Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy.

Advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonstrates major alterations in the expression of signal transduction molecules in T cells of leprosy patients. These alterations were most frequently observed in lepromatous leprosy (LL) patients. Of 29 LL patients, 69% had decreased T-cell receptor zeta-chain expression, 48% had decreased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-kappaB p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid leprosy patients had only minor signal transduction alterations. These novel findings might improve our understanding of the T-cell dysfunction observed in leprosy and other infectious diseases and consequently might lead to better immunologic evaluation of patients.

Prevention advice rates of women and men physicians.

BACKGROUND: As the number of women in medicine and the emphasis on prevention and primary care increase in the United States, it is important to know the extent to which female and male physicians advise patients about prevention. It is also important to know whether any gender-based differences are attributable to women's higher rates of choosing primary care specialties. Prior studies have examined only small populations of physicians, limited physician specialties, or few prevention-related outcomes. METHODS: Telephone survey from a systematic random sample of the Physician Masterfile maintained by the American Medical Association. One thousand US physicians (167 women and 833 men); a 48% response rate. Self-reported frequency with which physicians review patients' health behaviors and initiate counseling about unhealthy behaviors. RESULTS: Of the surveyed physicians, 44% stated that they always reviewed the patient health behaviors in question, and 36% usually systematically counseled patients when unhealthy behaviors were known. Female physicians were significantly more likely than were male physicians to report systematic counseling about unhealthy behaviors (52% vs 37.8%, P < .001, chi 2). We also analyzed our data by adjusting for age and including only family and general physicians and internists. After these adjustments, gender-based differences remained in the direction of female physicians being more likely than male physicians to report reviewing patients' health practices and providing systematic counseling, although these differences no longer reached statistical significance. Gender-related differences were greatest for more sensitive behaviors (ie, drug use and sexual behaviors). Primary care physicians were more likely than other physicians to review and counsel patients about health behaviors. This specialty-based difference was more significant among male than among female physicians. CONCLUSIONS: In this random sample, although all physicians counseled patients inconsistently about prevention, female physicians reported systematically counseling patients more than did male physicians, and primary care physicians reviewed and counseled more often than did physicians in other specialties.

Structural analysis of tamarind seed xyloglucan oligosaccharides using beta-galactosidase digestion and spectroscopic methods.

The borohydride-reduced forms (oligoglycosyl alditols) of two isomeric octasaccharides (Glc4Xyl3Gal) that are released from xyloglucans of various plant species upon treatment with a fungal endo-(1-->4)-beta-glucanase were isolated and structurally characterized. A mixture of oligosaccharides that is released from tamarind seed xyloglucan by the endo-(1-->4)-beta- glucanase was digested with a commercially available beta-galactosidase (Aspergillus niger). The beta-galactosidase selectively hydrolyzed the galactosyl residue of one of the two isomeric octasaccharides present in the mixture. A homogeneous preparation of the beta-galactosidase-resistant octasaccharide was prepared by high-resolution gel-permeation chromatography of the enzyme-digestion products. Spectroscopic characterization of the oligoglycosyl alditol prepared by reduction of this octasaccharide confirmed the previously proposed structure that had been based on analysis of the mixture of isomeric octasaccharides. The availability of large amounts of the pure, reduced octasaccharide and of a pure, reduced pentasaccharide (Glc3Xyl2) made it possible to completely assign their 1H and 13C NMR spectra. In addition, the borohydride-reduced form of the beta-D-galactosidase-susceptible octasaccharide isomer was purified by high pH anion-exchange chromatography of the endo-(1-->4)-beta-glucanase-released octasaccharides from rape-seed xyloglucan (no beta-galactosidase treatment), and its 1H and 13C NMR spectra were assigned. Additional correlations between specific structural features of xyloglucan oligoglycosyl alditols and the positions of specific resonances in their NMR spectra were deduced and added to the extensive list that we have compiled. The effects of recording the NMR spectra of the xyloglucan oligoglycosyl alditols in the presence of borate salts, which could lead to incorrect structural assignments, are also described.

Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells.

The causes of the decreased immune responsiveness in tumor-bearing hosts are incompletely understood. The impact of a decreased immune response in cancer patients on the clinical response in immunotherapy trials has not been evaluated. The present report demonstrates a marked decrease in the therapeutic efficacy of adoptively transferred T lymphocytes obtained from murine hosts bearing tumor for greater than 30 days [late tumor-bearing mice (TBM)] as compared with normal mice and mice bearing tumor for less than 21 days (early TBM). In vitro analysis of the functions of the T lymphocytes from late TBM showed an apparently normal proliferative response to anti-CD3 and IL-2 with adequate lymphokine production from CD4+ cells, but a significant decrease in the cytotoxic function of CD8+ cells. The decreased cytotoxicity was not because of cell-mediated suppression. The expression of granzyme B mRNA was significantly delayed and decreased in magnitude in CD8+ cells from late TBM. Culture supernatants from two unrelated tumor cell lines were able to inhibit the cytotoxic activity of normal CD8+ cells in vitro. The tumor-derived suppressive factor is not transforming growth factor-beta (TGF-beta), but it has not been further characterized. The data suggest that one potential mechanism responsible for immunologic defects in patients with large tumor burdens is a tumor-induced defect that compromises the function of CD8+ effector T cells.

The temporal patterning of tension reduction: stress and alcohol use on weekdays and weekends.

A sample of 328 students provided reports of drinking episodes and ratings of situational stress experienced during two series of 4-hour time blocks covering early and late evening hours on weekdays (Tuesday and Wednesday) or weekends (Friday and Saturday). Although baseline levels of "predrinking" stress were not strongly related to the onset of drinking episodes in subsequent time blocks, analyses of temporal changes in stress from "predrinking" to "drinking" blocks show a significant tension-reduction effect among respondents who used alcohol--in contrast to those who did not drink--on both weekday evenings and early Friday evening (4-8 PM). No significant changes in stress ratings occurred among late Friday or Saturday evening drinkers. Multivariate analyses indicate that the weekday tension reduction effect is not systematically contingent on questionnaire measures of individual characteristics (age, sex, coping motives and typical drinking patterns) nor on situational measures of consumption and intoxication. The results suggest that weekday drinking after work or class is a culturally defined occasion for "time out" from stress.

Health access America--strengthening the US health care system.

Although Americans remain generally satisfied with the health care provided to them, sufficient access to high-quality, affordable health care for citizens without health care insurance has become an increasing problem in the last decade. Using the policy development process of the American Medical Association, Health Access America was conceived by the Association to improve access to affordable, high-quality health care. The proposal consists of six fundamental principles and 16 key points. This article specifically focuses on the five points that, if enacted into law, would improve access to health care for Americans who are, for various reasons, without health insurance.

Attitudes of US primary care physicians about HIV disease and AIDS.

Telephone interviews were conducted with 500 primary care physicians, drawn from a stratified random sample of internists, family practitioners, pediatricians, general practitioners, and OB/GYN physicians. Respondents were asked to report their experience treating AIDS patients and to estimate the percentage of their patients they felt were at high risk for HIV infection. Nineteen questions designed to assess practices and attitudes towards AIDS and HIV-related issues were asked. Results suggest that physicians underestimate their patients' level of risk for HIV infection and are not taking adequate drug use and sexual histories. The level of concern for personal risk of infection was high, although a strong ethical obligation to treat HIV patients was expressed. Physicians also expressed support for mandatory reporting and contact tracing, although this diminished as contact with HIV patients increased.

A trial using early preoperative administration of cefonicid for antimicrobial prophylaxis with hysterectomies.

A single dose of cefonicid given 3.5-5.0 hours or 0.5-1.0 hour preoperatively was compared with cefoxitin given as five doses beginning 0.5-1.0 hour preoperatively for prophylaxis of infection in 202 patients undergoing vaginal or abdominal hysterectomy. The administration of cefonicid 3.5-5.0 hours preoperatively was intended to simulate situations where surgery may be delayed or prolonged. The trial was double-blind, and patients were randomized to one of the three regimens. Operative site infections were noted in 6.2 percent of patients (7/113) who received cefonicid 3.5-5.0 hours preoperatively, in 7.0 percent of patients (3/43) who received cefonicid 0.5-1.0 hour preoperatively, and in 4.3 percent of patients (2/46) who received cefoxitin (p greater than 0.05). Enterococci were isolated most frequently from operative-site infections. When administered 3.5-5.0 hours preoperatively, cefonicid was as effective as more traditional regimens.

Antibiotic therapy of osteomyelitis in outpatients.

The therapy of osteomyelitis utilizing 481 courses of intravenous antibiotics in outpatients was analyzed to identify the types of bone infection most frequently treated by this form of therapy. The efficacy of this form of treatment is also discussed.