Mania associated with serotonin selective reuptake inhibitors.
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Biomedical subjects
Publications and source records attributed to P Fischer.
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To determine the prevalence of onchocerciasis in western Uganda following deforestation and vector control, three foci were re-examined 20 years after previous surveys. In the Ruteete focus Simulium neavei had apparently disappeared and the prevalence of onchocerciasis declined in adults from about 70% in 1971 to a standardised prevalence of 12% in 1992. An increase of population density together with extended deforestation was assumed as cause of this strong reduction. In Bugoye, a S. damnosum s.l. focus, the standardised prevalence of microfilaria carriers declined from 62% in 1972 to 4.7% in 1992. Entomological data indicated the absence of man biting blackflies in the nineties. It can be suggested that the vector control using DDT performed during the seventies had lead to a change of the species composition from anthropophilic to non-anthropophilic S. damnosum s.l. In the focus Kicheche environmental changes were insignificant, deforestation was not progressive and S. neavei was abundant. Here the standardised prevalence of microfilaria carriers was still high (61%).
In order to identify Onchocerca volvulus larvae from vectors, DNA of filaria larvae from dissected blackflies was isolated, and a 150-bp long tandemly repeated DNA sequence (0-150), which occurs in many Onchocerca species, was amplified using polymerase chain reaction (PCR). Subsequently, the PCR product was blotted onto a nylon membrane and hybridized with DNA probes specific for O. volvulus or Onchocerca ochengi. Filaria larvae from 395 infected Simulium neavei were examined and 259 samples produced detectable PCR products. Among these samples, 239 (92%) reacted with an O. volvulus-specific oligonucleotide. A sample of 69 PCR products was tested using an O. ochengi DNA probe, but all failed to hybridize. Filaria larvae from 64 infected Simulium damnosum, presumably of the cytotypes "Nyamagasani" and "Nkusi" were studied and 0-150 was amplified from 38 samples. From these samples, 35 (92%) hybridized specifically with an O. volvulus probe but none with the O. ochengi-specific DNA sequence. Nonamplified samples were obtained mainly from blackflies that contained only 1 or 2 filaria larvae, and therefore, an insufficient DNA extraction was assumed. It can be concluded that few, if any, filaria species of animal origin were transmitted by S. neavei and S. damnosum s.l. in Kabarole and Kasese districts in Uganda.
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Annexin VII (synexin) is a member of the annexin family of proteins, which are characterized by Ca(2+)-dependent binding to phospholipids. In normal skeletal muscle annexin VII is located preferentially at the plasma membrane and the t-tubule system [Selbert et al. (1995) J. Cell. Sci. 108, 85-95]. Here we have analyzed the distribution of annexin VII in muscle disorders in which the Ca2+ regulation is affected. A remarkable difference was observed in muscle specimens from patients suffering from Duchenne muscular dystrophy and also in muscle from the MDX mouse where annexin VII was gradually released from the sarcolemmal membrane into the cytosol and into the extracellular space during progression of the disease. Hypercontracted muscle fibers positive in Ca2+ staining were devoid of cytosolic annexin VII. Annexins IV and VI were similarly released into the extracellular space. Whereas normal skeletal muscle showed specifically the 51-kDa annexin VII isoform, in dystrophic muscle different ratios of the 51-kDa and the muscle-atypic 47-kDa isoforms were observed. The potential of annexin VII to serve as a tool with which cellular Ca2+ levels can be studied and different muscular disorders classified is discussed.
Depressive disorder causes cognitive symptoms. In the case of severe cognitive symptoms or when psychometric procedures measure cognitive decline in the range of dementia, depressed patients may be diagnosed as Depressive Pseudo-Dementia (DPD). There is no data that depressive disorder can cause dementia without coexisting depressive symptoms. The latter symptoms are frequently overseen because cognitive symptoms are equated with organic brain disease. There are typical neuropsychological features of cognitive decline in depressive disorders, like psychomotor retardation and the slow-start phenomenon. Most patients referred to as DPD, suffer from depression-induced cognitive symptoms outside the range of dementia, but complain of memory disturbance and inability to think or concentrate. The diagnosis of DPD draws attention to a problem in the diagnosis of psychiatric disorders in the elderly: Old people suffering from depression are at particular risk of being labelled as demented. The most important step to diagnose depression causing dementia is the search for signs and symptoms of affective disorder even after having found cognitive symptoms.
Quantitative clinicopathological correlation studies are one way to address the question of the relevance of morphological abnormalities in Alzheimer's dementia (AD). This paper summarizes results of the Vienna Longitudinal Study on Dementia obtained during the past few years and presents a critical discussion on the relevance of clinicopathological correlation studies for the pathogenesis of AD. Plotting of psychometric test scores against the numbers of plaques, tangles and neuropil threads in various cortical areas shows that significant correlations are due primarily to very high lesion counts in severely demented patients. These data indicate that neocortical neurofibrillary pathology can be considered an end-stage marker in the pathology of AD. On the other hand, the topographical staging of neuritic Alzheimer changes proposed by Braak and Braak (1991) appears to be a better reflection of the progression of the degenerative process than numerical lesion counts; there is a linear correlation between the Braak stages and Mini-Mental State scores in 122 aged individuals. Significant correlations are further obtained between the severity of dementia and the levels of a number of synaptic proteins including synaptophysin and the chromogranins. Taken together, our data suggest that none of the classical AD lesions, plaques and tangles, play a central role in the pathogenesis of dementia, a fact that is supported by a molecular biological study showing that there is no close relationship between these lesions and the neurons undergoing degeneration in AD. Whereas neuritic pathology is a useful histopathological marker for the diagnosis and staging of AD, the major correlate of cognitive deficits is the loss of corticocortical and subcorticocortical connections reflected by a depletion of synapses. This pathology may be induced by a mismetabolism of the beta-amyloid precursor proteins or their interaction with cytoskeletal proteins related to neuronal degeneration.
Karyotyping of dog chromosomes is a difficult task owing to the high diploid number of chromosomes (2n = 78) and the similar morphology of autosomes, all of which are acrocentrics. In this report 22 of the 39 G-banded chromosome pairs and their corresponding ideograms have been standardized. The ideogram comprises altogether 235 bands. The need for the introduction of molecular techniques such as chromosome painting and physical mapping of genetic markers for the identification of small acrocentrics is discussed.
A polymerase chain reaction (PCR) of a 150-bp tandem repeat of Onchocerca volvulus (O-150) combined with Southern-blot hybridization to species-specific DNA probes was employed for DNA detection. O-150 was amplified from parasites originating from Uganda, Benin, Cameroon, Liberia, Ghana, Burkina Faso, Mali, and Zaire and was successfully hybridized to digoxigenin-labeled oligonucleotides. To investigate the sensitivity of the PCR, 2 skin biopsies were taken from each of 227 persons from Uganda with proven O. volvulus infections but with low microfilaria (mf) densities due to ivermectin treatment. One biopsy was tested by PCR and the other was digested using collagenase to assess the total number of mf. The PCR revealed 76.2% of the samples to be positive, and the collagenase method showed that 78.9% were positive, indicating similar sensitivity for the two methods. It is probable that for both techniques the biopsy must contain at least one live mf or fragments of a dead mf. In this study, no free or circulating O. volvulus DNA could be detected in skin biopsies by PCR.
Polymorphism of MHC class Ia molecules severely constrains vaccine development against intracellular pathogens. Antigen presentation by MHC class Ib molecules, which are generally conserved between different individuals, may circumvent this obstacle. Herein, we use tandem mass spectrometry to identify a Listeria monocytogenes pentapeptide antigen that is presented to T lymphocytes by the H2-M3 MHC class Ib molecule. The peptide contains N-formyl methionine at the N terminus and exclusively hydrophobic amino acids. Mice of the H-2 d, H-2 b,and H-2 k haplotypes respond to this peptide upon infection with Listeria monocytogenes. Identification of antigens presented by MHC class Ib molecules is feasible and may provide opportunities for relatively unrestricted vaccine development.
Polymerase chain reaction (PCR) combined with non-radioactive DNA hybridization was applied for the detection and characterization of a 150 bp tandem repeat of Onchocerca volvulus. DNA of worms from western Uganda was amplified and then probed with a digoxygenin-labelled oligonucleotide, specific for the forest form of O. volvulus and compared to samples from various African countries. Hybridization was only observed with PCR products from the forest in Liberia, south-eastern Ghana, Benin and southern Cameroon, but not with worms from Uganda or the savannah in Burkina Faso and northern Ghana. A nested PCR using primers derived form the forest form-specific DNA sequence confirmed these results. Morphometric studies revealed length differences between the microfilariae of Ugandan O. volvulus to those of West Africa, especially to those of the savannah in Burkina Faso. It is concluded that the forest/savannah classification of O. volvulus from West Africa is not suitable for Simulium neavei-transmitted O. volvulus from Uganda.
The relationship of conflict between sex role ideology and sex role orientation with eating-disorder behaviors and attitudes was examined. American participants were 321 female college students who completed the Bem Sex Role Inventory (Bem, 1974), Sex Role Ideology Scale (Kalin & Tilby, 1978), and Eating Disorders Inventory (EDI; Garner, Olmsted, & Polivy, 1983). The results indicated that conflict between ideology and self-perception had little effect on responses to the Inventory. Instead, students with higher levels of self-rated social desirability and lower levels of masculinity reported higher prevalence of eating-disorder behaviors and attitudes. Analyses of sex role orientation data revealed that participants categorized as undifferentiated had the most pathological responses to the EDI. Overall, the results suggested that social desirability and masculinity, more than sex role orientation or conflict, are strongly related to eating-disorder behavior, perhaps because of a third mediating factor.
Metastatic renal cell carcinoma (RCC) is a tumor with a poor prognosis resistant to chemotherapy and irradiation. However, in rare cases, spontaneous regressions of metastases after nephrectomy have been reported that were ascribed to destruction of the tumor by the immune system. In earlier studies, we and others identified the expression of modified antigens in RCC. In particular, a concanavalin A-binding isoform of gamma-glutamyltransferase (gamma GT) comprises about 50% of the enzymatic activity found in the tumor tissue of many RCC patients. The monoclonal antibody 138H11, directed against all human gamma GT isoforms, revealed a membranous expression of gamma GT around RCC cells compared to the restricted, apical pattern of renal cells. These data raised the question why the RCC-specific gamma GT, exposed to the immune system in vivo, is not immunogenic in patients with RCC. To address this question, we generated mouse hybridomas against highly purified human RCC gamma GT. Although we obtained a large panel of hybridomas that produced antibodies reacting immunohistochemically in a gamma GT-specific manner, all antibodies stained normal kidney gamma GT as well as RCC gamma GT. These results suggest that the biochemical features specific for RCC gamma GT are not necessarily reflected by specific antigenic determinants that could be differentiated by the immune system of the challenged mice. The lack of immunogenic epitopes different from normal gamma GT enzyme may offer an explanation why gamma GT produced by RCC can escape immunological surveillance.
The prevalence of the apathogenic filaria Mansonella perstans was studied in four parishes in western Uganda as part of an onchocerciasis control programme to avoid futile treatment. Blood samples from 1543 persons aged over 14 years from 19 villages were examined for the presence of microfilariae using a modified Knott method. The prevalence of microfilaraemic persons ranged between the parishes from 39% (95% CI 35.9-42.0%) to 81% (95% CI 76.2-84.8%). With exception of single microfilariae of Onchocerca volvulus no other filaria species was detected. Onchocerciasis mass treatment campaigns did not reduce the prevalence of M. perstans infection, since 6-12 months after treatment with a single dose of 150 micrograms/kg ivermectin the prevalence in 124 persons was about the same as before treatment. The QBC-fluorescence technique was employed for the detection of microfilariae in samples from outpatients of the government hospital in Fort Portal: in 16% of 120 children and 24% of 369 adults microfilariae of M. perstans were detected.
Recently, MRI was described as a method in the diagnosis of changes of muscle after acute neurogenic muscle atrophy. This study was performed to compare MRI results with myopathological findings, to document the appearance of the MRI changes and to check the sensitivity of this method. We performed a segment resection of the suprascapular nerve resulting in a denervation of the supraspinatus and infraspinatus muscles on 18 Newzeeland white rabbits. MRI changes were followed and documented for two months in short periods of time. The results were compared with histological findings. In myopathology and MRI we found systematical changes: Apart from the reduction of the muscle diameter visual assessment revealed increased signal intensities on the 21st and 35th examination day after denervation. On the 2nd, 5th, 11th and 64th examination day signal intensities were normal. The changes were represented by calculated T2 times, too.
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It seems necessary to characterize electrophysiological properties of human nicotinic acetylcholine receptors (nAChR) to obtain reference values for the study of diseased muscles. We therefore investigated nAChRs in aneurally grown human myotubes using the patch-clamp technique. Pulses of acetylcholine (ACh) were applied to outside-out patches with a fast application system. The peak and the rise time of the current elicited by pulses of various concentrations of ACh were evaluated. The results were interpreted using the circular reaction scheme developed recently for the nAChR of embryonic mouse muscle. In addition, the burst duration and the slope conductance of the ACh activated channel were evaluated.