Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE--To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN--Longitudinal study of 138 adults with asthma. SETTING--Leicestershire Health Authority. SUBJECTS--48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES--Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS--Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS--These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.     

Developmental phenotypic plasticity: Where ecology and evolution meet molecular biology

The plastic response of phenotypic traits to environmental change is a common research focus in several disciplines - from ecology and evolutionary biology to physiology and molecular genetics. The use of model systems such as the flowering plant Arabidopsis thaliana has facilitated a dialogue between developmental biologists asking how plasticity is controlled (proximate causes) and organismal biologists asking why plasticity exists (ultimate causes). Researchers studying ultimate causes and consequences are increasingly compelled to reject simplistic, ‘black box’ models, while those studying proximate causes and mechanisms are increasingly obliged to subject their interpretations to ecological ‘reality checks.’ We review the successful multidisciplinary efforts to understand the phytochrome-mediated shade-avoidance and light-seeking responses of flowering plants as a pertinent example of convergence between evolutionary and molecular biology. In this example, the two-way exchange between reductionist and holist camps has been essential to rapid and sustained progress. This should serve as a model for future collaborative efforts towards understanding the responses of organisms to their constantly changing environments.     

Physiological responses of Sargasso Sea picoplankton to nanomolar nitrate perturbations

A study was conducted in July 1989 at three stations in thenorthern Sargasso Sea, where picoplankton (<1 µm)provided approximately half of the standing crop of chlorophyll.Temporal changes in the position of the nitracline at a singlelocation indicated that the vertical supply of nitrate was notat ‘steady-state’ and phytoplankton distributionstracked the nitracline. Our main experimental objective wasto examine the short-term effects of ecologically significantnitrate perturbations (+20 and +100 nM) on the physiologyof <1 µm communities growing at low (nanomolar)ambient nitrate concentrations. A chemiluminescent nitrate methodwas used to measure the time course (up to 4 h) of nitratedisappearance at in situ irradiance, in parallel with measurementsof photosynthetic ¹⁴CO₂ assimilation. Picoplankton growing at<60 nM nitrate rapidly responded to nanomolar nitratesupplements with luxury consumption and enhanced photosynthesisin proportion to their ambient nitrate environment. Light-saturatedSynechococcus populations from the most nitrate-depleted waters(13 nM) had doubled their cellular rate of photosynthesisafter 4 h, in response to a 20 nM nitrate pulse.     

Homozygous paracentric inversion 12 in a mentally retarded boy: a case report and review of the literature

Summary A mentally retarded male was found to be homozygous for a paracentric inversion of the long arm of chromosome 12(inv(12)(q21.1q23.2)). His parents, who are first cousins, and his phenotypically normal younger brother are inversion heterozygotes. Homozygous structural rearrangements are discussed and cases of paracentric inversions, including a further nine previously unpublished, are reviewed.     

Effect of methionine sulfoximine on asparaginase activity and ammonium levels in pea leaves

In developing leaves of Pisum sativum the levels of ammonium did not change during the light-dark photoperiod even though asparaginase (EC 3.5.1.1) did; asparaginase activity in detached leaves doubled during the first 2.5 hours in the light. When these leaves were supplied with 1 millimolar methionine sulfoximine (MSX, an inhibitor of glutamine synthetase, GS, activity) at the beginning of the photoperiod, levels of ammonium increased 8-to 10-fold, GS activity was inhibited 95%, and the light-stimulated increase in asparaginase activity was completely prevented, and declined to less than initial levels. When high concentrations of ammonium were supplied to leaves, the light-stimulated increase of asparaginase was partially prevented. However, it was also possible to prevent asparaginase increase, in the absence of ammonium accumulation, by the addition of MSX together with aminooxyacetate (AOA, which inhibits transamination and some other reactions of photorespiratory nitrogen cycling). AOA alone did not prevent light-stimulated asparaginase increase; neither MSX, AOA, or elevated ammonium levels inhibited the activity of asparaginase in vitro. These results suggest that the effect of MSX on asparaginase increase is not due solely to interference with photorespiratory cycling (since AOA also prevents cycling, but has no effect alone), nor to the production of high ammonium concentration or its subsequent effect on photosynthetic mechanisms. MSX must have further inhibitory effects on metabolism. It is concluded that accumulation of ammonium in the presence of MSX may underestimate rates of ammonium turnover, since liberation of ammonium from systems such as asparaginase is reduced by the effects of MSX.     

DNA sequence changes in mutations induced by ultraviolet light in the gpt gene on the chromosome of Escherichia coli uvr+ and urvA cells

Summary Sequence changes in mutations induced by ultraviolet light are reported for the chromosomal Escherichia coli gpt gene in almost isogenic E. coli uvr ⁺ and excision-deficient uvrA cells. Differences between the mutagenic spectra are ascribed to preferential removal of photoproducts in the transcribed strand by excision repair in uvr ⁺ cells. This conclusion is confirmed by analysis of published results for genes in both uvr ⁺ and uvr ^– cells, showing a similar selective removal of mutagenic products from the transcribed strand of the E. coli lacI gene and of the lambda phage cl repressor gene. Comparison of these data with published results for ultraviolet mutagenesis of gpt on a chromosome in Chinese hamster ovary cells showed that a mutagenic hot spot in mammalian cells is not present in E. coli; the possibility is suggested that the hot spot might arise from localized lack of excision repair. Otherwise, mutagenesis in hamster cells appeared similar to that in E. coli uvr ⁺ cells, except there appears to be a smaller fraction of single-base additions and deletions (frameshifts) in mammalian than in bacterial cells. Phenotypes of 6-thioguanine-resistant E. coli showed there is a gene (or genes) other than gpt involved in the utilization of thioguanine by bacteria.     

Stimulation of rat Sertoli cell adenylate cyclase by germ cells in vitro

The effect of germ cells or germ cell fractions on adenylate cyclase (AC) activity in membrane preparations from cultured rat Sertoli cells has been examined. Whole germ cells or 30,000 X g pellet or supernatant fractions of germ cells have the ability to stimulate Sertoli cell AC to levels comparable to those measured in follicle-stimulating hormone-stimulated Sertoli cell membranes. Treatment at 100 degrees C but not 60 degrees C for 1 min abolished the ability of germ cell preparations to stimulate Sertoli AC. Germ cell stimulation of Sertoli cell AC was not calcium dependent, was not blocked by propranolol, and was observed to be dose dependent.     

Fibrinogen Manchester. Detection of a heterozygous phenotype in the intraplatelet pool.

Family members heterozygous for the congenitally abnormal fibrinogen designated fibrinogen Manchester, A alpha 16Arg----His, have previously been shown by h.p.l.c. and amino acid analysis to release a variant fibrinopeptide, [His16]fibrinopeptide A, from plasma fibrinogen after the addition of thrombin. The present study was designed to determine if the same abnormal phenotype was also present in the intraplatelet fibrinogen pool. Fresh platelets were washed in buffers containing EDTA until it could be shown that all washable plasma fibrinogen was removed. Normal platelets were then lysed by freezing and thawing to release their intracellular proteins, which were then treated with thrombin. The fibrinopeptides, cleaved from the intraplatelet fibrinogen, could be detected by an optimized h.p.l.c. technique. Quantification of the intraplatelet fibrinogen gave a result (means +/- S.D., n = 5) of 110 +/- 30 and 90 +/- 30 micrograms/10(9) platelets, when determined by h.p.l.c. quantification of fibrinopeptide B content and fibrinogen fragment E radioimmunoassay respectively. Examination of fibrinopeptides released from the platelet fibrinogen from the family with fibrinogen Manchester with the same techniques showed elution peaks in the same positions as both [His16]fibrinopeptide A and normal fibrinopeptide A. The identity of these peaks was further substantiated by analysis of the h.p.l.c. peaks by using specific radioimmunoassay to fibrinopeptide A. Our results therefore demonstrate that platelet fibrinogen expresses the heterozygous A alpha 16His phenotype. This supports the view that the A alpha chains of platelet and plasma fibrinogen are produced from a single genetic locus.