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Biomedical subjects

J Gebhard

Publications and source records attributed to J Gebhard.

6 recordsLinked to original sources
PubMed1999

The role of B lymphocytes in coxsackievirus B3 infection.

Coxsackieviruses are important human pathogens, frequently causing myocarditis, pancreatitis, and a variety of less severe diseases. B lymphocytes appear central to the interaction between these viruses and their mammalian hosts, because agammaglobulinemic humans, genetically incapable of antibody production, are susceptible to chronic infections by coxsackieviruses and related enteroviruses, such as poliovirus and echovirus. However, recent studies show that Type B coxsackievirus (CVB) infects B lymphocytes soon after infection, suggesting the possibility that these cells may play some role in virus dissemination and/or that the virus may be able to modulate the host immune response. We analyzed the role of B lymphocytes in CVB infection and confirmed that CVB infects B lymphocytes, and extended these findings to show that this is a productive infection involving approximately 1 to 10% of the cells; however, infectious center assays show that other splenocytes are infected at approximately the same frequency. Virus is readily detectable by in situ hybridization in the spleen of immunocompetent mice but is difficult to detect in mice deficient in B cells (BcKO mice), consistent with much of the splenic signal being the result of B cell infection. Surprisingly, given the extent of their infection, B cells express barely detectable levels of the murine coxsackievirus-adenovirus receptor (mCAR), suggesting that another means of cell entry may be used. We found no evidence of B cell depletion following CVB infection, indicating that this is not the explanation for the transient immunosuppression previously reported. Virus replication and dissemination are slightly delayed in BcKO mice, consistent with B cells' playing a role as an important early target of infection and/or a means to distribute the virus to many tissues. In addition, we show that BcKO mice recapitulate a central feature of human agammaglobulinemia: CVB establishes chronic infection in a variety of organs (heart, liver, brain, kidney, lung, pancreas, spleen). In most of these tissues the viral titers remain high (10(5)-10(8) plaque forming units (pfu) per gram of tissue) for the life of the mouse, and in several there is severe pathology, particularly severe myocardial fibrosis with ventricular dilation, reminiscent of the dilated cardiomyopathy seen in humans with chronic enteroviral myocarditis. Transfer of B and/or T cells from non-immune mice had no discernible effect, whereas equivalent transfers from immune mice often resulted in transient or permanent disappearance of detectable CVB.

Adoptive Transfer↗
PubMed1995

Starnberg trial on epidemiology of Parkinsonism and hypertension in the elderly. Prevalence of Parkinson's disease and related disorders assessed by a door-to-door survey of inhabitants older than 65 years.

OBJECTIVE: To investigate the prevalence of different types of parkinsonism (PS) in the elderly, regardless of health care service or drug prescription, by a door-to-door survey in two German villages. DESIGN: We investigated the prevalence of PS in a rural Bavarian population of individuals older than 65 years (982 participants; response rate, 82.5%) using a door-to-door-survey and a biphasic approach. MAIN OUTCOME MEASURES: Two investigators employed a pretest screening questionnaire and motor tests for signs of PS. Individuals suspected of suffering from PS were reinvestigated by two neurologists trained in movement disorders, and computed tomographic scans were performed. RESULTS: The prevalence of Parkinson's disease in individuals older than 65 years was 0.71% (95% confidence interval, 0.19% to 1.23%), with a male predominance (five men, two women). Parkinsonism of other pathogenesis included drug-induced PS (0.41%, four of 982 inhabitants), vascular PS (0.20%, two of 982), multiple system atrophy (0.31%, three of 982), and Fahr's disease (0.10%, one of 982). The high prevalence of normal-pressure hydrocephalus (0.41%, four of 982 inhabitants) was an unexpected finding that was confirmed by computed tomography. Fifty percent of cases of PS were newly diagnosed. CONCLUSIONS: This study represents the first door-to-door survey on PS in Germany. In addition, for the first time, it includes a clinical differentiation between Parkinson's disease, multiple system atrophy (of the striatonigral type), and PS of other pathogenesis. The prevalence of Parkinson's disease corresponds to that reported in other surveys of people older than 65 years. Normal-pressure hydrocephalus and multiple system atrophy, on the other hand, were more prevalent than expected, and all these cases were newly diagnosed.

Adult↗
PubMed1994

Prevalence, awareness, treatment and control of hypertension in a population over the age of 65 years: results from the Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly (STEPHY).

OBJECTIVE: To assess the prevalence of hypertension and isolated systolic hypertension and the level of awareness, treatment and control of hypertension, in a population aged over 65 years. DESIGN: Cross-sectional survey of the total population aged > or = 65 years of two Bavarian villages with a representative age distribution. PATIENTS: From a total of 1190 inhabitants aged > or = 65 years, 982 (394 male, 588 female) participated (response rate 82.5%). METHODS: All of the participants were visited at home by physician observers. After a standardized questionnaire, blood pressure was measured three times on one occasion with the subject in the sitting position, using a standard mercury sphygmomanometer. 'Actual' hypertension was defined as systolic blood pressure (SBP) > or = 160 or diastolic blood pressure (DBP) > or = 95 mmHg, or both, or current use of antihypertensive drugs given for the indication hypertension in patients with blood pressure < 160/95 mmHg. Isolated systolic hypertension was defined as SBP > or = 160 and DBP < 90 mmHg. All 'actual' hypertensives were further classified as 'unaware' of hypertension, 'aware' (but not treated), 'treated' (current use of antihypertensive drugs for the indication hypertension and blood pressure > or = 160/95 mmHg) or 'controlled' (treated and blood pressure < 160/95 mmHg). RESULTS: Mean +/- SD blood pressure was 154.5 +/- 24.4/84.9 +/- 11.6 mmHg (when 52 institutionalized participants were excluded, 155.6 +/- 24.4/85.3 +/- 11.6 mmHg). The SBP was significantly higher in females than in males and increased up to the age group 80-84 years both in males and in females. The DBP decreased with age. The prevalence of 'actual' hypertension was 53% and increased up to the age group 75-79 years in males and 80-84 years in females. The prevalence of isolated systolic hypertension was 17% (with patients currently using antihypertensive drugs excluded). Of the patients with 'actual' hypertension, 34% were 'unaware' of the diagnosis, 12% 'aware', 32% 'treated' and 22% 'controlled'. CONCLUSIONS: In central Europe hypertension, with a prevalence of > 50%, remains the most common cardiovascular risk factor in the elderly. Although most elderly hypertensives are currently treated with antihypertensive agents, less than one-quarter are controlled, and more than one-third are still unaware of the diagnosis. These levels of awareness and control call for better strategies in the diagnosis and treatment of hypertension in the elderly.

Age Factors↗
PubMed1989

Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity.

The cytotoxic T-lymphocyte (CTL) response to lymphocytic choriomeningitis virus infection determines the outcome of infection. Here we show that this response in BALB/c mice (H-2d), when analyzed both at the primary CTL level and using CTL clones, is predominantly monospecific. The vast majority of CTL have a common specificity for a single epitope in the virus nucleoprotein, which can be minimally identified by amino acids GVYMG. This epitope is presented by the Ld class I glycoprotein. We used these data to design a subunit CTL vaccine, whose effectiveness is demonstrated in the accompanying report (L. S. Klavinskis, J. L. Whitton, and M. B. A. Oldstone, J. Virol. 63:4311-4316, 1989). Further analysis indicates that, while CTL clones share a common minimal epitope, they differ in their ability to recognize cells infected with a related but distinct strain of lymphocytic choriomeningitis virus. Studies on the molecular nature of CTL cross-reactivity indicate that CTL induced by similar sequences may cross-react in a unidirectional manner. These novel observations suggest that CTL vaccines, to achieve optimal effectiveness, should not simply include virus sequences which will yield a CTL response; the immunizing sequences should also be selected to ensure that the fine specificities of the induced CTL are such that they maximize the chance of recognizing serotypically diverse strains.

Amino Acid Sequence↗