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Biomedical subjects

P Fischer

Publications and source records attributed to P Fischer.

At least 235 records · Page 13Linked to original sources
PubMed1990

Isolation and partial characterization of angiotensinase A and aminopeptidase M from urine and human kidney by lectin affinity chromatography and high-performance liquid chromatography.

Angiotensinase A (ATA) and aminopeptidase M (APM) were partially purified from human urine specimens and human kidney particles using wheat germ lectin affinity chromatography, anion-exchange Fast Protein Liquid Chromatography (FPLC) (Mono Q), chromatofocusing (Mono P, FPLC) and Superose 12 gel filtration. APM, a globular 5-nm glycoprotein, is localized in the brush border membrane of the proximal tubule; angiotensin II-degrading ATA is present on glomerular endothelia and podocytes and, to lesser extent, in the brush border. For the first time, both peaks of ATA and APM activity from urine samples were separated by the above-mentioned techniques with only slight overlap; ATP (146,000 dalton: pI4.8) was enriched more than 20-fold and APM (153,000 dalton, pI4.7) more than 50-fold compared with the activity of the starting material. Using similar separation steps, ATA and APM solubilized from kidney particles could not be resolved into two distinct peak fractions, however, except after hydrophobic interaction chromatography. Thus urine is a major source for the preparation of individual ATA and APM fractions, necessary to generate specific anti-enzyme antibodies for diagnostic purposes.

Aminopeptidases↗
PubMed1990

Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies.

We have purified gamma-glutamyltransferases (GGT) from human kidneys and renal cell carcinomas, and fractionated them according to different lectin-binding properties of the isoenzymes. Native polyacrylamide gel electrophoresis and isoelectric focusing revealed different GGT-bands (even after desialylation) not only among kidney and renal carcinoma, but also among Con A-affine tumor fractions separated by ion-exchange chromatography. Mr of native GGTs were between 106 to 161 kDa, the pI ranged from pH 3 to 4 (pH 5 to 6 after desialylation). Monoclonal antibodies to GGT were produced. One of these, of IgG1 class and designed 138H11, recognizes human kidney GGT and, in addition, GGT from renal cell carcinomas and liver carcinomas. The specificity of mAb 138H11 for GGT was confirmed by Western blotting, by immunohistochemistry and by immunoprecipitation. The potential usefulness of mAb 138H11 in monitoring renal cancer patients and in identification of renal cancer metastases is currently being studied.

Antibodies, Monoclonal↗
PubMed1990

The amyloid precursor protein of Alzheimer's disease is released by human platelets.

Western blots of normal human platelets, employing a monoclonal antibody raised against the full-length amyloid precursor protein of Alzheimer's disease (APP695), revealed major bands of 100-110 and 120-130 kDa in both cytosolic, membrane, and released fractions. These species were similar in size to forms seen in brain preparations and in plasma. There was no difference in Western blots of platelet preparations from Alzheimer patients compared with controls. Purified platelet amyloid precursor proteins were sequenced and shown to be amino terminally homogeneous. Immunohistochemistry localized the antigen to the platelet and megakaryocyte and demonstrated weak immunostaining of some lymphocytes. Immunoprecipitation of material released from platelets demonstrated that sedimentable full-length APP with the carboxyl-terminal epitope, and soluble APP lacking the carboxyl-terminal epitope, may exist in the circulation. Western blots and carboxyl-terminal and amino-terminal APP radioimmunoassay of material released by platelets in response to stimulation revealed that platelets release APP during degranulation. The function of platelet APP is yet to be determined, but the present studies suggest a role in regulation of the coagulation cascade or in platelet aggregation.

Alzheimer Disease↗
PubMed1990

Dioxygenolytic cleavage of aryl ether bonds: 1,2-dihydro-1,2-dihydroxy-4-carboxybenzophenone as evidence for initial 1,2-dioxygenation in 3- and 4-carboxy biphenyl ether degradation.

A bacterial strain, Pseudomonas sp. POB 310, was enriched with 4-carboxy biphenyl ether as sole source of carbon and energy. Resting cells of POB 310 co-oxidize a substrate analogue, 4-carboxybenzophenone, yielding 1,2-dihydro-1,2-dihydroxy-4-carboxy-benzophenone. The ether bond of 3- and 4-carboxy biphenyl ether is cleaved analogously by initial 1,2-dioxygenation, yielding a hemiacetal which is hydrolysed to protocatechuate and phenol. These intermediates are degraded via an ortho and meta pathway, respectively. Alternative 2,3- and 3,4-dioxygenation can be ruled out as triggering steps in carboxy biphenyl ether degradation.

Benzoates↗
PubMed1990

A high ratio of chromogranin A to synaptin/synaptophysin is a common feature of brains in Alzheimer and Pick disease.

Chromogranin A and synaptin/synaptophysin were characterized by immunological methods in human autopsy brain tissue from patients with Alzheimer's and Pick's disease. In immunoblots there was no qualitative difference between the antigens in control and diseased brain, but significant quantitative differences were found. In all Alzheimer cases there was a significantly lower level of synaptin/synaptophysin, whereas chromogranin A was higher in 4 out of 5 cases and in all cases relative to synaptin/synaptophysin. An analogous finding was obtained for Pick's disease. Immunohistologically a consistent staining of neuritic plaques for chromogranin A, but not for secretogranin II was found in Alzheimer cases. In Pick's disease the characteristic Pick bodies showed an analogous specific immunostaining.

Aged↗
PubMed1990

A new human B-cell non-Hodgkin's lymphoma cell line (Karpas 422) exhibiting both t (14;18) and t(4;11) chromosomal translocations.

A unique B-cell non-Hodgkin's lymphoma (NHL) cell line (Karpas 422), bearing both t(14;18) and t(4;11) chromosomal translocations as well as several other chromosomal abnormalities, has been established from the pleural effusion of a patient with chemotherapy-resistant NHL. This cell line has the same karyotypic features as malignant cells from the patient. The major cell clone is characterized chromosomally by 46,XX t(2;10)(p23;q22.1), t(4;11)(q21.3; q23.1), t(14;18)(q32.1;q21.3), t(4;16)(q21.3;p13.1). Both phenotypically and genotypically, the cell line has features of a mature B-cell neoplasm with no evidence for commitment to other lineages. Rearrangements of the C-ETS-1 oncogene and N-CAM-1 and CD3 genes that map to 11q23 were not detected by conventional Southern analysis. BCL-2 was rearranged within the major breakpoint cluster. The K422 cell line has a unique karyotype; this is the first occasion that the t(4;11) translocation has been described in a t(14;18) lymphoma. The cell line will be of value in determining the molecular nature of the t(4;11) translocation.

Antigens, CD↗
PubMed1990

Time of repletion of subadult Ixodes ricinus ticks feeding on diverse hosts.

For a comparison of the times of day at which the subadult stages of Ixodes ricinus detach from nocturnal vs diurnal hosts, these ticks were placed on a variety of indigenous and experimental animals. The time of detachment appears to depend more on properties of the host than on the periodicity of tick behavior. Ticks on rodents, regardless of host periodicity, tended to detach late in the afternoon; those on the hedgehog detached around midnight, and those on lizards and birds, during the morning. Ticks on carnivores (dog, cat) detached throughout the daylight hours. The ability of these parasites to survive to the next developmental stage and, ultimately, to come into contact with another suitable host may be influenced by the identity of the host and, hence, by the circumstances of detachment. Subadult I. ricinus probably concentrate in the host's nest when feeding on mammals but are scattered over the ground when feeding on lizard or avian hosts, an aspect of engorgement behavior that may profoundly affect the capacity of this tick as a vector of agents of Lyme disease and other infections.

Animals↗
PubMed1990

Memory deficits in advanced Parkinson's disease.

Apart from global dementia various isolated cognitive deficits have been described in Parkinson's disease (PD). We investigated 31 non-demented Parkinsonian patients in their late stages of disease and 50 control subjects with regard to verbal memory. Eleven patients suffered from an isolated verbal memory deficit as defined by two list learning tasks using the Buschke selective reminding procedure. The isolated memory impairment did not depend on depression but was associated with longer duration of PD. Twelve demented PD patients were comparable to PD patients with isolated memory impairment with regard to age at onset and duration of PD. We speculate that the isolated memory impairment in PD is associated with isolated neuronal loss in the nucleus basalis of Meynert, without cortical or limbic pathology of the Alzheimer's type.

Aged↗
PubMed1990

Recency-primacy recognition in Parkinson's disease.

Early parkinsonian patients and matched controls were tested with a newly designed, short recency-primacy recognition task. Parkinsonian patients showed a significant impairment of recency recognition which could neither be explained by deficits in intelligence, attention, and content memory nor by depression.

Aged↗
PubMed1990

Clinicopathological analysis of dementia disorders in the elderly.

The relative incidence of the major types of dementia disorders and the agreement rates between clinical and pathological diagnosis were analysed in consecutive autopsy series of 675 demented subjects from 3 hospitals (mean age 79.5 years, SD 9.6). Clinical assessment followed the DSM-III and ICD-9-NA criteria and NINCDS/ADRDA criteria for probable Alzheimer disease (AD) (McKhann et al. 1984), histological criteria for the diagnosis of AD those of the NIH/AARP Work Group (Khachaturian 1985) using a 4-degree rating scale for plaques and tangles in neocortex and hippocampus (Morris et al. 1988), and the criteria by Tierney et al. (1988) for 'pure' AD. Vascular dementia (MID) and other disorders were diagnosed according to current pathologic criteria. Clinical diagnosis of AD/SDAT was made in 59.2%, of MID in 21.7%, of mixed AD + MID in 3.1%, and of Parkinson's disease (PD) and other disorders in 16%. At autopsy, 76.7% fulfilled histological criteria for AD/SDAT, but only 60% were 'pure' forms, while 8.2% had additional features of PD and 7.9% coexisting vascular lesions indicating mixed SDAT + MID. 15.7% were MID with no or very little AD pathology, 7.4% other CNS disorders. 0.3% of the brains showed no abnormality beyond age-related changes. AD/SDAT had its highest incidence in a psychiatric population, MID and PD + SDAT in general and geriatric hospital cohorts. The overall coincidence rates for clinical and pathological diagnosis of AD/SDAT were 85.2%, for MIX and MID 60.5-61.9%, but only 51% for PD-PD/AD. These data and the results of other recent studies emphasize the need for more appropriate clinical and pathological criteria in the diagnosis of the dementias.

Aged↗
PubMed1990

Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.

In the brains of aged humans and cases of Alzheimer disease, deposits of amyloid in senile plaques are located in proximity to nerve processes. The principal component of this extracellular amyloid is beta/A4, a peptide derived from a larger amyloid precursor protein (APP), which is actively expressed in brain and systemic organs. Mechanisms that result in the proteolysis of APP to form beta/A4, previously termed beta-amyloid protein, and the subsequent deposition of the peptide in brain are unknown. If beta/A4 in senile plaques is derived from neuronally synthesized APP and deposited at locations remote from sites of synthesis, then APP must be transported from neuronal cell bodies to distal nerve processes in proximity to deposits of amyloid. In this study, using several immunodetection methods, we demonstrate that APP is transported axonally in neurons of the rat peripheral nervous system. Moreover, our investigations show that APP is transported by means of the fast anterograde component. These findings are consistent with the hypothesis of a neuronal origin of beta/A4, in which amyloid is deposited in the brain parenchyma of aged individuals and cases of Alzheimer disease. In this setting, we suggest that APP is synthesized in neurons and delivered to dystrophic nerve endings, where subsequent alterations of local processing of APP result in deposits of brain amyloid.

Acetylcholinesterase↗
PubMed1990

Subadult Ixodes ricinus (Acari: Ixodidae) on rodents in Berlin, West Germany.

To identify hosts that may serve as reservoirs for the agent of Lyme disease in Central Europe, we determined whether Ixodes ricinus L. feed most frequently on certain rodents and whether the abundance of these hosts corresponds to the season of feeding activity of the tick in four sites in Berlin, Federal Republic of Germany. In addition, we correlated abundance of I. ricinus with that of particular rodent hosts. Two small rodents were more abundant than any others; a mouse, Apodemus flavicollis, predominated in a wooded site and a vole, Clethrionomys glareolus, in three brush- or grass-covered sites. The tick was most abundant in the mouse-infested site. Although A. flavicollis comprised only about a third of rodents collected, nearly 60% of all such rodent parasitizing I. ricinus fed on this mouse. These ticks were more abundant on mice than voles in each of the study sites and throughout the year, and more larvae fed on these rodents than did nymphs. Although larval as well as nymphal I. ricinus are most abundant during midsummer, they feed on rodents from April through October. Taken together, these observations suggest A. flavicollis as a potentially important reservoir host for I. ricinus-borne infections.

Animals↗
PubMed1990

Nocturnal detachment of the tick Ixodes hexagonus from nocturnally active hosts.

To determine whether the pattern of engorgement of Ixodes hexagonus Leach (Acarina: Ixodidae) in Central Europe may influence host specificity, the host relationships of the sub-adult stages of this tick were examined and the time of detachment compared with the activity patterns of various candidate vertebrate hosts. The main hosts for I. hexagonus appear to be hedgehog and fox. This tick species seems to be incapable of feeding on any rodent commonly encountered in the study region, or on reptiles or birds. Virtually all of these ticks detach during the scotophase, becoming replete mainly during the late evening and early morning hours, regardless of the kind of host or of the time of attachment. These nocturnally detaching ticks, paradoxically, focus their feeding on nocturnally active hedgehogs and foxes, in spite of the possibility that such behaviour might cause them to disperse from the nests of the host. Dispersion is prevented, however, by the tendency of these ticks to detach while their host naps. The tick-host association of I. hexagonus with hedgehogs may serve to perpetuate such zoonotic, Ixodes-borne infections as Lyme disease.

Animals↗
PubMed1990

Course characteristics in the differentiation of dementia of the Alzheimer type and multi-infarct dementia.

Clinico-pathological studies have shown that the clinical diagnosis of multi-infarct dementia (MID) is even more difficult than that of dementia of the Alzheimer type (DAT). The study evaluated the significance of course characteristics for the diagnosis of MID and DAT. Course characteristics were rated when 57 demented patients were admitted to our neurogeriatric department. Diagnosis of MID and DAT, respectively, was established after a follow-up study with repeated neurological, psychiatric and neuropsychological investigations. In 21 cases diagnosis was confirmed by postmortem neuropathology. MID lacked the typical course of the disease in about two thirds of patients, while most DAT patients presented with the typical course of primary degenerative dementia. Features of the "typical" clinical course of MID (abrupt onset, stepwise deterioration) helped to exclude DAT, whereas MID could not be excluded on the basis of a history of insidious onset and gradual decline.

Aged↗
PubMed1990

Enzymatic formation, stability, and spontaneous reactions of 4-fluoromuconolactone, a metabolite of the bacterial degradation of 4-fluorobenzoate.

Enzymatic conversion of 4-fluorocatechol in the simultaneous presence of partially purified preparations of catechol 1,2-dioxygenase from Pseudomonas cepacia and muconate cycloisomerase from Alcaligenes eutrophus 335 yielded a product that was unambiguously identified as (+)-4-fluoromuconolactone [(+)-4-carboxymethyl-4-fluoro-but-2-en-4-olide]. This compound was shown to be the only major product formed from 3-fluoro-cis,cis-muconate by the action of muconate cycloisomerases from A. eutrophus 335, A. eutrophus JMP134, and P. cepacia as well as by the action of dichloromuconate cycloisomerase from A. eutrophus JMP134. This finding implies that dichloromuconate cycloisomerase, like the muconate cycloisomerases, catalyzes primarily a cycloisomerization reaction, which only in the case of chloro- and bromo-substituted substrates is connected to a dehalogenation. 4-Fluoromuconolactone at pH 7 decomposes by spontaneous reactions mainly to maleylacetate, which then decarboxylates to give cis-acetylacrylate. Although significant amounts of an unidentified compound are also formed from the fluorolactone, HF elimination to the two isomeric dienelactones (4-carboxymethylenebut-2-en-4-olides) is negligible. However, all spontaneous reactions proceed so slowly that an enzymatic conversion of 4-fluoromuconolactone must be assumed. Participation of dienelactone hydrolases in this reaction is indicated by their induction during growth of various strains with 4-fluorobenzoate. However, experiments with cell extracts of P. putida A3.12 suggest that at least one other hydrolytic enzyme is able to contribute to 4-fluoromuconolactone conversion. In light of these observations, earlier proposals for a 4-fluorobenzoate degradative pathway are discussed.

Adipates↗
PubMed1990

Depression in dementia of the Alzheimer type and in multi-infarct dementia.

The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia.

Aged↗