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Biomedical subjects

W A Müller

Publications and source records attributed to W A Müller.

At least 19 recordsLinked to original sources
PubMed2001

Influence of anti-Helicobacter triple-therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora.

BACKGROUND: Proton pump inhibitor-based therapy including two antibiotics is the treatment of choice for Helicobacter pylori infection. Oral antibiotic treatment can lead to intestinal overgrowth of potentially pathogenic bacteria. AIM: To investigate the intestinal microflora before and at different times after H. pylori treatment with omeprazole, clarithromycin and metronidazole. METHODS: Bacterial growth in faecal samples from 51 patients infected with H. pylori was determined qualitatively and quantitatively. During the same period of time, stool samples from 27 H. pylori-negative controls were taken and investigated at the same intervals. RESULTS: The microflora of H. pylori-infected patients was different from that in H. pylori negative controls. It was characterized by a high concentration of lactobacilli, mainly Lactobacillus acidophilus. Immediately after therapy there was an increased colonization with yeasts, while the growth of lactobacilli and other species was inhibited. Clostridium difficile was cultured from three cases, but without clinical manifestations of pseudomembranous colitis. After 4 weeks of therapy, the microflora returned to normal and was not different from that of the H. pylori-negative control group. CONCLUSIONS: In H. pylori-positive patients the intestinal flora is characterized by an increase in growth of acid-tolerant L. acidophilus. Eradication therapy exerts only a short-term influence on intestinal flora, whereas in the long term, the intestinal microflora is restored to a pattern similar to that of the control group.

Anti-Bacterial Agents↗
PubMed1999

Differentiation: A central topic in developmental and cell biology.

The concept of "differentiation" encompasses all processes leading to differently specialized cell types, beginning with the progressive divergence of developmental pathways and ending with the successive programming and final elaboration of each particular cell type. Guidance and positional information are provided by external cues, by differentially allotted cytoplasmic determinants such as mRNA for transcription factors, and by cascades of intercellular signals. Eventually cell type specific selector genes, such as the muscle cell determining MyoD/myogenin genes and neural key genes (e. g., achaete scute-C, neurogenin), are switched on which control entire sets of subordinate effector genes. In multiplying cells "cell heredity" based on an epigenetic cellular memory enables transmission of the cell type determining program from parental to daughter cells. This memory can be based on autocatalytic self-activation of cell type specific selector genes and on the enduring action of gene groups such as the Polycomb and thrithorax complexes that code for proteins which bind to DNA sequences called cellular memory modules. These modules confer permanent accessibility (potentiation) or inaccessibility (silencing) upon many different gene loci on the chromosomes.

Animals↗
PubMed1999

Effect of oral ZnDTPA on late effects of injected plutonium in rat.

PURPOSE: To reduce the long-term toxicity of 239Pu in rats by lifetime drinking of ZnDTPA solution and to investigate possible side-effects of the drug. MATERIALS AND METHODS: Male Sprague-Dawley rats received a single injection of 239Pu citrate, alone or plus oral ZnDTPA. Additional groups were administered only ZnDTPA. Late tissue changes were evaluated by post-mortem examination, X-rays and histologically. RESULTS: The incidence of rat bearing osteosarcoma decreased after treatment to 35% as compared with 53% in untreated controls. The proportional incidence of osteosarcomas was reduced after ZnDTPA by more than the corresponding removal of 239Pu. Unexpectedly in the male rat, mammary tumours, mostly malignant, developed in 20% of rats that received 239Pu as compared with 0.5% in the untreated controls. After a lifetime drinking solely 3 x 10(-3) M ZnDTPA the incidence of diffuse glomerulosclerosis reached 29% as compared with 10% in controls. CONCLUSIONS: In rat, protracted oral administration of ZnDTPA reduced the incidence of osteosarcomas after injection of 239Pu, even if treatment started with a delay of 1 month. In the latter case, however, more soft tissue damage was found than after treatment beginning at 4 days post-239Pu. An increased incidence of diffuse glomerulosclerosis was observed as a side effect of oral ZnDTPA only when given continuously, alone and in high amounts.

Administration, Oral↗
PubMed1998

Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a region of Germany.

To evaluate the prevalence of resistance among Helicobacter pylori in Germany, the minimum inhibitory concentrations of amoxicillin, tetracycline, clarithromycin, and metronidazole were determined by means of the E test, for 271 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1996 and 1997. The prevalence of metronidazole resistance was 32.1%, with resistance found more frequently in women (38.5%) than in men (24.4%). Clarithromycin resistance was rare (3.3%). Eight of nine strains resistant to clarithromycin were also resistant to metronidazole. Resistance to either metronidazole or clarithromycin was significantly (P=0.022) higher in patients with duodenal ulcer. No strain was found to be resistant to amoxicillin or tetracycline.

Adult↗
PubMed1998

Serodiagnosis of acute toxoplasmosis using a recombinant form of the dense granule antigen GRA6 in an enzyme-linked immunosorbent assay.

We developed an indirect enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of acute toxoplasmosis that used the recombinant granule antigen GRA6-GST as diagnostic antigen for the detection of IgG antibodies to Toxoplasma gondii in human sera. A total of 431 sera obtained from 336 patients with acute and chronic toxoplasmosis and from patients who were not infected with T. gondii were tested. Sera from patients with acute T. gondii infection, chronic infection, and no infection showed different absorbance values. For discrimination between the presence and the absence of acute toxoplasmosis the assay reached a specificity of 99.6%. Only one of the sera without significant anti-T. gondii. IgM antibodies showed a positive reaction to rGRA6-GST. The assay showed good intra- and interassay reproducibility (CV 6%/14%). We included a glutathione S-transferase (GST)-IgG enzyme immunoassay as a control assay in this study. Only 7 (4%) of 159 random sample sera reacted positively with GST.

Acute Disease↗
PubMed1998

Modeling carcinogenesis under a time-changing exposure.

A model of carcinogenesis for fractionated and continuous exposure is developed. The model is discussed from two points of view. First a "surface" statistical model is introduced by making assumptions about the hazard function for the time of tumor latency. Later it is shown that the model can be interpreted in a mechanistic sense as a discrete and a mixed discrete/continuous counterpart of a model of carcinogenesis recently proposed by Yakovlev and Polig [A. Yakovlev, E. Polig, Math. Biosci. 132 (1996) 1]. Two counteracting effects are combined: a protective multiplicative effect of the exposure on the hazard function along with an additive effect of cancer induction responsible for an additional hazard. The model is used to revisit the analysis by Yakovlev et al. [A. Yakovlev, W. Müller. L. Pavlova, E. Polig, Math. Biosci. 142 (1997) 107] of lymphoma-free survival in irradiated mice under acute and fractionated exposure.

Animals↗
PubMed1998

Hormonal factors from the mammalian pineal gland interfere with cell development in Hydra.

A partially purified, melatonin-free low-molecular-weight extract from the ovine pineal gland with antitumor activity (YC05R), interferes with terminal differentiation in the interstitial cell line of Hydra. Nematoblasts developed into defective nematocytes that were subject to cell death and the tentacles eventually became devoid of nematocytes. In an attempt to identify the causative components of the extract, several known potential constituents were assayed. Two factors were found to have similar effects, although only in rather high concentrations: 1alpha, 25 dihydroxyvitamin D3 (>150 nM) and pinoline (>5 microM), a natural tryptophan-derived beta-carboline. The proliferative activity in the interstitial cell line was only slightly reduced by these factors. Two other beta-carbolines that occur in the mammalian brain, harmine (10 microM) and n-butyl-beta-carboline-3-carboxylate (beta-CCB), caused the premature death of epithelial cells and thus the development of dwarfish animals which, however, continued to generate new animals by budding. The pineal extract probably contains some more, still unidentified components that interfere more potently with cell development, in Hydra as well as in mammals.

Animals↗
PubMed1998

Low-molecular-weight hormonal factors that affect head formation in Hydra.

Support or inhibition of DAG-induced head formation: Hydra magnipapillata can be caused to form ectopic head structures by periodictreatmentwith PKC activators such as diacylglycerol (DAG). This ectopic head formation is supported by an extract from the ovine pineal gland that contains low-molecular-weight compounds. The frequency of ectopic head formation is also increased when DAG is paired with one of several lipophilic hormonal factors: (1) pinoline, a putative pineal hormone derived from tryptophan, (2) 12-S-HETE, a paracrine derivative of arachidonic acid, or (3) 1alpha, 25 dihydroxyvitamine D3, a hormonal factor also known as calcitriol. Dose-response curves were non-monotonic passing a maximum at low dosages. By contrast, DAG lost its capacity to induce ectopic head structures when it was paired with the provitamin D3, cholecalciferol. Patterning the head: one eicosanoid was found which influences patterning without being combined with DAG: 12-R-HETE caused growth-based elongation of the tentacles and an increase in the number of tentacles without affecting the longitudinal body pattern. Similar effects are brought about by substances that interfere with tyrosine phosphorylation, most potently bythe phosphotyrosine phosphatase inhibitor bisperoxo-(1,10-phenanthroline)-oxovanadate (V). The results speak for the existence of head-inducing hormonal factors, underline the significance of content protein kinases to pattern formation and point to a negative influence of the vitamin D3 content of the food on the capacity of the animals to develop head structures.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

[Microalbuminuria in diabetes mellitus--illness or symptom?].

Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and 200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all authors. In addition, various methods may influence the results. The significance of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes nephropathy is the most important complication. In adult type 2 diabetics the prognosis concerns mainly cardiovascular death. The excess mortality to be attributed to MA is several fold in type 1 diabetes, less in the adult onset type variety. MA is the expression of an incipient general disease of blood vessels touching as much the kidney as the heart. According to the presence or absence of other vascular damage. MA develops toward nephropathy or cardiovascular complications. The features leading to or worsening MA are elevated blood pressure, poor glucose control, elevated lipoproteins, diminished insulin sensitivity and probably smoking. Retinopathy is an indicator for particularly sensitive patients responding with the development of MA upon only mildly elevated blood pressure or poor metabolic control. The prevalence of MA is close to 20% for both types of diabetes. Non-diabetic persons under 60 years of age exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with hypertension MA is reported to be present in 19%. Over a time span of 5 years, 19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours. In a third of cases albumin excretion normalises. In the remaining half a small progression of MA occurs. For type 2 patients the increased mortality risk is restricted to the first 5 years, thereafter the survival curves return to those of patients without MA. In these patients the excess mortality is already present at albumin excretion rates above 10 micrograms/min. Higher values have, therefore, to be considered pathological. For the treatment of the syndrome ACE-inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine, nifedipine) are recommended. They reduce albumin excretion by 50%. In a single study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would imply that the excess mortality could be halved in patients undergoing this treatment.

Adult↗
PubMed1996

Pattern formation in the immortal Hydra.

Well-documented experimental studies with Hydra, done 10-20 years before Mozart was born, marked the dawn of modern developmental biology. Since those days, the immortal and perpetually embryonic hydra has been a classic model system, but despite its deceptively simple appearance, hydra has not yielded its secrets readily. Recent evidence points to a pivotal role of PI-PKC-type signal transduction pathways in morphogenesis: interference with these pathways results in polyps with multiple heads or feet. While molecular techniques are revealing genes involved in pattern realization, a new model of pattern regulation, based on competition for hormonal factors by autoregulatory receptors, emphasizes epigenetic interactions.

Animals↗
PubMed1996

Signals and signal-transduction systems in the control of development in Hydra and Hydractinia.

Pattern control in Hydra has traditionally been assigned to the determining influence of morphogens and neuropeptides. However, at present, arachidonic acid and its derivative 12-S-HETE are the only identified, potential signal molecules known to promote head and bud formation. More potent factors might exist but are not yet identified. Nonetheless, it is possible to evoke the development of an almost unlimited number of supernumerary head structures and to induce ectopic foot formation by interference with the PI-PKC signal transducing system. Such an interference can also rescue the regeneration-deficient mutant reg-16. Regarding signals in the development of Hydractinia, metamorphosis is induced by an external key stimulus, i.e. a lipid derived from environmental bacteria. The reception of this stimulus involves PKC-mediated responses. Upon its reception, a neuropeptide is released as an internal, synchronising signal. Members of the novel LWamide family of peptides appear to represent this internal signal. In postmetamorphic development, a glycoprotein SIF serves as an inducer of stolon formation.

Animals↗
PubMed1996

Head formation at the basal end and mirror-image pattern duplication in Hydra vulgaris.

Head and foot in Hydra are organizing centers and considered to be sources of long-range inhibitory morphogens that prevent head and foot formation elsewhere. In a previous study the apparent long-range head inhibition was shown to coincide with long-range foot promotion exerted by the head. Here it is shown that: (1) ring-shaped pieces of the body column taken from a near-foot position form feet - frequently circular - if inserted into the midgastric region; this ectopic foot formation is strongly dependent on assistance by the head. (2) Bisection causes a transient increase in positional value at the wounded basal end of the upper body column. This transient development in the head direction in turn promotes ectopic foot formation by transplants and thus has an effect as though the source of a foot-inhibiting morphogen were removed. The existence of long-range foot inhibition is open to question. (3) If a ring with low positional value is present in the midgastric region, the increase in positional value at the basal end is stable and results in mirror-image head formation instead of foot regeneration in up to 100% of cases. Even before the ring forms a foot it acts like a ligature and subdivides the body column into two developmental compartments. (4) The basal head in turn organizes a mirror-image duplication of the body pattern. In pattern regulation, Hydra follows rules of intercalation known from other organisms.

Animals↗
PubMed1996

Competition-based head versus foot decision in chimeric hydras.

The decision head versus foot in a regenerating fragment of Hydra has been proposed to result from long-range competition for resources such as head-specific precursor cells and hormonal factors, with the winning end of the body column forming the head and the losing end forming the foot. The present study presents new experimental support for this hypothesis. Chimeras prepared from two strains of Hydra magnipapillata with high and low capacity for head regeneration reveal that the low capacity of reg-16 to regenerate a head resides in a low ability to recruit head-promoting resources. When confronted with competing wt105 tissue taken from the same body region, reg-16 tissue is caused to form feet while wt105 is enabled to from enlarged heads which sometimes split into two. Triplet chimeras prepared with labeled donor animals and two competing unlabeled recipients indicate that head-forming wt105 tissue incorporates migrating cells more effectively then head-forming reg-16 tissue.

Animals↗
PubMed1995

Competition for factors and cellular resources as a principle of pattern formation in Hydra. I. Increase of the potentials for head and bud formation and rescue of the regeneration-deficient mutant reg-16 by treatment with diacylglycerol and arachidonic acid.

The mutant strain reg-16 of Hydra magnipapillata has less capacity to regenerate a head than the wild-type strain 105 when examined in a standard test. The present comparative study with various strains of Hydra shows: (1) The head-forming potential of reg-16 and also of a widely used strain of Hydra vulgaris is severely impaired by the presence of a just-emerging or latent bud. (2) Periodic treatment with dioctanoylglycerol (DAG), a known activator of protein kinase C (PKC), plus arachidonic acid (AA), the mother compound of the eicosanoid signal substances, enabled reg-16 and H. vulgaris to insert additional tentacles into their original whorl while the export of cells by budding was reduced. (3) On the other hand, during the period of daily treatment with DAG+AA, potentials for head and bud formation were stored. Gastric segments excised from pretreated animals formed more tentacles than untreated wild-type 105 and even formed supernumerary head structures; in addition, segments excised from all body regions quickly resumed budding in spite of starvation and while they regenerated a head. (4) With continued treatment supernumerary tentacles were elicited in all strains although with high frequency only in Hydra magnipapillata, wt105. However, while wt105 formed supernumerary head structures preferentially at ectopic sites, reg-16, H. vulgaris, and Hydra oligactis instead increased the number of tentacles in the apical head, which occasionally split into two heads. (5) The treatment with DAG+AA caused the budding zone to shift closer to the foot end. (6) In H. vulgaris a pulse treatment with a high dose of DAG frequently caused a mirror image duplication of the budding zone; in wt105 mere excessive feeding over 2-3 weeks may have the same effect. The hypothesis is proposed that a regenerating head and a beginning bud compete for hormone-like factors, which enable the cells to increase positional value, and for precursor cells. Periodic treatment with activators of PKC plus AA leads to an augmentation of these resources, and head structures and buds can be produced simultaneously. Traditional terms are reinterpreted correspondingly: the high level of "head inhibition" in reg-16 is interpreted as a low level of resources, in particular, of head-promoting factors, and the low head activation level as a low ability to make use of resources.

Animals↗
PubMed1995

Competition for factors and cellular resources as a principle of pattern formation in Hydra. II. Assistance of foot formation by heads and buds and a new model of pattern control.

In Hydra long-range interactions between head, bud, and foot formation take place in addition to short-range interactions which are recognized as induction phenomena, occurring when transplants are placed into an environment of disparate positional value. Here the long-range promotion of foot formation is analyzed. The data show: (1) While head regeneration and the onset of budding are mutually inhibitory, in particular in Hydra vulgaris and strain reg-16 of Hydra magnipapillata, fully developed heads and advanced buds cooperatively support foot formation in both the bud and the parent. Utilizing these interdependences H. vulgaris can be caused to form ectopic feet and to regenerate feet at both ends of excised segments. (2) The foot-promoting activity returns late in head regeneration, as late as the apparent long-range "head inhibition" determined in transplantation studies. (3) While periodic treatment with diacylglycerol (DAG) increases the capacities to form heads and buds, the potency to form feet is transiently reduced. (4) When treatment with DAG is finished the elevated capacities to form heads and buds subside, in reg-16 and H. vulgaris there followed a phase of ectopic foot formation. (5) The foot does not promote head regeneration. Based on the results of this and previous studies the following hypotheses are proposed: (1) Heads and buds compete for resources, such as precursor cells and soluble head-promoting factors that are distributed in the interstitial spaces. (2) The ability to make use of these resources is associated with positional value and decreases down the body column. The decreasing capability is attributed to a decreasing complement of receptors for the head-promoting factors. (3) Feet are made by body regions which are the losers in the competition for these factors. (4) Superiority in the ability to compete for the locally available factors enables transplants to develop head structures, and inferiority causes them to form a foot. (5) Depletion of the head-promoting factors in the whole body column is a significant component of the "head inhibition potential" and mediates the assistance of heads and buds in foot formation. (6) A surplus of resources causes supernumerary head structures and delays or prevents foot regeneration. These interpretations have reference to a new receptor-based model of pattern control and are contrasted with prevailing hypotheses.

Animals↗
PubMed1994

[Malignant melanoma in life insurance--thickness or anatomic layer?].

The incidence of malignant melanoma has tripled during the last 40 years and continues to increase. Among clinical criteria the single and most significant prognostic factor is the extent of tumor invasion expressed by thickness rather than anatomical structure. Patients with melanoma thinner than 0.76 mm have a five year survival of 96%. Thicker tumors bear a poor prognosis. Patients having survived 10 years have a life expectancy close to the normal population.

Cause of Death↗