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Biomedical subjects

N Kock

Publications and source records attributed to N Kock.

At least 19 recordsLinked to original sources

Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17).

Spinocerebellar ataxia 17 (SCA17) is a rare genetic disorder characterized by cerebellar, extrapyramidal, pyramidal as well as psychiatric signs. The pathoanatomical basis of this disorder is still not well known. A total of 12 patients and 12 age- and sex-matched controls were examined by in vivo MRI voxel-based morphometry (VBM). Besides general patterns of disease-related brain atrophy, characteristic syndrome-related morphological changes in SCA17 patients were studied. In comparison with normal controls, SCA17 patients showed a pattern of degeneration of the grey matter centred around mesial cerebellar structures, occipito-parietal structures, the anterior putamen bilaterally, the thalamus and other parts of the motor network, reflecting the cerebellar, pyramidal and extrapyramidal signs. A correlation analysis revealed a clear association between the clinical cerebellar, extrapyramidal and psychiatric scores and degeneration in specific areas. Two degeneration patterns were found as follows: regarding motor dysfunction, atrophy of the grey matter involved mainly the cerebellum and other motor networks, in particular the basal ganglia. In contrast, correlations with psychiatric scores revealed grey matter degeneration patterns in the frontal and temporal lobe, the cuneus and cingulum. Most interestingly, there was a highly significant correlation between the clinical Mini-Mental State Examination scores and atrophy of the nucleus accumbens, probably accounting for the leading psychiatric signs.

Adult↗

Functional MRI reveals activation of a subcortical network in a 5-year-old girl with genetically confirmed myoclonus-dystonia.

We investigated a five-year-old girl suffering from genetically confirmed, action-induced myoclonus-dystonia (M-D) with functional magnetic resonance imaging (MRI). We compared the activation pattern by movements of her right hand as if drawing a picture, which elicited M-D, with simple snapping movements (without overt M-D). The drawing and snapping conditions resulted in activation of a motor network including the motor cortex, the putamen, and the cerebellar hemispheres. The direct comparison of the drawing condition with snapping as control revealed specific activations within the thalamus and the dentate nucleus. An age matched healthy control did not show significant activation within the thalamus or dentate nucleus.

Brain↗

Genetic heterogeneity in ten families with myoclonus-dystonia.

BACKGROUND: Myoclonus-dystonia (M-D) is a movement disorder with autosomal dominant inheritance and reduced penetrance but may also occur sporadically. Recently, mutations in the epsilon-sarcoglycan gene (SGCE) were shown to cause M-D. Furthermore, single variants in the dopamine D2 receptor (DRD2) and DYT1 genes were found in combination with SGCE mutations in two M-D families, and another M-D locus was recently mapped to chromosome 18p11 in one family. METHODS: The authors clinically and genetically characterised ten consecutive cases with myoclonus-dystonia; seven familial and three sporadic. Twenty nine M-D patients and 40 unaffected family members underwent a standardised clinical examination by a movement disorder specialist. Index cases were screened for mutations in the SGCE, DYT1, and DRD2 genes and for deletions of the SGCE gene. Suitable mutation negative families were tested for linkage to the SGCE region and to chromosome 18p11. RESULTS: Two SGCE mutations were detected among the seven familial but no mutation in the sporadic cases. Haplotype analysis at the new M-D locus was compatible with linkage in two families and excluded in another family, suggesting at least one additional M-D gene. There were no obvious clinical differences between M-D families with and without detected mutations. CONCLUSION: M-D is genetically heterogeneous with SGCE mutations accounting for the disease in only part of the clinically typical cases.

Adolescent↗

Isolation and characterization of Sarcocystis from brain tissue of a free-living southern sea otter (Enhydra lutris nereis) with fatal meningoencephalitis.

A protozoan was isolated in cell culture from the brain of a free-ranging sea otter with fatal meningoencephalitis. The biological history of this otter, a study animal being monitored via an intraperitoneal radio transmitter, is summarized. Histologically, protozoal parasites were associated with areas of brain inflammation and necrosis in the cerebrum and cerebellum. Morphology and measurements of fixed, Giemsa-stained protozoal zoites growing on coverslips were consistent with Sarcocystis. These parasites reacted only with polyclonal antisera raised against S. neurona on immunohistochemistry. Cell culture-derived zoites reacted strongly with polyclonal antiserum to S. neurona on indirect fluorescent antibody tests. Amplification of portions of the 18S ribosomal DNA and the adjacent first internal transcribed spacer were performed. The resulting sequences were compared with published sequences from similar apicomplexan protozoa. This isolate (SO SN1), was indistinguishable from S. neurona, based on parasite morphology, antigenic reactivity and molecular characterization.

Animals↗

Production of monokines in patients under polysulphone haemodiafiltration is influenced by the ultrafiltration flow rate.

BACKGROUND: Chronic haemodialysis patients show various clinical signs of immunodeficiency and there is growing evidence that a dysregulated monocyte cytokine production is heavily involved in this deficiency. The production of monokines in vitro has been proposed to correlate closely with the in vivo immune status and to be of high clinical relevance in cuprophane haemodialysis. Even though it is well known that the biocompatibility of dialyser membranes has a significant impact on immune functions, little is known about the influence of the ultrafiltration flow rate (UFR). The aim of this study was to investigate the potential long-term effects of UFR on the production of interleukin-10 (IL-10), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in an intra-individual study design. METHODS: In 11 patients previously treated with polysulphone haemodiafiltration, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7-10 ml/min before it was reinstated at 40-46 ml/min for periods of 4 weeks each. Monokine secretion into culture supernatants and mRNA expression (assessed using a novel Taqman PCR technique), were determined in a whole blood assay after lipopolysaccharide stimulation. RESULTS: Reduction of UFR led to a significant increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a substantial (but not complete) decrease was observed when UFR returned to initial levels. In contrast, supernatant concentrations of IL-1beta (P=0.04) and IL-6 (P=0.003), and mRNA expression of both monokines (P<0.001, P<0.001) decreased significantly when UFR was reduced. Calculation of the IL-1beta/IL-10 ratio also revealed a decrease when UFR was reduced, with an increase again being observed when the initial degree of UFR was reinstated (P<0.001). CONCLUSIONS: These results indicate a significant impact of UFR on the production of monokines at both the transcriptional and the protein level. We suggest that middle molecule removal has to be considered as a possible pathophysiological mechanism to explain our findings. Since monokine production in vitro was shown to be closely correlated with the in vivo immune status in patients on cuprophane haemodialysis, further investigations are necessary to clarify the impact of UFR on the immunocompetence of patients under polysulphone haemodiafiltration.

Adult↗

[An interuniversity comparison of the supervision of doctoral candidates--should the promotion procedures be changed?].

BACKGROUND AND OBJECTIVE: There are only few investigations on supervision of medical dissertations that allow a comparison between different universities. This article discusses how the medical dissertation can be incorporated into a new medical curriculum. METHODS: A questionnaire was sent to all medical students in Lübeck who wrote dissertations in 1998. It contained 28 questions on duration, supervision, impact on medical studies and possible changes in the dissertation process. The data were compared statistically to previous studies. RESULTS: 70 questionnaires could be evaluated (63%) which allowed a comparison with studies in Hannover and Erlangen-Nürnberg. The Lübeck students assessed their supervision to be significantly better, they worked more frequently on experimental topics and data of their research were published more often than was the case in the other two institutions. The students regularly needed one extra semester for their dissertation, especially those working on experimental topics. Those who wrote dissertations expressed criticism of the dissertation process: only one third were in favour of making no change in the process. When asked to suggest possible improvements they proposed having a central facility for the announcement of dissertation subjects and one free semester to work solely on the dissertation. CONCLUSION: In order to evaluate and compare supervision of dissertations, a comparable questionnaire should be used by all medical universities. If the medical curriculum is changed, the dissertation either has to be firmly integrated in the curriculum or it should be undertaken after completion of the studies.

Academic Dissertations as Topic↗

Outbreak of meningitis in weaner pigs caused by unidentified asaccharolytic gram-negative bacterium.

Several organisms are known to cause outbreaks of meningitis in pigs, with Haemophilus species being the most frequently implicated. We report such an outbreak in which necropsied pigs manifested an unusual combination of meningitis, tracheitis, and bronchitis. The causative agent appeared to be an asaccharolytic gram-negative nonfermentative bacterium whose classification has yet to be determined. The organism was isolated from the brain and was extremely capnophilic, growing in air only after several serial subcultures.

Animals↗

Antitumor effect of locally injected low doses of recombinant human interleukin-2 in bovine vulval papilloma and carcinoma.

In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.

Animals↗

Reproductive parameters in free-ranging female black rhinoceroses (Diceros bicornis) in Zimbabwe.

Samples and data were collected from twenty-eight female black rhinoceroses (Diceros bicornis) during translocation efforts carried out by the Department of National Parks and Wildlife Management in Zimbabwe. Biological data were collected, cytological examination of vaginal smears was performed, and serum concentrations of follicle stimulating hormone, luteinizing hormone, progesterone, oestriol, and 17-beta-oestradiol were determined by radio-immuno-assay. Prolactin levels were determined for 3 pregnant animals, 1 of which was sampled before and after parturition. Vaginal cytology was not found to be helpful for indicating the oestrous cycle stage for the black rhinoceros, but progesterone and 17-beta-oestradiol levels were found to be useful indicators of pregnancy and possibly of oestrous cycle stage as well.

Animals↗

Some properties of pineal gland hydroxyindole-O-methyltransferase from black rhinoceros (Diceros bicornis).

Pineal glands were obtained from two young female black rhinoceri that had died as a result of postcapture trauma during a translocation exercise. Hydroxyindole-O-methyltransferase (HIOMT) from these pineal glands showed a peak activity at pH 8.2, although high activity extended over a fairly wide pH range (7.8-8.4). N-acetylserotonin was the best hydroxyindolic substrate for the enzyme, although other hydroxyindoles were methylated, the relative affinities being similar to values previously reported for bovine HIOMT. Kinetic analyses revealed that black rhinoceros HIOMT was subject to substrate inhibition by both substrates at high concentration; this observation is unlikely to have physiological significance. The catalytic mechanism was found to be ordered Bi-Bi, in which S-adenosylmethionine is the obligatory first substrate to bind to the enzyme, such binding allowing for binding of the hydroxyindolic substrate followed by catalysis, products again leaving the catalytic site in a sequential fashion.

Acetylserotonin O-Methyltransferase↗

Cerebral coenurosis in a cat.

Coenurus serialis, the intermediate stage of Taenia serialis, was the cause of progressive, fatal, intracranial disease in a 5-year-old cat. X-Ray computed tomographic findings were identical to those associated with intracranial parasitic cysts in people, in whom x-ray computed tomographic features are considered pathognomonic and superior to those of other diagnostic methods. The presumed source of the coenurus was the owner's dog.

Animals↗