Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.     

Kidney Transplant in Black Recipients: Are African Europeans Different from African Americans?

Despite recent improvement, significant racial disparities in outcome still persist after renal transplantation among African American patients in the United States. This study evaluated the association of race and ethnicity with allograft outcomes in a French population of 952 Caucasian (Cauc) patients and 140 African European (AE) patients who underwent renal transplantation in our center between 1987 and 2003. Demographic characteristics were similar for the two cohorts other than cause of end-stage renal failure (more hypertension among AE and more polycystic kidney disease among Cauc) and cold ischemia time (significantly longer for AE). Immunosuppressive treatment was comparable between groups. There were no significant differences between AE and Cauc in the incidence of acute rejection (31% vs. 30%). At 5 years post-transplant, patient survival (93% vs. 92%), graft survival (83% in both groups) and graft function (creatinine clearance 48 mL/min vs. 45 mL/min) were also similar among the AE and Cauc patients. We demonstrate that ethnic origin does not affect outcome after renal transplantation in France. Therefore, differences observed in the United States cannot be only related to immunologic or pharmacologic factors. The results of renal transplantation in patients of African origin could be improved with universal immunosuppressive drug coverage.     

Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation.

Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing.     

Blood pressure and excretion of sodium, potassium, calcium and magnesium in 8- and 9-year old boys from 19 European centres

We have measured systolic and diastolic blood pressure and excretions of sodium, potassium, calcium and magnesium in groups of about 50 8- and 9-year-old boys from 19 European centres using standardized methods for the measurement of blood pressure and collection of urine, and by carrying out all analyses in one laboratory. Weight, height, pulse rate and environmental temperature were also studied. Mean systolic blood pressure ranged from 91 to 105 mm Hg and diastolic blood pressure from 51 to 66 mm Hg. Mean 24-h excretion of sodium was between 91 and 146 mmol/d, that of potassium between 29 and 60 mmol/d, that of calcium between 1.5 and 2.6 mmol/d and that of magnesium between 2.7 and 4.2 mmol/d. Mean sodium excretion tended to be lower and potassium excretion tended to be higher in the boys from the north-western parts of Europe. Relations between either systolic or diastolic blood pressure and electrolyte excretions were generally weak or absent. Most remarkable is that only the association between mean diastolic blood pressure and 24-h magnesium excretion (partial regression coefficient (b +/- s.e., -5.04 +/- 2.08 mm Hg/mmol/d) was statistically significant after adjusting for differences in creatinine excretion and environmental temperature. Mean systolic blood pressure was not significantly related with any of the variables measured. The partial regression coefficient (b +/- s.e.) for diastolic blood pressure on weight was 0.186 +/- 0.062 mm Hg/kg, on height 0.165 +/- 0.056 mm Hg/cm, on pulse rate 0.364 +/- 0.100 mm Hg/beats per min and on outside temperature -0.25 +/- 0.07 mm Hg/degrees C.     

Interspecies comparison of cellular localization of the cyanide metabolizing enzyme rhodanese within olfactory mucosa

The observation of high levels of xenobiotic metabolizing enzyme activity in the olfactory mucosa has produced speculation on the functional significance of these enzymes in the nose. Hypothesized roles include protection of the nasal epithelium, lung, and other downstream tissues, and termination or modification of olfactory responses. The enzyme rhodanese metabolizes cyanide, which is a commonly inhaled toxicant and an odorant and therefore of interest to both toxicologists and olfactory neurobiologists. The cellular localization of this enzyme within the olfactory mucosa will have important consequences for its ability to protect specific cells, as well as its ability to alter the concentration of inhaled cyanide at receptors, and therefore could provide clues as to its function in this tissue. We have compared the distribution of this enzyme in two species, the rat and the cow, using immunohistochemical localization techniques employing species-specific polyclonal antisera raised in our laboratory. In the rat, rhodanese-like immunoreactivity was greatest within the apical portion of the sustentacular cells, the basal cells, and the duct cells of Bowman's glands. Very little to no reaction was observed in the acinar cells of Bowman's glands. In the cow, however, the acinar cells and duct cells of Bowman's glands showed intense immunoreactivity with little to no reaction observed in the sustentacular or basal cells. The differences in localization of rhodanese in these two species may have important implications for cell types at risk during inhalation of cyanide or organonitrile compounds metabolized to cyanide within the nasal mucosa. In addition, the difference in distribution in the two species emphasizes the importance of considering enzyme activity and localization in the determination of an appropriate animal model for study of both nasal toxicology and olfactory responsiveness in humans.     

Streptococci from root canals in teeth with apical periodontitis receiving endodontic treatment.

OBJECTIVES: The object of this study was to investigate the diversity among streptococcal species isolated from root canals in conjunction with endodontic therapy and to characterize their production of extracellular proteins. STUDY DESIGN: Consecutive root canal samples (RCS) taken as bacteriological controls during root canal treatment of teeth with apical periodontitis were analyzed in a total of 100 clinical cases. Bacteria were isolated and classified by selective media and gas liquid chromatography. Streptococcal strains were identified by carbohydrate fermentation, hydrolysis of aesculin/arginine, and production of enzymes. Releases of extracellular proteins by streptococci and Enterococcus spp in fluid culture media were examined with SDS-PAGE and 2-dimension gel electrophoresis (2 DE). Extracellular proteins produced were quantified and qualitatively analyzed. Specific proteins were targeted with Western immunoblot assays. Comparisons were made with type strains. RESULTS: Of a total of 241 bacterial strains recovered in the first samples submitted, Streptococcus gordonii, S anginosus, and S oralis were the most frequently isolated streptococci. In 49 of 89 resubmitted samples showing bacterial growth, S gordonii and S oralis still predominated among streptococci. Other common bacterial isolates were Enterococcus spp, Lactobacillus paracasei, and Olsenella uli. Quantitative and qualitative differences in extracellular protein production were observed among clinical isolates and laboratory streptococcal strains. In similar conditions for growth, S intermedius, S anginosus, S oralis, and S gordonii were strong producers of extracellular proteins (>3.0 microg/mL), while Enterococcus spp and S mutans were weak. Whole cell protein extracts showed a different profile from that of extracellular proteins. The chaperone protein DnaK was recognized to be produced extracellularly by S gordonii, S oralis, S anginosus, and S parasanguis. CONCLUSIONS: Being strong producers of extracellular proteins and by virtue of common presence in teeth undergoing endodontic therapy, S gordonii, S anginosus, and S oralis may be of pathogenic significance in posttreatment apical periodontitis.     

WHERE ARE THE GATES IN GAP JUNCTION CHANNELS?

1. In the formation and function of gap junction channels two types of gates ought to be discriminated: the docking gate and the channel gates proper. The docking gate is involved in the transformation of a closed hemichannel to a patent gap junction channel. By definition the trigger mechanism for this gate and maybe even the gate itself is contained within the extracellular loops of the gap junction proteins, the connexins. The channel gates proper determine the open and closed states of the complete gap junction channels. 2. Probing the docking gate by mutagenesis of connexins and by synthetic peptides indicates that this gate is the consequence of complex interactions between a large fraction of the amino acids comprising the extracellular loops. Probably both inter- and intra-molecular interactions are involved, and disulfide exchange may be entailed in the stabilization of the open and closed states. 3. Of the various effectors on the channel gate(s) the voltage effects have obtained the most scrutiny to date. The response of gap junction channels and hemichannels is diverse, the various channels respond differently to transjunctional and membrane potential. No equivalent to the S4 segment representing the voltage sensor in other voltage dependent ion channels is present in the connexin sequences, instead mutations in various segments of connexins have been reported to affect the voltage dependence of gap junction channels. To understand the complexity of voltage effects on gap junction channels, non-connexin peptides may need to be considered as voltage sensors or as modifiers thereof.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.