Elastic properties of superconducting Chevrel-phase compounds.
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Journal Article↗
Biomedical subjects
B Wolf
Publications and source records attributed to B Wolf.
Screening by genomic linkage studies and mutation analysis of hereditary adenomatous polyposis coli: usefulness for clinical practice.
A heterogeneous group of patients suffering from adenomatous polyposis coli (APC) were evaluated by clinical and genetic investigations for the first time in Austria. The patients belonged to eight unrelated APC families. In six families several family members were affected with APC, and linkage analysis with highly informative markers was used to estimate the risk of single individuals in these families to develop APC. All index patients were also tested for the most frequent mutation in the APC gene (mutation cluster region, exon 15). Clinical investigations included ophthalmologic tests for congenital hypertrophy of retinal pigment epithelium and colonoscopy. According to DNA analysis, 5 of 19 at-risk individuals had to be considered to be at high risk of having inherited the disease. Four of them underwent proctocolectomy, one patient at risk is under colonoscopic surveillance. The predictive value of indirect genotype analyses reached 83.3%; direct mutation analyses allowed risk estimation in 50% of cases. Ophthalmologic investigation was informative in 75% of the families. Direct and indirect genotyping using a panel of highly polymorphic, closely linked microsatellite markers is a valuable, rapid, reliable method for establishing a presymptomatic diagnosis of APC, especially in families in which more than one affected individual is available for analysis. With regard to the onset of APC and extracolonic manifestations, the variability of APC demands clinical investigations in addition to the molecular tests for all patients and their first-degree relatives.
Adenomatous Polyposis Coli↗
Crosstalk between cellular morphology and calcium oscillation patterns. Insights from a stochastic computer model.
Agonist-induced oscillations in the concentration of intracellular free calcium ([Ca2+]i) display a wide variety of temporal and spatial patterns. In non-excitable cells, typical oscillatory patterns are somewhat cell-type specific and range from frequency-encoded, repetitive Ca2+ spikes to oscillations that are more sinusoidal in shape. Although the response of a cell population, even to the same stimulus, is often extremely heterogeneous, the response of the same cell to successive exposures can be remarkably similar. We propose that such "Ca2+ fingerprints' can be a consequence of cell-specific morphological properties. The hypothesis is tested by means of a stochastic computer simulation of a two-dimensional model for oscillatory Ca2+ waves which encompasses the basic elements of the two-pool oscillator introduced by Goldbeter et al. (Goldbeter A., Dupont G., Berridge M.J. Minimal model for signal-induced Ca(2+)-oscillations and for their frequency encoding through protein phosphorylation. Proc Natl Acad Sci USA 1990; 87: 1461-1465). In the framework of our extended spatiotemporal model, single cells can display various oscillation patterns which depend on the agonist dose, Ca2+ diffusibility, and several morphological parameters. These are, for example, size and shape of the cell and the cell nucleus, the amount and distribution of Ca2+ stores, and the subcellular location of the inositol(1,4,5)-trisphosphate-generating apparatus.
Biological Clocks↗
Deletion/insertion mutation that causes biotinidase deficiency may result from the formation of a quasipalindromic structure.
Biotinidase is responsible for recycling the vitamin biotin from biocytin that is formed after the proteolytic degradation of the biotin-dependent carboxylases. We have identified a deletion/insertion mutation within exon D of the human biotinidase gene in a child with biotinidase deficiency. The mutation causes a frame shift and premature termination which are predicted to result in a truncated protein. We propose that the mutation occurred during DNA replication by either of two mechanisms. Both mechanisms involve formation of a quasipalindromic hairpin loop in the template and dissociation of DNA polymerase alpha. This mutation supports the formation of palindromic structures as a possible cause of deletions in eukaryotes, and supports the proposal, derived from in vitro studies, that polymerase alpha may preferentially arrest or dissociate at specific template sequences.
Amidohydrolases↗
Implications of acidic tumor microenvironment for neoplastic growth and cancer treatment: a computer analysis.
The acidic microenvironment found in most solid tumors appears to be a main regulator for the self-organized development of neoplastic growth and invasion. Induced by mitogenic stimulation and/or oncogenic alterations in their signal transduction network, tumor cells develop an improved capability for acid extrusion. This clamps intracellular pH to slightly alkaline values permissive for growth and proliferation and provides tumor cells with an enhanced resistance against acidic extracellular conditions. Since rapid tumor cell growth under hypoxic conditions is accompanied by glycolytic metabolism, and consequently, acid production, acid export is further enhanced. Local extracellular acidification is facilitated by microcirculatory inadequacy resulting in both reduced buffering capacity and functional heterogeneity inside the tumor. Significant microenvironmental pH gradients promote tumor cell invasion and inhibit the immune response. The scenario is checked by means of a dynamic computer model. The stochastic minimal model supports the hypothesis that acidification of the microenvironment by malignant cells cannot only be regarded as a supplementary side effect of tumor cell metabolism, but rather as a strategic principle to 'enslave' processes normally counteracting neoplastic growth and invasion. The results are discussed with respect to current concept for cancer treatment.
Animals↗
Drug targeting and metabolic investigations of cryoprepared tumor cells with analytical electron energy loss spectroscopy.
Analytical electron microscopy is an ideal tool for holistic data acquisition on biological systems. The use of analytical electron microscopy for both, the investigation of micropharmacokinetic problems and metabolic studies, is becoming more and more important. Depending on the mode of investigation, it is possible to localize drugs and xenobiotics precisely in situ under optical control or to quantify their uptake and distribution in the corresponding target cells without disintegrating the cell or tissue material. In this paper, we present instructive examples for the application of analytical electron energy loss spectroscopy in transmission electron microscopy in order to investigate the cellular uptake and distribution of cisplatin and cyclophosphamide and the metabolic changes induced by an alteration in the extracellular calcium concentration in a holistic manner.
Animals↗
Benchmark analysis on diabetics at high risk for lower extremity amputation.
After the 1990 establishment of a multidisciplinary foot salvage clinic, 1346 diabetic patients, at high risk for the development of foot ulcers and eventual lower limb amputation, were followed for 4 years. Of the 224 high-risk patients admitted to the hospital, 74 amputations (5.5%) of all or part of a lower limb were performed. Patients undergoing amputation were younger, more severely ill, and required more frequent hospitalizations because of greater organ system involvement. They were also more likely to be institutionalized after discharge. Overall, patients with long-standing adult-onset diabetes, identified as at high risk for foot ulcer development, have a substantially increased risk for lower limb amputation, multiple organ system failure, hospitalization, and institutionalization than do diabetic patients as a whole. Clinical benchmarking facilitates the identification and reduction of unnecessary variations in patient care practices. Here, a formal benchmark analysis provides the current outcome expectations for amputation rates and co-morbidities in patients with diabetes who are classified as at high risk for lower extremity amputation. Management of these patients in a structured, multidisciplinary foot salvage clinic, augmentation of baseline services, and preliminary benchmark data may provide a standard for the measurement of therapeutic interventions that improve patient care.
Adult↗
Respiratory and cutaneous evaporative water loss at high environmental temperatures in a small bird
We measured rates of respiratory and cutaneous evaporative water loss as a function of air temperature in a small desert bird, the verdin Auriparus flaviceps. Birds were placed in a two-compartment metabolic chamber that separately collected water evaporated from the bird's head and body. Cutaneous and respiratory evaporative water loss, as well as CO2 production, were measured in resting birds at 2 °C intervals between 30 and 50 °C. Metabolic rate was lowest at 38 °C (19 mW g-1) and increased to 28 mW g-1 at 50 °C. At the lowest air temperature, 30 °C, resting metabolic rate was 34 mW g-1. As air temperature increased from 30 to 50 °C, cutaneous water loss increased from 3.3 to 10.3 mg g-1 h-1 and respiratory water loss increased from 2.1-64.1 mg g-1 h-1. At moderate air temperatures (30-36 °C), water loss was divided almost evenly between respiratory and cutaneous components. As air temperature increased, however, verdins became heavily dependent on respiratory evaporation for heat dissipation. Evaporative water loss data for other species at high air temperatures suggest that partitioning of water loss may follow two different patterns. Evaporative heat dissipation may depend primarily on either cutaneous or respiratory modes of evaporative heat transfer. The physiological mechanisms and functional significance of these contrasting patterns of evaporative heat loss remain unknown.
Journal Article↗
[Microsensory systems in cell biology basic research and medical diagnostics].
The development of an integrated sensor system, called the physiocontrol microsystem, is presented. It is suited for microscopy, and works with both adherent cell types and cultures growing in suspension, as well as with tissue biopsies. The central part, a miniaturized culture chamber equipped with differently constructed microsensors, allows continuous observation of important physiological parameters even in the course of long-lasting experiments. Besides a description of the physical components, the study provides a summary of selected applications of the physiocontrol microsystem in basic cellular research and biomedical diagnostics.
Animals↗
[Ready for the year 2000. The Federation of German Vocational Rehabilitation Centers has revised the fundamental concepts].
The Federation of German Vocational Retraining Centres have recently completed a fundamental revision and update of their conceptual approach, adjusting it to the technological advances at hand as well as to a changing labour market. Novel educational concepts offer broader space for accommodating the needs of individual rehabilitees and for enhancing their competence, technical, methodological and social, in terms of present-day, wholistic rehabilitation. New approaches are being implemented, the vocational training centres opening up for new groups (such as one-parent families) and offering rehabilitation programmes on a non-residential basis as well. Further-training schemes have been devised to ensure that disabled people, too, have access to the current state-of-the-art. An indispensable part of vocational rehabilitation programmes also in the future, the Specialized Services of the vocational retraining centres are going to adapt to the changing situation as well.
Combined Modality Therapy↗
Biotinylation of biotinidase following incubation with biocytin.
Human serum biotinidase, purified to homogeneity (1920 units/mg protein), was incubated with biocytin prior to electrophoresis and transblotting with avidin-peroxidase. Avidin reacted with biotinidase maximally when incubated at pH 7.5-9, less at pH 7 and none below pH 7. No avidin reactivity occurred when biotinidase was incubated with biotin or in the absence of biocytin. Inclusion of the nucleophilic acceptors, ethanolamine or hydroxylamine, to the incubation mixture with biocytin and biotinidase resulted in loss of avidin reactivity. High concentrations of mercaptoethanol also prevented avidin reactivity. These results suggest that biotinidase can be biotinylated in the presence of biocytin at neutral to alkaline pH probably through a thioester bond formed with a cysteine residue in the active site of the enzyme. Biotinidase may then function as a biotinylating enzyme when incubated with appropriate nucleophilic acceptors.
Amidohydrolases↗
Dot-ELISA for the rapid detection of gentamicin in milk.
A dipstick dot-ELISA for the detection of gentamicin in milk of dairy cattle is reported for the first time. The test is based on a sandwich ELISA using high affinity monoclonal antibodies to gentamicin. Antibodies were adsorbed to nitrocellulose filters, blocked, dried, and stored for several weeks before use. The dipstick ELISA detected gentamicin at a concentration of 0.1 microgram/ml and produced strongly positive results at 0.2 microgram-0.3 microgram/ml. This ELISA is highly specific and no false positives were detected when tested against various aminoglycoside analogs including streptomycin, kanamycin, bekanamycin, amikacin, neomycin, and tobramycin. Further, the elimination in cow milk of gentamicin residues following intramammary administration of the drug was studied in two dairy cattle using dot-ELISA. Milk gentamicin levels were detected at post injection hours up to 120 hr in each of the two dairy cattle. It therefore, appears that gentamicin residues can still be detected in milk after 5 days using dot-ELISA. Based on the simplicity of performance and the economical nature of the test system, dipstick is recommended as a suitable method for wide scale use in field studies and diagnostic laboratories.
Animals↗
Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency.
Serum biotinidase has biotinyl-transferase activity in addition to biocytin hydrolase activity. A sensitive assay for biotinyl-transferase activity was developed based on the transfer of biotin from biocytin to histones. Biotinidase biotinyl-transferase occurs at physiological and alkaline pHs, whereas hydrolysis of biocytin occurs optimally at pH 4.5 to 6.0. Measurement of hydrolysis requires micromolar concentrations of biocytin, whereas biotinylation of histones can be detected readily at 1.5 nM biocytin. Because polylysine is readily biotinylated by biotinidase in the presence of biocytin, whereas polyarginine is not, the enzyme likely transfers biotin to the epsilon-amino group of lysyl residues. To determine if patients who are deficient in biocytin hydrolase activity are also deficient in biotinyl-transferase activity, serum from 103 children (25 identified by exhibiting clinical symptoms and 78 detected by newborn screening) with profound biotinidase deficiency (less than 10% of mean normal biotinyl-p-aminobenzoate hydrolyzing activity) were assessed for biotinyl-transferase activity and for the presence of cross-reacting material (CRM) to antibodies prepared against purified serum biotinidase. Sera from all symptomatic patients, both CRM-negative and CRM-positive, had no biotinyl-transferase activity. Sera that was CRM-negative from children ascertained by newborn screening also had no biotinyl-transferase activity, whereas sera from 67% of the CRM-positive children identified by newborn screening had varying degrees of biotinyl-transferase activity. These results indicate that there is a large group of enzyme-deficient children detected by newborn screening who are different biochemically from those who are symptomatic. The clinical relevance of having some degree of biotinyl-transferase activity for individuals with biotinidase deficiency remains to be determined. In addition, it is important to determine if biotinyl-transferase activity, especially biotinylation of histones, is a physiological function of biotinidase.
Amidohydrolases↗
Reversible metabolic myopathy in biotinidase deficiency: its possible role in causing hypotonia.
A 5-year-old girl diagnosed with biotinidase deficiency at 9 months of age demonstrated limb and axial hypotonia which improved on biotin therapy. In this patient, electromyographic (EMG) studies prior to treatment were compatible with a mild myopathic process. Serial EMGs performed on biotin therapy demonstrated a gradual resolution of the myopathy. This is the first documented case of a reversible myopathy in a patient with biotinidase deficiency, which may contribute to the clinical findings of hypotonia.
Amidohydrolases↗
Mutational hotspot in the human biotinidase gene causes profound biotinidase deficiency.
Biotinidase deficiency is an autosomal recessive inherited disorder that is characterized by neurological and cutaneous symptoms. Biotinidase-deficient children cannot recycle endogenous biotin, an essential water-soluble B vitamin. Biotin is covalently attached to epsilon-amino groups of lysyl residues of four carboxylases. These carboxylases are subsequently degraded to biocytin (biotin-epsilon-lysine). Biotinidase cleaves biocytin to biotin and lysine, thereby completing the biotin cycle. The symptoms of biotinidase deficiency can be resolved or prevented by treatment with biotin. Therefore, it is important that biotinidase deficiency is diagnosed early so that permanent neurological damage can be prevented. Many states and countries currently perform newborn screening for biotinidase deficiency. We have recently isolated and characterized the cDNA for normal human biotinidase and localized the gene to chromosome 3p25 (ref. 9). We have now identified the first mutation that causes profound biotinidase deficiency. It occurs in a distinct region of the gene that encodes the putative signal peptide. Fifty percent of symptomatic children studied have a 7-bp deletion coupled with a 3-bp insertion in at least one of their alleles of the biotinidase gene. This mutation appears to be a common cause of biotinidase deficiency in symptomatic children.
Alleles↗
Variation in the respiratory quotient of birds and implications for indirect calorimetry using measurements of carbon dioxide production
Determination of animal power consumption by indirect calorimetry relies upon accurate estimation of the thermal equivalent of oxygen consumed or carbon dioxide produced. This estimate is typically based upon measurement or assumption of the respiratory quotient (RQ), the ratio of CO2 produced to O2 consumed. This ratio is used to indicate the mixture of lipids, carbohydrates and proteins in the metabolic substrate. In this analysis, we report the RQ for two bird species, Passer domesticus and Auriparus flaviceps, under several dietary and fasting regimes. RQ commonly differed substantially from those typically assumed in studies of energy metabolism and often included values below those explainable by current knowledge. Errors that could result from these unexpected RQ values can be large and could present the primary limit to the accuracy of power consumption estimates based upon measurement of carbon dioxide production.
Journal Article↗
[Results of surgical therapy of esophageal carcinoma in a general hospital].
From January 1987 until December 1994 103 patients were treated for esophageal cancer in our department. Operability was 77.7%, 75.7% were resected. Postoperative lethality was 9.0% within 30 days and 16.7% for the whole hospital stay. Concerning the resected patients 37.5% adenocarcinoma and 60.0% squamous cell carcinoma were found. The most common localisation of the tumor was the lower third of the esophagus (62.5%). 35.9% underwent an abdominothoracic resection whereas in 64.1% a transhiatal esophagectomy was carried out. The UICC-stage distribution was as follows: I 11.3%, IIa 10.0%, IIb 12.5%, III 40.0%, IV 26.3%. In 79.2% of the cases lymph node metastasis were already recognizable. The median survival time was 10 (3-72) months with better outcome for adenocarcinoma, lymph node negative patients and early tumor stages. Even if only palliation was the aim of the surgical procedure esophagectomy followed by collar esophagogastrostomy provides satisfying results to regain the ability to swallow.
Adenocarcinoma↗
Unusual B-T phase diagram of the heavy-fermion superconductor CeCu2Si2.
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Journal Article↗