Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.     

Depression in Alzheimer's disease: is there a temporal relationship between the onset of depression and the onset of dementia?

Alzheimer's disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated-57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences-MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.     

Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up.

BACKGROUND: The long-term observation of vegetarians in affluent countries can provide insight into the relative effects of a vegetarian diet and lifestyle factors on mortality. METHODS: A cohort study of vegetarians and health-conscious persons in Germany was followed-up prospectively for 21 years, including 1,225 vegetarians and 679 health-conscious nonvegetarians. Standardized mortality ratios compared with the German general population were calculated for all causes and specific causes. Within the cohort, Poisson regression modeling was used to investigate the joint effects of several risk factors on overall and cause-specific mortality. RESULTS: Standardized mortality ratios for all-cause mortality was significantly below 100: 59 [95% confidence interval (95% CI), 54-64], predominantly due to a deficit of deaths from circulatory diseases. Within the cohort, vegetarian compared with nonvegetarian diet had no effect on overall mortality [rate ratio (RR), 1.10; 95% CI, 0.89-1.36], whereas moderate and high physical activity significantly reduced risk of death (RR, 0.62, 0.64), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was however associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. CONCLUSIONS: Both vegetarians and nonvegetarian health-conscious persons in this study have reduced mortality compared with the general population. Within the study, low prevalence of smoking and moderate or high level of physical activity but not strictly vegetarian diet was associated with reduced overall mortality. The nonsignificant reduction in mortality from ischemic heart diseases in vegetarians compared with health-conscious persons could be explained in part by avoidance of meat intake.     

MORPHOMETRY AND PATHOLOGY OF THE PARASPINOUS MUSCLES IN IDIOPATHIC SCOLIOSIS

Muscle biopsies from the apex of both sides of the curve of 31 patients with idiopathic scoliosis showed abnormalities in fiber-type distribution in 68 per cent and in fiber size in 55 per cent. There was no preference for either side. Type 1 fiber predominance was as common as type 1 fiber deficiency. Atrophy occurred in 33 per cent and affected mainly type 1 fibers: atrophy of type 2 fibers was rare. Hypertrophy was limited to type 2 fibers, and occurred in 26 per cent. The strength factor for type 1 fibers exceeded that for type 2. Type 2A fibers were no larger than 2B fibers: there was a large type 2A predominance, more so on the convex side. Most of the muscle changes appear to be secondary and compensatory: none suggests a pathogenesis for the curve.     

Basophil releasability in severely burned patients.

Thermal injury is known to induce dysregulation of the immune system; however, the precise mechanisms have to be clarified. We investigated the histamine release of basophil granulocytes from severely burned patients (n = 12) after stimulation with anti-IgE or the Ca-ionophore A 23187, respectively. The anti-IgE-induced basophil histamine release of all patients was reduced in comparison to healthy donors beginning at day one postburn (p.b.) (5.0 +/- 2.3% vs. 30.5 +/-3.4%), while the Ca-ionophore-induced release was not decreased before day two p.b. Basophils of patients who finally succumbed to their injuries showed poor responsiveness (to zero levels) over the total time. In contrast, the basophil releasability of surviving patients returned to nearly normal levels (fifth to seventh week p.b.). Already in the second week p.b. there was a significant difference in histamine release between survivors and nonsurvivors [e.g., days 6-9 p.b.: 23.7 +/- 4.0 vs. 6.9 +/- 2.7 (p less than 0.005) after Ca-ionophore stimulation]. The altered basophil histamine release was neither due to a diminished dose- or a delayed time-response to the stimuli nor due to differences in the basophil counts or the cellular histamine content. Our data indicate that the decrease of the basophil releasability, which may be secondary to altered signal transduction pathways in severely burned patients correlates with the clinical outcome.     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Präimplantationsdiagnostik, Pränataldiagnostik und Schwangerschaftsabbruch

Preimplantation genetic diagnosis (PGD) has been vigorously debated in Germany ever since the Bundesärztekammer (BÄK) published a draft of guidelines for PGD in March 2000. Many stakeholders such as churches, medical societies, and diverse associations have participated in the discussion. However, little is known about the attitudes of experts, directly affected patient groups, and the public in Germany. In several studies that are part of the German research program on ethical implications of the Human Genome Project, representative surveys were undertaken to assess the attitudes of the general population (n=1017), five relevant expert groups (n=879), and couples at high risk for genetic disorders(n=324) towards PGD and prenatal diagnosis (PD). All groups favor legislation for PGD. Differences exist in regard to the extent of their approval. For 17% of the high-risk couples with a persisting desire for a child, PGD performed in a neighboring country is the most probable reproductive option. These results should be carefully considered in the ongoing legislation process on human reproduction in our country.