Über die Aldosteronausscheidung bei Schwangerschaften und bei Schwangerschaftstoxikosen

Ohne ZusammenfassungMit Unterstützung der Deutschen Forschungsgemeinschaft.     

Memory Deficits in Aged Cebus Monkeys and Facilitation With Central Cholinomimetics

Cebus monkeys of 3 different age groups were trained to perform an automated behavioral task (delayed response), intended to measure recent memory ability. In in initial study, the aged monkeys (18 years and older) exhibit prprogressively greater performance impairments (relative to young monkeys) as they were required to remember the location of a visual stimulus for increasingly longer durations (0 to 20 sec). This deficits replicated previously published results from aged Rhesus monkeys and appeared similar to the primary memory deficits reported in elderly humans and demented patients. In subsequent studies, the effects of three different cholinomimetics were evaluated for their ability to improve the aged monkey's performance on this task. Each monkey was tested under several acute doses of the cholinergic precursor, choline, the anticholinesterase, physostigmine, and the cholinergic muscarinic receptor agonist, arecoline. The results revealed clear differences in the ability of these drugs to improve performance on this task. Choline exerted no apparent effects in the aged monkeys at any dose tested. Physostigmine clearly enhanced performance in certain aged monkeys, but the optimal dose varied dramatically between subjects, replicating previously published results with aged Rhesus monkeys and humans. Arecoline produced clear improvement within a restricted dose range, with little variation in optimal dose between subjects. In addition to demonstrating differences in the effects of different cholinomimetics on memory performance in aged primates, these data also suggest a possible rationale for future investigations. Assuming that each of these drugs primarily affected cholinergic function in the manner conventionally attributed, these data suggest that, within the cholinergic system, the more directly one stimulates the receptor, the more one might expect robust and consistent effects on memory performance in aged subjects.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

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Ohne Zusammenfassung     

Isolation and characterization of C-reactive protein and serum amyloid P component in the rat.

C-reactive protein (RP) and serum amyloid P component (SAP) have been identified for the first time in rat serum and isolated by calcium-dependent affinity chromatography. Rat CRP closely resembled human CRP in its amino acid composition, in having five subunits per molecule and in its electron microscopic appearance as a pentameric annular disc. It differed, however, from all other mammalian CRP's characterised hitherto in being a glycoprotein bearing a single complex oligosaccharide on each polypeptide subunit. Furthermore one pair of tis subunits per molecule was linked by a interchain disulphide bridges whereas in other animals the subunits of both CRP and SAP are all non-covalently associated. The serum concentration of CRP in normal healthy laboratory rats and in specific pathogen-free rats was 300-600 micrograms/ml which is much greater than has been described in any other species and exceeds even maximal acute phase levels of CRP in man. Following injections of casein or croton oil, serum CRP levels rose to a maximum of about 900 micrograms/ml. Rat CRP bound to pneumococcal C-polysaccharide (CPS( but, in marked contrast to the behaviour of CRP from man, rabbit and marine teleost fish, it did not precipitate with CPS solutions, agglutinate CPS-coated sheep erythrocytes or initiate complement activation. Rat SAP, like SAP of other species, was a glycoprotein but unlike them it was composed only of a single pentameric disc not two such discs interacting face-to-face. The normal level of SAP in rat serum was 20-50 micrograms/ml, very similar to the levels seen in man, and it did not behave as an acute phase reactant in response to casein or croton-oil injections. In this respect it resembled human SAP but differed from murine SAP which is a major acute phase reactant.     

Experimental SARS-CoV-2 Infection of Bank Voles

After experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Thus, bank voles are unlikely to establish effective transmission cycles in nature.     

Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology,Germany, 2018–2020

Human bornavirus encephalitis is a severe and often fatal infection caused by variegated squirrel bornavirus 1 (VSBV-1) and Borna disease virus 1 (BoDV-1). We conducted a prospective study of bornavirus etiology of encephalitis cases in Germany during 2018–2020 by using a serologic testing scheme applied along proposed graded case definitions for VSBV-1, BoDV-1, and unspecified bornavirus encephalitis. Of 103 encephalitis cases of unknown etiology, 4 bornavirus infections were detected serologically. One chronic case was caused by VSBV-1 after occupational-related contact of a person with exotic squirrels, and 3 acute cases were caused by BoDV-1 in virus-endemic areas. All 4 case-patients died. Bornavirus etiology could be confirmed by molecular methods. Serologic testing for these cases was virus specific, discriminatory, and a practical diagnostic option for living patients if no brain tissue samples are available. This testing should be guided by clinical and epidemiologic suspicions, such as residence in virus-endemic areas and animal exposure.     

Comparative study of a biochemical index for the estimation of bone demineralization and dual photon absorptiometry

Multivariate classification methods were used to create an early detection technique for determining bone density. This biochemical index (QuiOs) is clinically useful as a potential adjunct in identifying the presence of biochemical deficiencies known to cause osteopenia and the devastating effects of osteoporosis. The test uses the following serum concentrations of a predetermined set of blood constituents: calcium, phosphorus, alkaline phosphatase (ALP), two alkaline phosphatase isoenzymes (liver and intestine), estradiol, and progesterone. Using the results of these six biochemical and hormonal tests, a correlation equation was developed that demonstrates a nonlinear relationship between QuiOs and Ward's triangle of DPA. A sensitivity of 86% and a specificity of 80% was demonstrated for this biochemical index against DPA in this clinical trial.     

Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses

PROBLEM: Placental lesions of 71 women with documented recurrent spontaneous abortions of unknown etiology were evaluated using immunohistochemical staining. METHOD OF STUDY: Placental tissue blocks (less than 12 weeks gestation) from prior pregnancy losses were obtained, recut, and analyzed utilizing monoclonal antibody to identify the trophoblast (cytokeratin 8/18) and natural killer (NK) cells (CD57) at the implantation site. The following features were evaluated: trophoblast invasion pattern; syncytium formation; vasculitis and thromboembolism of decidual vessels; decidual inflammation; decidual necrosis; fibrin deposition at the decidual necrosis site; mononuclear-cell infiltration in villi and intervillous space; perivillous fibrin deposition; trophoblast morphology; and quantitation of CD57+ NK cells within the decidual tissue near the implantation site. Controls consisted of 20 healthy women with no history of recurrent pregnancy losses, who had their pregnancies electively terminated. RESULTS: Of the women studied, 29.6% demonstrated elevated CD57+ NK cells at the implantation site (P = 0.030), 54.1% had inadequate cytotrophoblast invasion depth (P = 0.000), 44.1% demonstrated inadequate syncytium formation (P = 0.004), and 33.9% presented thromboembolism in decidual vessels (P = 0.025). CONCLUSION: Some women with recurrent spontaneous abortions demonstrate abnormal placental lesions at the implantation site. Immunopathologic evaluation of the placental implantation site that terminated in a spontaneous abortion may reveal the immunopathogenesis of previous pregnancy losses.