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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 127 records · Page 7Linked to original sources
PubMed1999

[Monochorionic twins after treatment of sterility using assisted reproduction methods].

OBJECTIVE: The goal of this study has been to determine frequency of occurrence of monochorial twins within the study group consisting of 521 pregnancies conceived through the In Vitro Fertilization (IVF) programme. DESIGN: An observational study. SETTING: Sanatorium Pronatal, Na Dlouhé mezi 4/12, 147 00 Praha 4-Hodkovicky. METHODS: A condition to be included in the study group was that there was a gestation sac detected by ultrasound. The first ultrasound examination was performed transvaginally and was done between the fifth and the sixth week of each pregnancy. A multiple pregnancy has been classified as monochorial in case when gestation sac contains two yolk sacs and two fetuses. RESULTS: Within the whole study group there were 13 monochorial twins which presents 2.5% of all pregnancies. The incidence of monochorionicity among all multiple pregnancies is 6.4%, in IVF cycles without micromanipulation techniques the occurrence of monochorial twins has been 0.9%, following cryoembryotransfer 3.9%, with micromanipulation (ICSI, AH) it reaches 5.7% of all pregnancies. CONCLUSION: Monochorial twins were detected seven time more frequent in comparison within occurrence in ordinary population. The occurrence rises in connection with the number of fetuses in uterus. In comparison with simple IVF cycles we have proved higher occurrence of monochorionicity in connection with micromanipulation techniques and cryoembryotransfer.

Chorion↗
PubMed1999

[Heterotopic pregnancy and its occurrence in assisted reproduction].

OBJECTIVE: To assess the incidence of heterotopic pregnancy after infertility treatment using the technology of assisted reproduction. DESIGN: A prospective study of 618 women who became clinically pregnant following assisted reproduction technology (ART) procedures. SETTING: Sanatorium Pronatal, Na dlouhé mezi 4/12, 147 00 Praha 4-Hodkovicky. METHODS: Study group consists of clinical pregnancies conceived after ART procedures within the period from January 1, 1997 until June 30, 1998. A condition to be included in survey group was that there was a gestation sac detected by ultrasound or histological confirmation of ectopic pregnancy. RESULTS: Six-hundred-eighteen clinical pregnancies resulted and 23 of the pregnancies were ectopic gestations (3.7%). Seven out of the 23 (30.5%) ectopic pregnancies were heterotopic. Thus heterotopic pregnancy rate after ART was, 1.14% (1 in 88). CONCLUSION: The incidence of heterotopic pregnancy following assisted reproduction technique is relatively frequent. This condition represents a live-threatening complications of pregnancy. The prognosis for intrauterine gestation in case of heterotopic pregnancy is usually good. About 78% delivered living child at term.

Female↗
PubMed1998

Repaglinide and related hypoglycemic benzoic acid derivatives.

The structure-activity relationships in two series of hypoglycemic benzoic acid derivatives (5, 6) were investigated. Series 5 resulted from meglitinide (3) when the 2-methoxy was replaced by an alkyleneimino residue. Maximum activity was observed with the cis-3, 5-dimethyl-piperidino (5h) and the octamethyleneimino (5l) residues. Series 6 resulted from the meglitinide analogon 4 bearing an inversed amido function when the 2-methoxy, the 5-fluoro, and the alpha-methyl residue were replaced by a 2-piperidino, a 5-hydrogen, and a larger alpha-alkyl residue, respectively. An alkoxy residue ortho to the carboxy group further increased activity and duration of action in the rat. The most active racemic compound, 6al (R4 = isobutyl; R = ethoxy), turned out to be 12 times more active than the sulfonylurea (SU) glibenclamide (1). Activity was found to reside predominantly in the (S)-enantiomers. Compared with the SUs 1 and 2 (glimepiride), the most active enantiomer, (S)-6al (AG-EE 623 ZW; repaglinide; ED50 = 10 micro/kg po), is 25 and 18 times more active. Repaglinide turned out to be a useful therapeutic for type 2 diabetic patients; approval was granted recently by the FDA and the EMEA. From investigations on the pharmacophoric groups in compounds of type 5 and 6, it was concluded that in addition to the two already known-the acidic group (COOH; SO2NH) and the amidic spacer (CONH; NHCO)-the ortho residue R1 (alkyleneimino; alkoxy; oxo) must be regarded as a third one. A general pharmacophore model suitable for hypoglycemic benzoic acid derivatives, SUs, and sulfonamides is proposed (Figure 6). Furthermore, from superpositions of low-energy conformations (LECs) of 1, 2, and (S)-6al, it was concluded that a common binding conformation (LEC II; Figure 10B) may exist and that differences in binding to the SU receptor and in the mechanism of insulin release between repaglinide and the two SUs may be due to specific hydrophobic differences.

ATP-Binding Cassette Transporters↗
PubMed1998

Sequential immunotyping and genotyping of tumor cells in bone marrow of cancer patients: a model study.

Epithelial cells can be detected in bone marrow or peripheral stem cell preparations of patients with various kinds of cancer and their presence in bone marrow is of prognostic significance. Characterization of these cells has been hampered by their low frequency. Here we present a method that may allow sequential immunophenotyping and genotyping of epithelial cells in bone marrow. To simulate in vivo situations, cells from the colon cancer cell line HT29 were seeded into bone marrow and were first detected by the Fab fragment of the A45-B/B3 anticytokeratin antibody. Expression of Ki67, p53, Her-2/ neu (c-erbB2), and 17-1A could be detected on A45-B/B3-stained cells by immunofluorescence using a fluorescein-labeled anti-mouse immunoglobulin specific for the Fc part of mouse immunoglobulins. Reactivity for all antigens except for Ki67 persisted after A45-B/B3 labeling even when a scoring step for the presence of epithelial cells was performed before proceeding with the immunophenotyping. After immunophenotyping, numerical chromosomal aberrations and amplifications of the Her-2/neu oncogene could be assessed by fluorescence in situ hybridization in the same A45-B/B3-stained cells. This combination of immunophenotyping and genotyping may help in establishing the role of epithelial cells in bone marrow or peripheral stem cell harvests for tumor relapse and formation of metastases.

Animals↗
PubMed1998

Release of phospholipids from erythrocyte membranes by taurocholate is determined by their transbilayer orientation and hydrophobic backbone.

Bile salts mediate a specific release of phosphatidylcholine (PC) from the canalicular membrane into the bile fluid. We utilized human red blood cells (RBC) as a model system to study the release of endogenous phospholipids as well as phospholipid analogues from plasma membranes in the presence of the bile salt taurocholate (TC). Short- and long-chain fluorescent as well as spin-labeled analogues with various headgroups were chosen. RBC were labeled either on the exoplasmic or on the cytoplasmic leaflet with the analogues and incubated with various concentrations of TC. Analogues on the exoplasmic layer could be readily released by TC. Release was most efficient above the critical micellar concentration (CMC) of TC. Release was independent of the headgroup, but depended on the fatty acid chain length of the analogues; i.e., it was lower for long-chain than for short-chain labeled phospholipids. Analogues on the cytoplasmic leaflet were efficiently shielded from TC-mediated release. The preferential release of endogenous PC and sphingomyelin (SM) from the erythrocyte membrane above the CMC supports the conclusion that TC-mediated release of phospholipids occurs preferentially from the exoplasmic leaflet independent of their headgroup. However, the extent of release of endogenous phospholipids was significantly lower in comparison to that of analogues, endorsing the relevance of the hydrophobic backbone for bile salt mediated release of phospholipids. Implications for the mechanism of the release of PC from the canalicular membrane into the bile fluid are discussed.

Bile↗
PubMed1998

Bayesian optimal design in population models for haematologic data.

We introduce a population model to design optimal apheresis schedules to collect blood stem cells from cancer patients. Blood stem cells are collected prior to the patient undergoing high-dose chemoradiotherapy and are returned after this treatment to enable reconstitution of the white blood cell components. Maximizing the number of cells collected in as few apheresis as possible is desirable. We use a longitudinal data model with random effects to describe profiles of individual patients. A hierarchical prior model introduces common mean profiles for patients undergoing different treatments. We find the optimal apheresis schedule for a new patient by minimizing an expected loss over the posterior predictive distribution of the patient's predicted CD34 profile. We implement estimation of the model and solution of the optimal design problem by a simulation approach, which allows us to accommodate arbitrary shapes for the profiles and realistic loss functions that include relative penalties for the number of scheduled stem cell collections and for collecting fewer than a specified target quantity of total collected stem cells.

Antigens, CD34↗
PubMed1998

[Right-heart endocarditis after pacemaker implantation as a cause of a round pulmonary infiltrate].

HISTORY AND CLINICAL FINDINGS: A 57-year-old man developed intermittent fever and fatigue 11 months after a two-chamber cardiac pacemaker had been implanted because of 2 degrees and 3 degrees A-V block. Antituberculosis treatment was initiated as tuberculosis was suspected. The infiltrate regressed, but the other symptoms persisted. Four months later he was admitted as an emergency because of septicaemia. INVESTIGATIONS: In addition to a recently discovered cardiac murmur there was a raised erythrocyte sedimentation rate (116 mm) and leucocytosis (13 600/microliters) with shift to the left. Coagulase-negative staphylococci were grown on several blood cultures. Transoesophageal echocardiography (TOE) demonstrated vegetation on the tricuspid valve, the pacing wires and the right ventricular outflow tract. DIAGNOSIS, TREATMENT AND COURSE: After the diagnosis of infective endocarditis had been established, antibiotic treatment was give with imipenem, gentamycin and teicoplanin, the pacemaker system and adherent thrombotic material were removed and a DDD pacemaker implanted from the other side. The patient remained free of symptoms during a follow-up period of 12 months. INTERPRETATION: Delayed diagnosis of infective endocarditis is not uncommon, because of the scarcity of typical symptoms. Repeated blood cultures and TOE are essential for the diagnosis.

Anti-Bacterial Agents↗
PubMed1998

Components for the X-ray radiometry beamline at BESSY II.

Optical components for the X-ray radiometry beamline of the Physikalisch-Technische Bundesanstalt at BESSY II were investigated at BESSY I. Reflectometry measurements on different mirror coatings were used to calculate their capability to suppress higher-order radiation. An MgF(2) coating proved to be best suited for photon energies below 4 keV. The reflectance of silicon (111) monochromator crystals at low photon energies around 2 keV was homogeneous within +/-1%. In a test at a superconducting wavelength shifter the cooling system for the first crystal was shown to cope with the absorbed power of 14 W.

Journal Article↗
PubMed1998

Issues in Bayesian Analysis of Neural Network Models

Stemming from work by Buntine and Weigend (1991) and MacKay (1992), there is a growing interest in Bayesian analysis of neural network models. Although conceptually simple, this problem is computationally involved. We suggest a very efficient Markov chain Monte Carlo scheme for inference and prediction with fixed&hyphenarchitecture feedforward neural networks. The scheme is then extended to the variable architecture case, providing a data&hyphendriven procedure to identify sensible architectures.

Journal Article↗
PubMed1998

Differential immunosuppressive activity of monoclonal CD2 antibodies on allograft rejection versus specific antibody production.

CD2 is a co-stimulatory receptor involved in T cell activation. Here we report on immunosuppressive effects of three mouse CD2 monoclonal antibodies (OX34, OX54, OX55) directed against non-overlapping epitopes of the rat CD2 receptor on various modes of T cell activation in vitro and in vivo. Although non-ligand-blocking OX54 and OX55, in concert, activated T cells through CD2 in vitro, they individually suppressed the mixed lymphocyte reaction (MLR) and significantly prolonged allograft survival after rat heart transplantation in vivo. Phenotype analysis revealed that OX55 significantly down-modulated CD2 in vivo, whereas OX54 depleted T cells. Graft rejection coincided with re-expression of CD2 and clearance of OX55 from serum, whereas T cell depletion by OX54 outlasted the period of graft survival. The most suppressive antibody, OX34, down-modulated CD2 and inhibited T cell activation through the TCR or CD2 and the MLR and prolonged median allograft survival time from 7 days in controls to 45 days in the absence of any additional treatment. Graft survival was clearly dose dependent and correlated with the duration of CD2 down-modulation and the presence of circulating CD2 antibody in serum. Importantly, the specific antibody production to a T cell-dependent antigen as demonstrated by immunization with keyhole limpet hemocyanin in vivo remained unaffected after treatment with OX34. These results demonstrate the pivotal role of CD2 signaling in mediating allogeneic immune reactions after vascularized organ transplantation while allowing specific humoral immune responses in vivo.

Animals↗
PubMed1998

Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.

The prognosis of pancreatic adenocarcinoma is poor and current treatment is for the most part ineffective. We describe here a novel treatment strategy using a mouse model system for pancreatic cancer. Human embryonic epithelial cells have been genetically modified to express the cytochrome P450 2B1 enzyme under the control of a CMV immediate-early promoter. This CYP2B1 gene converts oxazaphosphorines (ifosfamide or cyclophosphamide) to their active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. A number of assays were performed to demonstrate the CYP2B1 gene function as well as toxic effects on neighbouring cells (bystander effect). The cells were then encapsulated in a cellulose sulphate formulation shown to be well tolerated in the pancreas of immunocompetent mice, and injected 1 cm away from pre-established tumours derived from a human pancreatic tumour cell line (PaCa-44). Intraperitoneal administration of low-dose ifosfamide to tumour bearing mice that received the encapsulated cells results in partial or even complete tumour ablation. Such an in situ chemotherapy strategy utilizing genetically modified cells in an immunoprotected environment may prove useful for solid tumour therapy in man.

Adenocarcinoma↗
PubMed1998

A second gene for type I signal peptidase in Bradyrhizobium japonicum, sipF, is located near genes involved in RNA processing and cell division.

The TnphoA-induced Bradyrhizobium japonicum mutant 184 shows slow growth and aberrant colonization of soybean nodules. Using a DNA fragment adjacent to the transposon insertion site as a probe, a 3.4-kb BglII fragment of B. japonicum 110spc4 DNA was identified and cloned. Sequence analysis indicated that two truncated ORFs and three complete ORFs were encoded on this fragment. A database search revealed homologies to several other prokaryotic proteins: PdxJ (an enzyme involved in vitamin B6 biosynthesis), AcpS (acyl carrier protein synthase), Lep or Sip (prokaryotic type I signal peptidase), RNase III (an endoribonuclease which processes double-stranded rRNA precursors and mRNA) and Era (a GTP-binding protein required for cell division). The mutation in strain 184 was found to lie within the signal peptidase gene, which was designated sipF. Therefore, sipF is located in a region that encodes gene products involved in posttranscriptional and posttranslational processing processes. By complementation of the lep(ts) E. coli mutant strain IT41 it was demonstrated that sipF indeed encodes a functional signal peptidase, and genetic complementation of B. japonicum mutant 184 by a 2.8-kb SalI fragment indicated that sipF is expressed from a promoter located directly upstream of sipF. Using a non-polar kanamycin resistance cassette, a specific sipF mutant was constructed which exhibited defects in symbiosis similar to those of the original mutant 184.

Amino Acid Sequence↗
PubMed1998

On the reintroduction of the Mhorr gazelle in Tunisia and Morocco.

The Mhorr gazelle (Gazella dama mhorr) became extinct in the wild in the 1960s. The current world zoo population amounts to some 240 animals, going back to only 12 founders. In a cooperate international operation Mhorr gazelles of European zoo populations were successfully reintroduced to national parks and nature reserves in Morocco and Tunisia in the years 1990/1992. The genetical and ecological prerequisites as well as the breeding aspects are discussed.

Animals↗
PubMed1998

Biophysical characterization of the interaction of bovine seminal plasma protein PDC-109 with phospholipid vesicles.

PDC-109 is the major protein of bovine seminal plasma. It binds to the bovine sperm surface at ejaculation and modulates sperm capacitation. PDC-109 displays phosphorylcholine- and heparin-binding activities which are thought to account for its sperm surface coating and glycosaminoglycan-induced sperm capacitating activities, respectively. We have characterized the interaction of isolated PDC-109 with membranes of phospholipid vesicles using a biophysical approach. Our results show that PDC-109 interacts not only with the solvent-exposed phosphorylcholine head group but also with the hydrophobic core of liposomes. Binding of PDC-109 to membranes is a very rapid, biphasic process with half times of less than one second. Maximal binding of PDC-109 to small unilamellar vesicles was achieved with a stoichiometric ratio of 10-11 phosphatidylcholine molecules/PDC-109 molecule. Incorporation of phosphatidylethanolamine or phosphatidylserine into phosphatidylcholine vesicles reduced the binding of PDC-109, suggesting that both the density of phosphorylcholine groups and the surface charge determine the interaction of the seminal plasma protein with the surface of the membrane. Electron spin resonance measurements showed that binding of PDC-109 to phosphatidylcholine vesicles caused a rigidification of the membrane. The relevance of the data for describing the role of PDC-109 in the modulation of sperm capacitation is discussed.

Animals↗
PubMed1998

Gastric carcinoma risk index in patients infected with Helicobacter pylori.

Epidemiological data show an association between Helicobacter pylori gastritis and gastric carcinoma. However, most people infected with H. pylori do not develop gastric cancer. We have therefore evaluated histological criteria indicating an increased risk for gastric cancer. H. pylori gastritis was investigated in 117 patients with small (O<2 cm) early gastric carcinomas and in 117 age-matched duodenal ulcer patients infected with H. pylori, who are known to have a low risk for developing gastric carcinoma. The results showed that infiltration with lymphocytes/plasma cells and infiltration with neutrophils predominating in the corpus, and intestinal metaplasia in antrum and corpus were associated with both types of gastric carcinoma (intestinal and diffuse, P<0.0001). If an index is computed by giving one point to each of these features, the predictive value for the presence of gastric carcinoma was 0.79 with a score of 2, and 0.94 with a score of 3 (all points on the index used). Application of this index might be a simple method of identifying patients infected with H. pylori and carrying a higher risk for gastric carcinoma.

Adult↗
PubMed1998

Exopolysaccharide (EPS) synthesis in Bradyrhizobium japonicum: sequence, operon structure and mutational analysis of an exo gene cluster.

The nucleotide sequence of a 8330-bp DNA fragment from Bradyrhizobium japonicum 110spc4 was determined. Sequence analysis revealed that six ORFs were present and the deduced amino acid sequences were homologous to enzymes involved in exopolysaccharide (EPS) biosynthesis. The genes appear to be organized into at least four different operons. One gene was found to be homologous to exoB, which encodes a UDP-galactose 4'-epimerase. Other ORFs were homologous to UDP-hexose transferases and one ORF showed similarity to Sinorhizobium (Rhizobium) meliloti ExoP, which has been suggested to be involved in EPS chain-length determination. A set of deletion and insertion mutants was constructed and the resulting B. japonicum strains were tested for their symbiotic traits. Deletion mutant deltaP22, which lacks the C-terminal part of ExoP, the UDP-hexose transferase ExoT and the N-terminal part of ExoB, shows a delayed nodulation phenotype and induces symptoms of plant defense reactions; its EPS does not contain galactose and no high molecular weight fraction is synthesized. In contrast, insertion mutant EH3, which expresses an exoP gene product that is truncated in its putative periplasmic domain, produced an EPS containing both HMW and LMW fractions. However, the interaction of EH3 with soybeans was severely perturbed. As a rule, only the initial steps of nodule formation were observed.

Bacterial Proteins↗
PubMed1998

Differential effect of cyclooxygenase metabolites on proinflammatory cytokine release by Kupffer cells after liver ischemia and reperfusion.

BACKGROUND: Liver ischemia and reperfusion (I/R) induce Kupffer cell (KC) activation with increased release of proinflammatory cytokines. Prostaglandins are potent counterregulatory mediators to control the production of cytokines by macrophages. METHODS: To study the role of cyclooxygenase metabolites for the release of proinflammatory cytokines by KC in liver I/R, Sprague-Dawley rats were subjected to 20-minute global hepatic ischemia and 60 minutes of reperfusion. Sham-operated animals were used as controls. Kinetics of spontaneous and lipopolysaccharide (LPS)-induced release of proinflammatory cytokines and prostaglandin E2 (PGE2) by KC were assessed both in the presence and absence of the cyclooxygenase inhibitor ibuprofen. RESULTS: Early after liver I/R (4, 16 hours) the spontaneous secretion of TNF-alpha (+1,058%), IL-1alpha (+152%), and IL-6 (+161%) by KC was increased (P <0.05), while PGE2 release in the I/R group was reduced by 51% (P <0.05) in comparison with the sham-operated group. Increased release of PGE2 in the later period (32 hours) after I/R was associated with decreased TNF-alpha release by KC. Inhibition of PGE2 production by ibuprofen induced a prolonged and enhanced production of TNF-alpha, while the release of IL-1alpha and IL-6 was not affected. CONCLUSIONS: Liver I/R leads to a temporary suppression of PGE2 release by KC, while the release of TNF-alpha is increased. Thus, during early reperfusion, excessive secretion of TNF-alpha by KC may be the result of the absent negative feedback control of cyclooxygenase metabolites.

Animals↗