A wheat glutathione-S-transferase gene with transposon-like sequences in the promoter region.
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Biomedical subjects
Publications and source records attributed to J Bull.
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We have used a cDNA clone encoding a pathogen-induced putative wheat peroxidase to screen a genomic library of wheat (Triticum aestivum L. cv. Cheyenne) and isolated one positive clone, lambda POX1. Sequence analysis revealed that this clone contains a gene encoding a putative peroxidase with a calculated pI of 8.1 which exhibits 58% and 83% sequence identity to the amino acid sequence of the turnip (Brassica rapa) peroxidase and a pathogen-induced putative wheat peroxidase, respectively. The two introns in the wheat gene are at the same positions as introns in the peroxidase genes of tomato and horseradish. Results of S1-mapping experiments suggest that this gene is neither pathogen- nor wound-induced in leaves but is constitutively expressed in roots.
Intestinal permeability to a monosaccharide and a disaccharide was compared by simultaneous measurement of the urinary excretion of L-rhamnose and lactulose after oral ingestion of an hypertonic solution containing both sugars. Urine samples were analysed for sugar content by quantitative thin-layer or paper chromatography. Results in thirteen patients with untreated villous atrophy were compared with those in twelve healthy volunteers. Urinary L-rhamnose excretion was significantly decreased (-40%, p less than 0.02) in patients with villous atrophy, whereas lactulose excretion was paradoxically and significantly increased (+345%, p less than 0.01). The median value of the lactulose/L-rhamnose urinary excretion ratio was sevenfold higher in the patients with villous atrophy; there was no overlap of values for patients and volunteers (p less than 0.01). It is postulated that reduced L-rhamnose urinary excretion in untreated villous atrophy is due to a decreased absorptive area in the small bowel, whereas increased lactulose excretion indicates leakiness of the abnormal mucosa to larger polar molecules.
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5% of 2612 homosexual males attending genitourinary clinics were found to be hepatitis-B surface-antigen (HBsAg) positive. Liver biopsy was done in 25 who had abnormal liver-function tests but no symptoms or signs of liver disease, and 14 (56%) of these proved to have chronic active hepatitis or active cirrhosis. Neither the liver-function tests nor the viral markers in serum reflected the severity of the liver disease. 38% of a group of 118 HBsAg positive patients were HBeAg positive, and sexual contacts of these individuals may be at serious risk of infection.
The intercurrent administration of doxorubicin hydrochloride to a patient undergoing whole-body hyperthermia for the treatment of metastatic cancer repeatedly produced ventricular irritability and cardiac dysfunction. Individually, doxorubicin and hyperthermia were tolerated by the patient without incident. Catecholamine determinations showed that the administration of doxorubicin under hyperthermic conditions increased the liberation of both epinephrine and norepinephrine. The acute synergistic cardiotoxic effects occurred with doxorubicin dosages that were severalfold less than those associated with only mild and transient ECG disturbances under normothermic conditions.
A teacher with breathlessness of insidious onset developed acute symptoms on return home following his discharge from hospital. His flat was found to have extensive dry rot (Merulius lacrymans). Precipitins and specific IgE and IgG antibody against M. lacrymans were present and intracutaneous testing gave a typical dual skin reaction. Pulmonary physiology demonstrated airflow obstruction with a low DLCO and KCO, and a chest X-ray showed diffuse micronodular shadowing, maximal in the mid-zones. Inhalation challenge testing provoked a combined asthmatic reaction without a change in DLCO. Rapid clinical recovery and more gradual radiographic and physiological improvement followed cessation of exposure to the antigen.
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The intrinsic factor (IF) output during basal and Histalog-stimulated gastric secretion has been estimated in two series of patients with chronic duodenal ulcer before and 3 months or more after treatment by either highly selective vagotomy or truncal vagotomy and pyloroplasty. The effects of the two different vagotomy operations appear to be virtually identical and each produced significant reductions in intrinsic factor secretion after Histalog stimulation. This confirms the view expressed by previous workers that it is the vagotomy as such which is responsible, excluding the drainage procedure from any possible role. Furthermore, as these results were demonstrated 3 months after operation, it is likely that the depressed IF secretion is a permanent feature and one which, it is postulated, may become progressively more severe. In both series there is a marked reduction in IFoutput during the second hour of stimulated gastric secretion, indicating an early wash-out of preformed IF. This persists after vagotomy.
The effects of exposure of bone marrow to specific methotrexate (MTX) concentrations were studied by constant infusion of the drug into C57BL mice. The residual marrow nucleated cell count was determined in 168 mice at specific intervals. In vitro culture of colony-forming cells (CFU-C) was also performed in 69 of these mice. Duration of exposure varied from 12 to 72 hr. Plateau plasma MTX concentrations were studied in the range from 10(-8) to 10(-5) M. The total number of nucleated cells per femur fell to a nadir of 30% of control for all drug concentrations studied. The nadir was reached earliest with the highest drug concentrations. The percentage of CFU-C per 7.5 X 10(4) nucleated cells plated increased after 48-hr infusions compared to the percentage after 24-hr infusions. This increase was seen at all plasma concentrations studied. The total number of CFU-C per femur at plasma MTX concentrations above 10(-6) M decreased in the first 24 hr to 40% of control, but then the number significantly increased to 66% of control between 24 and 48 hr. In contrast, no change was observed in CFU-C per femur between 24 and 48 hr during constant infusion at plasma concentrations below 10(-6) M. Wright's-stained smears showed no change in the differential count of marrow specimens at 24 and 48 hr that might account for the increased percentage of CFU-C at 48 hr. The increase in CFU-C per femur during high-dose infusions is probably the result of recruitment of CFU-C. The increased percentage of CFU-C suggests recruitment at the lower concentrations as well, but selective elimination of non-CFU-C cells cannot be excluded. Marrow [6-3]deoxyrudine incorporation studies in vivo during exposure to 10(-7) M MTX showed that the phenomenon of recruitment observed in vitro was initiated during the absence of DNA synthesis in vivo.
A phase 1 to 2 evaluation of a combination of adriamycin (ADR) and dibromodulcitol (DBD) was performed in patients with progressive, metastatic breast carcinoma. All but one patient had been treated previously with chemotherapy. ADR was given on Day 1 or Days 1 and 8, and DBD was given on Days 1 to 10 of each 21- to 28-day treatment cycle. Side effects were evaluable in 54 patients, and 50 patients were evaluable for therapeutic response. The dose-limiting toxicities were leukopenia and thrombocytopenia. The severity of both toxicities increased as both the ADR and DBD doses increased; however, the effect of increases in DBD dose was much more profound. The mean white blood cell count and platelet nadirs occurred, respectively, on Days 15.3 and 15.9; both nadirs were delayed for 0.6 day by each 30-mg/sq m/day increase in the DBD dose and delayed for 1.7 to 3.9 days using the Day 1, 8 rather than the Day 1 ADR schedule Recovery of the peripheral counts by Day 29 was prolonged by the Day 1, 8 ADR schedule and by increasing the DBD dose. A tolerable dose schedule for previously treated patients was considered to be ADR, 40 mg/sq m on Day 1, and DBD, 135 mg/sq m on Days 1 to 10 repeated every 28 days. Responses were observed in 46% (23 of 50) of the patients. There were 1 complete remission, 19 partial remissions, and 3 improvements. Thirteen patients showed no change and 14 developed progressive disease. There were responses in 13 of 37 (36%) with visceral dominant disease as compared to 7 of 8 (87%) with osseous and 3 of 5 (60%) with soft tissue-dominant disease. There were 22 of 48 (46%) responses in patients previously exposed to alkylating agent therapy. Twnety-two patients had responded and 19 had failed to respond to prior alkylating agent-containing regimens; the response rates to DBD in these groups were respectively, 45 and 42%. The median time to remission was 29 days. The median time to therapeutic failure was 5.1 months for responders, 2.3 months for patients with no change, and 29 days for progressors. The combination of ADR and DBD appears to be an active and well-tolerated program in patients with previously treated metastatic breast carcinoma.
Dibromodulcitol was administered orally on Days 1-10 every 3-4 weeks to 29 patients with metastatic breast carcinoma refractory to previous combination chemotherapy. Initial doses between 70 and 280 mg/m2/day were utilized. The dose was escalated as tolerated in subsequent cycles in individual patients. Hematosuppression was dose-limiting. At doses of greater than 200 mg/m2/day leukopenia (greater than 1000 cells/mm3) and thrombocytopenia (greater than 25,000 platelets/mm3) occurred in one of 28 cycles and two of 27 cycles respectively. In contrast, at doses of less than or equal to 200 mg/m2/day leukopenia and thrombocytopenia occurred in four of 18 cycles and five of 18 cycles respectively. Recovery of leukocytes (less than 4000 cells/mm3) and platelets (less than 100,000 platelets/mm3) by Day 29 after the start of therapy was also delayed at higher doses. Responses were observed in three of 29 evaluable patients and subjective improvement of osseous disease in one additional patient. A dose of 180 mg/m2/day X 10 Every 28 days is recommended in previously treated patients to avoid severe hematologic side effects.
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Three patients in whom serious haemorrhagic complications occurred as a result of interaction of phenylbutazone with warfarin are described. A suggestion as to how this could be avoided is put forward.