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Biomedical subjects

S Forster

Publications and source records attributed to S Forster.

At least 19 recordsLinked to original sources

Large outbreak of infection with Escherichia coli O157 PT21/28 in Eccleston, Lancashire, due to cross contamination at a butcher's counter.

An outbreak of infection with Escherichia coli O157 Phage Type 21/28 occurred between the 23rd November 2001 and the 7th December 2001 in Eccleston, Lancashire. There were 30 confirmed cases (23 with positive faecal isolates and seven serologically positive). Eccleston is a village of approximately 5,000 inhabitants with a single medical practice where many of the cases were patients. Initial investigations identified the suspected source as a butcher's counter, operated as a franchise, in a supermarket in Eccleston. The butcher closed voluntarily on the 24th November. The median age of cases was 60 with a mean of 56 and a range of 2-91 years. Of the 30 confirmed cases, 22 were admitted to hospital. Two patients developed serious complications but all 30 made a full recovery. Microbiological investigations confirmed the butcher's counter as the source of the outbreak. The epidemiological evidence implicated cooked meats and microbiological evidence confirmed that contamination had occurred between raw and cooked meats. The deficiencies in meat hygiene practice that were identified could have led to the cross contamination. This outbreak illustrates the risk associated with the handling of raw and cooked meats in the same shop. Complete physical separation of raw and cooked meat operations reduces the risk of such outbreaks.

Disease Outbreaks↗

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3 g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3 g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (micro g). The contrary physiological and behavioral results indicate a facilitation of 1 g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of micro g or 3 g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Adaptation, Physiological↗

Microsatellite instability in sporadic carcinomas of the proximal colon: association with diploid DNA content, negative protein expression of p53, and distinct histomorphologic features.

BACKGROUND: Microsatellite instability (MIN) seems to characterize a particular subset of sporadic colorectal adenocarcinomas with the studies indicating a better clinical outcome for patients with MIN-positive tumors than for those with MIN-negative ones. The goal of this study was to further clarify whether a genotype-specific histomorphology of the right-sided colonic carcinomas can be identified. METHODS: MIN status, DNA content, and p53 protein expression were evaluated in cryoconserved specimens from 20 adenocarcinomas of the proximal colon and correlated to stage, grade, and other histomorphologic features. The study was restricted to tumors of the proximal colon because approximately 90% of all MIN-positive tumors were found in the proximal colon, and differences between right- and left-sided tumors cannot be excluded a priori. RESULTS: By using four microsatellite markers, instability was detected in 35% of the tumors analyzed. The clinicopathologic features in the MIN-positive tumors were found to differ markedly from the MIN-negative tumors in their poorly differentiated histologic pattern, extracellular mucin production, and favorable lymph node and distant metastatic behavior. A marked association was found between MIN positivity and DNA diploid status, as well as negative p53 immunostaining. CONCLUSIONS: The MIN-positive colonic carcinomas were characterized by distinct histomorphologic features that are recognizable at routine diagnostic evaluation. Poorly differentiated adenocarcinomas of the proximal colon, with only a few lymph nodes and no distant metastases at presentation, and lack of p53 accumulation are highly suggestive of being MIN positive. These tumors should be discriminated from the other poorly differentiated carcinomas, because they seem to be associated with an improved prognosis compared with the tumors without microsatellite instability.

Adenocarcinoma↗

Genetic changes and telomerase activity in human renal cell carcinoma.

Using the sensitive telomeric repeat amplification protocol assay, we detected telomerase activity in 26 of 35 (74.3%) renal cell carcinomas analyzed. Subdivision of the tumors according to telomerase activity did not reveal an obvious association between the presence of telomerase activity and histomorphological stage, grade, tumor size, or DNA ploidy. Furthermore, no association was found between telomerase activity and a distinct chromosomal aberration pattern; namely, loss of genetic material on the short arm of chromosome 3. Telomerase activity was also detected in 6 of 35 (17.1%) normal corresponding renal tissue samples, which seems interesting in light of the supposed biological role of telomerase expression in carcinogenesis. Interestingly, telomerase activity was detected in three of the four (75%) kidneys bearing non-clear cell tumor types, whereas of the 31 kidneys with clear cell carcinomas, telomerase activity was found in only 3 (9.7%) normal tissue samples. In addition, the two renal angiomyolipomas and one of the two analyzed transitional cell carcinomas of the renal pelvis were telomerase negative.

Adult↗

Vertical Migration in the Sediment-Dwelling Sulfur Bacteria Thioploca spp. in Overcoming Diffusion Limitations.

In order to investigate the environmental requirements of the filamentous sulfur bacteria Thioploca spp., we tested the chemotactic responses of these sedimentary microorganisms to changes in oxygen, nitrate, and sulfide concentrations. A sediment core with a Thioploca mat, retrieved from the oxygen-minimum zone on the Chilean shelf, was incubated in a recirculating flume. The addition of 25 (mu)mol of nitrate per liter to the seawater flow induced the ascent of the Thioploca trichomes (length, up to 70 mm) in their mostly vertically oriented gelatinous sheaths. The upper ends of the filaments penetrated the sediment surface and protruded 1 to 3 mm into the flowing water before they bent downstream. By penetrating the diffusive boundary layer, Thioploca spp. facilitate efficient nitrate uptake in exposed trichome sections that are up to 30 mm long. The cumulative length of exposed filaments per square centimeter of sediment surface was up to 92 cm, with a total exposed trichome surface area of 1 cm(sup2). The positive reaction to nitrate overruled a negative response to oxygen, indicating that nitrate is the principal electron acceptor used by Thioploca spp. in the anoxic environment; 10-fold increases in nitrate fluxes after massive emergence of filaments strengthened this hypothesis. A positive chemotactic response to sulfide concentrations of less than 100 (mu)mol liter(sup-1) counteracted the attraction to nitrate and, along with phobic reactions to oxygen and higher sulfide concentrations, controlled the vertical movement of the trichomes. We suggest that the success of Thioploca spp. on the Chilean shelf is based on the ability of these organisms to shuttle between the nitrate-rich boundary layer and the sulfidic sediment strata.

Journal Article↗

Geographic factors and plasma selenium in uremia and dialysis.

The importance of selenium (Se) as an essential trace element for man has been increasingly recognized. Blood Se levels in chronic uremic patients are frequently reported to be lower than in controls. Definitive determination of the Se status in uremic patients, however, is hampered by the wide range of blood Se content in humans from different parts of the world. The present study was designed to assess and compare the Se status in two European populations from Rostock (Germany) and Chieti (Italy). Plasma Se levels were evaluated in healthy controls, chronic renal failure nondialyzed patients (CRF) and hemodialysis patients (HD). All Se determinations were performed in a single laboratory. The Se concentration was significantly higher (p < 0.005) in Italian healthy controls than in German healthy controls. In contrast, Se levels were similar in both CRF and HD patients from both cities. In both countries, the Se concentration in CRF and HD patients was significantly lower (p < 0.001) than in their corresponding controls, but no difference between CRF and HD was found. CRF and HD patients from the two countries showed quite similar laboratory and anthropometric data. In CRF patients in Chieti, a significant (p < 0.05) negative correlation between plasma Se and serum creatinine was found. In both HD groups, the length of time on HD and type of membrane dialyzer used did not influence the Se status. A significant positive correlation (p < 0.01) between Se levels and the protein catabolic rate was found in both HD groups. Uremia seems to be a strong factor which overrules the difference in Se levels that is present in healthy adults from different European countries. Uremia in itself may influence and level the Se concentration in patients with geographic diversity.

Adult↗

Simultaneous detection of microorganisms in soil suspension based on PCR amplification of bacterial 16S rRNA fragments.

The effect of buffer composition on simultaneous PCR amplification of 16S rRNA gene fragments of five bacterial species was examined using a number of different buffer systems. Tris-based PCR buffers at final concentrations of 10 mM proved unreliable. However, when the final concentration of Tris was increased to 75 mM, all five samples were routinely detected. The use of other buffers, 3-[(1,1-dimethyl-2-hydroxyethyl)amino]-2-hydroxypropanesulfonic acid (AMPSO) and 3-[cyclohexylamino]-2-hydroxy-1-propanesulfonic acid (CAPSO), resulted in PCR amplification of five products even at low final concentrations (10 mM). The presence of certain proteins in the amplification reaction could overcome an inhibitory effect seen when soil suspension was present in the reaction, as might occur when testing field samples for the presence of bacteria. Bovine serum albumin was found to be the most effective additive tested in overcoming inhibition.

Alkanesulfonic Acids↗

Effects of selenium supplementation on immune parameters in chronic uraemic patients on haemodialysis.

BACKGROUND: The involvement of selenium (Se) in immune response has been increasingly recognized, cell-mediated immunity being principally affected by Se deficiency. Blood Se levels in chronic uraemic patients are frequently lower than in controls, and in these patients cellular immunity in generally impaired. METHODS: The present study was designed to assess the effects of Se supplementation over 6 consecutive months on immune parameters in haemodialysis (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five patients were supplemented with Se (500 micrograms thrice weekly for 3 months, then 200 micrograms thrice weekly for the next 3 months), whereas another five patients received placebo. All Se determinations were performed in a single laboratory. RESULTS: In both cities, basic plasma Se levels were significantly lower in patients than in their corresponding normal controls. After beginning Se supplementation, plasma Se concentration promptly normalized and levelled off in the normal range throughout the study. Se administration was well tolerated by all patients, and no side-effects attributable to Se toxicity were observed. Although no major change in immunocompetent cells (white blood count, total lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock patients) and a significant progressive increase in delayed-type hypersensitivity (as evaluated in Chieti patients) was observed in supplemented patients. After 6 months of Se therapy, the increase in delayed-type hypersensitivity of supplemented patients proved to be significantly higher when compared to both presupplementation values and to the results found in non-supplemented patients. Three months after suspension of Se supplementation, plasma Se levels and delayed hypersensitivity significantly decreased in Chieti patients, with both parameters returning similar to presupplementation values. CONCLUSIONS: In accordance with previous studies done in non-uraemic subjects, our investigation demonstrates for the first time the immunostimulatory properties of Se in HD patients. Though several problems on Se metabolism in uraemia remain unresolved, in our opinion moderate and safe Se supplementation can be beneficial in chronic uraemic patients.

Adjuvants, Immunologic↗

Ultrastructure of the jejunal mucosa in human immunodeficiency virus infection.

The ultrastructural changes in the jejunal mucosa of 11 male patients, three with clinical AIDS, five with AIDS related complex-progressive generalized lymphadenopathy (ARC-PGL), and three who were only HIV antibody positive, were studied. In the enterocytes, major abnormalities were proliferation of smooth endoplasmic reticulum mitochondrial changes, vacuolization of cells, and fat hold up. In the lamina propria, degeneration of enteric nerve axons and smooth muscle were seen. Microvasculature showed both endothelial cell degeneration and hyperplasia. The presence of tubuloreticular inclusions in endothelial cells paralleled the stage of the disease. Since none of the 11 patients had any opportunistic infection, these changes are likely to be the effect of HIV infection.

AIDS-Related Complex↗

Mechanism of cystine reaccumulation by cystinotic fibroblasts in vitro.

It is well established that when cystine-depleted cystinotic cells are cultured in cystine-containing medium, they reaccumulate cystine within their lysosomes more rapidly than when cultured in cystine-free medium. This has been a puzzling result, since the lysosome membrane of cystinotic cells is impermeable to cystine. To probe the mechanism of cystine reaccumulation, we have measured reaccumulation in the presence of colchicine, an inhibitor of pinocytosis, or of glutamate, a competitive inhibitor of cystine transport into human fibroblasts. Colchicine had no effect, thus eliminating pinocytosis as a putative mechanism for cystine translocation from the culture medium to the lysosomes. Glutamate, however, strongly inhibited cystine reaccumulation. It is concluded that the true mechanism is as follows. 1. Exogenous cystine crosses the plasma membrane on the cystine-glutamate porter. 2. Cystine is reduced in the cytoplasm by GSH. 3. The cysteine that is generated enters the lysosome, where it becomes cystine by participating in the reduction of cystine residues during intralysosomal proteolysis, or by autoxidation.

Biological Transport↗

Mechanisms and modulation of multidrug resistance in primary human renal cell carcinoma.

Human renal cell carcinomas show a high degree of intrinsic multidrug resistance. In experimental cell lines, the membrane bound P-170 glycoprotein and the glutathione redox cycle seem to contribute to this phenomenon. P-170 may be inactivated by calcium antagonists; the glutathione redox cycle by buthionine sulfoximine. We studied the resistance patterns of 35 human renal cell carcinomas against vinblastine, doxorubicin and carboplatinum in a tetrazolium-based microculture assay. Concomitantly, P-170 expression was traced immunohistochemically using moab C219 and the glutathione content was determined enzymatically. Reversal of multidrug resistance was examined by applying the R-stereoisomer of verapamil and/or by addition of buthionine sulfoximine. A high degree of chemoresistance was seen in 27 tumors against vinblastine, in 30 tumors against doxorubicin and in 31 tumors against carboplatinum. Chemoresponse was found in eight, five or four cases respectively. P-170 was detected in 70% of highly vinblastine resistant and in 63% of highly doxorubicin resistant tumors, but in none of the less resistant cases. Resistance against carboplatinum and doxorubicin was significantly associated with elevated glutathione levels as compared to less resistant renal cell carcinomas. R-verapamil lead to a strong reversal of vinblastine resistance and to a distinct circumvention of doxorubicin resistance, but revealed no effect in carboplatinum resistance. Buthionine sulfoximine overcame carboplatinum resistance and modified doxorubicin resistance, but had no influence on vinblastine resistance. The combined application of R-verapamil and buthionine sulfoximine reversed doxorubicin resistance but did not act synergistically in vinblastine or carboplatinum resistance. Both mechanisms, P-170 and glutathione, occurred independently of each other and may well explain multidrug resistance of human renal cell carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effects of decreased growth temperature on the cystine content of cystinotic fibroblasts.

Cystinotic fibroblasts transferred from 37 degrees C to 28 degrees C accumulated additional cystine over the period from 4 to 7 days of incubation at 28 degrees C, after which the additional cystine was lost; warming (to 37 degrees C) of cells with elevated cystine stores led to rapid cystine loss. These results, taken together with previously published data showing cystine release from cystinotic fibroblasts incubated at above-normal temperature, are interpreted as indicating the presence in the cystinotic fibroblast lysosome membrane of a cystine-porter whose efficacy is increased by an increase in membrane fluidity. This porter may be the residual activity of the cystine porter that is known to be deficient in cystinosis, or it may be a second as yet unrecognized porter. It is further proposed that this porter is responsible for the presumed efflux of cystine from cystinotic lysosomes.

Cell Division↗

Kaposi's sarcoma of the head and neck in patients with AIDS.

Over a 40 month period, 219 patients with AIDS were seen at St. Mary's Hospital, London. Kaposi's sarcoma, one of the criteria for diagnosing the syndrome, was the presenting feature in 62 patients. Eighty four patients developed Kaposi's sarcoma at some stage of their disease and the head and neck region was involved in 56 of them. Although Kaposi's sarcoma is rarely life threatening in AIDS, potential airway obstruction, pain or cosmetic disfigurement may justify treating the lesion. Whilst cutaneous tumours may be managed by using radiotherapy (16 Gray in four fractions over four days), this treatment produces a sever mucositis when used to treat mucosal disease; we, therefore use a combination of vincristine and bleomycin for this.

Acquired Immunodeficiency Syndrome↗

The recognition and management of the otolaryngological manifestations of AIDS.

Between October 1984 and December 1987, 219 patients who fulfilled the criteria for Acquired Immune Deficiency Syndrome (AIDS), as set out by the Centers for Disease Control, Georgia, were seen at St. Mary's Hospital, London. The most common otolaryngological manifestations of the disease in these patients were oral candidiasis (60%), oesophageal candidiasis (16%), persistent generalized lymphadenopathy (27%) and Kaposi's sarcoma (26%). Our management of the patients is described.

AIDS-Related Complex↗

Interferon effects on osteoinduction.

Xenografts of human osteosarcoma growing in athymic mice are inhibited in growth rate by human interferon-alpha (IFN-alpha) treatment. In addition, differentiation of trabecular bone occurs external to the osteosarcomatous tissue and this is entirely dependent on IFN treatment. We have used species-specific anticollagens and antivimentin antibodies to determine the species origins of this trabecular bone. By using immunohistochemical procedures, it was found that this bone is host-derived. These results suggest that IFN provoked the production of a bone-inducing agent by the human osteosarcomas.

Animals↗