A Third world international health elective for U.S. medical students. The 16-year experience of the State University of New York,Health Science Center at Brooklyn

The Department of Preventive Medicine and Community Health at the State University of New York, Health Science Center at Brooklyn (SUNY, HSCB) instituted an eight-week third world international health elective for fourth year medical students in 1980. Since that time, ninety students have participated. The purposes of this elective are to provide fourth year medical students with an opportunity to observe and study the structure and functions of a health care delivery system in a third world country, to provide medical service, and to have a crosscultural experience. The emphasis in this elective is on public health, preventive medicine, and primary care. There is a high level of student competition for this elective, with 46.9% of applicants having been accepted over a fifteen-year period. Although women comprise 40% of the average medical school class, they represent 50% of participants in this elective program. The percentage of African-American and Hispanic students has been 20%. These two minority groups represented from 8% to 10% of the student body during the period under study. Careful screening, including an examination of academic records and personal interviews, has resulted in the selection of highly motivated, adaptable, and dedicated students who have performed well at overseas sites. Student satisfaction levels with this elective are extremely high, with most rating it the best experience of their medical school years. Students undergo extensive preparation prior to going overseas. This covers issues related to individual health and safety, travel and lodging, and the nature of the host country culture, health care system, and assignment site. Our students are especially experienced at cross-cultural understanding because of the unusual diversity of the patients they treat in Brooklyn, and the ethnic diversity of local hospital staffs and the medical school class. This Brooklyn experience in cross-cultural understanding has been cited by many participants as having been the best preparation for functioning in a foreign culture. The Alumni Fund of the College of Medicine has strongly and consistently supported this elective both with philosophical commitment and financial grants to help defray travel costs. This type of support is unusual among medical schools in New York City. Overseas preceptors have willingly given of their time and institutional resources to make these experiences available and meaningful for students.     

Pneumonitis associated with coinfection by human herpesvirus 6 and Legionella in an immunocompetent adult.

The authors report a case of pneumonitis in a young healthy man caused by coinfection with human herpesvirus 6 (HHV-6) and Legionella pneumophila. The patient's course was complicated by severe respiratory, renal, hepatic, and central nervous system dysfunctions, which were believed to be primarily the results of his Legionella infection. Aggressive antibiotic treatment produced no response, and Legionella remained isolatable from lung tissue throughout several weeks of antimicrobial therapy. Human herpesvirus 6 was isolated from a sample of peripheral blood during the acute stage of the patient's illness, and numerous HHV-6--infected macrophages and lymphocytes were detected by immunohistochemical staining of biopsy-derived lung tissue. Paradoxically treatment of the patient with high-dose corticosteroids resulted in dramatic improvement of his condition, including clearance of the Legionella infection. The demonstration that corticosteroids efficiently inhibit HHV-6 replication in vitro suggests that the virus may have contributed to the patient's pneumonitis by enhancing tissue inflammation, by compromising the function of pulmonary macrophages, and, perhaps, by destroying the patient's CD4+ T lymphocytes. Human herpesvirus 6 may be able to function as a synergistic cofactor in lung infections by Legionella and other pathogens.     

A qualitative and quantitative analysis of the entorhinal cortex in schizophrenia

The entorhinal cortex (ERC) has been implicated in schizophrenia by a number of studies. There is anatomical observation of neuronal heterotopias in the rostral ERC, which is consistent with a hypothesis of neurodevelopmental abnormalities in this disease. In view of the significant cytoarchitectonic variation of the ERC throughout its rostro-caudal extent, we performed a detailed subareal analysis of the rostral two-thirds of the entorhinal cortex (ERCr) in 14 postmortem schizophrenic brains and 14 matched controls (mean ages of 48 and 47 respectively). This systematic evaluation included both a qualitative microscopic analysis of morphogenetic anomalies that would be consistent with neurodevelopmental pathology and quantitative measurements of total neuronal number, average neuronal density, laminar volume and laminar depth from the cortical surface in cytoarchitectonically matched subareas of schizophrenic and control brains. Parcellation of the entire ERC on the basis of cytoarchitectonic criteria identified five distinct regions, similar to those described in the macaque, except that in the human brain three of the regions were further divisible into two or three subareas, yielding nine distinct cellular compartments. Five rostral areas, prorhinal (Pr), lateral (28L), intermediate rostral and caudal (281r and 281c), and sulcal (28S), comprise the ERCr. Gross and microscopic examination of these subdivisions throughout the ERCr failed to reveal laminar disorganization in any of the schizophrenic brains. The brains also did not differ significantly with respect to total neuronal number, total volume and neuronal density per laminar and subareal subdivision, or laminar thickness per entorhinal subarea. However, neuronal number and density were reduced by 12-18% in Pr and 28L, suggesting that mild quantitative abnormalities may exist in the ERCr and might possibly be revealed in a larger sample of schizophrenic brains. We have failed to confirm previous reports of laminar disorganization in the ERCr in brains of patients with schizophrenia; to the extent that this region is implicated in schizophrenia, the structural changes are likely to consist of more subtle cellular disturbances.      

肿瘤坏死因子对牛肺动脉内皮细胞的损伤及蛋白激酶C抑制剂的抑制作用

研究表明:肿瘤坏死因子(TNF)可剂量依赖地引起牛肺动脉内皮细胞乳酸脱氢酶释放率(LDH%)升高,促进中性粒细胞向内皮细胞粘附,并可抑制内皮细胞增殖和DNA合成。蛋白激酶C(PKC)抑制剂1-(5-异喹啉磺酰基)-2-甲基哌嗪(H-7)和槲皮素一方面可剂量依赖地抑制TNF对内皮细胞的直接损伤,另方面又可通过抑制TNF诱导的中性粒细胞对内皮细胞粘附增加,减轻TNF对内皮细胞的间接损伤作用,同时还可抑制TNF对内皮细胞增殖和DNA合成的影响,从而间接加强内皮细胞对损伤的自我修复。     

Reversible repression and activation of measles virus infection in neural cells.

Conversion of acute measles virus infection to an indolent state has been achieved by treatment of infected cells of neural origin with agents that affect cyclic nucleotide metabolism. Striking results were obtained with papaverine, an inhibitor of cAMP phosphodiesterase that is capable of enhancing neural differentiation. In papaverine-treated cultures, decreased production of infectious virus was accompanied by selective disappearance of intracellular matrix proton, as detected by immunofluorescence. Viral nucleocapsid protein was enhanced in the cytoplasm while three other structural proteins--polymerase, hemagglutinin, and fusion protein--showed little change in distribution or intensity of staining. These results were specific for cells of neural origin and not observed in CV-1 or Vero cultures. cAMP, dibutyryl cAMP, 8-bromo-cAMP, and isobutylmethylxanthine all inhibited replication of virus but less so than did papaverine. Inhibition of virus replication by any of these agents was rapidly reversible, either by removal of the agent or by addition of cGMP to the culture medium and was accompanied by reappearance of the matrix protein. These results suggest that measles virus replication in neural cells depends on host factors, particularly those affecting endogenous cAMP and cGMP. Viral persistence may thus be related to the state of neural differentiation. This model system may yield information on mechanisms of recrudescence observed in some chronic diseases of the nervous system.     

Transforming growth factor-β (TGF-β) activity in urine of patients with glomerulonephritis is related to their renal functional and structural changes

SUMMARY: Transforming growth factor-β (TGF-β) has been considered the principal cytokine involved in the pathogenesis of renal fibrosis. In the present study, we evaluated TGF-β activity in occasional samples from 22 normal individuals and 29 patients (11 with focal glomerulosclerosis, 11 with membranous nephropathy, five with Berger disease, one with type I membranoproliferative glomerulonephritis and one with postinfectious glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay.
A significantly increased urinary TGF-β activity (reported in relation to urine creatinine, Ucreat, and median) was observed in patients with glomerulonephritis compared with normal individuals ( P <0.01). the patients with Berger disease [median (Md) = 9.96/10 μg Ucreat.], membranous glomerulonephritis (Md = 7.23/10 μg Ucreat.) and focal glomerulosclerosis (Md = 16.6/10 μg Ucreat.) showed higher urinary TGF-β than normal individuals (Md = 1.09/10 μg Ucreat.) ( P <0.01). We found a positive correlation between the TGF-β activity in the urine of these patients and the incidence of segmental glomerulosclerosis ( r = 0.45, P <0.05) and their plasma creatinine levels ( r = 0.87, P <0.01). A negative correlation was observed between the TGF-β activity in the urine of these patients and their creatinine clearance ( r =−0.75, P <0.01).
Our data suggest that measurement of urinary TGF-β activity could be a useful non-invasive procedure for the evaluation of renal TGF-β production, permitting the assessment of prognosis and the evaluation of therapeutic efficacy in patients with renal disease.     

Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes

Eosinophils are involved in the inflammatory response seen in allergy and helminthic infestations. Eosinophils synthesize transforming growth factor-alpha (TGF-alpha), which may play a role in the development of the characteristic fibrosis seen in longstanding high eosinophilia. Using immunoelectron microscopic techniques, eosinophils from peripheral blood of healthy individuals and from one patient with high eosinophilia showed presence TGF-alpha in matrix of the specific crystalloid-containing granules. In cryosections, TGF-alpha was also visualized in a vesicular compartment of the cytoplasm. In double- labeling experiments, the TGF-alpha of this latter compartment did not colocalize with CD63, a marker for lysosomes, nor with albumin of secretory vesicles. In extracts from eosinophils, obtained from healthy donors, immunoreactive TGF-alpha could be detected by enzyme-linked immunosorbent assay-technique. In addition, sera from two patients with high eosinophilia showed TGF-alpha concentrations of 1.5 ng/mL and 164 pg/mL, respectively, whereas TGF-alpha could not be detected in serum from healthy controls. In conclusion, TGF-alpha is present in the specific granules, and in an additional vesicular compartment of the cytoplasm of eosinophils.