Reaction of cytochrome P450 with cumene hydroperoxide: ESR spin-trapping evidence for the homolytic scission of the peroxide O-O bond by ferric cytochrome P450 1A2

ESR spin trapping was used to investigate the reaction of rabbit cytochrome P450 (P450) 1A2 with cumene hydroperoxide. Cumene hydroperoxide-derived peroxyl, alkoxyl, and carbon-centered radicals were formed and trapped during the reaction. The relative contributions of each radical adduct to the composite ESR spectrum were influenced by the concentration of the spin trap. Computer simulation of the experimental data obtained at various 5,5-dimethyl-1-pyrroline N-oxide (DMPO) concentrations was used to quantitate the contributions of each radical adduct to the composite ESR spectrum. The alkoxyl radical was the initial radical produced during the reaction. Experiments with 2-methyl-2-nitrosopropane identified the carbon-centered adducts as those of the methyl radical, hydroxymethyl radical, and a secondary carbon-centered radical. The reaction did not require NADPH-cytochrome P450 reductase or NADPH. It is concluded that the reaction involves the initial homolytic scission of the peroxide O-O bond to produce the cumoxyl radical. Methyl radicals were produced from the beta-scission of the cumoxyl radical. The peroxyl adduct was not observed in the absence of molecular oxygen. We conclude that the DMPO peroxyl radical adduct detected in the presence of oxygen was due to the methylperoxyl radical formed by the reaction of the methyl radical with oxygen. At a higher P450 concentration, a protein-derived radical adduct was also detected.     

One or two incisions for nephroureterectomy in transitional cell renal pelvis tumours

A retrospective study comprising 18 patients with transitional cell renal pelvis tumours (TCPT) was carried out to evaluate the results after two different surgical procedures for nephroureterectomy. The kidney was removed by a flank incision and the lower part of the ureter by either an incision in the lower part of the abdomen or intussusception of the ureter followed by transurethral resection of the ureteral orifice. Eight patients were subjected to nephroureterectomy by means of two incisions and another eight patients underwent a simple nephrectomy followed by ureteral intus-susception and transurethral resection. Two patients received other treatments. After nephroureterectomy with a separate incision for ureterectomy, the average hospital stay was 12 days, compared with 7.5 days in patients operated upon with only one abdominal incision. Recurrence of tumour or survival was not significantly different in the two groups.     

Manual dexterity of older Mexican American adults: a cross-sectional pilot experimental investigation

This paper reports results from an experimental pilot study performed to quantify the manual dexterity of older Mexican American adults. The Purdue pegboard test, a two-arm coordination test, and a hand-tool dexterity test were used in this study. To enable cross-sectional comparisons of manual dexterity measures of older Mexican American adults with young Mexican American adults, these tests were administered to 18 older Mexican American adults aged 63–85 (mean age: 71.3 years, SD: 7.0 years), recruited from senior recreation centers in El Paso, and eighteen young adults aged 21–32 (mean age: 25.6 years, SD: 3.8 years) recruited from the student body at the University of Texas at El Paso. For the Purdue pegboard test, the number of pegs placed in 30 s using the preferred hand, the non-preferred hand, and both hands were first individually monitored. Then, scores on an assembly task using the Purdue pegboard were obtained. For the two-arm coordination test, participants were required to trace a star pattern with a stylus using both hands. The time for task completion and the number of errors made during task performance were monitored. For the hand-tool dexterity test, participants were required to use common hand tools and remove nuts and bolts from one side of a wooden upright, and to assemble nuts and bolts in the corresponding holes on the other side of the upright. The time taken for task completion was recorded. Since modified Levene's test showed equality of variances, two sample t-tests, comparing the mean responses of older adults with the mean responses of young adults for each individual test, were conducted. Results indicate that responses for the older adults were statistically significant different (p<0.001) from young adults for all Purdue pegboard tasks. On the average, older adults performed significantly slower (p<0.001) than young adults on the two-arm coordination test, and committed more errors before task completion (p<0.05). Older adults also took longer to complete the hand-tool dexterity task compared to their younger counterparts (p<0.05). In addition to the t-tests, manual dexterity performance measures from older adults were regressed with age to determine the cross-sectional age effects on manual dexterity measures. Results indicate that all Purdue pegboard performance measures were significantly affected by age (p<0.05). The time to complete the two-arm coordination test was significantly linearly related to age (p<0.05). However, the number of errors committed by older adults in the performance of the two-arm coordination test was not significantly linearly related to age. Time to complete the hand-tool dexterity was also significantly linearly related to age (p<0.05). Accommodating age-related changes in manual dexterity is important for job design in industry, especially in industries employing older adults requiring significant assembly and hand-tool use.

Relevance to industry

Given the aging of the industrial workforce, it is important to understand how manual dexterity is affected by age, so that jobs requiring significant manual dexterity for task initiation, task performance and task completion are designed to fit older adult dexterity levels.     

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.     

Surgical release for intubation purposes in postburn contractures of the neck

One hundred and twenty-four patients over the age of 75 years were assessed for the cause of their macrocytosis (MCV > 95 fl). A definitive diagnosis was reached in 75/124 (60%) by non-invasive techniques. The remainder underwent a bone marrow biopsy yielding a definitive diagnosis in a further six patients who had an identifiable myelodysplastic syndrome (MDS). A high proportion of the remainder had morphological abnormalities which fitted with no recognized pathological entity. It is suggested that these may represent MDS in evolution.     

Effect of guanine nucleotides and temperature on calcitonin gene-related peptide receptor binding sites in brain and peripheral tissues

Recent data have suggested the existence of at least two major classes of calcitonin gene-related peptide (CGRP) receptors in brain and peripheral tissues [Henke et al., Brain Res., 410 (1987) 404-408; Dennis et al., J. Pharmacol. Exp. Ther., 251 (1989) 718-725; ibid, 254 (1990) 123-128; Quirion et al., Ann. NY Acad. Sci., 657 (1992) 88-105]. However, little is currently known in the structure characteristics of CGRP receptors as cloning as yet to be reported. In the present study, the sensitivity of [125I]humanCGRP alpha binding to guanine nucleotides and temperature was investigated in guinea pig atria (prototypical CGRP1 tissue) guinea pig vas deferens (prototypical CGRP2 tissue) and in the rat brain and cerebellum (mixed assay). Binding isotherms of [125I]hCGRP alpha in those four tissue preparations were curvilinear and best fitted to a two-site model under most assay conditions. The high affinity binding component was highly temperature-sensitive and accounted, under experimental conditions, for up to 18% of the total population of receptors. Moreover, these high affinity sites were also highly sensitive to guanine nucleotides (Gpp(NH)p, 100 microM) in all preparations although to a different extend depending upon assay temperatures. Taken together, this suggests that the different CGRP receptor subtypes present in these tissue all belong to a G-protein coupled receptor family.     

Activity of quinolones in the Ames Salmonella TA102 mutagenicity test and other bacterial genotoxicity assays

Eight quinolones were examined for their bacterial mutagenicity in the Ames Salmonella TA102 assay and for their effects in other bacterial genotoxicity assays. In the quantitative Ames plate incorporation assay, all eight quinolones induced His+ deletion reversion in Salmonella tester strain TA102, with maximum reversion observed at about two to eight times the MIC. The quinolones also induced the SOS response. At quinolone concentrations close to the MIC, SOS cell filamentation gene sulA was induced in sulA::lacZ fusion strain Escherichia coli PQ37. RecA-mediated cleavage of lambda repressor in lambda::lacZ fusion strain E. coli BR513 was measurable at about 10 times the MIC, though no induction occurred at 20 micrograms of nalidixic or oxolinic acid per ml. Genotoxicity of quinolones also was observed in the Bacillus subtilis DNA repair assay, in which the mutant strain M45 (recA) was more susceptible to quinolones than its parent strain, H17 (rec+). The results from these analyses indicate that quinolones induce SOS functions and are mutagenic in bacteria; these properties correspond to their antimicrobial activities.     

Guided tissue regeneration without a stage 2 surgical procedure

In the two cases described, the problems of insufficient bone and insufficient soft tissue in the edentulous ridge were addressed concurrently. Freeze-dried demineralized bone was used to fill the osseous defect. Freeze-dried fascia lata was used to prevent epithelial migration into the defect, act as a barrier, and eliminate a second surgery for membrane removal. This regeneration procedure can provide increased alveolar bone for better implant placement and esthetics.