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Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 19 recordsLinked to original sources

Immunization of hu-PBL-SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries.

Antibodies are usually prepared from recently boosted animals and reflect ongoing immune responses. In humans, this is restrictive as ethical constraints generally prevent antigen-boosting. Therefore the rich memory compartment of human antibody responses remains largely untapped. Severe combined immune deficiency (SCID) mice populated with human cells allow the stimulation of human antibody memory without the usual constraints. Here we show how peripheral blood lymphocytes can be stimulated by antigen to produce large secondary responses after transfer to SCID mice. Specific monoclonal human Fab fragments can then be isolated from the mice by repertoire cloning even when the human donor's last contact with antigen was more than 17 years ago.

Amino Acid Sequence

Stage-associated risk of transmission of the Lyme disease spirochete by European Ixodes ticks.

To more closely define the risk of infection by the agent of Lyme disease in Europe, we determined whether spirochetal prevalence increases throughout the development of the Ixodes ricinus vector tick. Of all ticks that could be flagged from vegetation, I. ricinus were by far the most abundant. Spirochetal infection rates in the adult stage of this tick (15%) are no higher than those in nymphs (18%) but greatly exceed those in larvae (0.7%). This tick therefore appears to attain infection mainly from the host of its larval stage, generally feeds on hosts that are noncompetent as reservoirs in its nymphal stage, and rarely inherits infection. Risk of human infection mainly derives from contact with the nymphal stage of the vector tick because the larva is rarely infected and the adult is large enough to be noticed and promptly removed.

Animals

Immunoscintigraphic localization of renal tumours in an extracorporeal perfusion model with a monoclonal antibody against gamma-glutamyltransferase.

Monoclonal antibody 138H11 against human gamma-glutamyltransferase has been shown to react immunohistochemically with 98% of all tested clear-cell type and chromophilic renal cell carcinomas, but not with renal chromophobic carcinomas, Duct-Bellini carcinomas or oncocytomas. In normal kidney the target epitopes of mAb 138H11 are located in the luminal brush-border membrane of proximal tubule cells, whereas in renal carcinomas the epitopes are found surrounding the whole tumour cells. These results form the basis of the present immunoscintigraphic study designed to evaluate mAb 138H11 in an extracorporeal perfusion model. Immediately after nephrectomy, human tumour-bearing kidneys were perfused with 99mTc-labelled mAb 138H11 in Euro-Collins solution. High specific uptake in 4/4 renal clear cell carcinomas could be demonstrated by planar immunoscintigraphy and single-photon-emission computed tomography, "regions of interest" investigation and immunohistochemistry. In contrast, a perfused oncocytoma showed up as an unlabelled lesion. The results indicate a possible use for mAb 138H11 in immunoscintigraphy or even therapy, provided high tumour uptake can be confirmed in patients.

Adenocarcinoma

Release signs in Parkinson's disease with and without dementia.

Release signs have been described in both age-associated diseases and in the healthy elderly. We investigated the palmomental, snout, grasp, corneomandibular and glabellar reflexes in demented and non-demented Parkinson-patients compared to Alzheimer's disease and age-matched controls. The palmomental reflex and a persisting glabellar reflex were linked to parkinsonism irrespective of dementia and were found also in Alzheimer's disease. A corneomandibular reflex was observed more frequently in demented than non-demented Parkinson-patients and in Alzheimer's disease. The snout-reflex was present in nearly all individuals irrespective of diagnosis. Thus, various release signs react quite differentially to degenerative brain disease and dementia.

Aged

Complex chromosomal rearrangements in an unusual variant of hairy cell leukemia.

An unusual case of variant HCL with multiple ribosomal lamellar complexes and complex chromosomal changes is described. The karyotype of the main cell clone is characterized by involvement of chromosome 5 at q13.3 and interstitial deletion of 7q. However, there is no other evidence of myelodysplasia and the abnormal cells are of lymphoid origin with a B-cell immunophenotype. The clonal chromosomal evolution involves rearrangements at sites known to be specifically altered in lymphoid tumors.

Aged

Synaptic pathology in Alzheimer's disease: immunological data for markers of synaptic and large dense-core vesicles.

We have analysed several markers for small synaptic vesicles (synaptin-synaptophysin, p65 and SV2) and large dense-core vesicles (chromogranin A, secretogranin II/chromogranin C) in the brains of patients with Alzheimer's disease, and normal controls by immunoblotting and immunohistochemistry. In comparison to age-matched controls the levels of all three synaptic vesicle markers were decreased in temporal cortex of Alzheimer patients. On the other hand, the levels of chromogranin A were increased, and those of secretogranin II lowered. This resulted in a significant increase of the ratios of chromogranin A to synaptophysin, p65 or SV2 and of that for chromogranin A to secretogranin II. These increases were significantly correlated to clinical severity of dementia and extent of neuropathological changes. By immunohistochemistry a high percentage of senile plaques was found to contain chromogranin A-reactive dystrophic neurites, whereas synaptophysin reactivity within plaques was rare. These results indicate that the number of synaptic vesicles is lowered in Alzheimer's disease, and that one component of large dense-core vesicles, i.e. chromogranin A, is elevated. We, thus, suggest that in Alzheimer's brain distinct changes occur for both types of synaptic organelles.

Aged

Capacity of European animals as reservoir hosts for the Lyme disease spirochete.

The abundance of spirochete-infected Ixodes ricinus ticks naturally derived from endemic rodents was compared to identify the reservoir hosts of the agent of Lyme disease at a series of enzootic sites in Central Europe. Black-striped mice appear to be the most important rodent host for the tick and infect more ticks with Borrelia burgdorferi than do other mice and voles tested. Although rodents infect about half of the ticks that feed on them, lizards infect none. These spirochete-incompetent hosts dilute the force of transmission because many nymphal ticks feed on them. Older male hosts are more heavily infested by subadult ticks than are younger or female hosts. The intensity of transmission of the agent of Lyme disease at particular Central European sites appears to correlate directly with the presence of black-striped mice and inversely with that of lizards.

Animals

Presence of viable mould propagules in indoor air in relation to house damp and outdoor air.

The presence of viable mould propagules in indoor air was investigated using the N6-Andersen sampler in combination with DG18-agar, in relation to house damp (characterized with a checklist) and in relation to the presence of moulds in outdoor air. The first part of the study was conducted in 46 houses in the autumn of 1987, the second part in 84 houses in May 1989. Further, in the second part, the results obtained with settlement plates (OPD) were compared with those obtained with the N6-Andersen sampler. The number of CFU/m3 in the indoor and outdoor air varied widely. A large variety of mould genera and species was isolated. Species of Cladosporium, Penicillium and Wallemia predominated. The variability in time was high and the reproducibility of the measurements in terms of CFU/m3 and of species isolated was only moderate. The low predictive value of these measurements limits their use in epidemiological studies of the relationship between exposure to moulds and respiratory symptoms. Overall, the geometric mean concentration was somewhat higher outdoors than indoors. However, the clear differences found between the number of CFU/m3 belonging to different mould species in in- and outdoor air show that the presence of viable mould propagules in indoor air is not simply a reflection of the presence of moulds in outdoor air. The presence of moulds in indoor air was only weakly related to house damp as characterized by the checklist. High, statistically significant correlations were found between the CFU yield obtained with the OPD and the CFU/m3 yield obtained with the N6-Andersen sampler.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants

Comparison of duplex ultrasound with angiography in assessment of carotid bifurcation disease.

This is a study comparing duplex ultrasound against the "gold standard" of angiography in assessing atherosclerotic disease of the carotid bifurcation, prior to prospective endarterectomy surgery. Thirty-nine patients were studied with both sonography and angiography studies being performed within one month of each other. Plaques were described by sonography as being "smooth" or "irregular" in surface and "homogeneous" or "heterogeneous" in composition. Ultrasound showed an overall 92% sensitivity, against the standard of angiography, in its ability to assess the degree of internal carotid stenosis. There was only a 63% sensitivity with the common carotid arteries and only a 65% sensitivity with the external carotid arteries. Ultrasound did not show a high accuracy in detecting plaque ulceration when compared against angio-graphy.

Adult

[Epidemiology of suicide in Austria 1980 to 1990].

This article investigates the suicide rates in Austria from 1980 to 1990 according to age groups and the methods used. In the years investigated the overall suicide rate increased until 1986, followed by a decline until 1990. The suicide rate in women shows a gradual linear increase with age, whilst in men there is a biphasic curve with a steep increase in teenagers and young men in their early twenties, followed by a plateau and a second steep increase as from 65 years of age, whereby the increase from "60-64 years" to the age group "over 85 years" is 134%. Regarding the age groups the decline over the past years in women is biggest in the groups "35-39 years" and "65-69 years", with men a decrease is present in the age groups from 20 to 50 years. Concerning the methods used, hanging is the most common mode of suicide in both women (36.4%) and men (48.8%). Suicide in the elderly--particularly in old men--which has increased internationally over the past few decades is targeted as the major area for vigorous preventive measures in Austria.

Adolescent

[Coincidence of lung diseases caused by Mycobacterium fortuitum and esophageal achalasia--case report and review of the literature].

We report on a case of lung infection due to mycobacterium fortuitum in conjunction with esophageal achalasia. A review of literature and a discussion on pathophysiological, clinical and therapeutical aspects are included. We conclude that bacterial poly-resistance in case of infections resembling tuberculosis should prompt a search for atypical mycobacteria. Patients suffering from nontuberculous mycobacteriosis of the lung should be subject to oesophageal examination.

Adult

Wittgenstein.

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Humans

Identification of a cDNA clone specific for the oligodendrocyte-derived repulsive extracellular matrix molecule J1-160/180.

A cDNA clone specific for the oligodendrocyte-derived extracellular matrix glycoproteins J1-160/180 was obtained from a lambda ZAPII expression library using polyclonal antibodies generated against mouse J1-160. The library was constructed from poly(A)(+)-RNA isolated from O1 antigen-positive rat oligodendrocytes. The cDNA clone expressed a fusion protein that was recognized by the J1-160/180-specific monoclonal antibodies 596, 619, and 620, and, weakly, 597. The fusion protein was not recognized by polyclonal antibodies to mouse J1/tenascin. The cDNA clone with an insert of approximately 5.6 kb in size contained the nucleotide sequence coding for the amino acid sequence of the N-terminus of a tryptic peptide derived from mouse J1-160. The developmental and tissue distribution of the mRNA recognized by the cDNA clone is in agreement with the described expression of the J1-160/180 proteins.

Amino Acid Sequence

Clinical and epidemiological aspects of dementia in the elderly.

Dementia of the Alzheimer's type (DAT) is the most significant disease of the aging brain. Descriptive epidemiology of DAT found a constant doubling of prevalence rates every 5 years. Analytic epidemiology so far failed to reliably detect risk factors for DAT other than age. This might depend on the difficulties encountered in the clinical diagnosis and differential diagnosis of dementia in the elderly, which are discussed with special reference to 1) the definition of dementia, to 2) the grading of severity of dementia, to 3) the differentiation between dementia and depression, and to 4) the differentiation between multi-infarct dementia and DAT.

Aged