Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection

We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed.     

HLA and alopecia areata in Jerusalem

A study of 46 patients with Alopecia areata in Jerusalem showed a significant increase in the frequency of HLA-B18 (23.9%) as compared to the control population (7.4%) with a relative risk of 3.9%. This association of HLA-B18 with AA was independent of the origin of patients, sex, age of onset and type of alopecia areata.     

Understanding the relationship between market competition and students' ratings of the managed care content of their undergraduate medical education.

PURPOSE: The increase in managed care has led to questions about the inadequacy of instruction undergraduate medical students receive in curricular areas related to managed care. This study examined (1) the percentages of graduating medical students who felt they had received inadequate instruction in six curricular content areas (CCAs): primary care, care of ambulatory patients, health promotion and disease prevention, medical care cost control, teamwork with other health professionals, and cost-effective medical practice; and (2) whether the market competitiveness of these students' medical schools affected their reports of inadequacy of instruction in these CCAs. METHOD: Data from the Association of American Medical Colleges' Graduation Questionnaires (GQs) from 1994 to 1997 were analyzed. The GQ asked graduating students to rate the adequacy of instruction they had received in the six CCAs. Students' ratings were collapsed into the dichotomous variables "inadequate" and "not inadequate." The market competitiveness of medical schools was determined using the four-stage Market Evolution Model developed by the University HealthSystem Consortium. Only responses from students graduating from medical schools that could be staged for all four years of the study were analyzed. Statistical analyses were performed to determine trends for each CCA by year, across the entire study period, by market stage, and by market stage across the entire study period. RESULTS: A total of 39,136 respondents from 86 medical schools were used in the study. The percentages of graduating medical students who reported inadequate instruction decreased over the study period for five of the six CCAs: primary care (27.6% in 1994 to 13.7% in 1997), ambulatory care (37.4% to 23. 9%), medical care cost control (62.9% to 52.9%) cost-effectiveness of medical practice (62.7% to 53.9%), and health promotion and disease prevention (44.4% to 23.7%); all at p <0.001. The responses for inadequacy of instruction for teamwork with other health professionals remained steady from 1994 to 1996 (10.2% to 10.6%), then increased 21.8% in 1997. Over the course of the study, students graduating from schools in more competitive markets (Stage 3 or Stage 4) were more likely to report inadequate instruction in three CCAs, primary care, ambulatory care, and health promotion and disease prevention, than were those graduating from schools in less competitive markets (Stage 1 and Stage 2). Conversely, students graduating from schools in the more competitive health care markets were less likely to report inadequate instruction in cost-effectiveness and cost control than were students from schools in less competitive markets. CONCLUSION: Graduating students' reports of inadequacy of instruction decreased over the study period for five of the six CCAs, increasing only for teamwork with other professionals. Findings were mixed with regard to the relationship of medical schools' market competitiveness and graduating students' reports of inadequacy of instruction. More research is needed to confirm graduating students' perceptions of the inadequacy of their instruction in CCAs related to managed care, particularly once they have gained experience treating patients in managed care environments.     

HLA–DRw4 in Pemphigus Vulgaris Patients in Israel

Pemphigus vulgaris (PV) is relatively common in Jews. Three HLA antigens were significantly more frequent in 39 Israeli Jewish PV patients than in controls: A26 – 59% vs 20%; Bw38 – 61% vs 20%; and DRw4 – 90% vs 38%. The joint occurrence of A26–Bw38–DRw4 was observed in 46% of PV patients and in 10% of controls. Similar results were recently reported for Jews in the Los Angeles area. Yet, when our patient sample was grouped into Ashkenazi and non-Ashkenazi Jews, it was evident that each of the three antigens had a higher frequency both in Ashkenazi patients and controls as compared to non-Ashkenazim. The relative risk for DRw4 in Ashkenazim was 33.8 as compared to 14.4 in the total sample of Israeli PV patients. The phenotype A26–Bw38–DRw4 was present in 57% of Ashkenazi patients and in 13% of controls. Ashkenazi Jews have the highest prevalence of PV, and HLA associations were strongest with Ashkenazi PV patients. These associations were with three antigens, all of high frequency in that group.     

The mechanism of action of soluble lymphocytic mediators: I. A pulse exposure test for the measurement of macrophage migration inhibitory factor

Culture supernatants containing macrophage migration inhibitory factor (MIF) were obtained by incubating lymphocytes of guinea-pigs, immunized with Freund's complete adjuvant (FCA), with tuberculin PPD in vitro. Exposure of normal peritoneal macrophages to MIF-containing supernatants for 2 hours at 37° (pulse exposure), followed by suspension in culture medium and transfer to capillaries, resulted in inhibition of migration in vitro for the next 24 hours. No inhibition was seen when macrophages were incubated with MIF at 4°. On the other hand when exposure to MIF at 4° was followed by incubation of the cells for 2 hours at 37° in culture medium, in the absence of MIF, inhibition of migration was obtained. These results indicate that: (a) macrophages possess a specific receptor able to bind MIF at either 4° or 37°, and (b) inhibition of migration by receptor bound MIF requires a temperature-dependent active process, the nature of which remains unknown.

Passage of lymphocytes through columns of glass beads resulted in a population of cells with intact or heightened MIF-forming ability, as assessed by both conventional and pulse exposure techniques.

     

Beitrag des Brotes zur Bedarfsdeckung der schweizerischen Bev?lkerung mit einigen wichtigen N?hrstoffen

Ohne Zusammenfassung

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The long-term effect on intraocular pressure of a procedure combining trabeculectomy and cataract surgery, as compared with trabeculectomy alone

The long-term reduction of intraocular pressure (IOP) resulting from a procedure combining extracapsular cataract extraction and posterior chamber lens implantation with trabeculectomy was compared retrospectively with the IOP-lowering effect of trabeculectomy alone. Forty patients who underwent the combined procedure and 38 who underwent trabeculectomy alone had been followed for an average of 22 +/- 7 months. Both these surgical procedures significantly reduced IOP, but after a year or more, pressure levels were significantly lower in the trabeculectomy group than they were in the combined group: 12.8 +/- 4.2 mm Hg, and 16.5 +/- 5.6 mm Hg, respectively, at 18 months. Also, the mean postoperative fall in IOP was greater in the "filtered" eyes than it was in the combined group (9.8 +/- 4.6 mm Hg and 12.1 +/- 5.2 mm Hg, respectively, at 18 months). Finally, the number of medications required to maintain controlled IOP in the combined group was greater (and resumed preoperative values at 2 years) than it was in the trabeculectomy group (62.5% of the filtered eyes remained controlled unaided).     

Abruptio placentae and disseminated intravascular coagulation: use of thrombelastography and sonoclot analysis

We report a case in which thrombelastography (TEG) and Sonoclot analysis were used for diagnosis and treatment decisions in a patient with abruptio placentae and disseminated intravascular coagulation. In addition to providing enough information for evaluation and treatment of this patient, the TEG and Sonoclot results were obtained more quickly, with smaller blood samples and with less expense to the patient in comparison to the standard coagulation tests in our institution. Although the TEG and Sonoclot results were assessed independently of the other test and each provided similar information in this case, the TEG may be the preferred tool in evaluating coagulopathies, based on computerization and strong literature support.