Monocyte chemotactic protein expression during schistosome egg granuloma formation. Sequence of production, localization, contribution, and regulation.

The present study explored the role of murine monocyte chemotactic protein (MCP) in the T cell-mediated hypersensitive granulomatous response to Schistosoma mansoni eggs. The study examined the time course of local production, contribution to cellular infiltration, and the role of T cells in endogenous regulation. Synchronized pulmonary granulomas were induced under conditions of primary and secondary states of immunity. Primer-directed polymerase chain reaction analysis showed increased MCP mRNA expression in granulomatous lungs, mainly in the secondary response. Levels of MCP were measured by enzyme-linked immunosorbent assay in cultures of intact granulomas. Spontaneous MCP production was modest in primary granuloma cultures, reaching a maximum of 5.7 +/- 0.9 ng/ml by 16 days. In contrast, the secondary response showed augmented and accelerated production, achieving 13 +/- 2.0 ng/ml by 2 days. Immunohistochemical staining revealed the strongest MCP expression within microvascular adventitial cells or pericytes as well as in scattered mononuclear cells associated with granulomas. Staining was not detected in normal lungs. Passive immunization with anti-MCP-1 antibodies caused a 40% reduction in the secondary granuloma area but did not significantly affect the primary response. With adoptive cell transfer and T cell subset depletion, it was shown that Thy-1+ and CD5+ cells augmented, whereas CD8+ cells appeared to impair, MCP production. This provides direct evidence that MCP is involved in secondary Th2-mediated response to schistosome eggs and is subject to regulation by T cells.     

The impact of AIDS on state and local health departments: issues and a few answers.

Owing to large differences in the incidence of AIDS (acquired immunodeficiency syndrome) and in public health resources and priorities, the impact of AIDS on state and local health departments has been variable. Nonetheless, health departments everywhere are being held responsible for surveillance and control of the HIV (human immunodeficiency virus) epidemic which we believe requires, at minimum, convenient, free HIV testing and counseling; expanded HIV services in sexually transmitted diseases clinics and substance treatment centers; locally oriented AIDS information/education; notification of persons unknowingly exposed to HIV; restrictive measures for HIV-infected persons who, after counseling, persist in exposing others; regulation or closure of public establishments in which HIV transmission is likely to result; and confidential reporting of all HIV test results to public health departments. In Colorado new legislation was passed to require reporting of HIV test results, to provide the reports with near absolute protections against unauthorized disclosure, and to modify quarantine statues to incorporate rights to due process, appeals, and confidentially. States in which there is a legal basis for discrimination against gay men will need to rectify this problem first. There is no evidence that reporting of HIV infections in Colorado has adversely affected the rate at which persons with HIV risk behaviors volunteer to be tested. For Denver and Colorado Departments of Health, more than 70 per cent of the estimated $2,796,000 expended in AIDS activities during 1987 was federal.     

Biochemical consequences of 5-fluorouracil gastrointestinal toxicity in rats; effect of high-dose uridine

Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa.     

Hemodynamic shifts during physical exercise in patients with ischemic heart disease

In 82 CHD male patients aged 35-54 years with well-preserved working capacity (threshold load, 600-750 kgm/min) who had underwent bicycle ergometer test, the time course of changes in the major hemodynamic parameters was found to be significantly similar to that of healthy individuals. The cases who stopped performing bicycle ergometer tests because of anginal attacks, and ST segment depression or either showed a more significant elevation in systolic and diastolic blood pressure at the maximum load rate and lower increase in heart rate than in healthy subjects, which may be regarded as a compensatory mechanism that prevents a further decrease in coronary flow. Diminished increase in stroke index and cardiac index suggests reduced myocardial contractility.     

Case Control Study of Chronic Bronchitis in glass Bangle Workers

Eighty-nine cases of chronic bronchitis were matched against167 asymptomatic controls from the glass bangle industry ofFirozabad. Factors of age, social status, smoking habit andduration of exposure were studied. Duration of exposure wasfound to be a factor contributing significantly to the causationof disease. Requests for reprints should be addressed to: Dr B. N. Gupta, Division of Epidemilogy, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow P.O. Box 80, 226001, India     

Receptor-dependent regulation of the concentration of Ca2+ in the cytoplasm of thrombocytes in hypertensive patients

Platelet activation factor (PAF)-, ADP and vasopressin-induced increments of platelet Ca2+ concentration were measured by quin-2 in 64 patients with essential hypertension and 16 normal donors. Basal concentration of free Ca2+ was 87 +/- 4 nM in donors, 106 +/- 5 nM in patients with labile hypertension (LH) and 122 +/- 6 nM in those with stable hypertension (SH) (p less than 0.01). PAF, ADP and vasopressin, added to platelets, increased [Ca]in by 448 +/- 58, 397 +/- 66, and 277 +/- 50 nM, respectively, in the donors, by 473 +/- 57, 479 +/- 54 and 195 +/- 32 nM, in LH patients, and by 607 +/- 85, 584 +/- 73 and 245 +/- 41 nM in SH patients. There were no significant variations between the three samples, using the ANOVA test. In 20 patients, whose both parents had essential hypertension, [Ca]in increment was 738 +/- 8 nM for PAF, 682 +/- 90 nM for ADP, and 320 +/- 61 nM for vasopressin. In 19 patients, who admitted to no essential hypertension in the family, these parameters were significantly lower: 310 +/- 40 nM for PAF, 389 +/- 61 nM for ADP, and 147 +/- 26 nM for vasopressin. The demonstrated changes may be making an important contribution to the maintenance of elevated vascular tone and provide an evidence in favor of a genetically-predetermined EH variety.     

Confounders contributing to the reported associations of coffee or caffeine with disease

The role of caffeine or coffee in causing or promoting the incidence of serious disease is equivocal. Two design factors may account for the discrepancies in reported findings on the effects of coffee drinking: (a) imprecision of measurement and (b) confounding variables. A study of 2,714 white U.S. adults disclosed that, of 32 risk factors analyzed by linear and logistic regression, only sex and cigarette smoking were found to be important potential confounders of caffeine and coffee intake. Partial R2 values of the other 30 risk factors were relatively small and were inconsistent for each sex. It is unlikely that any of these factors could explain any of the reported associations between caffeine or coffee consumption and certain diseases. However, certain weak associations with caffeine or coffee intake should be included in the study design when they are known to be risk factors of a disease under investigation. These factors for men are dietary fat intake, vitamin C intake, and body mass index; and for women are vitamin use, alcohol intake, stress, and perceived health status.