped this assessment, it should be regarded as tentative and subject to further adjustment.

Agaricus↗

A clinical evaluation of a blood conservation device in medical intensive care unit patients.

OBJECTIVES: This study was designed to a) document the efficacy of a device intended to conserve blood in critically ill patients; b) determine the effect of this blood conservation on hemoglobin concentration and the need for blood transfusions; c) determine if the blood conservation device resulted in interference with arterial pressure waveforms; d) determine if use of the blood conservation device resulted in a difference in the number of accidental needle punctures suffered by healthcare workers. DESIGN: Prospective, randomized, controlled trial. A clinical trial using prospective, random allocation of consecutive eligible patients. SETTING: The medical intensive care unit (ICU) of a university hospital located in a large metropolitan area. PATIENTS: A total of 100 patients who were admitted to the medical ICU, required arterial line monitoring for clinical purposes, and were managed by the ICU medical service. Exclusion criteria included active bleeding or chronic renal failure at the time of ICU admission. INTERVENTIONS: Patients in the experimental group had a blood conservation device incorporated into the arterial pressure monitoring system, while patients in the control group received a conventional arterial pressure monitoring system. MEASUREMENTS AND MAIN RESULTS: Data gathered included: age; gender; ICU discharge status; the duration of ICU stay; time in the study; volume of all blood drawn, discarded, or lost due to leakage; hemoglobin concentrations; blood transfusions; and accidental needle injuries. Arterial pressure waveforms were recorded and inspected for dampening or other deformation. Mean hemoglobin concentrations were compared on ICU admission and at 12-hr intervals. Demographic and clinical characteristics of the two groups were not significantly different. The volume of blood drawn and discarded from arterial catheters was significantly lower in the blood conservation group (blood conservation device: 5.7 +/- 7.5 mL; control: 96.4 +/- 88.5 mL; p < .0001), as was the total volume of blood discarded (blood conservation device: 19.4 +/- 47.4 mL; control: 103.5 +/- 99.9 mL; p < .0001). Mean hemoglobin concentration on admission was similar in the two groups (blood conservation device group: 11.8 +/- 2.5 g/dL; control group: 12.6 +/- 2.3 g/dL). In both groups, the mean hemoglobin concentration declined most rapidly in the first 24 hrs of ICU care and, thereafter, declined more slowly. Although the mean hemoglobin concentration was higher in the blood conservation group after 6 days, statistical significance was not reached until 9.5 days of ICU care. The mean change in hemoglobin concentration (overall: 1.2 +/- 2.2 g/dL) during the study represents a statistically significant (p < .0001) decrease of 9.7%. Hemoglobin concentration during the study decreased by 1.4 +/- 2.2 g/dL in the control group and 1.0 +/- 2.3 g/dL in the blood conservation group (p = nonsignificant). Univariate and multiple regression analysis demonstrated discarded blood volume to be a significant and independent predictor of the decline in hemoglobin concentration. Transfusion requirements were similar in both groups. The blood conservation system did not alter or interfere with pressure waveforms. There were no accidental needle injuries noted. CONCLUSIONS: The conservation of blood in critically ill patients must be a high-priority concern of all healthcare workers. Our data indicate that the blood conservation system eliminates a significant factor in the decline in hemoglobin concentration. With devices as described here, there is no reason to continue the practice of wasting the blood of critically ill patients in order to prevent preanalytic error.

Adult↗

Cancer induction in mice by feeding the raw false morel mushroom Gyromitra esculenta.

One of the false morel mushrooms, Gyromitra esculenta, was administered p.o. to Swiss mice that were 6 weeks old at the beginning of the experiment. The mushrooms were fed to the mice for 3 days and were followed by a semisynthetic diet for 4 days each week for life. The treatment induced tumors in the lungs, nasal cavity, blood vessels, forestomach, glandular stomach, cecum, and liver in the following incidences: 80, 10, 50, 16, 4, 28, and 6% in females, and 70, 12, 32, 18, 20, 22, and 12% in males. In the untreated controls, the corresponding tumor incidences were 28, 0, 14, 0, 0, 8, and 0% in females and 38, 0, 6, 0, 0, 8, and 2% in males. The light microscopic examination revealed the typical appearance of adenomas and adenocarcinomas of lungs, adenomas and adenocarcinomas of nasal cavities, hemangiomas and hemangiosarcomas of blood vessels, squamous cell papillomas and carcinomas of the forestomach, adenomas and adenocarcinomas of the glandular stomach, polypoid adenomas and adenocarcinomas of the cecum, and hepatomas. The work demonstrates the carcinogenic action of the raw G. esculenta mushroom.

Animals↗

Poisoning by Gyromitra esculenta--a review.

Gyromitra esculenta (Pers.: Fr.) Fr. and a few other mushrooms have caused severe poisonings and even deaths in humans. Clinical data are characterized primarily by vomiting and diarrhoea, followed by jaundice, convulsions and coma. Gastrointestinal disorders distinguish this poisoning. Frequent consumption can cause hepatitis and neurological diseases. The species of concern are mainly G. esculenta and G. gigas (Kromb.) Cooke (non Phill.). Nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other Ascomycetes species also may prove toxic. Gyromitrin (acetaldehyde methylformylhydrazone, G) and its homologues are toxic compounds that convert in vivo into N-methyl-N-formylhydrazine (MFH), and then into N-methylhydrazine (MH). The toxicity of these chemicals, which are chiefly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments using animals, cell cultures and biochemical systems. When we consider the chemical nature and the reactivity of these natural compounds, we suggest that chemical and biochemical mechanisms may explain their intrinsic biological activity.

Animals↗