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Biomedical subjects

A L Jones

Publications and source records attributed to A L Jones.

At least 127 records · Page 7Linked to original sources
PubMed1994

Characterization of mutagenic activity in cooked-grain-food products.

Wheat gluten or flour from several plant sources heated at 210 degrees C for 1 hr produced 0-1800 revertant colonies/g in the Ames/Salmonella test using strain TA98 with metabolic activation. Baked or toasted foods and a heated grain beverage showed a mutagenic response in all cases from 2 to 320 revertants/g, with higher values seen when overcooked. Fried meat-substitute patties showed 0-23 revertants/g when fried at 210 degrees C. A greater mutagenic response in bacterial strain TA98 than in strain TA100 and a requirement for metabolic activation suggests that one or more aromatic amine mutagens are formed at normal cooking temperatures, but the mutagenic activity measured cannot be accounted for by the known heterocyclic amines commonly found in cooked meats. We conclude that grain products from aromatic amine chemicals during heating that are mutagenic in bacterial mutation tests.

Amines↗
PubMed1994

Formation of mutagenic activity from amino acids heated at cooking temperatures.

To investigate the formation of aromatic amine-like mutagenic activity in cooked grain foods, amino acids were heated alone or in binary combinations at either 150 or 210 degrees C. About half of the binary mixtures of arginine heated with other amino acids produced potent mutagenic responses in the Ames/Salmonella assay, but only cysteine produced mutagenic products when heated alone. One-to-one molar ratios of arginine heated with threonine, valine, cystine, cysteine or tryptophan produced reaction products that gave 1200-3200 revertants/mmol in Salmonella strain TA98 with metabolic activation. 1-Methylguanidine, a fragment of arginine, produced a mutagenic response when heated alone or in binary mixtures with all amino acids tested. Analysis of reaction product extracts by solid-phase extraction and HPLC failed to find the known heterocyclic amines commonly found in cooked meats that would explain the measured mutagenic activity. As judged by biological and chemical characterization, several new aromatic amine mutagens are formed by heating some simple amino acids combined with arginine, and these reactants may be the source of the mutagenic products detected in the extracts of some cooked grain-based foods.

Amino Acids↗
PubMed1994

Preparation of a pure 99mTc-F(ab')2 radioimmunoconjugate by direct labeling methods.

Intact IgG and Fab' can be labeled directly with 99mTc to give quantitative incorporation of radioactivity into the protein. With F(ab')2 the reductive conditions yield a mixture of 99mTc-F(ab')2 and 99mTc-Fab'. We now report a direct labeling method to produce only 99mTc-F(ab')2 in quantitative yield and contaminated with 99mTc-Fab'. The properties, stability and biodistribution of the 99mTc-F(ab')2 have been compared to 99mTc-Fab'. This new technology will allow us to compare technetium direct-labeled IgG, F(ab')2 and Fab' derivatives of the same antibody for radioimmunodetection.

Animals↗
PubMed1994

A pilot study of intraperitoneal cisplatin in the management of gastric cancer.

BACKGROUND: This phase II trial was designed to evaluate the feasibility, toxicity, relapse pattern and survival following adjuvant intraperitoneal cisplatin in patients with gastric cancer at high risk of relapse. PATIENTS AND METHODS: Patients who had undergone complete surgical resection of adenocarcinoma of the stomach and who had positive serosa and/or regional lymph nodes and/or peritoneal washings has insertion of either a Tenckhoff catheter or temporary peritoneal dialysis catheter and were treated with cisplatin 60 mg/m2 intraperitoneally every 21 days for 4-6 courses. Peritoneal lavage or cytology was done before each treatment. RESULTS: Eighteen patients were studied. Seventeen patients had serosal involvement, 11 had regional lymph node involvement and 2 had positive peritoneal washings before treatment. The median number of courses of chemotherapy was 4 (range 2-6). Radioisotope tracer studies (6 patients) showed good distribution throughout the peritoneal cavity. No WHO grade 3/4 toxicity was seen. Twelve patients (67%) have relapsed, 6 (33%) intra-abdominally, 4 (22%) with hepatic metastases and 2 (11%) outside the abdominal cavity. The median survival was 17 months. CONCLUSIONS: Cisplatin can be administered safely as adjuvant therapy to patients with gastric cancer, however, as single agent therapy the pattern of relapse and subsequent death was similar to that expected. The occurrence of distant metastases may argue for systemic rather than local adjuvant treatment.

Adenocarcinoma↗
PubMed1994

The product of the virB4 gene of Agrobacterium tumefaciens promotes accumulation of VirB3 protein.

The process of T-DNA transfer from Agrobacterium tumefaciens to plant cells is thought to involve passage of a DNA-protein complex through a specialized structure in the bacterial membrane. The virB operon of A. tumefaciens encodes 11 proteins, of which 9 are known to be located in the membranes and 10 have been shown to be essential for virulence. Sequence comparisons between proteins encoded by the virB operon and those encoded by operons from conjugative plasmids indicated that VirB proteins may form a structure similar to a conjugative pilus. Here, we examine the effects of mutations in virB4 on the accumulation and localization of other VirB proteins. VirB4 shares amino acid sequence similarity with the TraC protein of plasmid F, which is essential for pilus formation in Escherichia coli, and with the PtlC protein of Bordetella pertussis, which is required for toxin secretion. Polar and nonpolar virB4 mutants were examined, and all were shown to be unable to accumulate VirB3 protein to wild-type levels. A low level of VirB3 protein which was present in induced NT1RE cells harboring virB4 nonpolar mutant pBM1130 was found to associate with the inner membrane fraction only, whereas in wild-type cells VirB3 associated with both inner and outer membranes. The results indicate that for VirB3 to accumulate in the outer membrane, VirB4 must also be present, and it is possible that one role of VirB4 is in the correct assembly of a VirB protein membrane structure.

Agrobacterium tumefaciens↗
PubMed1994

Portal and systemic haemodynamic action of N-acetylcysteine in patients with stable cirrhosis.

The effects of intravenous N-acetylcysteine on hepatic and systemic haemodynamics were investigated in 11 patients with stable cirrhosis (eight alcohol; two primary biliary cirrhosis; one cryptogenic). N-acetylcysteine administration had no effect on the mean heart rate or mean arterial blood pressure despite a significant fall in systemic and pulmonary vascular resistance. Cardiac index increased but estimated liver blood flow and portal venous pressure did not change significantly. Administration of N-acetylcysteine resulted in increased oxygen delivery to the tissues because of the increased cardiac index but this was not accompanied by a rise in either arteriovenous oxygen extraction ratio or mean tissue oxygen consumption. Therefore N-acetylcysteine administration seems to confer no haemodynamic benefit to patients with cirrhosis.

Acetylcysteine↗
PubMed1994

Purification and characterization of a protease from Pseudomonas pseudomallei.

Pseudomonas pseudomallei is the causative agent of melioidosis, a glanders-like disease of humans and animals. The pathogenesis of melioidosis is not well understood, and the role of various extracellular enzymes produced by P. pseudomallei in the development of this disease is not known. The present studies were designed to purify and characterize an extracellular protease produced by P. pseudomallei isolates and to test the hypothesis that this protease may play a role in melioidosis. The protease was present in culture supernatants as an enzyme with a molecular weight of 36,000 that was optimally active at 60 degrees C and at pH 8.0. The P. pseudomallei protease was shown to be a metalloenzyme requiring iron for maximal activity, and activity was inhibited in the presence of ethylenediaminetetraacetic acid (150 mM). Antibodies directed against an alkaline protease produced by Pseudomonas aeruginosa cross-reacted with the P. pseudomallei protease. These data indicate that the P. pseudomallei protease belongs to the family of alkaline proteases sensitive to metal chelators. Purified P. pseudomallei protease was capable of digesting a variety of eucaryotic protein substrates including immunoglobulins. A P. pseudomallei strain deficient in protease production was shown to be less virulent than the parental strain in an animal model of lung infection. These data suggest that this protease may be a significant pathogenic determinant in infections caused by P. pseudomallei.

Amino Acid Sequence↗
PubMed1994

Phase II study of continuous infusion fluorouracil with epirubicin and cisplatin in patients with metastatic and locally advanced breast cancer: an active new regimen.

PURPOSE: To investigate the efficacy and toxicity of continuous infusion fluorouracil (5-FU) with every-3-weeks epirubicin and cisplatin (ECF) in advanced breast cancer in a phase II study. PATIENTS AND METHODS: Forty-three patients with metastatic (n = 29) or locally advanced/inflammatory (n = 14) breast cancer were treated with 5-FU 200 mg/m2/d via a Hickman line using an ambulatory pump for 6 months with epirubicin 50 mg/m2 intravenously (IV) and cisplatin 60 mg/m2 IV every 3 weeks, for eight courses. RESULTS: The overall response rate (complete plus partial) was 84% (95% confidence interval [Cl], 76% to 96%), with a complete response rate of 24% (95% Cl, 9% to 40%) in patients with metastatic disease and 36% (95% Cl, 11% to 61%) in patients with locally advanced disease. The main World Health Organization [WHO] grade 3 or 4 toxicities included leukopenia, emesis, and alopecia. CONCLUSION: Infusional ECF is a highly active regimen in advanced breast cancer and warrants evaluation in high-risk early breast cancer.

Adult↗
PubMed1994

Interobserver agreement in the classification of open fractures of the tibia. The results of a survey of two hundred and forty-five orthopaedic surgeons.

The system of Gustilo and Anderson for the classification of open fractures is commonly used as a basis for treatment decisions and for comparison of the published results of treatment. The reliability of this classification system was tested on the basis of the responses of 245 orthopaedic surgeons to a survey. The respondents were asked to provide data about their age, type of practice, and type of training; the number of open fractures of the tibia that they treated each year; and their use of the Gustilo-Anderson classification system. They were also asked to classify twelve open fractures of the tibia on the basis of a series of videotaped case presentations. Each case presentation on the color videotape included demographic data on the patient, a history of the injury, the results of the physical examination, the appearance and dimensions of the open wound before the operation, preoperative radiographs, and selected portions of the operative débridement with narration. The level of agreement for the classification of each fracture was determined according to the largest percentage of observers who chose a single classification type. The average agreement among the observers for all twelve fractures was 60 percent. The over-all agreement for each fracture ranged from 42 to 94 percent. The average agreement in the subgroup of surgeons who were considered to have the least experience (residents and fellows) was 59 per cent (range, 33 to 94 percent).(ABSTRACT TRUNCATED AT 250 WORDS)

Fractures, Open↗
PubMed1994

Prognostic factors in lumbar spinal fusion.

The charts of 234 patients who underwent 260 spinal fusions for degenerative spinal disease were reviewed to determine prognostic factors for predicting successful surgical outcome. All patients were evaluated for fusion success and symptomatic relief. Pseudarthrosis occurred in 26 patients (10%) and 14 others failed to have symptomatic improvement despite successful fusion. Outcome was found to be significantly related to smoking status, diagnosis, use of hardware, insurance status, preoperative SGPT level, prior operations or decompressions, and age. The relative risk associated with smoking was 2.9. The association with smoking was present for both subjective and objective poor outcomes. A predictive function based on smoking status and diagnosis was developed. Ninety-two percent of nonsmokers with favorable diagnoses had a good outcome, compared to 77% of those with unfavorable diagnoses. The percentages for the comparable groups of smokers were 77% and 54%.

Adolescent↗
PubMed1994

Navelbine and the anthrapyrazoles.

This article reviews the preclinical and early clinical development of navelbine and the anthrapyrazoles. The differences in structure from the "parent" compounds that may confer clinical advantages are discussed. The preclinical data, clinical pharmacology, and Phase I trials are reviewed. Further development of these drugs in Phase II trials and comparative studies is also discussed.

Anthraquinones↗
PubMed1994

Organic nitrates in portal hypertension.

In conclusion, chronic administration of organic nitrates, allowing for a nitrate-free interval each day, to cirrhotic patients reduces portal pressure with a variable, dose-dependent effect on azygos blood flow. The mechanisms of portal pressure reduction may vary according to the different doses and severity of liver disease. No studies to date have used dose-titration to determine the optimal beneficial effects in an individual patient, but some have at least compared the effect of different doses. Perhaps an end-point of mean arterial blood pressure reduction to 70 mm Hg could be suggested for future studies. The prophylactic benefit of nitrates for variceal bleeding still remains to be tested by controlled clinical trials. However, several problems in this evaluation need to be addressed, including patient compliance, selection of responders, evaluation of treatment, dose, and the duration of treatment. In contrast to the diminished expectations of propranolol for the prevention of rebleeding, there is mounting evidence of a major role for nitrates.

Animals↗
PubMed1993

The human phenolsulphotransferase polymorphism is determined by the level of expression of the enzyme protein.

We have examined the expression of platelet phenolsulphotransferase (PST) in 60 individuals. Using an antibody which recognizes both forms of PST present in man (P-PST and M-PST), we determined that the polymorphism of platelet P-PST activity is determined by the level of expression of the enzyme protein. The implications for susceptibility to adverse drug reactions and chemical carcinogenesis are discussed.

Arylsulfotransferase↗
PubMed1993

Common food additives are potent inhibitors of human liver 17 alpha-ethinyloestradiol and dopamine sulphotransferases.

Interactions between dietary xenobiotics, drugs and biologically active endogenous compounds are a potential source of idiosyncratic adverse pathology. We have examined the inhibition of the sulphation of a number of xenobiotics and endobiotics in human liver cytosol by 15 food additives and constituents. Sulphation of dehydroepiandrosterone was resistant to inhibition by all compounds tested; however, dopamine sulphotransferase (ST) activity was inhibited strongly by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine and vanillin. Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was inhibited by vanillin, erythrosin B and octyl gallate. Of these compounds, only vanillin was found to be sulphated to a significant extent by both human liver and platelets, and vanillin was determined to be a substrate for the monoamine-sulphating isoenzyme of phenolsulphotransferase. Vanillin was found to inhibit 50% of liver EE2 ST activity (IC50) at a concentration of approximately 1.3 microM and the mode of inhibition was non-competitive. The implications of these results for the adverse side effects associated with food additives and oral contraceptives are discussed.

Arylsulfotransferase↗
PubMed1993

Rapid induction of microsomal delta 12(omega 6)-desaturase activity in chilled Acanthamoeba castellanii.

The activity of microsomal delta 12-desaturase in Acanthamoeba castellanii was increased after growing cultures were chilled from the optimal growth temperature (30 degrees C) to 15 degrees C. This increase was detectable in microsomes isolated from organisms subjected to only 10 min chilling. The mechanism of induction was investigated. The increase in activity on chilling was greatly reduced when protein synthesis was blocked before the temperature shift. Thus the major mechanism for the induction of delta 12-desaturase is increased protein synthesis. delta 12-Desaturase activity was higher when assayed at 20 degrees C than when assayed at 30 degrees C, but these changes were not due to the increased solubility of O2 at 20 degrees C. The major substrate of delta 12-desaturase was found to be 1-acyl-2-oleoyl phosphatidylcholine.

Acanthamoeba↗