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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 343 records · Page 19Linked to original sources

Surveillance in hereditary nonpolyposis colorectal cancer: an international cooperative study of 165 families. The International Collaborative Group on HNPCC.

During its second meeting at Amsterdam in 1990, the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) decided to carry out a pilot study on colorectal cancer surveillance in HNPCC. The objectives of the study were to ascertain in each of the participating centers the number of HNPCC families, the recommended screening procedures, the age at diagnosis of colorectal cancer (CRC), and the occurrence of interval cancers. Nine centers in seven countries including Denmark, Finland, Italy, Japan, The Netherlands, Switzerland, and the United States participated. Data were derived from a total of 165 families. With respect to screening, half of the centers advise colonoscopy as the only procedure. The interval between the consecutive examinations varies from one to three years. In the majority of the centers, screening begins at 20 to 25 years. Lifelong screening is recommended by three centers, while the rest advise discontinuation at age 60 to 75 years. The family material included 840 patients with colorectal cancer. The mean age at diagnosis was 45 years, and about 15 percent were diagnosed at age 60 or later. A total of 682 high-risk relatives are being followed. After the follow-up of 1 to 10 years in these families, only six cases of interval cancers were encountered.

Adolescent↗

Induction and removal of interstrand crosslinks in the ribosomal RNA genes of lymphoblastoid cell lines from patients with Fanconi anemia.

The repair of interstrand crosslinks has been investigated in Fanconi anemia (FA) and normal cells as there is evidence suggesting that FA patients have a defect in DNA repair. Lymphoblasts were treated with the crosslinking agent mitomycin C (MMC) and the removal of the induced DNA lesions investigated at the level of the actively transcribed ribosomal RNA (rRNA) genes. MMC-induced crosslinks appeared to be a rather stable lesion in the rRNA genes for all cell lines studied. Variable repair efficiencies were found between the different cells lines but they could not be used to distinguish normal cells from FA cells. Therefore, we propose that the specific sensitivity of FA cells towards MMC cannot be directly correlated with a deficient repair in interstrand crosslinks and that probably the complexity of the repair process is greater than previously described.

Autoradiography↗

Familial and genetic aspects of colorectal carcinogenesis.

There is abundant clinical and pathological evidence which suggests that colorectal cancer arises in a sequential manner through a series of events that can be followed during the progression of the disease from early adenoma through to metastatic disease. The molecular events that are associated with the initiation and progression of the disease are gradually being unravelled. As the molecular characterisation of colorectal cancer continues, new mechanisms by which the disease progresses are becoming evident. In this short review, a brief description of current knowledge of colorectal cancer development is presented.

Adenomatous Polyposis Coli↗

Cytokine (interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6)-possessing cells in lymph nodes of malignant lymphoma.

Interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, and IL-6 are the most important triggers in the response of the immune system to infection and neoplasia. We examined the histochemical distribution of cytokine-possessing cells in neoplastic lymph nodes of 68 malignant lymphomas. The HLA-DR positive interdigitating reticulum cells (IRCs), histiocytes/macrophages (H/Ms) and epithelioid histiocytes with these cytokines were frequently encountered in Hodgkin's disease, B cell lymphoma of lymphoplasmacytic/cytoid, centroblastic and immunoblastic types, and T cell lymphoma of Lennert's and anaplastic large cell types. In almost all cases of B cell lymphoma of chronic lymphocytic leukemia, centrocytic, follicular centroblastic/centrocytic, Burkitt's types and T cell lymphoma of lymphoblastic, angioimmunoblastic lymphadenopathy and pleomorphic types, the cytokine-possessing cells were rarely or occasionally present. These lymphomas with less cytokines had also few or occasionally encountered IRCs, while H/Ms were frequently or occasionally present. Well-developed dendritic reticulum cells in some types of lymphoma had few cytokines. The population of cytokine-possessing cells was related with histologic type of lymphoma and the volume of IRCs. The IRCs might act as an important initiator of reactive cells against tumor cells. In addition, neoplastic T cells influenced the cytokines' possession of IRCs and H/Ms. Although lacunar, Hodgkin's and Reed-Sternberg cells in Hodgkin's disease and the neoplastic cells in peripheral T cell lymphoma showed weak positive reaction of TNF alpha in one third of the cases, lymphoma cells in the majority might have few cytokines, especially IL-1s and IL-6.

Adolescent↗

[Genetic counseling and interdisciplinary management of retinoblastoma].

The rare childhood malignancy retinoblastoma (Rb) serves as one of the most important models in modern cancer genetics, since the study of its familial and sporadic occurrence has lead to the identification of the first so-called tumor suppressor gene. The nature of the Rb-predisposition and its mode of transmission could also hold true for many other familial cancers. An important goal of medical care is prevention, either by preventing the manifestation of retinoblastoma and of secondary malignancies related to the same predisposition or of their reaching an advanced stage of exacerbation. This can only be achieved by the close collaboration of several medical specialists. The human geneticist can contribute by offering genetic counselling, including risk estimates for offsprings of affected individuals, and by the molecular estimation of the Rb-trait.

Child, Preschool↗

ECOSYS-87: a dynamic model for assessing radiological consequences of nuclear accidents.

The time-dependent radioecological simulation model ECOSYS-87 has been developed to assess the radiological consequences of short-term depositions of radionuclides. Internal exposure via inhalation and ingestion, as well as external exposure from the passing cloud and from radioactivity deposited on the ground, are included in the model. The site-specific parameter values of the model are representative of Southern German agricultural conditions; however, the model design facilitates adaption to other situations. The ingestion dose is calculated as a function of time considering 18 plant species, 11 animal food products, and 18 processed products. The ingestion and inhalation exposure is estimated for six age groups using age-dependent consumption and inhalation rates and age-dependent dose factors. Results demonstrate a pronounced influence regarding the time of year (season) of deposition on the ingestion dose and on the relative importance of the exposure pathways. Model results compare well with activities in foods measured after the Chernobyl accident.

Accidents↗

137Cs transfer after Chernobyl from fodder into chicken meat and eggs.

The distribution and the biological half-lives of 137Cs in poultry after continuous intake of foodstuffs contaminated by the Chernobyl fallout were studied in order to determine transfer coefficients to yolk, albumen, and shell of eggs as well as transfer coefficients to chicken meat. Mean values for laying hens were found to be 0.2 d kg-1 (whole consumable egg), 1.2 d kg-1 (leg meat), and 1.6 d kg-1 (breast meat) when radiocesium was fed in contaminated grass pellets, and about twice as large [i.e., 0.4 d kg-1 (whole consumable egg), 2.8 d kg-1 (leg meat), and 3.0 d kg-1 (breast meat)] when radiocesium was fed in contaminated wheat. Reducing effects of the feed additive ammonium-ferric-cyano-ferrate in concentrations of 0.66 g kg-1 of feed mixture on the contamination of hen products were quantified to be a factor of 3 to 4 (whole consumable egg and meat after grass pellet feeding) and 8 to 14 (whole consumable egg and meat after wheat feeding). A drastically higher reduction with an ammonium-ferric-cyano-ferrate dose twice as large (1.33 g kg-1) was achieved. For broiler chickens, activity concentration ratios of meat to feed were derived for various fattening periods, with mean values of about 0.3 (leg), 0.4 (breast), and 0.2 (liver). The addition of ammonium-ferric-cyano-ferrate reduced the activity concentrations in meat by factors of more than 6.

Accidents↗

Molecular and biological characteristics of avian polyomaviruses: isolates from different species of birds indicate that avian polyomaviruses form a distinct subgenus within the polyomavirus genus.

The isolation and characterization of two avian polyomaviruses, from chicken (BFDV-2) and a parrot (BFDV-3), is reported. Both isolates are closely related to the non-mammalian polyomavirus budgerigar fledgling disease virus (BFDV) isolated from budgerigars (now called BFDV-1), and all three viral genomes are shown to have the same basic size of 4981 bp. A 151 bp insertion was, however, observed in the non-coding region of BFDV-2 which represented an exact duplication of the left half of the non-coding region, including the putative early promoter and amino terminus of the large T antigen. With a further 15 base pairs exchanged elsewhere throughout the three genomes, these viruses have distinct degrees of tropism for various avian species. The production of antibodies directed against a beta-galactosidase-large T antigen fusion protein of BFDV-1 is described. These antibodies detected the large T antigen, with an M(r) of approximately 80K, and the small t antigen, with an M(r) of approximately 24K, in cells infected with BFDV isolates. Whereas these antibodies bind with low affinity to the large T antigen of simian virus 40 (SV40), SV40- or mouse polyomavirus-specific antibodies will not bind to the BFDV large T antigen. Antibodies directed against BFDV structural polypeptides exhibit broad, reciprocal cross-reactivities with all three structural proteins of mammalian polyomaviruses. The significance of polyomavirus infections in various avian species is discussed. Based on unique structural and biological properties we propose that these viruses should be placed in a distinct subgenus (Avipolyomavirus) within the polyomaviruses.

Animals↗

The genetic basis for the antigenicity of the VP2 protein of the infectious bursal disease virus.

The genomic region coding for the antigenic structure responsible for the induction of neutralizing antibodies was localized in the central variable region of the VP2 gene by comparing the nucleotide sequence of five escape mutants derived from the standard infectious bursal disease virus strain Cu-1. Exchange of a single amino acid at one of the prominent hydrophilic parts of this region proved to be sufficient for altering the neutralizing properties. The reactivity of neutralizing antibodies with peptides expressed in vitro encompassing both hydrophilic areas suggests that the entire variable region is engaged in the formation of this conformation-dependent antigenic site. VP2-specific, non-neutralizing monoclonal antibodies directed against the sequence-dependent epitope of the serotype I strain Cu-1 and the serotype II strain 23/82 cross-reacted with peptides located towards the carboxy terminus of VP2; no reaction occurred with peptides derived from the amino-terminal side adjacent to the variable region.

Amino Acid Sequence↗

Different effects of two methods of low-density lipoprotein apheresis on the coagulation and fibrinolytic systems.

OBJECTIVE: Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown. DESIGN: The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy. SUBJECTS: All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks. INTERVENTION: Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation. MEASURES: Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy. RESULTS: DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients. CONCLUSION: DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.

Adsorption↗

A new oxygen applicator for simultaneous mouth and nose breathing.

We have developed a new O2 applicator to try to overcome the problems of long-term oxygen therapy that ensures a sufficient oxygen supply for both nasal and oral breathing and prevents mucosal irritation. Placed on the upper lip, it is unobtrusive. The principle is as follows: due to an enlarged outlet area, turbulence occurs and the oxygen is reduced. Thus, an oxygen cloud is formed that can be inhaled by both mouth or nose. The efficiency of our O2 applicator was compared with a face mask in six healthy subjects and patients with COPD. A similar increase in PO2 was found up to an oxygen flow of 2 L/min for nasal and oral breathing. Mild hypercapnia resulted in three patients with COPD only when a face mask was used and only when patients breathed through the nose. All patients preferred the new applicator.

Adult↗

[Morphometric, cytochemical and immunohistochemical studies on the proliferative activity of urinary bladder carcinomas].

58 carcinomas of the urinary bladder as well as 11 carcinomata in situ and 10 biopsies of normal mucosa were investigated for their proliferative activity by means of nuclear area morphometry, silver staining of nucleolar organizing regions (NOR) and immunohistochemical staining of the proliferating cell nuclear antigen (PCNA) and the Ki67 antigen. In comparison to normal bladder mucosa, the values were increased significantly (p < 0.05) in all carcinomata in situ and carcinomas. Within the carcinomas, there was an increase from G1- to G3-carcinomas. For all four parameters, the values of the carcinomata in situ and the G2-carcinomas were similar. All parameters correlated with each other and allowed a significant differentiation between G1- and G2-carcinomas (p < 0.05), whereas they allowed only a less optimal differentiation between G2- and G3-carcinomas. Of all markers of proliferation, the Ki67 antigen was the most useful criterium to differentiate between invasive and noninvasive carcinomas. A Ki67 index of 30% seems to be a borderline between these two groups. This could be of prognostic relevance especially for the heterogeneous G2-carcinomas.

Aged↗

[Effect of preparation and preservation modality on thrombocyte quality].

In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.

Acute Disease↗

[The transmission of maternal Newcastle disease antibodies in pheasants].

After vaccination of breeding pheasants against Newcastle disease the transmission of antibodies to chicken was investigated by serological methods (hemagglutination inhibition test). The vaccination was carried out about 4 weeks before the start of the laying season. High levels of antibodies were found in egg yolk and blood serum of three days old pheasant chicks. The antibody level dropped at the end of laying season about 10 1/2 weeks after vaccination slightly. Antibodies were found in all of the investigated eggs.

Animals↗

[A comparison of the two anticholinergic agents atropine and glycopyrrolate during antagonism of a muscle relaxation with pyridostigmine].

Central, peripheral and cardiac side-effects of both anticholinergic drugs atropine and glycopyrrolate were compared during the antagonism of muscle relaxation with pyridostigmine. In a randomized, double-blind fashion 50 patients were given 10 micrograms/kg of atropine and 50 were given 5 micrograms/kg of glycopyrrolate with 125 micrograms/kg pyridostigmine intravenously. Continuous Holter ECG-monitoring over 3 hours was performed. The procedure was divided into the following phases: control (5 minutes before application of antagonists), phase I (application of antagonists and the following 5 minutes), phase II (subsequent 30 minutes), phase III (until 3 hours had passed). The first 32 minutes were subdivided into periods of 4 minutes. Analysed were: 1st: The number of patients with supraventricular, junctional and ventricular beats, 2nd: The mean heart rate per period, 3rd: The incidence of central-anticholinergic syndromes and the peripheral antimuscarinic side-effects. Supraventricular beats were found after atropine in 42 patients and after glycopyrrolate in 18 patients (p < 0.001). The differences mainly occurred during phase I (atropine 15 vs. glycopyrrolate 4 p < 0.05) and III (atropine 38 vs. glycopyrrolate 18, p < 0.01). Junctional beats were found after both drugs (atropine 7 vs. glycopyrrolate 10), above all during phase III. Ventricular beats were observed after atropine (21) and glycopyrrolate (18). Atropine as well as glycopyrrolate caused an increased heart rate within the first 4 minutes (atropine 47% vs. glycopyrrolate 27%, p < 0.01). During phase III after atropine, the heart rate decreased below the control value (p < 0.05). None of the patients showed central anticholinergic syndromes after either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The cycle of SEC4 function in vesicular transport.

Sec4 is a Ras-like GTP-binding protein required for exocytosis in yeast. Unlike Ras, it is the ability of Sec4 to cycle between the GTP- and GDP-bound forms rather than the absolute levels of the GTP-bound form that is critical for function. This cycle may be coupled to an observed cycle of Sec4 localization within the cell. Sec4 binds to secretory vesicles which then fuse with the plasma membrane in exocytosis. Sec4 can recycle from the plasma membrane through a soluble pool to rebind to a new round of vesicles. We have found an activity in yeast (Saccharomyces cerevisiae) comparable to that of the GDP dissociation inhibitor protein isolated from mammalian cells that releases GDP-bound Sec4 from membranes. DSS4-1, a dominant suppressor of the sec4-8 temperature-sensitive mutation, encodes a nucleotide exchange protein. The cycle of Sec4 may function to allow the assembly and subsequent disassembly of a set of proteins necessary for exocytosis. Candidates for members of this set of proteins are encoded by sec genes which show strong genetic interactions with sec4-8. Two of these (SEC8 and SEC15) encode large proteins which form a complex that is peripherally associated with the plasma membrane.

Biological Transport↗

Semiquantitative determination of IL-1 alpha, TNF-alpha, PDGF-A, PDGF-B, and PDGF-receptor in term human placenta using polymerase chain reaction (PCR).

Eight placenta samples derived from normal term human placenta were examined for the expression levels of Il-1 alpha+, TNF-alpha+, PDGF-A+, PDGF-B+, and PDGF-receptor+ using a semiquantitative PCR protocol. The expressional level of beta-actin was proven to be constant, therefore beta-actin could serve to equilibrate sample size in our procedure. Differences were found in the mRNA levels of IL-1 alpha and TNF-alpha. The expression of PDGF-A, BDGF-B and PDGF-R seemed to be relatively constant in our group of samples. Further investigation and improved quantitative PCR protocols are needed to correlate clinical outcome of pregnancy with cytokine expression at the placental level. +Il-1 alpha (interleukin-1 alpha) +TNF-alpha (tumor necrosis factor-alpha) +PDGF-A (platelet derived growth factor A) +PDGF-B (platelet derived growth factor B) +PDGF-Rezeptor (platelet derived growth factor-rezeptor).

Actins↗