Mode of the autocrine/paracrine mechanism of growth hormone action

GH is synthesized at multiple extrapituitary sites suggestive of an autocrine/paracrine mechanism of action. We have investigated a possible autocrine/paracrine mechanism of GH action, compared the cellular response to exogenous versus endogenously produced GH, and determined the nature of the interaction between external stimuli and endogenously produced GH. BRL cells expressing the GH receptor were transiently transfected with expression plasmids containing either the hGH or the bGH gene and the response of the cell was measured by CAT reporter plasmids requiring either STATs 1 and 3 or STAT5 for their response. Transient transfection of the hGH gene resulted in hGH accumulation in the cell and secretion into the media. The functional response through STATs 1 and 3 and STAT5 obtained with endogenously produced hGH was comparable or greater in magnitude to that obtained with the maximal stimulatory dose of exogenous hGH. Similar results were obtained with an expression plasmid containing the bGH gene. Endogenously produced hGH interacted in an additive manner when combined with submaximal doses of both exogenous hGH and serum. Such results were also observed in a more physiologically relevant mammary carcinoma cell line (MCF-7). The nonreceptor-dimerizing hGH antagonist, hGH-G120R, used in cells expressing the homologous receptor extracellular domain was able to only partially inhibit the response of the cell to endogenously produced hGH, in contrast to full inhibition of exogenous hGH. We therefore conclude that GH can function in an autocrine/paracrine manner, additive in effect to external stimuli.     

Delayed delivery of surviving triplet after fetal reduction and spontaneous abortion

In multiple pregnancies, survival of remaining fetuses after premature death and delivery of one fetus is uncommon. We report a case of a triplet pregnancy that was reduced to twins at the 14th gestational week and then had preterm premature rupture of membranes and intrauterine fetal death of one twin at the 17th gestational week. To save the surviving fetus, delivery of the dead fetus and ligation of the umbilical cord at the cervical level were performed. We also performed McDonald cervical cerclage to keep the placenta of the dead fetus as well as that of the surviving one in the uterine cavity. After a series of aggressive procedures, including immediate administration of tocolytic agents, and antibiotic prophylaxis to prevent infection and preterm labor, the surviving fetus was delivered vaginally 73 days later due to intractable uterine contractions. After a 10-week hospital stay, the infant boy, weighing 2,500 g, was discharged without any sequelae. To our knowledge, this was the longest interval between deliveries in a triplet pregnancy reported in Taiwan. With adequate intensive management, a satisfactory outcome of the fetus and mother in such cases is possible.     

Exceptional convergent evolution in a virus

Replicate lineages of the bacteriophage phiX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.     

A comprehensive approach to the solution of direct-coupledmultislice model of skewed rotor induction motors using time-steppingeddy-current finite element method

Normally a complicated three-dimensional (3-D) approach is needed to study the field pattern of induction machines with skewed rotor bars. In this paper, a time-stepping two-dimensional (2-D) eddy-current finite element method, based on multislice technique, is described to study the steady-state operation and the starting process of skewed rotor induction machines. The fields of the multislices are being solved en bloc simultaneously, and thus, the effects of the eddy current and saturation can be taken into account directly. New forms of the governing equations for the multislice model are derived, which allow the meshes of multislices to be taken as one 2-D mesh so that the algorithm is very similar to that of general 2-D problems. Special techniques required for the mesh generation in the multislice model and the salient structures of the software are also described. The results obtained by using the program being developed have very good correlation with test data     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.