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Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 793 records · Page 44Linked to original sources
PubMed1996

[Treatment concept in deep pelvic-leg venous thrombosis].

The treatment of choice in acute deep vein thrombosis continues to be controversial. Conservative treatment with heparin and anticoagulation, systemic thrombolysis, thrombectomy and the combination of local thrombolysis and surgical unblocking are possible therapies. Regarding long term results; both after non operative treatment or after venous thrombectomy, many authors describe a majority of patients who suffer from chronic venous insufficiency in varying clinical severity. Requirements for normal venous function are complete phlebographic patency and valvular competence without venous reflux. Our proposed treatment for thromboses not older than 7 days combines local thrombolysis with venous thrombectomy to achieve these requirements and contains the following operative proceeding: An incision is made in the groin or - for more distal thromboses - on the proximal end of the clot. For the removal of the clot in the iliac vein a Fogarty-catheter is used. Urokinase is administered through a vein puncture in the instep while the blood flow is blocked by a pneumatic cuff around the thigh. After at least 20-30 minutes the clots can be removed through the proximal incision after removal of the cuff and manual massage of the leg. During this procedure the vein proximal of the venotomy is occluded by a soft clamp. An analysis of the results of 34 patients on average 3 1/2 years after combined therapy confirms normal valvular function of the popliteal vein in 27 (79%) cases. This improved long term outcome is going to be checked in an prospective study evaluating anticoagulation versus our treatment concept.

Blood Vessel Prosthesis↗
PubMed1996

Tissue factor expression during human and mouse development.

In the adult organism the cellular distribution of tissue factor (TF) expression corresponds to biological boundary layers forming a hemostatic barrier ready to activate blood coagulation after tissue injury. Whether TF expression might also play a role in development is unknown. To determine the significance of TF in ontogenesis, we examined the pattern of TF expression in mouse development and compared it with the distribution of TF in human post-implantation embryos and fetuses of corresponding gestational age. At early embryonic periods of murine (6.5 and 7.5 pc) and human (stage 5) development, there was strong expression of TF in both ectodermal and entodermal cells. In situ hybridization and immunohistochemistry demonstrated that TF mRNA and protein were expressed widely in epithelial areas with high levels of morphogenic activity during organogenesis. Staining for TF was seen during ontogenetic development in tissues such as epidermis, myocardium, bronchial epithelium, and hepatocytes, which express TF in the adult organism. Surprisingly, during renal development and in adults, expression of TF differed between humans and mice. In humans, maturing stage glomeruli were stained for TF whereas in mice, TF was absent from glomeruli but was present in the epithelia of tubular segments. In neuroepithelial cells, there was a substantial expression of TF. Moreover, there was robust TF expression in tissues such as skeletal muscle and pancreas, which do not express it in the adult. In contrast, expression of the physiological ligand for TF, factor VII, was not detectable during early stages of human embryogenesis using immunohistochemistry. The temporal and spatial pattern of TF expression during murine and human development supports the contention that TF serves as an important morphogenic factor during embryogenesis.

Adult↗
PubMed1996

Immunohistochemistry of new type I alveolar epithelial cell markers of the rat.

The presence of pan-cadherin and the MEP-I antigen in normal and diseased rat lung was established by employing immunoperoxidase and double label fluorescence techniques. The binding of a mouse monoclonal antibody (MEP-1) reacting specifically with type I pneumocytes was assessed on paraffin sections of normal specimens as well as those with pulmonary fibrosis induced by bleomycin or radiation treatment. In injured alveolar epithelium, a diminished type I cell and a focal type II cell immunoreactivity was found. Electron microscopy of immunogold-labelled lung tissue confirmed the type I cell specificity of MEP-1. In severely injured pulmonary parenchyma MEP-1-negative areas occurred, which were also negative with the type II pneumocyte marker Maclura pomifera lectin. Similarly, a polyclonal pan-cadherin antibody uniformly decorated luminal surfaces of alveoli except the type II pneumocytes. Furthermore, pleural mesothelial cells, bronchiolar epithelial cells, endothelial cells of large blood vessels and alveolar macrophage surfaces exhibited pan-cadherin immunoreactivity. After injury, a remarkable loss of pan-cadherin immunoreactivity in the MEP-1-positive type I epithelial cells was detectable. These findings suggest that characterization of normal alveolar epithelial cells and monitoring of the epithelial remodelling in pulmonary pathohistology are sufficiently described by the antibodies MEP-1 anti pancadherin.

Animals↗
PubMed1996

Detection of circulating tissue factor and factor VII in a normal population.

The plasma tissue factor (TF) concentration was correlated to factor VII concentration (FVIIag) and factor VII activity (FVIIc) in 498 healthy volunteers ranging in age from 17 to 64 years. Immunoassays using monoclonal antibodies (mAbs) were developed for the determination of TF and FVIIag in plasma. The mAbs and the test systems were characterized. The mean value of the TF concentration was 172 +/- 135 pg/ml. TF showed no age- and gender-related differences. For the total population, FVIIc, determined by a clotting test, was 110 +/- 15% and the factor VIIag was 0.77 +/- 0.19 microgram/ml. FVII activity was significantly increased with age, whereas the concentration demonstrated no correlation to age in this population. FVII concentration is highly correlated with the activity as measured by clotting assay using rabbit thromboplastin. The ratio between FVIIc and FVIIag was not age-dependent, but demonstrated a significant difference between men and women. Between TF and FVII we could not detect a correlation.

Adolescent↗
PubMed1996

Correction or transfer of immunodeficiency due to TNF-LT alpha deletion by bone marrow transplantation.

BACKGROUND: Mice with inactivated tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) genes have profound abnormalities of the immune system including lymphocytosis, lack of lymph nodes, undifferentiated spleen, hypoimmunoglobulinaemia, and defective Ig class switch. Here, we asked whether this phenotype is due to incompetent lymphohemopoietic progenitors or to a defective environment. MATERIALS AND METHODS: Lethally irradiated TNF-LT alpha-deficient and wild-type mice received bone marrow cells from either TNF-LT alpha-deficient or wild-type mice. The reconstitution and transfer of the phenotype was followed by morphological and functional analyses. RESULTS: Bone marrow cells from wild-type mice restored the synthesis of TNF and LT alpha, corrected the splenic microarchitecture, normalized the lymphocyte counts in the circulation, and repopulated the lamina propria with IgA-producing plasma cells of TNF-LT alpha-deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell dependent antigen was corrected, while no lymph nodes were formed. Conversely, the TNF-LT alpha phenotype could be transferred to wild-type mice by bone marrow transplantation after lethal irradiation. CONCLUSIONS: These data demonstrate that most TNF- and LT alpha-producing cells are bone marrow derived and radiosensitive, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow cell transplantation. The genotype of the donor bone marrow cells determines the functional and structural phenotype of the TNF-LT alpha-deficient adult murine host, with the exception of lymph node formation. These findings may have therapeutic implications for the restoration of genetically defined immunodeficiencies in humans.

Animals↗
PubMed1996

[Changes in somatosensory evoked potentials after sevoflurane and isoflurane. A randomized phase III study].

Monitoring of somatosensory evoked potentials (SEP) is used to identify critical phases of cerebral ischaemia by means of characteristic changes in the signal patterns. A correct interpretation of the results is possible, however, only if the influence of drugs that act on the central nervous system is known. We were able to show that volatile anaesthetics have an impact on latencies and stimulus amplitudes. In this study, we examined the influence of sevoflurane as compared with isoflurane on the conduction of SEP by the median nerve at various concentrations. In addition, we determined how the addition of nitrous oxide (N2O) influenced the stimulus response of median-nerve SEP. Both isoflurane and sevoflurane caused a dose-dependent increase in latency of the primary cortical complex, while the influence on the cervical components of the SEP with respect to increased latency was only slight. No significant difference was found between both study groups. Under the influence of N2O, there were marked reductions in amplitude of the cortical stimulus response. Thus, it can be recommended that supplementation with N2O should be avoided in the presence of low initial amplitudes. Based on our results, the use of isoflurane and sevoflurane concentrations up to 1.0 MAC seems to be compatible with intraoperative monitoring of SEP.

Anesthetics, Inhalation↗
PubMed1996

Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver.

An organic anion-transporting polypeptide that mediates sodium-independent uptake of negatively charged sulfobromophthalein and bile salts has recently been cloned from rat liver (Jacquemin et al., 1994). In this study we have extended the substrate specificity studies to neutral and positively charged organic compounds with use of the Xenopus laevis oocyte expression systems. We found that the same transporting polypeptide can also transport the neutral cardiac glycoside ouabain (apparent Km approximately 1.7mM); the endogenous steroids aldosterone (Km approximately 15nM), cortisol (Km approximately 13 microM) and dexamethasone; the anionic steroid-conjugates estrone-3-sulfate (Km approximately 4.5 microM) and estradiol-17-glucuronide (Km approximately 3.0 microM) and the exogenous amphipathic organic cation N-(4,4-azo-n-pentyl)-21-deoxyajmalinium, a permanently charged photolabile derivative of the antiarrhythmic drug N-propylajmaline. These data demonstrate that the previously cloned hepatic organic anion-transporting polypeptide can in fact transport a wide range of differently charged lipophilic organic compounds including exogenous and endogenous organic anions, neutral steroids and organic cations. Hence, a single sinusoidal (or basolateral) transporting polypeptide can account, at least in part, for charge-independent steroid and drug clearance in mammalian liver.

Aldosterone↗
PubMed1996

[Form deprivation myopia caused by keratitis scrophulosa].

Zrenner and Schaeffel reported that translucent occluders may induce axial eye elongation in animals. This axial growth is also called form deprivation myopia (FDM). Searching for a clinical correlate we examined in a retrospective study 115 patients with keratitis scrophulosa peracta, mainly corneal transplant patients. These patients had an average refraction of -4.27 dpt. In epidemiologic studies Stenström found +0.5 dpt as the mean refraction in the general population. When the onset of the corneal disease was before the age of 5 years, the myopia was found to be higher than in patients with later age of onset. In 43 patients we determined axial length by ultrasound biometry and found an average axial length of 26.89 mm, whereas the general average is 24.00 mm. In conclusion, these results confirm that not only in animal experiments but also in clinical cases FDM is responsible for the axial growth of eyes.

Adolescent↗
PubMed1996

Role of multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells.

The human multidrug resistance protein (MRP), a 190-kDa member of the ABC-protein superfamily, is an ATP-dependent glutathione S-conjugate carrier (GS-X pump) and is present in membranes of many, if not all, cells. Overexpression of MRP in tumor cells contributes to resistance to natural product drugs and oxyanions. The function and specificity of the GS-X pump MRP is very similar to the canalicular multispecific organic union carrier (cMOAT) present in the canalicular membrane domain of hepatocytes and functioning in primary-active excretion of multivalent anionic conjugates into bile. In this review we discuss the function of MRP as GS-X pump in mammalian cells, its putative role in multidrug resistance, its relation to the hepatocyte cMOAT system and its dysfunction in the mutant TR- Wistar rat.

ATP-Binding Cassette Transporters↗
PubMed1996

Pharmacokinetic characteristics of a new liquid sustained-release formulation of theophylline designed for the elderly and children: microcaps as sachet.

A new sustained-release theophylline formulation was especially designed for the elderly and children. Microcapsules of theophylline, administered as a suspension in water, proved to be a suitable dosage form for a clientele with impaired or difficult deglutition. Pharmacokinetic characteristics of 2 batches at the lower (T1) and the upper (T2) in vitro dissolution specification range of this new formulation and a pellet formulation (R) as a comparator were evaluated in an open, randomized, 3-way, multiple-dose, crossover study design with an asymmetric dosage regimen of 400 mg and 200 mg theophylline. Smooth and safe plasma concentrations with a high and long-lasting plateau were achieved with this new formulation. Plateau times which are independent of the asymmetric dosage regimen ranged from 16.4 hours (T1) to 13.8 hours (T2) and could therefore span sufficient time of the dosage interval. Maximum serum levels of 9.6 micrograms/ml and 10.0 micrograms/ml were attained 6.6 and 6.1 hours after dosing of T1 and T2, coinciding perfectly with the time of the critical morning dip at 2-4 a.m. With a nocturnal excess of 15.5% (T1) and 17.9% (T2) this circadian-tailored asymmetric dosage regimen proved to take into account the chronopathology of asthma and the chronopharmacokinetics of theophylline sustained-release preparations. Bioequivalence of all 3 formulations versus each other with regard to rate (Cmaxss) and extent (AUC(tau)ss) of absorption could be established for the 2 batches at the upper and lower in vitro specification range and for both batches of the new formulation compared to the reference. All in all, safety and efficacy of this new liquid prolonged-release theophylline could be established. Furthermore, in vitro specifications could be justified according to current EU guidelines.

Aged↗
PubMed1996

[Training with a simulator--experiences in space flight].

High technology and automation have not been able to significantly improve flight safety within the last two decades. The main cause of aviation accidents was and is human error. Therefore, the most powerful tools to reduce risks in aviation deal with the human operator on the flight deck. Pilot selection, training and teamwork are of the utmost importance. The simulator is a valuable training aid. Simulation provides realistic scenarios that can be used to train optimal pilot behavior in emergency situations. Many complex abnormal situations can be only managed in teamwork. That is the reason why training programmes for improved team behavior (crew resource management) are becoming more and more important.

Accidents, Aviation↗
PubMed1996

[Nurses' and patients' experience of combined health service delivery to all population groups in a hospital].

In a community hospital in Gauteng, the hospital management had, on short notice, to provide combined health services to all population groups. In the past different health services were delivered to each population group. The integration of health service delivery was a sudden change. Based on this, research questions arose, namely: how do nurses and patients experience this change, and how could they be assisted to adjust to the change. The research objectives were twofold, namely: to explore and describe nurses and patients' experience of combined health delivery to all population groups and based on the results to make recommendations to assist them with adjustment to a combined health delivery system. An exploratory, descriptive and contextual research design was followed. Trustworthiness was ensured by applying Guba's approach. Phenomenological and individual focus interviews were conducted with forty nurses and patients who were selected purposively. Field notes were written after completion of each interview. The transcribed data was analysed by using Giorgi's and Kerlinger's methods combined. Results were discussed and a literature control completed. The most important conclusions reached were: there was an insufficient administrative structure in the hospital as a result of insufficient preparation for the combined health service delivery for all population groups; the whites' perception of different populations groups is based on an ethnocentric Western approach. This led to their experience of culture shock that resulted in feelings of anger/frustration, fear and sadness; the willingness of other populations groups to adjust to combined health service delivery led to their experience of happiness; there exists communication problems between population groups because of their not being able to communicate in their own language and the difference in communication styles; the verbalised Christian viewpoint and values of whites nurses and patients are not congruent with their prejudiced perception of people of other population groups and cultures, and the different population groups do not know each other's lifeworlds and that leads to prejudices that block open communication. Several recommendations were made based on these conclusions.

Black or African American↗
PubMed1995

Early phase in the infection of cultured cells with papillomavirus virions.

The fate of full bovine papillomavirus (BPV) virions and virus-like particles after binding to C127 or CV-1 cells was studied by electron microscopy and indirect immunofluorescence. After incubation at 4 degrees for 1 hr, BPV virions were found to be bound to the plasma membrane, and most viruses were absorbed by the cells after 30 min incubation at 37 degrees. Ninety minutes after the virions had been bound to the plasma membrane, the uptake of the virions was completed and most of the antigen was found to be localized in the nucleus. The viruses were transported in phagosomes and the uptake and transportation could be inhibited by cytochalasin B and taxol, suggesting the possible involvement of microfilaments and microtubules in the virus particle uptake and transportation. The capsid proteins could be detected for about 14 hr, until degradation and deposit of the viral antigen in the Golgi complexes. Although binding to the plasma membrane and uptake of virions into large cytoplasmic vesicles could be monitored by electron microscopy, no complete virions were observed in the nucleus of infected cells despite a very strong nuclear fluorescent staining for both L1 and L2 proteins. This may indicate that disintegration of the virions occurs in the cytoplasm and the L1/L2 proteins migrate to the nucleus via their nuclear localization signals.

Animals↗
PubMed1995

Drug-stimulated ATPase activity of a deletion mutant of the human multidrug-resistance protein (MDR1).

The baculovirus-insect cell system has been used for the functional expression of the human multidrug resistance protein (MDR1) and a mutant MDR1 variant lacking a twenty amino acid segment from the first extracellular loop (delta aa78-97 MDR1). Both MDR1 proteins were found to be correctly inserted into the insect cell membrane as indicated by their interaction with MRK 16 antibody. The removal of the 78-97 segment from the first extracellular loop dramatically altered drug-stimulated ATPase activity. Rhodamine 123 or vinblastine were not able to stimulate the mutant protein and Calcein AM had also little effect. In contrast, verapamil increased the ATPase activity of the mutant almost to the same maximal level as that of the wild type. However, the verapamil concentration needed for the half maximal stimulation of the ATPase activity was found to be about hundred times higher than that for the wild type MDR1. These results indicate that a partial deletion of an extracellular loop modulates the affinity of MDR1 for its transportable substrates in a variable fashion.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Sequences required for the nuclear targeting and accumulation of human papillomavirus type 6B L2 protein.

The L2 protein of the human papillomaviruses is a minor structural protein and is not necessary for the major L1 protein to assemble into capsids. However L2 protein binds DNA and enhances the efficiency of HPV capsid assembly, suggesting an important role in the production of infectious papillomaviruses. L2 accumulates rapidly in the nucleus after synthesis in the cytoplasm. To identify L2 sequences responsible for nuclear targeting and accumulation, full-length HPV6bL2 protein and L2 proteins containing sequence deletions were expressed in CV-1 cells, using recombinant vaccinia viruses. beta gal protein fused to C-terminal and N-terminal L2 sequences were localized in the nucleus and demonstrated that both the C-terminal putative nuclear localization signal (NLS) and N-terminal DNA binding sequences of the L2 protein, which are rich in arginine and lysine, are functional in targeting proteins into the nucleus. L2 mutants lacking amino acids (aa 286-306) do not accumulate in nucleus even when the C-terminal NLS and N-terminal DNA binding sequences are intact. Accumulation in the nucleus of L2 protein lacking aa 286-306 could be also achieved by increasing the L2 protein size via insertion of a portion of L1 protein. Amino acid sequence alignment of L2 proteins from sequenced papillomaviruses showed that sequences in this region are relatively conserved. Our results indicate that in the L2 protein, the nuclear targeting and accumulation are controlled by two different sequences and the rapid nuclear translocation and accumulation may play an important role in papillomavirus life cycle.

Amino Acid Sequence↗