Biomedical subjects
Publications and source records attributed to W Müller.
Duplications of the male urethra are rare congenital malformations. They do not represent a uniform entity making it difficult to find an unequivocal and comprehensive classification. Management is directed by the individual functional situation. In this presentation two morphologically and functionally differing cases of a sagittal urethral duplication are described and aspects of diagnosis and treatment discussed.
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Optimization of crushing strength and disintegration time of a high-dose plant extract tablet was reached after extensive experimentation. Effects of the processing parameters, like compression force and tooling, and also of the excipients were found to be significant. Best results for both disintegration time and crushing strength were obtained with a plant extract that was granulated by roller compaction before compression. To gain more information about the different effects, artificial neural networks (ANNs) and a conventional multivariate method (partial least squares [PLS]) were used for data analysis. The topologies of the neural networks of the feed-forward type were optimized manually and by pruning methods. All methods were tested for contemplated parameters, crushing strength, and disintegration time. In general, ANNs were found to be more successful in characterizing the effects that influence crushing strength and disintegration time than the conventional multivariate methods.
Opioidergic modulation plays an important role in the control of oxytocin and vasopressin release by magnocellular neurons (MCNs) in the supraoptic and paraventricular nuclei of the hypothalamus. We have used whole cell patch-clamp recording in acute slices of the supraoptic nucleus (SON) of the hypothalamus to study opioidergic modulation of voltage-dependent K+ currents in MCNs that are involved in release activity. The mu-receptor agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO, 2 microM) affected K+ currents in 55% of magnocellular neurons recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed rectifier current (IK(V)) amplitude by approximately 50% without significant effects on its activation kinetics. The transient A current (IA) was enhanced by DAMGO by approximately 36%. Its inactivation kinetic was accelerated slightly while the voltage dependence of steady-state inactivation was shifted by -6 mV to more negative potentials. All DAMGO effects were blocked by the preferential non-kappa-opioid antagonist naloxone (10 microM). The kappa-opioid agonist trans-(+/-)-3, 4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 microM) strongly suppressed IK(V) by approximately 57% and evoked a 20-mV hyperpolarizing shift and an acceleration of activation in both, DAMGO-sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced IA by approximately 29% and tau of inactivation by -20% in DAMGO-sensitive cells. In contrast, in DAMGO-insensitive cells U50,488 increased IA by approximately 23% and strongly accelerated inactivation (tau -44%). The effects of U50,488 were suppressed by the selective kappa-receptor antagonist nor-binaltorphimine (5 microM). We conclude that mu- and kappa-opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulation of voltage-dependent K+ currents. In vasopressinergic MCNs, kappa-opioidergic inputs differentially modulate these K+ currents. The modulation of K+ currents is assumed to significantly contribute to opioidergic control of hormone release by MCNs within the supraoptic nucleus and from the axon terminals in the neural lobe.
Membrane-permeable arachidonic acid (AA) is liberated in a Ca2+-dependent way inside cells. By using whole cell patch clamp we show that intracellular AA (1 pM) selectively reduces IA in rat hippocampal neurons, whereas extracellular application requires a 10(6)-fold concentration. The nonmetabolized AA analogue ETYA mimics the effect of AA that is blocked by ascorbic acid or intracellular glutathione, suggesting an intracellular oxidative mechanism. We conclude that intracellular AA is extremely potent in reducing IA by an oxidative mechanism, particularly during oxidative stress.
The cholinergic system is critically involved in synaptic models of learning and memory by enhancing dendritic [Ca(2+)](i) signals. Diffuse cholinergic innervation suggests subcellular modulation of membrane currents and Ca(2+) signals. Here we use ion-selective microelectrodes to study spread of carbachol (CCh) after focal application into brain slice and subcellular muscarinic modulation of synaptic responses in CA1 pyramidal neurons. Proximal application of CCh rapidly blocked the somatic slow afterhyperpolarization (sAHP) following repetitive stimulation. In contrast, the time course of potentiation of the slow tetanic depolarization (STD) during synaptic input was slower and followed the time course of spread of CCh to the dendritic tree. With distal application, augmentation of the somatic STD and of dendritic Ca(2+) responses followed spread of CCh to the entire apical dendritic tree, whereas the sAHP was blocked only after spread of CCh to the proximal dendritic segment. In dendritic recordings, CCh blocked a small sAHP, augmented the STD, and rather reduced dendritic action potentials. Augmentation of dendritic Ca(2+) signals was highly correlated to augmentation of the STD. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) blocked approximately 55% of the STD in control and during CCh application. In conclusion, muscarinic suppression of the proximal sAHP can augment firing and thereby Ca(2+) responses. Dendritic augmentation of the STD by blockade of the sAHP and direct enhancement of N-methyl-D-aspartate (NMDA) receptor-mediated currents potentiates Ca(2+) signals even when firing is not affected due to suprathreshold input. In this way, subcellular muscarinic modulation may contribute to parallel information processing and storage by dendritic synapses of CA1 pyramidal neurons.
OBJECTIVE: Our purpose was to investigate how many preterm infants with a birth weight </=1,250 g and how many newborns with one >1,250 g with clinical symptoms had Ureaplasma urealyticum in their endotracheal tube aspirates, and how many of them had pneumonia. METHODS: The patients were divided into two groups (group 1: birth weight </=1,250 g, n = 25; group 2: birth weight >1,250 g, n = 45), and these two groups were subdivided into two subgroups (subgroup a: U. urealyticum in aspirate without pneumonia; subgroup b: U. urealyticum in aspirate with pneumonia). RESULTS: In group 1, there were 25 patients. Nine patients (36%) had U. urealyticum in their aspirates, 5 patients (20%) had pneumonia (group 1b), and 4 patients (16%) did not (group 1a). Infants with pneumonia showed a significant increase in parameters of mechanical ventilation, in the duration of mechanical ventilation, and in the duration of oxygen dependence as compared with subgroup 1a. In group 2, there were 45 patients. Six patients of group 2 (13%) had U. urealyticum in their aspirates, 2 patients (4.4%) had a pneumonia (group 2b), and 4 patients (8.8%) did not (group 2b). CONCLUSIONS: In preterm infants as well as in term newborns one should consider U. urealyticum as a potential cause of neonatal pneumonia.
Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection.
Volvox has two cell types: mortal somatic cells and immortal germ cells. Here we describe the transposon-tagging, cloning and characterization of regA, which plays a central role as a master regulatory gene in Volvox germ-soma differentiation by suppressing reproductive activities in somatic cells. The 12.5 kb regA transcription unit generates a 6,725 nucleotide mRNA that appears at the beginning of somatic cell differentiation, and that encodes a 111 kDa RegA protein that localizes to the nucleus, and has an unusual abundance of alanine, glutamine and proline. This is a compositional feature shared by functional domains of many 'active' repressors. These findings are consistent with the hypothesis that RegA acts in somatic cells to repress transcription of genes required for growth and reproduction, including 13 genes whose products are required for chloroplast biogenesis.
Together with the faecal and the urinary discharge of animals and humans natural and synthetic estrogenes are excreted into the environment. About their degradation in the environment only few facts are known. Their reduction is probably of microbial enzymatical nature. For looking into that question it was investigated by in-vitro-attempts whether Escherichia coli or Clostridium perfringens influence the estrone. Therefore estrone was incubated together with the microorganisms tested (experimental groups) and without those (control groups) in nutrient medium for these bacteria over 48 hours with 37 degrees C (aerobic) or 42 degrees C (anaerobic). For the executed procedure an enzyme immunoassay was used. It could be seen that E. coli does not show a provable effect on the estrone concentration under this conditions. Whereas C. perfringens might have a potency for the degradation of the hormone tested. The experiments shows that there exists obviously a difference between estrone and 4-pregnene-20 beta-o1-3-one in the same system of test.
82 Dichelobacter nodosus strains isolated from 9 footrot affected sheep flocks in south west Germany were serotyped and tested for virulence. Serovar B was present in all flocks, representing 64.4% of all isolated D. nodosus field strains. Other serovares found were type A, C, E, G and H. Virulent strains were identified in 5 flocks, while intermediate strains were isolated from all 9 flocks. All serological untypeable strains proved to be avirulent. Based on these epidemiological findings the use of currently available commercial footrot vaccines is appropriate in south west German sheep populations.
In the context of medicine cutting is one of the most important operations. Many surgical tasks start with an incision, allowing the surgeon to access the region of interest, using either conventional or minimal invasive surgery techniques. The work presented herein should be seen in the context of surgical training and preoperative planning using computer assisted medical simulation systems. The main result of this work is the proposed cutting algorithm based on predefined templates. To integrate this approach in the existing surgical training simulator and to handle additional tasks like soft tissue deformation, needed by the medical environment, a generic simulation framework was developed. This framework is able to utilize given multiprocessor- and network-environments to achieve the desired realtime interactivity.
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Articular cartilage has unique material properties that enable the cartilage to perform its physiological functions over a lifetime and under a wide range of loading conditions. Numerous studies have investigated the relationship between cartilage properties and composition/structure. For cartilage transplantation and regeneration, it is necessary to know how cartilage maintains its functionality and how cartilage responds to the ever-changing mechanical environment. In this review, we discuss theoretical and experimental studies on the behavior of articular cartilage to load. In the first part, the composition and structure of articular cartilage is presented. In the second part, theoretical models of the mechanical behavior of cartilage, experimental methods for the determination of cartilage properties, and material properties for normal, pathologic, and repair cartilage are summarized. In the third part, the relationship between mechanical loading of the cells and their corresponding biological responses are discussed. The goal for treating joint degeneration in the future lies in cartilage regeneration rather than prosthetic replacement. In order to achieve this goal, it has to be understood how structure and function, metabolic and biochemical properties, and biomechanical performance of articular cartilage can be restored.
BACKGROUND: Expression of nm23 has been shown to be inversely correlated with the metastatic potential of several human cancers. In the current study, the expression and prognostic impact of nm23 was immunohistochemically studied in 413 curatively resected gastric carcinomas. METHODS: Tumor sections of the 413 gastric carcinomas were stained with a polyclonal antibody that was raised against the nm23-H1/NDP kinase A, which is identical to the nm23-H1 gene product. RESULTS: Expression of nm23 was detected in 84.5% (n = 349) of all tumors, in the majority of cases (71.2%) causing a homogeneous staining reaction in more than 75% of tumor cells. Expression of nm23 was positively correlated with the intestinal type of tumor, according to the Lauren classification and advanced pT categories, and was also correlated with the presence of blood and lymphatic vessel invasion. In contrast, no correlation could be demonstrated between nm23 expression and lymph node involvement. As shown in univariate analysis, patients with nm23 positive tumors, especially those with nm23 positive diffuse-type carcinomas, had significantly shorter overall survival than patients with nm23 negative tumors (P = 0.03 and P = 0.0065, respectively). However, in a multivariate analysis that included the prognostic parameters pT category, pN category, and blood and lymphatic vessel invasion, this prognostic impact was not maintained. CONCLUSIONS: In contrast to results for breast and colorectal carcinomas, our results for 413 gastric carcinomas showed that expression of the designated metastasis suppressor gene nm23 is correlated with aggressive tumor growth and poor prognosis but is not an independent prognostic marker.
Lymphocyte migration into lymphoid organs is regulated by adhesion molecules including L-selectin and the beta7 integrins. L-selectin and alpha4beta7 are predominantly hypothesized to direct the selective migration of lymphocytes to peripheral lymph nodes and the gut-associated lymphoid tissues, respectively. To further characterize interactions between L-selectin and beta7 integrins during lymphocyte recirculation, mice deficient in both receptors (L-selectin/beta7 integrin-/-) were generated. The simultaneous loss of L-selectin and beta7 integrin expression prevented the majority of lymphocytes (>95% inhibition) from attaching to high endothelial venules (HEV) of Peyer's patches and other lymphoid tissues during in vitro binding assays. Moreover, the inability to bind HEV eliminated the vast majority of L-selectin/beta7 integrin-/- lymphocyte migration into Peyer's patches during short-term and long-term in vivo migration assays (>99% inhibition,p < 0.01). The lack of lymphocyte migration into Peyer's patches correlated directly with the dramatically reduced size and cellularity (99% reduced) of this tissue in L-selectin/beta7 integrin-/- mice. High numbers of injected L-selectin/beta7 integrin-/- lymphocytes remaining in the blood of wild-type mice correlated with markedly increased numbers of circulating lymphocytes in L-selectin/beta7 integrin-/- mice. Loss of either L-selectin or the beta7 integrins alone resulted in significant but incomplete inhibition of Peyer's patch migration. Collectively, the phenotype of L-selectin/beta7 integrin-/- mice demonstrates that these two receptors primarily interact along the same adhesion pathway that is required for the vast majority of lymphocyte migration into Peyer's patches.
The epidemiology of non-traffic-related, pedestrian injuries in the winter sports resort of Arosa (Switzerland) between 1968 and 1995 (beginning december to end april) was studied. A total of 2813 patients (1140 male and 1673 female patients) with 3010 injuries was surveyed in a general practice. The study showed in the examined period not only an increasing number of injuries and a culmination in February, but also a higher risk for females (60 versus 40 per cent) and an increasing incidence with age. 6% of all patients had more than one injury and 5% required hospitalization. Most pedestrians had injuries of the upper and lower extremity; fracture of the distal radius was the most often diagnosed injury, followed by distortions of the foot and wrist and fractures of the ankle. For accident prevention it is important, that the authorities do not abstain from mechanical cleaning of walking surfaces as soon as they become slippery and from giving out warnings via the mass media. For outdoor walking we postulate boots for ankle protection. The results are discussed and compared with already existing publications.
The pleiotrophic but overlapping functions of the cytokine family that includes interleukin (IL)-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin 1 are mediated by the cytokine receptor subunit gp130 as the common signal transducer. Although mice lacking individual members of this family display only mild phenotypes, animals lacking gp130 are not viable. To assess the collective role of this cytokine family, we inducibly inactivated gp130 via Cre-loxP-mediated recombination in vivo. Such conditional mutant mice exhibited neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects, demonstrating the widespread importance of gp130-dependent cytokines.