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R Müller

Publications and source records attributed to R Müller.

At least 145 records · Page 8Linked to original sources
PubMed2000

Role of Na(+)HCO(3)(-) cotransporter NBC1, Na(+)/H(+) exchanger NHE1, and carbonic anhydrase in rabbit duodenal bicarbonate secretion.

BACKGROUND & AIMS: HCO(3)(-) supply to the enterocyte is rate limiting for duodenal HCO(3)(-) secretion (J(HCO3-)). This study defines the molecular nature of the major HCO(3)(-) uptake pathways in rabbit duodenocytes and investigates their physiologic significance and regulation during basal and stimulated J(HCO3-). METHODS & RESULTS: pH gradient-driven (22)Na(+) uptake into duodenal basolateral membrane vesicles was partly HCO(3)(-) dependent, stilbene sensitive, and therefore mediated by Na(+)HCO(3)(-) cotransport, and partly HCO(3)(-) independent, Hoechst 642 sensitive, and therefore mediated by the Na(+)/H(+) exchanger isoform NHE1. Semiquantitative polymerase chain reaction (PCR) revealed high duodenal expression levels for the NBC1 isoform of the Na(+)HCO(3)(-) cotransporter gene family and NHE1. Cloning and comparison of full-length rabbit with human gastrointestinal and kidney NBC1 subtype revealed a conserved protein kinase A consensus sequence in the cytoplasmic N-terminus of the gastrointestinal NBC1. Inhibition of either Na(+)HCO(3)(-) cotransport or carbonic anhydrase reduced ouabain-sensitive J(HCO3-) in in vitro rabbit duodenal mucosae by approximately 50%, but did not affect 8-Br-cAMP-induced DeltaJ(HCO3-), suggesting cAMP-mediated up-regulation of the alternative pathway. However, inhibition of both Na(+)HCO(3)(-) cotransport and either carbonic anhydrase or NHE1 strongly reduced DeltaJ(HCO3-). CONCLUSIONS: NBC1 and NHE1 are the major base importers in rabbit duodenocytes. Na(+)HCO(3)(-) cotransport and CO(2) hydration/Na(+)/H(+) exchange are equally important pathways for duodenal HCO(3)(-) supply and are up-regulated during cAMP-mediated stimulation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

[Prenatal diagnosis: intestinal obstruction].

We present 4 cases of fetal intestinal obstruction and their ultrasonographical findings. With regard to the reported cases we discuss the diagnostic and differential-diagnostic considerations of this rare but not uncommon fetal malformation.

Adolescent↗
PubMed2000

[Hydrometrocolpos causing progressive unilateral hydronephrosis in agenesis of the contralateral kidney].

The number of detected fetal abnormalities in our prenatal diagnostic division illustrate the high frequency of fetal urogenitaly malformations. Moreover, we report on a case of hydrometrocolpos caused by sinus urogenitalis which effects a progressive unilateral hydronephrosis by agenesia of the contralateral kidney. The progressive hydronephrosis in conclusion leads to a preterm induction of labor in fetoprotective intension.

Adult↗
PubMed2000

[Fetal gallbladder and gallstones].

Fetal anomalies of the gallbladder and fetal gallstones are extremely rare. We report a prospective study to assess the gallbladder detection rate according to gestational age and the incidence of fetal gallstones. The gallbladder detection rate increases from 28.5% below the 16th up to 98% over the 32nd week of gestation. We find out a fetal gallstone incidence of 0.07%.

Cholelithiasis↗
PubMed2000

[Snowboarding accidents].

The present review summarises the related literature of the last ten years with request to snowboarding accidents. Sport accident statistics of snowboarding show high and increasing numbers of injuries. Already snowboarding ranks third of all sport accidents in Switzerland. According to the literature the injury risk in snowboarding is twice that of skiing, although the injuries are less serious. About 50% of the injured snowboarders are beginners. Beginners have a higher risk of injury than more advanced snowboarders. Additionally, and a relative large part of them are injured the first day of their snowboard career. The pattern of injury has changed over the last years. Today, injuries to the lower extremities account no longer for more than 50% but are now decreased to about 25%. Nowadays, wrist, knee, ankle, and shoulder are the most frequently injured body parts. It is the authors opinion that with up-to-date protectors, release bindings, and training of falling techniques the numbers and seriousness of injuries could be reduced, in particular injuries to the wrist and ankle.

Adult↗
PubMed2000

Acoustic flow perception in cf-bats: extraction of parameters.

The narrow-band portions of the echolocation pulses seen in cf-bats are a hypothetical substrate for target localization. This localization could be based on estimates of echo envelope amplitude and carrier frequency together with their derivatives. Evaluation of these parameters is referred to as "acoustic flow" in loose analogy to optic flow. It is assessed whether the requirements for this task may be reconciled with known principles of auditory function. For the evaluation of a single echo, this seems to be the case: auditory filter shapes provide sufficient frequency resolution; at the same time envelopes are preserved well and some noise removal is achieved. Nevertheless, should bats not be endowed with additional capabilities for noise removal, analysis of acoustic flow would be limited to favorable signal-to-noise ratios. Multiple, temporally overlapping echoes are probable in any realistic echolocation scenario. In this case, additional auditory processing steps have to be postulated, which allow simultaneous estimation of multiple carrier frequencies and reduction of demodulation distortions.

Acoustics↗
PubMed2000

Foliage echoes: a probe into the ecological acoustics of bat echolocation.

The research reported here aims at understanding the biosonar system of bats based on the properties of its natural inputs (ecological acoustics). Echoes from foliages are studied as examples of ubiquitous, natural targets. The echo properties and their qualitative relationship to plant architecture are described. The echoes were found to be profoundly stochastic and in general neither Gaussian nor stationary. Consequently, features useful for discrimination of such target classes will be confined to estimated random process parameters. Several such statistical signal features which are sufficiently invariant to allow a classification of the used example plants were identified: the characteristic exponent and the dispersion of an alpha-stable model for the amplitude distribution, a crest factor defined as the ratio of maximum squared amplitude and signal energy, the dispersion of the first threshold passage distribution, the structure of the correlation matrix, and a nonstationarity in sound channel gain. Discrimination error probability could be reduced by combining features pairwise. The best combination was the crest factor and the correlation coefficient of a log-linear model of the time-variant sound channel gain; it yielded an estimated Bayes risk of 6.9% for data pooled from different views.

Acoustics↗
PubMed2000

Inhibition of cyclin-dependent kinase activity and induction of apoptosis by preussin in human tumor cells.

In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; approximately 500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27(KIP-1) is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent antitumor drugs.

Anisomycin↗
PubMed2000

Quantification of periapical bone destruction in mice by micro-computed tomography.

Bacterial infections of the dental pulp result in tissue destruction and periapical bone resorption. The availability of genetically engineered mouse strains is a major advantage in the use of this model system for studies of periapical pathogenesis. The main limitation of the mouse model is its small size, and the necessity for laborious histologic analyses to quantify periapical bone destruction. In the present study, we evaluated the use of a new technology, high-resolution micro-computed tomography (micro-CT), for the rapid and non-invasive quantification of periapical bone destruction. Periapical lesions were induced in the lower first molars of mice by exposing the pulp to the oral environment. Mandibles were harvested on day 21 after pulp exposure, and were subjected to micro-CT analysis, with 17-microm-thick radiographic sections. Samples were then decalcified, embedded, and sectioned for histology. The cross-sectional area of periapical lesions was determined by image analysis of corresponding micro-CT and histologic sections. The results showed a highly significant correlation between micro-CT and histology (p < 0.0001), with mean differences of 4. 1% (range, 0.9 to 7.2%) between the two methods. The mean error associated with image analysis was 4.9% for images obtained by both micro-CT and histology. The variability of replicate (n = 5) independent micro-CT determinations was 3.4%, less than that associated with the image analysis error. These results demonstrate that micro-CT imaging is a rapid, reproducible, and non-invasive method, that gives results that are closely comparable with those obtained by histology. Micro-CT appears to have utility for the accurate quantification of changes in bone architecture in small biological specimens.

Animals↗
PubMed2000

Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice.

The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very different femoral peak bone densities and may serve as models for studying the genetic regulation of bone mass. Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitecture of the proximal femur, femoral midshaft, and lumbar vertebrae were evaluated in three dimensions using microcomputed tomography (microCT) with an isotropic voxel size of 17 microm. Mineralization of the distal femur was determined using quantitative back-scatter electron (BSE) imaging. MicroCT images suggested that C3H mice had thicker femoral and vertebral cortices compared with B6. The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and greater trochanter. The trabecular number (Tb.N) in the C3H vertebral bodies was about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs. 5.1(-1) +/- 0.2 mm(-1); p < 0.0001). The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs. 27.4 +/- 0.5N, p < 0.0001). In contrast, strengths of the lumbar vertebra were not significantly different between inbred strains (p = 0.5), presumably because the thicker cortices were combined with inferior trabecular structure in the vertebrae of C3H mice. These results indicate that C3H mice benefit from alleles that enhance femoral strength but paradoxically are deficient in trabecular bone structure in the lumbar vertebrae.

Animals↗
PubMed2000

Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia.

Recent studies suggest that high glucose concentrations impair insulin receptor phosphorylation and kinase activation in certain cell models. To examine whether such an effect of glucose can also be demonstrated in vivo, insulin receptor kinase activation was studied in erythrocytes from 11 patients with non-insulin-dependent diabetes (NIDDM), before and after reduction of hyperglycemia (from 14.6+/-1.6 to 6.6+/-0.5 mmol/l fasting plasma glucose within 8.6+/-0.6 days). For the measurement of receptor kinase activation, cells were incubated with insulin (0-400 nmol/l), solubilized and insulin receptors immobilized to microwells coated with anti-insulin receptor antibody. Kinase activity towards insulin receptor substrate-1 and insulin binding were then measured in these wells. Kinase activities (expressed as amol phosphate transferred per min and per fmol insulin binding activity) were similar before (2.4+/-0.4 and 32.2+/-2.0 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) and after improvement of metabolic control (2.4+/-0.5 and 32.0+/-2.3 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). Moreover, activities were also similar in 22 hyperglycemic patients with NIDDM (2.1+/-0.3 and 35.1+/-1.4 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) compared with those in 21 non-diabetic control individuals (2.1+/-0.3 and 34.2+/-1.2 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). We conclude that insulin activation of erythrocyte insulin receptor kinase is not impaired in NIDDM and is not influenced by hyperglycemia.

Blood Glucose↗
PubMed2000

["More is less": a retrospective study of haloperidol dosages in acute schizophrenia].

UNLABELLED: With the background of a number of meta-analyses on the optimal neuroleptic dosages [1,2] the average daily dosage for the treatment of acute schizophrenic episodes recommended in the internal treatment guidelines of our psychiatric clinic was reduced from 24 mg to 15 mg haloperidol equivalent. In the present retrospective study it was investigated what effect this change in guideline had on the actual dosing behavior and on the efficacy and the side effect rate of the antipsychotic treatment. For this purpose all haloperidol treated patients of a two year interval prior to the change of the guideline (1987/88, n = 103) were compared with all treated of a two year interval (1991/92, n = 87) following it. RESULTS: The evaluation of the treatment data showed that the dosing guideline was adhered to and in 1991/92 on the average actually only 15 mg haloperidol were prescribed daily in acute schizophrenic episodes. The antipsychotic efficacy was just as good under this dosage as under the average daily dose of 24 mg haloperidol given in the preceeding interval; the average time in hospital was even reduced from 76 to 67 days. Under the lower daily doses an additional medication with biperiden was less often required. CONCLUSION: Average daily doses of 15 mg haloperidol appear to be at least equally as effective and more tolerable for the treatment of acute schizophrenic episodes than average daily doses of 24 mg haloperidol.

Acute Disease↗
PubMed2000

Empirical advantages of adeno associated viral vectors in vivo gene therapy for arthritis.

OBJECTIVE: To evaluate the utility of the adeno associated viral (AAV) vector for gene delivery to joint cells in vivo and in vitro, and to assess its potential as a vector for arthritis gene therapy. METHODS: A recombinant AAV (rAAV) vector expressing the bacterial beta-galactosidase (beta-gal) gene (rAAV-CMV-LacZ) was directly introduced into healthy-normal mouse knees, or arthritic knees in mice overexpressing tumor necrosis factor-alpha (hTNFalpha-Tg). Beta-gal expression levels were determined by immunohistochemistry and chemiluminescence. The transduction efficiency of this vector on primary fibroblast-like synoviocytes (FLS) in vitro was determined by FACS. The effects of UV and gamma-irradiation as well as TNF-alpha on transduction efficiency were determined using the same methods. RESULTS: We found little evidence of rAAV transduction in the joint cells of healthy mice. Target gene expression was detected in all animals at Day 3, and peaked at Day 7 before returning to baseline levels 21 days after injection. In contrast, synoviocytes, articular chondrocytes, and meniscal cells of diseased mice were transduced by rAAV-CMV-LacZ in hTNFalpha-Tg animals. Transduction efficiencies correlated with joint damage, and target gene expression was up to 10-fold greater than that seen in the normal mice. In vitro, we found that rAAV transduction of FLS can be enhanced by pretreatment with UV or gamma-irradiation and TNF-alpha stimulation. CONCLUSION: We find that rAAV vectors have several empirical advantages for in vivo gene therapy for arthritis: (1) rAAV preferentially transduces arthritic joint cells in vivo. (2) rAAV can transduce both FLS and chondrocytes in vivo. (3) rAAV transduction of FLS can be augmented by pretreatment with agents that induce DNA repair enzymes.

Adenoviridae↗
PubMed2000

Synergistic antitumor effect of chemotherapy and antisense-mediated ablation of the cell cycle inhibitor p27KIP-1.

The fraction of noncycling cells found in most tumors represents a major obstacle for conventional chemotherapy. Here, we show that the cyclin-dependent kinase inhibitor p27KIP-1 accumulates to high levels in human tumors grown in immunodeficient mice. We have developed an antisense phosphorothioate oligodeoxynucleotide (ODN) that efficiently inhibits the expression of p27KIP-1 both in vitro and in vivo. Treatment of cultured tumor cells with this ODN sensitized the cells to all chemotherapeutic drugs tested, including the new kinase inhibitor flavopiridol. Furthermore, striking synergistic effects of the p27KIP-1 ODN and flavopiridol were observed in vivo with respect to both the induction of apoptotic cell death and the inhibition of tumor growth. Importantly, p27KIP-1 ODN treatment alone did not provoke any detectable tumor enhancement. A mechanistic explanation for these findings might be derived from the observation that p27 ODN treatment of cultured tumor cells led to a clear increase in the fraction of S-G2 cells in the absence of an efficient progression into M phase. These findings may have direct relevance to the development of new approaches for the treatment of human cancer.

Adenocarcinoma↗
PubMed2000

Phenotypical characterization of c-kit receptor deficient mouse femora using non-destructive high-resolution imaging techniques and biomechanical testing.

OBJECTIVE: Pathological processes in bone can lead to fatal health consequences. Therefore, it is important to study factors that possibly influence the activity of bone cells. The mast cell is a normal component of bone, storing and producing many potent bioactive substances. One of the most important factors to influence mast cell number, function, and phenotype is the c-kit ligand. A defect of the c-kit receptor leads to mast cell deficiency. In literature oversight, evidence for the importance of mast cells in skeletal homeostasis is compiled. METHODS: To investigate the influence of c-kit receptor deficiency on bone mass, geometry, microstructure, and strength, 30 femora of profoundly c-kit receptor deficient mouse mutants and 30 control group animals aged 8-20 weeks were phenotypically characterized using peripheral quantitative computed tomography (pQCT), micro-computed tomography (microCT) and 3-point-bending. RESULTS: The femora of the c-kit receptor and therefore mast cell deficient animals were significantly altered in bone mass and geometry but not in bone density and microstructure. The mutants had a lighter femur with a thinner shape. The lower load bearing capacity of the femora of mast cell deficient mouse mutants is more likely explained by the smaller amount of bone material than due to a change in intrinsic material properties. TECHNICAL CONSIDERATIONS: With the little dimensions of mouse bones, it is of prime importance to have precise methods to phenotypically characterize the bone. The pQCT allows the separate assessment and analysis of trabecular and cortical bone density, as well as a statement about bone geometry. Beyond it, the microCT-technique delivers a 3-D analysis of bone microstructure, which so far was only achieved with 2-D histomorphometry. microCT is an efficient alternative to destructive histological preparations allowing further biomechanical testing of the same specimens to also deliver measures for bone strength.

Animals↗