PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Population-based epidemiology of human immunodeficiency virus infection in Western Australia. Western Australian AIDS Advisory Committee

A total of 328 cases of infection with human immunodeficiency virus (HIV) in Western Australia in 1983-1987 was studied with respect to demographic factors, the risk profile, the clinical progression of disease, the utilization of inpatient services and trends in incidence over time. The crude incidence rates were 8.8 cases/100,000 person-years in men and 0.4 cases/100,000 person-years in women. Age-specific rates peaked at 25 to 29 years of age in men. The risk of HIV infection was associated with metropolitan residence, low socioeconomic level, and two specific occupational groups. Homosexual and bisexual men constituted 86% of all cases; the incidence rate of HIV infection in such men was approximately 1000-times higher than was the incidence rate by apparent sexual transmission in heterosexual persons. However, the proportion of cases that occurred in women or that apparently was caused by heterosexual sexual transmission increased from zero in 1983-1984 to 7.5% and 5.4%, respectively, in 1987. After two years of follow-up, 71% of preclinical (category-C) patients had developed signs, symptoms or evidence of immune dysfunction, and 12% of those patients with lymphadenopathy or with other early clinical features of disease (category-B) had progressed to the acquired immunodeficiency syndrome (AIDS). At 21 months of follow-up, the survival rate with AIDS was 9%. Patients with AIDS utilized an average of 68.9 short-stay hospital bed-days per person-year, while category-B patients used 11.5 hospital bed-days per person-year. Notifications of HIV infection increased each year from 1983 to 1986, but fell by 22% in 1987. The latter may have been as a result of chance, a screening artefact or a real reduction in the incidence rate.     

Chlordiazepoxide alters intravenous cocaine self-administration in rats

This investigation was designed to examine the effects of benzodiazepines on intravenous cocaine self-administration in rats. Pretreatment with low doses of the benzodiazepine receptor agonist, chlordiazepoxide (0.3 to 1.0 mg/kg, IP), resulted in small but nonsignificant increases in drug intake with 0.5 mg/kg cocaine, while higher doses (10 mg/kg, IP) significantly decreased drug intake in all rats tested. The effects of chlordiazepoxide on self-administration were attenuated when the concentration of cocaine was increased to 1.0 mg/kg, suggesting that chlordiazepoxide was opposing rather than augmenting the pharmacological actions of cocaine. Pretreatment with the benzodiazepine receptor antagonist, Ro 15-1788 (1.0 to 10 mg/kg, IP), had no effect on self-administration, suggesting that the reinforcing properties of cocaine do not result from direct interactions with benzodiazepine receptors. The result of this investigation demonstrate that chlordiazepoxide alters intravenous cocaine self-administration in rats. Although additional research will be necessary to confirm these data, the results of this investigation suggest that chlordiazepoxide may decrease the reinforcing efficacy of cocaine through indirect actions on dopaminergic neuronal activity potentially mediated through GABAergic mechanisms via benzodiazepine receptor activation.     

Determinants of chronic bronchitis and lung dysfunction in Western Australian gold miners

The relation of chronic bronchitis and respiratory dysfunction to age, tobacco smoking, and occupational exposure to surface and underground mining operations were examined in a cross sectional survey of 1363 men employed in the Kalgoorlie mining industry in 1985. Overall, the prevalence of chronic bronchitis was 14%. Eleven per cent of the workers had obstructive lung disorder (FEV1/FVC less than 0.70) and 9% had restrictive lung disorder (FVC less than 0.80 of predicted for height and age). There was little change in the prevalence of chronic bronchitis from that observed in a survey of the same industry in 1961-2. Only 1% of the workers in 1985 had radiographic signs of silicosis compared with 22% in 1961-2. Age, smoking, and underground mining experience all exerted strong effects on the development of chronic bronchitis with or without associated respiratory function abnormalities. After control of confounding by age and smoking, it was estimated that compared with a lifetime non-miner, the odds ratio (OR) of chronic bronchitis was 1.8 (95% confidence interval, 1.0-3.3) for one to nine years underground mining gold, 2.5 (1.2-5.2) for 10-19 years, and 5.1 (2.4-10.9) for 20 or more years. Underground mining of minerals other than gold was also associated with chronic bronchitis (OR = 5.1; 95% CI, 1.1-25.0) whereas exclusive surface mining had only a small empirical effect (OR = 1.3; 95% CI, 0.6-2.5). It is estimated that the proportion of cases of chronic bronchitis in working underground miners due to occupational factors is 50%. The results support the existence of an industrial cause of chronic bronchitis, although caution must be exercised in generalising the results to miners with progressive and sever respiratory impairment.