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Biomedical subjects

O Müller

Publications and source records attributed to O Müller.

At least 19 recordsLinked to original sources
PubMed1997

Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP.

The Min (multiple intestinal neoplasia) mouse with a germline mutation in the adenomatous polyposis coli gene serves as an animal model for familial adenomatous polyposis coli (FAP). The number and age at onset of colorectal adenomas varies in the offspring of Min mice crossed with other strains. The murine gene for the secretory phospholipase A2 (PLA2G2A) was found to be the main candidate for these variations. To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations. None of the individuals with FAP showed PLA2G2A germline alterations. However, a germline mutation was observed in one patient with an apparently sporadic colorectal tumor; the wildtype allele was somatically lost in the tumor of this patient.

Adenomatous Polyposis Coli↗
PubMed1997

The Gambian National Impregnated Bednet Programme: evaluation of the 1994 cost recovery trial.

Following the success of a controlled trial of insecticide-impregnated bednets in reducing mortality in children. The Gambia started a National Impregnated Bednet Programme (NIBP) in 1992. The objectives of this programme were to introduce impregnated bednets into all primary health care (PHC) villages and to establish a system of cost recovery over a three-year period. During the initial phase of the programme, when insecticide was given out free, a high uptake was achieved. However, after small user charges were introduced in 1993, coverage dropped to a low level. In 1994, different systems of insecticide distribution and permethrin formulations were tried in an attempt to improve coverage. A nationwide cross-sectional survey carried out during the 1994 rainy season measured coverage by distribution channel, as well as the knowledge, attitudes and practices of health workers and villagers during the intervention. Overall, only 16% of bednets were impregnated in 1994, compared to 80% when the insecticide was offered free of charge in previous years. Lack of money was the major reason given by villagers for not impregnating their bednets in 1994. Use of impregnated bednets was higher in areas where the sale of permethrin emulsion by village health workers was supplemented by the sale of insecticide in individual packages through shops. In villages where insecticide was distributed free to women with small children through governmental mother and child health (MCH) services, higher levels of coverage were achieved among women and young children than in villages where other distribution systems were used. We conclude that the sale of insecticide through the private sector may increase bednet impregnation rates in African communities, and that the free distribution of insecticide through MCH services may be an effective way of targeting young children, the group most at risk of malaria.

Adolescent↗
PubMed1996

DNA alterations in sporadic colorectal tumors do not correlate with tumor staging diagnosed by the TNM system.

Blood normal and tumor tissue samples of 23 patients with sporadic colorectal tumors were screened for DNA alterations in the tumor relevant genes APC, K-ras, DCC and p53. Six different microsatellite regions were analyzed for instability by a new developed non-radioactive method. Somatic DNA alterations were found in 17 tumor samples: 13 carried single or multiple changes in single genes; six carried alterations in microsatellites; two tumors showed tumor suppressor gene mutations in addition to microsatellite changes. We found no indications of correlations between current genetic models of colorectal tumor progression and the established TNM system for histopathological tumor classification.

Aged↗
PubMed1996

DNA sequence analysis of Prinker-modified restriction fragments after collection from capillary electrophoresis with replaceable matrices.

This paper demonstrates the procedure of sequencing DNA restriction fragments isolated by a recently developed fraction collector after CE separation. In particular, using pBr 322 plasmid as a model system, a double digest was performed with Eco RI and Pst 1 restriction enzymes to produce two fragments of 749 base pairs (bp) and 3612 bp, both with cohesive ends. Prinkers, specific linkers complementary to the cohesive ends, were then ligated to both fragments (increasing the size by 59 bp each). These Prinker-modified fragments were separated by CE and collected. The success of the collection was demonstrated by reinjection of each isolated fraction with laser-induced fluorescence detection, using ethidium bromide as intercalater. The 808 bp isolated fragment was then polymerase chain reaction-amplified with appropriate primers for the Prinker ends, followed by cycle sequencing. Both strands of the fragment were run on an ABI 373, sequencing 427 bases and 450 bases, respectively, with a read accuracy of 99.3%. This approach with Prinker-modified restriction fragment and automated CE fraction collection can be used as a general procedure for sequencing unknown genomic DNA as well as mutated DNA mixtures.

Automation↗
PubMed1996

Cultivation of Saccharomyces cerevisiae in a bioreactor in microgravity.

Yeast cells were cultured for 8 d in a newly developed bioreactor during the Spacelab IML-2 mission. Two bioreactors, one stirred and one without stirring, were installed in the Biorack facility in space. Two control units were installed in the Biorack module at the Kennedy Space Center. Samples were drawn on mission day 3, 5, 6, 7 and 8 and preserved either by freezing or chemically fixed for post-flight analysis. The values of pH, pH regulation, temperature and redox potential were transmitted on-line to the ground station throughout the mission. The performance of the bioreactor was satisfactory except for a partial failure of the medium micropump. Despite the failure of the pump, the data support the following conclusions: There is a significant difference in the distribution of the bud scars between cells cultured at 0 x g and at 1 x g. The percentage of randomly distributed bud scars was significantly higher in the flight (17%) than in the ground control cells (5%). No remarkable differences were noted in the cell cycle, ultrastructure, cell proliferation, cell volume, ethanol production and glucose consumption.

Bioreactors↗
PubMed1996

Increased levels of 4-hydroxynonenal in human monocytes fed with malarial pigment hemozoin. A possible clue for hemozoin toxicity.

In human monocytes, lipoperoxides were increased 3-fold at 2 h, 6-fold at 5 h and 7.5-fold at 12 h after hemozoin phagocytosis. 4-Hydroxynonenal (HNE) was also increased, reaching 40 nmol/10(10) cells at 2 h (approximate intracellular concentration [AIE] 8 microM) 230 nmol/10(10) cells at 5 h (AIE 46 microM) and 79 nmol/10(10) cells (AIE 16 microM) at 12 h. A moderate increase in HNE, approx. 20 nmol/10(10) cells (AIE 4 microM) was also observed after phagocytosis of anti-D IgG-opsonized erythrocytes. HNE in unfed controls was approx. 5 nmol/10(10) cells (AIE 1 microM) during the whole incubation period. An increased amount of protein kinase C (PKC)/HNE adduct was demonstrated in hemozoin-fed monocytes. Purified PKC was profoundly inhibited at HNE > 10 microM. The impairment of PKC previously observed in hemozoin-fed monocytes can thus be explained by direct interaction with increased HNE levels.

Adult↗
PubMed1996

Secondary structure of an armadillo single repeat from the APC protein.

The armadillo domain is a repeating sequence motif of a variety of proteins with different functions. Here we describe the structure of a synthetic single armadillo repeat solved by two-dimensional nuclear magnetic resonance spectroscopy. Our results indicate alpha-helical secondary structural elements in half of the residues.

Adenomatous Polyposis Coli Protein↗
PubMed1996

A randomized trial of chloroquine, amodiaquine and pyrimethamine-sulphadoxine in Gambian children with uncomplicated malaria.

The increasing occurrence of chloroquine-resistant Plasmodium falciparum in sub-Saharan Africa makes it essential to reconsider current recommendations for the treatment of uncomplicated P.falciparum malaria. In an open, randomized trial, we have compared chloroquine (CQ), amodiaquine (AQ), and pyrimethamine-sulphadoxine (PS) in rural Gambian children with uncomplicated P.falciparum malaria. Three hundred children were randomly assigned at the time of consultation (Do) to oral treatment with 25 mg/kg CQ, 25 mg/kg AQ (both given over 3 days), or 1.25/25 mg/kg PS. They were reviewed on day 7 (D7) and day 28 (D28) for symptoms, malaria parasitaemia, and packed cell volume (PCV). Significantly more children treated with PS compared to CQ (17 vs 7%, P = 0.03) or AQ (17 vs 3%, P = 0.001) returned with clinical complaints during the first 3 days after treatment. Five of these patients had a generalized convulsion (1 from the AQ group, 4 from the PS group), of whom 4 developed cerebral malaria. At D7, significantly more patients treated with CQ compared to AQ (25 vs 7%, P = 0.0009) or PS (25 vs 4%, P = 0.0001) were parasitaemic. By D28, the cumulative number of parasitological failures was significantly higher in the CQ group compared to the AQ group (65 vs 35%, P = 0.0001), and significantly higher in the AQ group compared to the PS group (35 vs 14%, P = 0.001). Overall, 91% of parasitological failures observed during the study period were symptomatic and were consequently treated with an alternative antimalarial drug. Over the 28-day study period the mean PCV increased significantly less in the CQ group than in the PS group (1.2 vs 3.8%, P = 0.016) and was lower in the CQ group than in the AQ group (1.2 vs 2.7%, P = 0.12, not significant). These results suggest that PS acts more slowly than 4-aminoquinolines in controlling the clinical features of malaria, and that AQ can be considered as an interim alternative to CQ in the first-line therapy of uncomplicated malaria in African areas of high CQ resistance.

Amodiaquine↗
PubMed1996

An open comparative study of azithromycin and roxithromycin in the treatment of acute upper respiratory tract infections.

An open, multicentre study was undertaken in order to evaluate the efficacies and safety profiles of azithromycin and roxithromycin in 440 adults with acute otitis media, sinusitis or acute beta-haemiolytic streptococcal pharyngitis/tonsillitis. Treatment with 500 mg azithromycin, administered orally once daily for 3 days, produced a satisfactory clinical outcome (cure or improvement) in 51/52 (98%) patients with otitis media, 91/91 (100%) patients with pharyngitis/tonsillitis and 64/68 (94%) patients with sinusitis. Treatment with 150 mg roxithromycin, given orally twice daily for 10 days, produced satisfactory clinical responses in 54/55 (98%), 91/92 (99%) and 69/73 (94%) patients with otitis media, pharyngitis/tonsillitis and sinusitis respectively. Of the 17 azithromycin-treated patients with sinusitis who were clinically and bacteriologically evaluable, Staphylococcus aureus persisted in two and Streptococcus pneumoniae in one. S. aureus also persisted in 1/12 clinically and bacteriologically-evaluable patient treated with roxithromycin. Of the 58 and 64 patients with pharyngitis/tonsillitis treated with azithromycin and roxithromycin, respectively, who were clinically and bacteriologically evaluable, Streptococcus pyogenes persisted at the end of treatment in 7/58 (12%) in the azithromycin group and in 13/64 (20%) in the roxithromycin group. At follow-up, there was no evidence of S. pyogenes reinfection in patients treated with azithromycin. Three episodes of reinfection occurred in the roxithromycin treatment group. Also, three patients showed evidence of clinical relapse at follow-up, although no pathogens were isolated. Azithromycin was associated with a lower incidence of adverse events. No azithromycin-treated patient was withdrawn prematurely because of a treatment-related event. Three roxithromycin-treated patients were withdrawn from treatment because of severe headache, thyroiditis or fatigue. In conclusion, for adults with acute upper respiratory tract infections, a 3-day course of once-daily azithromycin was found to be as effective and as well tolerated as a 10-day course of twice-daily roxithromycin.

Acute Disease↗
PubMed1995

Analysis of protein fractions by micropreparative capillary isoelectric focusing and matrix-assisted laser desorption time-of-flight mass spectrometry.

In this study, the use of capillary isoelectric focusing (cIEF) as a micropreparative tool for protein analysis by matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) is demonstrated. A newly designed, automated, collection interface equipped with a fiber-optic UV detector and a sheath flow connection was employed for collection of protein fractions. Multiple fractions were collected during a single cIEF run and further analyzed by MALDI-TOF-MS for mass assignment. The feasibility of the method was tested with a mixture of model proteins with different isoelectric points and molecular masses, and with variants of human hemoglobins differing in pI, but with negligible difference in M(r). Some practical considerations of the collection procedure and subsequent TOF analysis are presented.

Autoanalysis↗
PubMed1995

Design of a high-precision fraction collector for capillary electrophoresis.

A high-precision fraction collector for capillary electrophoresis has been developed. The device utilizes detection close to the end of the capillary and a sheath liquid at the exit of the capillary, allowing continuous collection (i.e., uninterrupted applied electrical field) of multiple species. The role of the sheath liquid flow rate and position of detection in the column on the collection precision was assessed. Fiber-optic detection at approximately 1 cm before the exit end of the capillary was found effective for precise timing of the collection. Up to 60 fractions of microliter or smaller volumes could be automatically collected into capillaries used as collection vials. The collection capillaries were placed on a cylinder, and a computer-controlled stepping motor aligned the appropriate capillary with the column exit. The effectiveness of the fraction collector was demonstrated in the collection of all 11 fragments of the HaeIII restriction digest of phi X-174 plasmid DNA. Polymerase chain reaction amplification of the 271 and 281 bp fragments revealed an inversion of the size-dependent migration order.

Bacteriophage phi X 174↗
PubMed1995

Sequence dependent migration behavior of double-stranded DNA in capillary electrophoresis.

Capillary electrophoresis (CE) with a replaceable linear polyacrylamide (LPA) sieving matrix was used to examine sequence-dependent migration of double-stranded DNA fragments. It has been found that DNA conformational effects were significant under high electric field separations, especially using high resolution matrices. Compared to linear DNA-ladder standards, both anomalously slow and rapid DNA fragments were observed, with the degree of anomalous migration depending on the electric field strength, polymer concentration, column temperature, and background electrolyte (denaturants, sodium and magnesium ions, DNA-intercalating dyes). By selecting a combination of electrophoretic conditions (e.g. 3% T LPA, elevated capillary temperature, lower electric field strength and addition of DNA intercalating dyes), molecular weight dependent separations were closely restored.

Bacteriophage phi X 174↗
PubMed1995

Sexual risk behaviour reduction associated with voluntary HIV counselling and testing in HIV infected patients in Thailand.

Sexual risk behaviour, measured by anonymously self-reported sexual activity, number of sexual partners, and condom use rates, was studied in age- and gender-matched HIV-1 positive consecutive patients from the Thai Red Cross Immune Clinic (IC) (study group, questioned after voluntary HIV counselling and testing) and the Thai Red Cross Anonymous Clinic (AC) (control group, questioned before voluntary HIV counselling and testing) in Bangkok, Thailand in 1993/94. More than 80% of study patients reported having decreased their sexual activity and their number of sexual partners since receipt of the positive HIV test result. Compared to control patients, study patients reported more often abstaining from sex (42% vs 14%), and more often using condoms during all their last three incidences of sexual intercourse (44% vs 14%). These findings give evidence for the value of voluntary HIV counselling and testing in contributing to the reduction of HIV transmission in Asia.

Adolescent↗
PubMed1995

[A transgenic animal model: new possibilities for cardiovascular research].

By means of molecular biology and genetic research the influence of genetic factors on a great variety of human diseases could be shown. In the field of cardiovascular research the genetic defects of a few monogenetic disorders, such as Marfan's syndrome and hypertrophic cardiomyopathy, have been characterized. In addition, candidate genes for polygenetic diseases, such as arterial hypertension and atherosclerosis, have been cloned. However, the identification of a candidate gene or its mutation does not prove its influence on the phenotype or the final cause of a particular disease. Only a targeted manipulation of a defined candidate gene in a transgenic animal model helps to understand the role of the gene and its product in the whole organism. Transgenic experiments can be divided into gene-addition and gene-deletion models. In a gene-addition experiment a fusiongene is microinjected into a fertilized oocyte. The fusiongene itself consists at least of a regulatory element promoter and of a DNA sequence coding for the gene product (protein) of intended overproduction. The choice of the right promoter is important for obtaining tissue-specific gene expression. The cardiac myosin light chain-2 promoter for example leads to a ventricle-specific gene expression in cardiomyocytes from early embryogenesis through adulthood. In a gene-deletion experiment on the other hand, the target gene is selectively knocked out by homologous recombination in embryonic stem (ES) cells. The selected ES-cells are then injected into blastocysts. If the ES-cells are integrated into the germ line and transmitted to the progeny, a transgenic line is established. This review article describes planning and development of transgenic animals and discusses established transgenic animal model systems with regard to cardiovascular physiology. In addition, animal models which may provide a basis for future gene therapy will be introduced.

Animals↗