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Biomedical subjects

R Keller

Publications and source records attributed to R Keller.

At least 73 records · Page 4Linked to original sources

["Microbial air pollutants--methods for detection of endotoxins, mycotoxins and MVOC"].

In the context of microbial emissions from composting facilities the methods for the detection and identification of the groups of substances released, i.e. endotoxins, mycotoxins and Microbial Volatile Compounds (MVOC) are discussed. With the aid of an overview of the different methods employed for the investigation of the single groups of compounds the current state of the art in this field is presented. In conclusion the enormous research needs, especially with regard to the mycotoxins and MVOC, are pointed out.

Air Microbiology↗

Road rash with a rotten odor.

As military physicians, our mission is to support the fighting force and keep our soldiers mission capable. One group of disorders that can quickly cripple a fighting force is disorders of the foot. A complete survey of dematologic conditions of the foot is quite extensive, but only one comes with its own distinctive odor. This foul rash is pitted keratolysis.

Adult↗

Characterization of the locus of enterocyte effacement (LEE) in different enteropathogenic Escherichia coli (EPEC) and Shiga-toxin producing Escherichia coli (STEC) serotypes.

All proteins involved in the attachment and effacement lesion produced by enteropathogenic Escherichia coli (EPEC) and Shiga-toxin producing E. coli (STEC) are encoded by the locus of enterocyte effacement (LEE). We studied the presence and insertion site of the LEE in different EPEC and STEC strains. In serotypes O119:H6/H-, O55:H6, O55:H7, O142:H6, O111ac:H9/H-, O111ab:H9/H- LEE is inserted downstream of selC as previously described for EPEC O127:H6 and STEC O157:H7. In serotypes O111ac:H8/H- and O26:H11/H- the LEE is inserted in pheU as previously described for STEC O26:H-. However in EPEC from serotype O111ab:H25 the LEE is not inserted in either site suggesting a third insertion site in the K12 chromosome. We also cloned fragments of 2.3 kb and 1.0 kb from the right and left hand sides of the LEE of a O111ac:H- strain and identified additional insertion sequences on these LEE fragments, suggesting that the LEE may be larger and may have undergone more recombination events in these serotypes.

Bacterial Adhesion↗

[Long-term home oxygen therapy: who? with what? how expensive?].

Since 1981 long-term oxygen therapy (LTOT) has become an important procedure for the rehabilitation of patients with chronic respiratory insufficiency in Switzerland too. As a result of long-term clinical experience as well as technical progress, there is, however, increasing need for an updated reassessment of guidelines and standardized management respectively: the indications for LTOT-so far restricted to patients with COPD-are extended to patients with pulmonary diseases other than COPD associated with chronic hypoxemia (pO2 < 7.3 kPa) provided there is enough evidence of clinical benefit. Another important aspect of LTOT focuses on the appropriate application of different oxygen sources. Oxygen concentrators are still accepted to be the most economic domiciliary source. For short-term outdoor activities, small portable cylinders in combination with an oxygen conserving system should be used. However, in regular mobile oxygen therapy liquid oxygen is the best choice, generally consisting of a domiciliary reservoir and portable canisters. Delivery of oxygen through a transtracheal catheter is superior to nasal cannula because of lower oxygen consumption, decreased breathing work and improved compliance respectively. To organize and follow-up LTOT in Switzerland, a very efficient concept was introduced many years ago which is characterized by economical cooperation between physicians, insurances, technical suppliers and social providers. Today more than 3000 patients-corresponding to 38/100,000 inhabitants-benefit from LTOT. Future perspectives should target an earlier start to continuous as well as mobile LTOT, in order to improve rehabilitation in still active conditions instead of merely palliating the terminal stages.

Cost-Benefit Analysis↗

[Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA)].

Long-term health effects of moderate ambient air pollution are rarely investigated. In Switzerland, no large-scale study has addressed this issue so far. Important results of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) are presented. During the period 1991-1993, SAPALDIA investigated a random population sample (18-60 years) in eight Swiss areas with different environmental characteristics (Aarau, Basel, Davos, Geneva, Lugano, Montana, Payerne, Wald). In total, 9651 adults (60%) participated in the cross-sectional investigation (part 1, 1991), consisting of the following standardized procedures: questionnaire (interview), forced expiratory lung function test, bronchial challenge with methacholine, atopy assessment (Phadiatop, unspecific total IgE), allergy skin tests, and endexpiratory CO-measurements. Subjects with a history of respiratory symptoms, increased bronchial reactivity, reduced lung function (FEV1/FVC < 80% predicted) and 150 healthy never-smokers were included in the subsequent diary study (part 2; n = 3281, 1992/93). Peak flow (morning and evening), symptoms, medication, personal activity and visits to the doctor were monitored. Across regions, annual mean values ranged from 9 to 52 mg/m3 (NO2) and 10 to 33 mg/m3 (PM10) respectively. Air pollution had effects on prevalence of dyspnea (+41% per 10 mg/m3 increment of the annual mean PM10, 95% CI 20-65%), on symptoms of chronic bronchitis (+31%, 10-55%), on FVC (-3.1%; -3.7 to -2.6%), and FEV1 (-1.1%; -1.7% to -0.5%), on the incidence of respiratory symptoms and the length of symptomfree intervals (11% change per 10 mg/m3 PM10), but not on the prevalence of asthma. Environmental tobacco smoke (ETS) showed impact on wheezing (OR 1.94; 1.39-2.70), asthma (1.39; 1.04-1.86), bronchitis (1.60; 1.24-2.08) and chronic bronchitis (1.50; 1.11-2.02). Health effects of moderate air pollution were confirmed in Switzerland. Although for the individual the relative risks are small, the public health impact may be considerable. An ongoing follow-up will investigate the mortality profile of the SAPALDIA cohort.

Adolescent↗

Quantification of crustacean hyperglycemic hormone by ELISA in hemolymph of the lobster, Homarus americanus, following various stresses.

An ELISA was developed for the crustacean hyperglycemic hormone (CHH) from the lobster, Homarus americanus. It is sensitive to as little as 0.2 fmol of peptide. The assay was used to measure CHH in the hemolymph of intact lobsters after various environmental stresses. Increases in CHH were observed following emersion, exposure to high temperatures (23 degrees and 28 degreesC), and salinity stress (50 and 150% seawater). During emersion, concentrations of hemolymph glucose increased concomitantly with increases in CHH. Significant levels of hemolymph CHH were also measured in lobsters that had been eyestalk-ablated. These latter observations indicate that there may be a source of CHH other than the X-organ/sinus gland in the lobster.

Animals↗

Novel regio- and stereoselective O-6-desulfation of the glucosamine moiety of heparin with N-methylpyrrolidinone-water or N,N-dimethylformamide-water mixtures.

The degree of completeness and selectivity of the solvolytic O-6-desulfation reactions of the glucosamine moiety adjacent to the 2-O-sulfoiduronic acid group of heparin was systematically studied. Using solutions of various ammonium salts of heparin (salts of tributylamine, quinoline and pyridine) in mixtures of 9:1 aprotic solvents and water (solvents of medium polarity, in order of decreasing polarity: Me2SO > Me2NCHO > Me2NAc > N-methylpyrrolidinone), the influence of different reaction conditions were studied. The ammonium salt of heparin with a strong base (e.g., tributylamine) in Me2SO showed almost no desulfation, while in Me2NCHO a relatively low degree of completeness of O-6-desulfation (30%) with moderate selectivity (15% [I-2(OS)]-desulfation) was observed. Weak bases like quinoline or pyridine in Me2SO-water resulted in nearly complete [A-6(OS)]-desulfation (95 and 94%, respectively) with low selectivity [I-2(OS)]-desulfation (49 and 35%, respectively). The heparin pyridinium salt in Me2NCHO-water showed both a relatively high degree of completeness and high selectivity (72% [A-6(OS)]- and 8% [I-2(OS)]-desulfation). The highest regioselectivity (i.e., a high degree of completeness accompanied by high selectivity) was achieved using an N-methylpyrrolidinone-water mixture (88% [A-6(OS)]-desulfation and 10% [I-2(OS)]-desulfation). A nearly complete O-6-desulfation (95%), accompanied by a lower selectivity (18% [I-2(OS)]-desulfation), was achieved when the reaction was carried out twice. Lower temperature improved selectivity (5% [I-2(OS)]-desulfation) but reduced the completeness of [A-6(OS)]-desulfation (72%). In comparison with the variety of O-6-desulfations reported to date, the novel reactions presented in this article led to remarkable increase in completeness and regioselectivity of the reactions that were investigated.

Dimethylformamide↗

Immunoscopy--a technique combining endoscopy and immunofluorescence for diagnosis of colorectal carcinoma.

BACKGROUND: Colorectal carcinoma is a common malignant disease with a high mortality rate. It arises most frequently in adenomas of the colorectum with different grades of dysplasia. Endoscopy and biopsy are among the most reliable diagnostic tools currently available. Diagnosis of malignancy at an early stage is sometimes difficult. This study reports on a new method, "immunoscopy", that combines endoscopy and immunofluorescent diagnostic procedures; it is the first reported use of locally applied fluorescein-labeled antibodies for detection of colorectal carcinomas. METHODS: A monoclonal antibody against carcinoembryonic antigen was fluorescein labeled. In phase I, formalin-fixed tissue samples, and in phase II, postoperative fresh tissue samples from tumorous and nontumorous areas of resected colorectal carcinomas were studied. After being incubated for 10 minutes, specific fluorescence was visualized with a conventional endoscope whose range was increased by means of two narrow band filters. RESULTS: Because of high levels of autofluorescence, evaluation of immunoscopic investigations using formalin fixed tissue (phase I) was not carried out. Immunoscopic investigation with postoperative fresh tissue samples could differentiate between tumorous and nontumorous areas (p < 0.001). Immunoscopic results were compared with data from immunohistochemical investigations with anti-carcinoembryonic antigen on the same tissue samples. CONCLUSIONS: Immunoscopy can differentiate between malignant and benign mucosal areas in fresh tissue samples. The high sensitivity of immunoscopy could potentially make it a useful diagnostic complement to routine endoscopy.

Adenoma↗

Dual microsporidial infection due to Vittaforma corneae and Encephalitozoon hellem in a patient with AIDS.

A 46-year-old human immunodeficiency virus-infected Swiss citizen living in Tanzania presented with respiratory, abdominal, and urogenital complaints. Microsporidial spores were isolated from urine and a sinunasal aspirate and were propagated in MRC-5 cell cultures. Western blot analysis and riboprinting identified the sinunasal isolate as Encephalitozoon hellem. Electron microscopic investigation of the urine isolate revealed spores with diplokaryotic nuclei and five to six isofilar coils of the polar tube and sporonts with two or three diplokarya. All stages were enveloped by two membranes, corresponding to a cisterna of host endoplasmic reticulum studded with ribosomes. These characteristics have been described for the genus Vittaforma. Western blot analysis of this isolate revealed a banding pattern identical to that of the Vittaforma corneae reference isolate. Part of the small subunit rRNA gene was amplified, sequenced (239 base pairs), and found to be identical to that of V. corneae. This is the second isolation of V. corneae and the first description of urinary tract infection due to V. corneae in a patient with AIDS.

AIDS-Related Opportunistic Infections↗

Occurrence of virulence-associated properties in Enterobacter cloacae.

Enterobacter cloacae is not a primary human pathogen but has been considered to be an important cause of nosocomial infections. Even so, there are almost no reports on its ability to produce recognized virulence-associated properties. In this study, we show that most of the E. cloacae strains examined were resistant to serum bactericidal activity and were able to produce aerobactin and mannose-sensitive hemagglutinin, and all of them could adhere to and invade HEp-2 cells. Since E. cloacae is part of the normal intestinal floras of many individuals, we believe that infectious disease due to endogenous E. cloacae might be a result of both host predisposing factors and the bacterial virulence determinants that we have detected in this survey.

Bacterial Adhesion↗

Increased levels of intracellular calcium are not required for the formation of attaching and effacing lesions by enteropathogenic and enterohemorrhagic Escherichia coli.

Elevated concentrations of intracellular calcium ([Ca]i) have been implicated as an important signalling event during attaching and effacing (A/E) lesion formation by enteropathogenic Escherichia coli (EPEC). The highly localized nature of the cytoskeletal and cell surface alterations occurring during A/E lesion formation suggests that there should be equally localized EPEC-induced signalling events. To analyze further the calcium responses to infection of HEp-2 cells by EPEC, we employed calcium-imaging fluorescence microscopy, which allows both temporal and spatial measurements of [Ca]i in live cells. Using this imaging technique, not only were we unable to detect any significant elevation in [Ca]i at sites of A/E EPEC adhesion, but, with several different classical EPEC and enterohemorrhagic E. coli (EHEC) strains and three different infection procedures, each of which resulted in extensive A/E bacterial adhesion, we were unable to detect any significant alterations in [Ca]i in infected cells compared to uninfected cells. In addition, chelation of intracellular free calcium with bis-(aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not, as previously reported, prevent A/E lesion formation. We conclude that increased [Ca]i are not required for A/E lesion formation by EPEC and EHEC.

Calcium↗

Associations between lung function and estimated average exposure to NO2 in eight areas of Switzerland. The SAPALDIA Team. Swiss Study of Air Pollution and Lung Diseases in Adults.

In this paper, we present results from the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults) regarding associations between lung function [forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)], as assessed during the cross-sectional study in 1991, and average levels of NO2 exposure within the eight study communities. We distinguished average home outdoor exposure and average personal exposure to NO2 and obtained exposure estimates by computing regional averages of passive sampler measurements performed by a random subsample of SAPALDIA participants in 1993. Previous analyses had revealed associations between average lung function and average air pollution levels between communities. The present results show that such associations may also be seen within communities: a 10-micrograms per m3 increase in average home outdoor and personal exposure to NO2 between zones of residence of the same community was associated with a change in average FVC by -0.59% [95% confidence limits (CL) = 0.01, -1.19] and -0.74% (95% CL = -0.07, -1.41), respectively. These values, however, are smaller than the ones found for the corresponding associations between study communities: -1.67% (95% CL = -1.01, -2.33) and -2.93% (95% CL = -2.11, -3.75), respectively. The different magnitudes of these two types of associations might be explained by differences in spatial variation between various components of air pollution.

Adult↗

Cold weather injuries in an arctic environment.

The cases of eight Special Forces soldiers who sustained cold weather-related injuries while conducting winter training as part of Operation Arctic Saber in the Northwest Territories and Arctic Circle are reported. Environmentally related injuries can represent difficult diagnostic and treatment challenges in the field. Moreover, they may compromise the overall mission if they are not identified and treated early. Cold weather injuries can also result in long-term disfigurement and disability that may limit a soldier's future worldwide deployability. Mission requirements, equipment utilization, and environmental exposure place soldiers at particular risk for cold weather-related injuries in such austere settings. Nonetheless, with appropriate education and safety precautions, these potentially life-threatening risks can be greatly minimized.

Adult↗

Cellular mechanism underlying neural convergent extension in Xenopus laevis embryos.

Convergent extension, the simultaneous narrowing and lengthening of a tissue, plays a major role in shaping and patterning the neural ectoderm in vertebrate embryos. In this paper, we characterize the cellular mechanism underlying convergent extension of the neural ectoderm in the Xenopus laevis late gastrula and neurula embryo. Neural ectoderm in X. laevis consists of two components, a superficial layer of epithelial cells overlying deep mesenchymal cells. To investigate the force contribution of the deep cells to convergent extension, we explanted single layers of neural deep cells from late gastrula stage embryos. These "neural deep cell explants" undergo active convergent extension autonomously, implying that these cells contribute force for neural convergent extension in vivo. Using time-lapse videorecording of these explants, we observed the neural deep cell behaviors (previously hidden behind an opaque epithelium) underlying convergent extension. We show that neural deep cells mediolaterally intercalate to form a longer, narrower tissue and that cell shape change and cell division contribute little to their convergent extension. Moreover, we characterize the neural deep cell motility driving mediolateral intercalation, also using time-lapse videorecordings. Analyses of these videos revealed that, on average, neural deep cells exhibit mediolaterally biased protrusive activity which is expressed in an episodic fashion. We propose that neural deep cells accomplish mediolateral intercalation by applying their protrusions upon one another, exerting traction, and pulling themselves between one another. This mechanism is similar to that previously described for convergent extension of the mesodermal cells. However, because the neural deep cells do not mediolaterally elongate during their convergent extension as the mesodermal cells do, we predict that a given intercalation will result in more extension for neural deep cells than for the mesodermal cells. Intercalation of neural cells also likely occurs in a more episodic manner than that of the mesodermal cells because the neural cells' mediolateral protrusive activity is episodic, whereas the protrusive activity of mesodermal cells is more continuous. These differences in protrusive activity and cell shape changes between the neural and mesodermal regions may reflect specializations of the same basic mechanism of mediolateral intercalation, tailored to accommodate other aspects of patterning and development of each tissue. These descriptions of the active cell motility underlying neural convergent extension in X. laevis are the first high-resolution video documentation of protrusive activity during neural convergent extension in any system. Our findings provide an important step in the investigation of neural convergent extension in X. laevis and further our understanding of convergent extension in general.

Animals↗

Epithelial cell wedging and neural trough formation are induced planarly in Xenopus, without persistent vertical interactions with mesoderm.

In this study we investigate the induction of the cell behaviors underlying neurulation in the frog, Xenopus laevis. Although planar signals from the organizer can induce convergent extension movements of the posterior neural tissue in explants, the remaining morphogenic processes of neurulation do not appear to occur in absence of vertical interactions with the organizer (R. Keller et al. , 1992, Dev. Dyn. 193, 218-234). These processes include: (1) cell elongation perpendicular to the plane of the epithelium, forming the neural plate; (2) cell wedging, which rolls the neural plate into a trough; (3) intercalation of two layers of neural plate cells to form one layer; and (4) fusion of the neural folds. To allow planar signaling between all the inducing tissues of the involuting marginal zone and the responding prospective ectoderm, we have designed a "giant sandwich" explant. In these explants, cell elongation and wedging are induced in the superficial neural layer by planar signals without persistent vertical interactions with underlying, involuted mesoderm. A neural trough forms, and neural folds form and approach one another. However, the neural folds do not fuse with one another, and the deep cells of these explants do not undergo their normal behaviors of elongation, wedging, and intercalation between the superficial neural cells, even when planar signals are supplemented with vertical signaling until the late midgastrula (stage 11.5). Vertical interactions with mesoderm during and beyond the late gastrula stage were required for expression of these deep cell behaviors and for neural fold fusion. These explants offer a way to regulate deep and superficial cell behaviors and thus make possible the analysis of the relative roles of these behaviors in closing the neural tube.

Animals↗