The role of the mutT gene of Escherichia coli in maintaining replication fidelity

Some general features of the respiratory chain and respiratory control were characterized in coupled mitochondrial preparations from Leishmania mexicana promastigotes. O2 uptake was sensitive to the electron-transfer inhibitors rotenone, flavone, malonate, 4,4,4-trifluoro-1-(2-thienyl) 1.3 butanedione (TTFA), antimycin A, 2n-nonyl-4-hydroxyquinoline-N-oxide (HQNO), myxothiazol, cyanide and azide. A high concentration of rotenone (60 microM) was required to inhibit O2 uptake effectively. Difference spectra revealed the presence of cytochromes (a + a3), b and c. Respiratory control was stimulated 2-fold by ADP with different exogenous oxidizable substrates. Calculated ADP/O ratios were consistent with the notion that ascorbate/N,N,N',N'-tetramethylphenylenediamine (TMPD)-linked and FAD-linked respiration proceeds, respectively, with one third and two thirds of the ATP producing capacity of NADH-linked respiration. State 3 was suppressed by the ATP synthase inhibitors oligomycin and aurovertin and by the adenine nucleotide translocator inhibitors atractyloside and carboxy atractyloside. The protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) provoked state 3u respiration. The mitochondrial preparation was capable of Ca2+ uptake and Ca2+ stimulated respiration. Data obtained suggests strongly that mitochondrial complexes I, II, III and IV are present in a major pathway of electron-transfer and that oxidative phosphorylation might proceed with high bioenergetic efficiency.     

Recovering urine from diapers: are test results accurate?

During dialysis the ion concentrations in many body fluids change significantly. The influence of these changes on the accuracy of volume measurements with bioimpedance spectroscopy is investigated by the following procedure: Plasma ion concentrations and impedance spectra (5-500 kHz) are measured during six standard haemodialyses. Intracellular ion concentrations are estimated using a multi-compartment model. Intra- (ICV) and extracellular (ECV) volumes are calculated using a fluid distribution model (FDM) based on Hanai's mixture theory. The input variables of the FDM are intra- and extracellular resistance data that have been fitted from impedance spectra with a Cole-Cole model. Resistivity changes (RCs) due to concentration changes of Na+, K+, Cl-, HCO3- and unspecified intracellular ions are estimated. The FDM is corrected for the RCs. Corrected ICVs and ECVs are calculated and compared with uncorrected values. The range of relative RCs between the start and end of the dialyses is -3.2% to 1.4% in the ECV and -3.7% to 1.7% in the ICV. From the RCs, volume estimation errors of -1.0% to 1.9% (ECV) and -1.2% to 2.1% (ICV) relative to the initial values have been calculated. At the end of dialysis, the percentage of the error with respect to the volume change is < 15% for the ECV but > 20% for the ICV. Consequently, a correction of the FDM for RCs is necessary to obtain more reliable ICV data.     

Pulmonary hypoplasia presented in adulthood as a chronic respiratory failure: report of two cases. Embryology, clinical symptoms and diagnostic procedures

The efficacy and safety of single-dose ceftriaxone and multiple-dose cefuroxime as antibiotic prophylaxis for pleuropulmonary surgery were compared in 160 patients undergoing thoracic surgery. 82 patients received a single-dose of 2 g ceftriaxone intravenous prior to surgery. Seventy-eight patients received 1.5 g of cefuroxime i.v. prior to surgery and 750 mg i.m. every 8 hours for the next 48 hours. Patients were observed daily for ten days postoperatively and monitored for signs of wound and systemic infections. Postoperative infections were studied in each treatment group. No adverse postoperative infections effects or laboratory abnormalities attributable to either drug were noted. Those results indicate that single-dose ceftriaxone was as effective and well-tolerated as a multiple-dose cefuroxime in preventing postoperative infections following pleuropulmonary surgery.     

Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators

Restenosis after coronary angioplasty occurs in at least 30% of patients in the first six months and, as yet, there is no known treatment to decrease this event. We tested a monoclonal antibody Fab fragment (c7E3) directed against the platelet glycoprotein IIb/IIIa integrin, the receptor mediating the final common pathway of platelet aggregation, to see whether it reduced the frequency of clinical restenosis. Patients who had unstable angina, recent or evolving myocardial infarction, or high-risk angiographic morphology, were randomised to receive c7E3 bolus and a 12 hour infusion of c7E3 (708 patients), c7E3 bolus and placebo infusion (695 patients), or placebo bolus and placebo infusion (696 patients). With maintenance of the double-blind state, patients were followed-up for at least 6 months to determine the need for repeat angioplasty or surgical coronary revascularisation and the occurrence of ischaemic events. By 30 days, 12.8% of placebo bolus/placebo infusion patients had had a major ischaemic event (death, myocardial infarction, urgent revascularisation), compared with 8.3% of c7E3 bolus/c7E3 infusion patients, yielding a 4.5% difference (35% reduction, p = 0.008). At 6 months, the absolute difference in patients with major ischaemic event or elective revascularisation was 8.1% between placebo bolus/placebo infusion and c7E3 bolus/c7E3 infusion patients (35.1% vs 27.0%; 23% reduction p = 0.001). The favourable long-term effect was mainly due to less need for bypass surgery or repeat angioplasty in patients with an initial successful procedure, since need for repeat target vessel revascularisation was 26% less for c7E3 bolus/c7E3 infusion than for placebo treatment (16.5% vs 22.3%; p = 0.007). The c7E3 bolus/placebo infusion group had an intermediate outcome which was not significantly better than that of the placebo bolus/placebo infusion group. These results extend the benefit of c7E3 bolus/c7E3 infusion from reducing abrupt closure and acute-phase adverse outcomes to a diminished need for subsequent coronary revascularisation procedures. Because this therapy carries a risk of bleeding complications and has been studied only in high-risk angioplasty patients, further evaluation is needed before it can be applied to other patient groups.     

Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes

To date, at least four genes involved in DNA mismatch repair (MMR) have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colon cancer: hMSH2, hMLH1, hPMS1, and hPMS2. Additionally, loss of MMR function has been demonstrated to lead to the phenomenon of microsatellite instability (MIN) in tumors from these patients. In this study, we have examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in paraffin-embedded tumors from 7 patients with MIN+ sporadic cancer, 13 patients with familial colorectal cancer, and 12 patients meeting the strict Amsterdam criteria for hereditary nonpolyposis colon cancer. The relationship between the expression of these two gene products, the presence of germline or somatic mutations, and the presence of tumor MIN was examined. Nineteen of the 28 tumors studied demonstrated MIN, whereas mutations in hMLH1 and hMSH2 were detected in 6 and 2 patients, respectively. Of the eight MIN+/mutation+ cases, the absence of protein expression was observed for the corresponding gene product in all but one case (missense mutation in hMLH1). However, seven MIN+/mutation- cases also showed no expression of either hMLH1 (n = 5), hMSH2 (n = 1), or both (n = 1), whereas four MIN+/mutation- cases demonstrated normal expression for both. None of the MIN-/mutation- cases (n = 9) demonstrated an altered expression pattern for either protein. These data suggest that examination of protein expression by immunohistochemistry may be a rapid method for prescreening tumors for mutations in the MMR genes.