A 17-year-old with rash, fever, myalgias, and nephritis

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.     

Characterization of serum antibody responses to recombinant HIV-1 gp160 vaccine by enzyme immunoassay. NIAID AIDS Vaccine Clinical Trials Network.

An enzyme immunoassay (EIA) was developed to measure serum antibody responses of healthy adult volunteers vaccinated with 40 or 80 micrograms of human immunodeficiency virus type 1 (HIV-1) recombinant gp160 (rgp160) vaccine at 0, 1, 6, and 18 months. This assay, which used purified rgp160 as antigen, was compared with the Biotech/Du Pont HIV-1 Western blot and the Abbott HIV-1 EIA. Of 33 volunteers who received three doses of rgp160 vaccine, seroresponses were detected in 91% by rgp160 EIA, 97% by Western blot, and 30% by HIV-1 EIA. The level of IgG rgp160 EIA antibody (mainly IgG1) peaked after the third immunization; 64% of 33 vaccinees still had detectable antibody by 12 months. The fourth immunization induced anamnestic IgG EIA antibody in 23 of 24 vaccinees, with titers ranging from 1:200 to 1:25,600. Neutralizing antibody was not detected in postvaccination sera by microtiter syncytium formation inhibition assay. Additional testing of sera by EIA indicated that the immune response to the vaccine was directed toward epitopes on both gp120 and gp41. Seroresponses to the immunodominant epitopes on gp41 were infrequent and none were detected to the neutralization epitope in the V3 region of gp120. This highly sensitive EIA is useful for characterizing HIV-1-specific antibody responses induced by an HIV-1 gp160 subunit vaccine.     

Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens

We have analyzed the expression of late differentiation antigens during terminal in vitro maturation of human macrophages (M phi) from blood monocytes (MO) in comparison to their distribution among mature M phi residing in various tissue sites. By immunizing mice with M phi derived from blood MO by culture on hydrophobic Teflon foils, monoclonal antibodies (mAbs) were developed (MAX.1, MAX.2, MAX.3, MAX.11) that reacted with lineage-restricted differentiation antigens. These antigens were expressed exclusively on M phi or were markedly increased after in vitro differentiation. The only overlap to another hemopoietic cell lineage was observed with MAX.3, which is shared by platelets and megakaryocytes. In the course of M phi maturation in vitro, the MAX.1 and MAX.3 antigens are detected within the cytoplasm two days before they appear on the cell surface. In contrast, the MAX.11 antigen is expressed simultaneously in the cytoplasm and at the cell surface, is found in varying degrees on a minor portion of blood MO and U937 cells, and is expressed rapidly at high density during early M phi differentiation in vitro. Among conventional mAbs that do not react with MO we found those against the transferrin (TF)-receptor, the BA-2, and the PCA1 antigen to label M phi. M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs. Distinctive patterns were observed with pulmonary M phi, exudate M phi from pleural and peritoneal effusions, synovial fluids, and early lactation milk. M phi from the alveolar space, for example, constantly expressed the MAX.2 antigen but not the MAX.3 antigen. Pleural effusion M phi, however, did not react with the MAX.1 mAb, but in most cases, it did react with the MAX.3 mAb. The detection of novel differentiation antigens, all expressed on monocyte-derived M phi but differently expressed on site-specific M phi in situ, underlines the remarkable heterogeneity among human M phi. The expression of these antigens is flexible because those MAX antigens that were not expressed in situ could be induced if cells from distinct tissue sites were cultured in vitro for several days. MAX mAbs may be of potential value to study both the sequential stages of maturation within the M phi lineage as well as differential developments induced by various culture conditions in parallel to environmental factors in vivo.     

Emphysema and dust exposure in a group of coal workers

The lungs of 450 coal miners who had been studied previously in a long-term epidemiologic project at 24 British mines have been examined post-mortem for signs of dust-related fibrosis and emphysema. Reliable estimates of cumulative (working-life) exposures to respirable mine dust were available for 342 of the men. The relative frequency of emphysema increased with age at death, and both panacinar and centriacinar emphysema occurred more frequently in smokers than in nonsmokers. The proportion of subjects with any emphysema was 47% in 92 men with no palpable dust lesions, 65% in 183 with small, simple pneumoconiotic lesions, and 83% in 175 miners with massive fibrosis (PMF). The chance of finding centriacinar emphysema in those with PMF increased significantly with increasing exposure to coal dust in life (p less than 0.025). A similar but less convincing relationship was found in those with simple pneumoconiosis (p less than 0.11), but in both groups, increasing amounts of ash with a given exposure to coal reduced the probability of finding centriacinar emphysema. The occurrence of centriacinar emphysema was associated also with increasing amounts of dust retained in the lungs. A preliminary exploration of this association did not support the hypothesis that emphysematous lungs clear dust less efficiently. We conclude that the association observed between exposure to respirable coal dust and emphysema in coal miners indicates a causal relationship. However, because it can be demonstrated only for men whose lungs show some dust-related fibrosis, it is suggested that the extent and nature of such fibrosis may be a crucial factor in determining the presence of centriacinar emphysema.     

内皮下脂蛋白滞留——动脉粥样硬化的始动过程

以动脉粥样硬化为基础的心血管疾病是人类健康面临的严重挑战.人们对动脉粥样硬化发生、发展进行漫长和不懈的探索.至今,其机制与过程仍不十分清楚.     

Silent myocardial ischemia: Current perspectives and future directions

Silent myocardial ischemia (SMI) is increasingly being recognized as part of the spectrum of ischemic heart disease. The spectrum of SMI ranges from asymptomatic coronary artery disease to critical illness necessitating intensive care. Although many diagnostic tools have been used to identify low- and high-risk subgroups, their use is limited by modest sensitivities and specificities. The present review identifies current concepts in the management of SMI in various clinical settings, as well as emerging technologies that may simplify the diagnosis and treatment of this condition.     

Neutrophil elastase produces 52-kD and 30-kD glucocorticoid receptor fragments in the cytosol of human leukemia cells

Characterization of glucocorticoid receptors in leukemia cells is important to understand mechanisms of glucocorticoid resistance but has been impeded by receptor fragmentation in cytosol extracts. We recently found that formation of 52- and 30-kilodalton (kD) glucocorticoid receptor fragments in cytosol of leukemia cells is due to proteolysis and is blocked by diisopropylfluorophosphate (DFP). In the present study, we identify a 28-kD serine protease in cytosol of leukemia cells that binds [3H]DFP and correlates with the formation of 52- and 30-kD receptor fragments. This protease is immunoprecipitated by antiserum to neutrophil elastase. Limited digestion of [3H]dexamethasone-21-mesylate- labeled receptors by purified neutrophil elastase produces 52- and 30- kD receptor fragments. Receptor fragmentation in the cytosol of leukemia cells in inhibited by methoxysuccinyl-alanyl-alanyl-prolyl- valyl-chloromethylketone, a highly specific inhibitor of neutrophil elastase. The addition of as few as 5% neutrophils to a lymphoid cell suspension provides sufficient elastase to produce receptor fragmentation. Our findings indicate that neutrophil elastase is responsible for receptor fragmentation in the cytosol of leukemia cells. The neutrophil elastase may be endogenous to the leukemia cells or may come from neutrophils that contaminate leukemia cell suspensions.