Screening and early intervention for COPD

Chronic obstructive pulmonary disease is on the increase. Therapeutic improvement is limited by the irreversible nature of lung tissue loss. Basic lung function tests can detect early loss of function, which may facilitate smoking cessation and other interventions likely to delay disease progression. The advent of inexpensive portable spirometers promises to permit such testing in the primary care physician's office.     

Activation-inactivation coupling in Myxicola giant axons injected with tetraethylammonium

Myxicola giant axons internally injected with tetraethylammonium chloride to block potassium currents were examined under voltage clamp. The sodium inactivation time constants obtained from the decline in INa during step depolarizations were substantially smaller than those obtained using conditioning prepulses to the same potentials and the ratios agreed with previous observations using TTX. Inactivation shifts were also measured and found to be comparable to previous results.     

Impaired processing of proopiomelanocortin in corticotroph macroadenomas

The p53 mutations in the reported 243 lung cancers and our 59 cases were analyzed. The common base substitutions found in the lung cancer were G to T transversion (35%), C:G to T:A (26%) and A:T to G:C transitions (11%). Four types of the hot spot, 1) G to T transversion, 2) A to G transition in ApT site, 3) C to T transition in CpG site and 4) mix of the transversion and transition were identified. It is suggested that A to G transition at ApT site in the non-transcribed strand may be a new hot spot in the p53 gene in lung carcinoma. We also show that microscopic selection of cancer cells will facilitate the detection of p53 mutations in adenocarcinomas.     

Evaluation of bleached kraft mill process water using Microtox(R), Ceriodaphnia dubia, and Menidia beryllina toxicity tests

We show herein that human DNA topoisomerase II beta is functional in yeast. It can complement a yeast temperature-sensitive mutation in topoisomerase II. The effect on human topoisomerase II beta of a number of topoisomerase II inhibitors was analysed in a yeast in vivo system and compared with that of human topoisomerase II alpha and wild-type yeast topoisomerase II. A drug permeable yeast strain (JN394 top2-4) was used to analyse the in vivo effects of known anti-topoisomerase II agents on human topoisomerase II beta transformants. A parallel analysis on human topoisomerase II alpha transformants provides the first in vivo analysis of the responses of yeast bearing the individual isoforms to these drugs. The strain was analysed at 35 degrees C, a non-permissive temperature at which only plasmid-borne topoisomerase II is active. A shuttle vector with either human topoisomerase II beta, human topoisomerase II alpha or yeast topoisomerase II under the control of a GAL1 promoter was used. The key findings were that amsacrine produced comparable levels of cell killing with both alpha and beta, whilst etoposide, doxorubicin and mitoxantrone produced higher degrees of cell killing with alpha than with beta or yeast topoisomerase II. Merbarone had the greatest effect on the yeast strain bearing plasmid-borne yeast topoisomerase II. Suramin, quercetin and genistein showed little cell killing in this system. This yeast in vivo system provides a powerful way to analyse the effects of anti-topoisomerase II agents on transformants bearing the individual human isoforms. This system also provides a means of analysing putative drug-resistance mutations in human topoisomerase II beta or to select for drug-resistance mutations in human topoisomerase II beta.     

Ion transport and structure of urinary bladder epithelium of Amphiuma

The urinary bladder of Amphiuma exhibits stable transport properties and an electrical potential difference in vitro. The lumen is significantly negative to the serosa and under short-circuited conditions flux rations for Na and Cl of 5.92 +/- 0.42 and 1.81 +/- 0.20, respectively, were observed. The close agreement between the short-circuit current and net Na flux suggests that most, if not all, of the current is carried by Na. Both ouabain and amiloride decreased the short-circuit current and the mucosal-to-serosal (M leads to S) flux of Na. Furosemide caused a transient increase in the M leads to S flux of Na and Cl but ADH was without effect. In bladders that had high transmural resistance, a net movement of K in the M leads to S direction under short-circuited conditions with flux ratios of up to 2 could be observed. The epithelium of the Amphiuma bladder consists of three cell types: granular cells, basal cells, and mitochondria-rich cells. No goblet cells are present. The mitochondria-rich cells comprise less than 5% of the population of the surface epithelium in Amphiuma in contrast to other amphibian bladders, where it accounts for up to 25% of the population.