A comparison between ((3)H)-thymidine incorporation and isothermal microcalorimetry for the assessment of antigen-induced lymphocyte proliferation.

Lymphocyte transformation tests (LTT) are time-consuming radioactive assays used in the clinic for the determination of allergic drug reactions and extensively in basic immunological research. In the present study we propose an alternative method in the monitoring of T-cell responses by isothermal microcalorimetric (IMC) measurements of overall cellular heat production as a function of time. For mitogen-induced lymphocyte proliferation, we analyzed a concentration dependent effect of phytohemaglutinin (PHA) and both tests showed a good correlation. This was also the case for specific antigenic stimulation with Varidase(R) or tetanus toxoid. On the other hand, antigen-induced lymphocyte proliferation analyzed by pre and post influenza vaccine (Inflexal(R) V) samples, showed no such correlation. Our study suggests that IMC measurements, despite the advantages of simplicity, on-line recording of metabolic activity and no use of radioactivity, may be limited to monitoring mitogen-induced lymphocyte proliferation.

Segregation analysis of esophageal cancer in 221 high-risk Chinese families.

BACKGROUND: Until recently, environmental factors were considered of greatest importance in the etiology of esophageal cancer. Recent studies, however, have suggested that genetic factors also have a role. PURPOSE: Since no formal genetic study of this cancer has been previously reported, we carried out a statistical analysis to determine how important genetic factors are in the etiology of esophageal cancer in high-incidence areas of North China. METHODS: Using a logistic regressive model, we performed a segregation analysis on 221 high-risk nuclear families from the Yaocun Commune, Linxian, Henan Province of China, with at least one affected family member and with all offspring aged 40 years or older. Three models, the mendelian, the environmental, and the no-transmission models, were each compared with the general-transmission model that incorporated both genetic and environmental factors. RESULTS: According to Akaike's Information Criterion, the mendelian model provided the best fit for the data. By the chi-square test, the mendelian inheritance model was not rejected, but the environmental and the no-transmission models were both rejected. CONCLUSION: The segregation analysis indicated an autosomal recessive mendelian inheritance, with the alleged mendelian gene present at a frequency of 19%, causing 4% of this population to be predisposed to develop esophageal cancer. Large, unmeasured, residual familial factors, however, were also significant. IMPLICATIONS: Both an autosomal recessive gene and unexplained environmental factors appear to be important in the etiology of esophageal cancer in the subpopulation studied.

Use of community health workers with inner-city children who have asthma.

Use of community health workers (CHWs) to obtain health, social, and environmental information from African-American inner-city children with asthma was one component of a larger intervention study designed to reduce morbidity in African-American children with asthma. A subset of 140 school-aged children with asthma was recruited and enrolled in a program to receive home visits by CHWs for the purposes of obtaining medical information and teaching basic asthma education to the families. Data obtained by the CHWs revealed low inhaled steroid use, high beta 2 agonist use, frequent emergency-room visits, decreased primary-care visits, and increased allergen and irritant exposure. Appropriately recruited and trained CHWs are effective in obtaining useful medical information from inner-city families with children with asthma and providing basic asthma education in the home.

Search for faster methods of fitting the regressive models to quantitative traits.

The regressive models describe familial patterns of dependence of quantitative measures by specifying regression relationships among a person's phenotype and genotype and the phenotypes and genotypes of antecedents. When the number of sibs in the pattern of dependence increases, as in the class D regressive model, computation of the likelihood becomes time consuming, since the Elston-Stewart algorithm cannot be used generally. On the other hand, the simpler class A regressive model, which imposes a restriction on the sib-sib correlation, may lead to inference of a spurious major gene, as already observed in some instances. A simulation study is performed to explore the robustness of class A model with respect to false inference of a major gene and to search for faster methods of computing the likelihood under class D model. The class A model is not robust against the presence of a sib-sib correlation exceeding that specified by the model, unless tests on transmission probabilities are performed carefully: false detection of a major gene is reduced from a number of 26-30 to between 0 and 4 data sets out of 30 replicates after testing both the Mendelian transmission and the absence of transmission of a major effect against the general transmission model. Among various approximations of the likelihood formulation of the class D model, approximations 6 and 8 are found to work appropriately in terms of both the estimation of all parameters and hypothesis testing, for each generating model. These approximations lessen the computer time by allowing use of the Elston-Stewart algorithm.

Effects of sucralfate on vacuolating cytotoxin activity and adherence of Helicobacter pylori to human gastric epithelial cells.

Sucralfate inhibits activity of certain Helicobacter pylori enzymes, implying that this medication may limit gastric cell injury associated with H pylori infection. This study evaluates the ability of sucralfate and its two major structural components, sucrose octasulfate and aluminum hydroxide, to reduce the cytotoxic effects of H pylori and to inhibit binding of H pylori to human gastric epithelial cells. Experiments were performed using human gastric epithelial cells isolated from gastric biopsy tissue taken at upper gastrointestinal endoscopy. Primary cultures of human gastric epithelial cells, when exposed to broth-culture supernatant from a vacuolating cytotoxin-positive H pylori strain, were shown to form cytoplasmic vacuoles. Preexposing H pylori brothculture supernatant to sucralfate reduced vacuole formation in human gastric epithelial cells; however, preexposure of H pylori broth-culture supernatant to aluminum hydroxide or sucrose octasulfate did not reduce vacuolation in human gastric epithelial cells. H pylori binding to human gastric epithelial cells was significantly reduced when H pylori was exposed to sucralfate prior to incubating the bacterium with human gastric epithelial cells. These data show that sucralfate, but not its two major components, reduces the toxicity of an H pylori-produced cytotoxin (VacA) and decreases H pylori adherence to human gastric epithelial cells. This reduction in H pylori cytotoxicity may contribute to sucralfate's ulcerhealing properties and to the lower ulcer recurrence rates seen in patients treated with this medication.

Home environmental risk factors in urban minority asthmatic children.

Urban minority families with children with asthma often live in homes with allergen and irritant exposures harmful to these children. We enrolled 392 African-American asthmatic children, male and female, aged 5 to 12, from 42 schools in Washington, DC and Baltimore, MD. The project is designed to test the effectiveness of school-based asthma education interventions, community-based asthma health workers' programs, and the combination on these children. Baseline telephone interviews were carried out with the primary home care-givers for demographic data and for environmental home exposures that exacerbated asthma. Exposures stated to cause wheezing in the children were cigarette smoke in 72%, dust in 53%, cats in 34%, dogs in 27%, and roach exposure in 15%. Fifty-six percent of children live with cigarette smoke exposure, 73% of which is from mothers. This was a highly symptomatic group with 44% reporting two or more days per week of restricted activity and 62% reporting two or more episodes of night symptoms per week. Those with mattress covers on beds had significantly fewer emergency department visits in the past 6 months than those without covers. Over one-third of parents reported children taking two bronchodilators without anti-inflammatory agents. Less than 20% were reported using anti-inflammatory medications. Decreasing asthma severity in this population entails the prevention and control of known risk factors in the home environment. Emphasis must be placed on cigarette smoking cessation programs, covering mattresses, and dust and animal dander control. Primary care physicians require education on the role of anti-inflammatory medications.

Coronary arteriographic findings in black patients and risk markers for coronary artery disease.

Coronary arteriographic results are reported in 1535 black patients: 751 men (mean age 57 +/- 11) and 784 women (mean age 59 +/- 11). Among the black men 19%, 15%, 21%, and 4% had single-, double-, and triple-vessel and left main disease, respectively. Among the black women there were 12%, 10%, 15%, and 3% with similar involvement. Logistic regression models showed that most of the recognized risk factors were positively correlated with significant (at least one artery with > or = 50% stenosis) coronary disease, but a history of hypertension was not a significant independent predictor in either sex. ECG evidence of previous infarction increased the odds of detecting significant coronary disease by the greatest amount when controlling for other significant risk markers in women. In men both previous infarction and atypical pain (negative) were equally important. This study confirms but does not explain previous reports that have revealed less than expected angiographic evidence of significant coronary artery disease in black compared with white persons.