A new proton-selective fluorescing indicator, 3,3′,5,5′-tetramethyl-
N-(9-anthrylmethyl)benzidine (TMANB) has been synthesized and applied in an optode membrane for the determination of lead ion that ...works on the basis of a cation-exchange mechanism. When embedded in a plasticized poly(vinyl chloride) (PVC) membrane containing lead ionophore (
tert-butylcalix4arene-tetrakis(
N,
N-dimethylthioacetamide)) and a lipophilic anionic site potassium tetrakis(4-chlorophenyl)borate, TMANB shows a significant fluorescence signal change on exposure to aqueous HCl solution containing lead ion, which exhibits the theoretically expected fluorescence response to lead ion concentration. The selectivity, response time, reproducibility and reversibility, and lifetime of the optode membrane were discussed.
Twenty-four Kenyan patients with visceral leishmaniasis were treated for 30 days with either conventional therapy (daily pentavalent antimony, n = 14) or experimental immunochemotherapy (daily ...antimony plus interferon-gamma IFN-gamma every other day, n = 10). All 24 patients responded clinically to treatment, and microscopic splenic aspirate scores rapidly decreased in both groups. As judged by splenic aspirate culture results, IFN-gamma-treated patients responded more quickly (50% versus 22% culture-negative after one week and 75% versus 58% culture-negative after two weeks). While not statistically significant, these differences raise the possibility that combination therapy using IFN-gamma, which was safe and well-tolerated, may accelerate the early parasitologic response in patients with visceral leishmaniasis.
The objective of this study was to investigate parenteral vitamin E for the prevention of peripartum disease in dairy cows. A randomized clinical trial was conducted in 21 commercial dairy herds. ...Cows (n=1142) were randomly assigned to receive either a single subcutaneous injection of 3000 IU of vitamin E, or placebo, 1 wk before expected calving. Serum α-tocopherol was significantly increased in treated cows at 7 and 14 d, but not at 21 d after injection. Overall, there were no significant differences between treatment groups in the incidence of retained placenta, clinical mastitis, metritis, endometritis, ketosis, displaced abomasum, or lameness. However, there was a conditional benefit of treatment for reduction of the incidence of retained placenta. Cows with marginal pretreatment vitamin E status (serum α-tocopherol to cholesterol mass ratio<2.5×10−3) that received an injection of vitamin E tended to have reduced risk of retained placenta. However, in cows with adequate serum vitamin E, there was no reduction in the incidence of any disease. For clinical application, primiparous animals were most likely to benefit from prepartum injection of vitamin E.
Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the ...pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and to develop future therapeutic approaches. By examining G6Pase in the liver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate proteins which are tightly coupled. We propose a modified translocase catalytic unit model for G6Pase catalysis.
Objective. Although smoking is the most important risk factor for lung cancer, nearly 10% of lung cancer is not attributable to smoking. Insights into risk factors for lung cancer other than smoking ...will become increasingly important, given decreasing trends in the prevalence of smoking. Prior research suggests asthma may increase the risk of lung cancer, particularly among nonsmokers. Methods. We used Cox regression analyses of data from a nationally representative sample of 9087 adults aged 30-75 years included in the NHANES II Mortality Study (1976-1992) to estimate the relative risk (RR) of death from lung cancer associated with self-reported asthma, independent of smoking. Results. Age-adjusted prevalence of smoking was 36.0%, and the age-adjusted prevalence of asthma was 6.1% (6.2% among nonsmokers) at baseline. During approximately 17 years of follow-up, 196 adults died of lung cancer (ICD-9 160-165). Among 6144 nonsmokers, the RR of lung cancer death comparing adults with asthma to those without was 1.69 (95% CI: 0.94-3.04) although the association was not statistically significant. For nonsmokers without a history of cancer, the RR was 2.53 (95% CI: 1.42-4.52). After exclusion of adults with emphysema and chronic bronchitis, the RR of lung cancer death associated with asthma was 3.54 (95% CI: 1.93-6.42). Conclusions. Consistent with prior reports, we observed an increased risk of lung cancer mortality associated with asthma among nonsmokers without a history of cancer.
Bacteriophage λ is a paradigm for understanding the role of cooperativity in gene regulation. Comparison of the regulatory regions of λ and the unrelated temperate bacteriophage 186 provides insight ...into alternate ways to assemble functional genetic switches. The structure of the C-terminal domain of the 186 repressor, determined at 2.7 Å resolution, reveals an unusual heptamer of dimers, consistent with presented genetic studies. In addition, the structure of a cooperativity mutant of the full-length 186 repressor, identified by genetic screens, was solved to 1.95 Å resolution. These structures provide a molecular basis for understanding lysogenic regulation in 186. Whereas the overall fold of the 186 and λ repressor monomers is remarkably similar, the way the two repressors cooperatively assemble is quite different and explains in part the differences in their regulatory activity.
: Although the myelin membrane contains only a small set of major proteins, more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody ...perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure, identified novel mRNAs that are activated during this period. One cDNA, TPO1, recognizes a 5.5‐kb mRNA that is strongly up‐regulated in oligodendrocytes after release of the differentiation block and that is expressed at high levels in brain tissue during active myelination. This cDNA represents at least two mRNAs differing from each other in their 5′‐termini. The TPO1 cDNA contains an open reading frame of 1,380 bp, encoding a protein of 51.8 kDa with a predicted pl of 9.1 that contains two regions homologous to nonclassic zinc finger motifs. Subcellular localization studies suggest the enriched presence of TPO1 in spherical structures along the major cytoplasmic processes of oligodendrocytes. TPO1, along with homologues expressed in testis, placenta, and PC12 cells, form a novel family of proteins with multiple hydrophobic domains possibly serving as membrane spanning regions. We postulate that in oligodendrocytes, TPO1 encodes a protein factor involved in myelin biogenesis.
Antimicrobial peptides isolated from the host defense systems of animals have been shown to exert their activity directly on the lipid bilayer of cell membranes, but the antimicrobial mechanisms are ...not clear, due chiefly to the difficulty of discerning the high-order structures formed by these peptides in membranes. Previously we have shown that these peptides insert into the membrane when their concentrations exceed a lipid-dependent critical value. With neutron in-plane scattering we now show that inserted alamethicin creates aqueous pores approximately greater than 18 A in diameter. The density of pores is consistent with the assumption that all of the alamethicin is involved in pore formation. Pores were not detected below the critical concentration. Thus concentration-dependent pore formation appears to be the molecular mechanism of antimicrobial action.
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