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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 415 records · Page 23Linked to original sources

Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase.

The effects of Clostridium botulinum C3 ADP-ribosyltransferase and of Clostridium botulinum C2 toxin were studied on the cytoskeleton of rat hepatoma FAO and human glioma U333 cells. After treatment of these cells for 24 to 48 h with C3 (3-30 micrograms/ml), the actin microfilaments disappeared, and the intermediate filament network was found to collapse, while microtubules remained intact. Similar alterations of the cytoskeletal filaments without affecting microtubules were induced by the actin-ADP-ribosylating C2 toxin. In FAO cells, C3 caused the rounding up of cells. Concomitantly, cytosolic 22 to 24 kDa proteins were ADP-ribosylated in a guanine nucleotide-dependent manner. Rounding up of cells and ADP-ribosylation of proteins in intact cells were observed at similar concentration of the transferase. These data suggest a role of the protein substrates of C3 in the regulation of the cytoskeletal integrity.

ADP Ribose Transferases↗

[Significance of family anamnesis in colorectal carcinoma].

To assess the familial risk of colorectal cancer among first-degree relatives of colorectal cancer patients, a tumour-related family history study was conducted in 1982-1988 on 184 patients (median age 60 [28-92] years). These family data were compared with the data recorded in the cancer register of the population of Basel. An enhanced risk among first-degree relatives was noted (relative risk: 1.8%; 95% confidence interval: 1.4-2.3). The enhanced risk was attributed exclusively to seven families involving 2-3 relatives each (the relative risk in these families being 34). In four of these seven families an autosomal dominant site-specific cancer of the colon (Lynch's syndrome I) was diagnosed. Hence, family case history of colorectal cancer patients enables the identification of relatives with a high risk for colorectal carcinoma.

Adult↗

[Prevention of familial tumor diseases using genetic counseling and early diagnosis].

Several types of familial cancer can be prevented from progressing into an advanced stage through genetic counselling and regular medical control of persons at risk. Measures of secondary cancer prevention and their efficacy are described for retinoblastoma, MEN2 syndrome, familial colorectal carcinoma with (FAP) or without (HNPCC) pre-existing polyposis coli, dysplastic naevi syndrome, basal cell naevi syndrome and von Hippel-Lindau syndrome. The prevention of malignancies is promising primarily for the familial forms, since persons at risk are motivated to employ preventive measures, especially if they can be identified through DNA diagnosis and counselled with concrete information. The establishment of familial cancer registries should be considered which improve the continuous medical care for all family members, even in the case of a change of the family physician or a loss of contact.

Adenomatous Polyposis Coli↗

Electron microscopic analysis of DNA forks generated by Escherichia coli DNA helicase II.

T7 phage DNA eroded with lambda exonuclease (to create 3'-protruding strands) or exonuclease III (to create 5'-protruding strands) was treated under unwinding assay conditions with DNA helicase II. Single-stranded DNA-binding protein (of Escherichia coli or phage T4) was added to disentangle the denatured DNA and the complexes were examined in the electron microscope. DNA helicase II complexes filtered through a gel column before assay retain the ability to generate forks suggesting that DNA helicase II unwinds in a preformed complex by translocating along the bound DNA strand. The enzyme initiates preferentially at the ends of the lambda-exonuclease-treated duplexes and is found at a fork on the initially protruding strand. It also initiates at the ends of the exonuclease-III-treated duplexes where, as with approximately 5% of the forks traceable back to a single-stranded gap, it is found on the initially recessed strand. The results are consistent with the view that DNA helicase II unwinds in the 3'-5' direction relative to the bound strand. They also confirm that the enzyme can initiate at the end of a fully base-paired strand. At a fork, DNA helicase II is bound as a tract of molecules of approximately 110 nm in length. Tracts of enzyme assemble from non-cooperatively bound molecules in the presence of ATP. During unwinding, DNA helicase II apparently can translocate to the displaced strand which conceivably can deplete the leading strand of the enzyme. Continued adsorption of enzyme to DNA might replenish forks arrested by strand switch of the unwinding enzyme.

Adenosine Triphosphatases↗

[Incidence and distribution of tumor disease in relatives. 1. Degrees of stomach carcinoma patients].

The incidence and distribution of malignancies have been analyzed in 435 first degree relatives of 56 patients with histologically proven stomach cancer following the collection of detailed family histories. Eleven stomach cancers were found whereas only three could be expected from age and sex matched incidence data of the local tumour registry. The incidence of all other cancer entities corresponded to that of the whole population. In general, more attention should be paid to the family history, since, among other criteria, it may help to identify individuals at risk and therefore allow the early detection of stomach cancer.

Adult↗

[Prevention and therapy of obesity with diet and sports, an ambulatory therapy program for overweight children].

Dietary restriction together with ongoing power-orientated training provide best results in the therapy and prevention of obesity. Diet can reduce the resting metabolic rate by up to 20% within 14 days. Physical activity stimulates the resting metabolic rate and counteracts this energy saving effect, but is especially important for maintaining a steady state after weight reduction. Exercise reduces the risk factors accompanying obesity by favorable adaptation of the sympathoadrenergic system to physical activity. This can be seen in the effects on heart rate, stroke volume, blood pressure, as well as glycogenolytic and lipolytic activities. Body fat especially in the abdominal area, which is particularly connected with atherogenic risk, is diminished. Weight reduction is accompanied by a decrease of the cardioprotective cholesterol fraction. Diets high in unsaturated fatty acids combined with a staying power training have a synergistic effect: they reduce a decrease of HDL. It is difficult to demonstrate risk factors connected with overweight children. However, from the preventive medicine point of view it is advisable to start with therapeutic measures during childhood. In an out-patient pilot project we surveyed 18 obese children aged 9 to 13 years. The therapy plan consisted of dietary restriction (1200 kcal/d), an exercise program performed 3 times a week, and psychological assistance. All children of 12 to 13 years arrived at an overweight level less than 20%, the younger ones displayed a lower weight reduction effect. All 18 improved their aerobic capacity. In the 1st months of treatment, HDL-cholesterol decreased slightly, but increased above pre-treatment level, later on. We did not see any vitamin deficiencies during the therapeutic regimen.

Cardiovascular System↗

Escherichia coli DNA helicase I. Characterization of the protein and of its DNA-binding properties.

Gene traI of the Escherichia coli F sex factor which encodes DNA helicase I was subcloned in a lambda pL-based plasmid vector and expressed in a background of pL non-repressing cells. Neither the non-repressed pL promoter nor the production of a high level of functional helicase I are toxic. Enzyme purified from this source was studied in the electron microscope. The results show that helicase I binds cooperatively to single-stranded DNA. DNA covered with the helicase appears in fixed, negatively stained specimens as a smooth-contoured filament with a diameter of 12.5 +/- 0.4 nm and an axial periodicity of 7.0 +/- 0.2 nm. In unfixed specimens, discrete particles with axes of 12.7 +/- 0.5 nm and 7.2 +/- 0.5 nm are visible. They are consistent in size with helicase I monomers (Mr 180,000) suggesting that the molecule is almost isometric, despite a frictional ratio of 1.71 calculated from its diffusion coefficient. Helicase I free of DNA appears as aggregates. For comparison, a truncated traI, lacking coding for the amino-terminus of the product, was cloned by fusing it to an MS2 replicase gene fragment. The chimeric gene product (named helicase I del29) retains strand-separating activity although it fails to show cooperative DNA binding behavior. Judged from the length of the helicase-I-specific sequence of this polypeptide, traI is located 1.3 kb nearer to the distal end of the F transfer operon compared to the position proposed in a previous genetic map. The revised location of traI has implications for understanding distal functions of the transfer operon.

Binding Sites↗

Electron microscopy of DNA.helicase-I complexes in the act of strand separation.

Electron microscopy was used to characterize the DNA-unwinding reaction catalysed by Escherichia coli DNA helicase I. Linear DNA with 5'-protruding strands as well as single-stranded gaps was incubated, under unwinding assay conditions, with the helicase. E. coli single-stranded-DNA-binding protein (SSB) was added to order the denatured DNA. Up to 70% of the sites of SSB-complexed DNA were observed as forks. The position of the strand-separating enzyme was indicated by a gap in the complex between fork and SSB on that arm which initially provided the binding site. The complex between DNA and helicase varied in length although in all cases it was long enough to comprise several helicase I molecules. A mutant helicase I (helicase I del29) which, unlike the wild-type enzyme, fails to show cooperative DNA-binding behaviour was found to prevent an abnormally short stretch of DNA near the fork from binding SSB. Apparently, one or very few helicase molecules would be sufficient for the opening of a DNA duplex although, typically, the fork is shifted by a tract of helicase I molecules. SSB displaces helicase I from single-stranded DNA but fails to do so from a fork or a single-strand/double-strand junction. The difference is consistent with the observation that SSB does not inhibit the unwinding reaction despite its rapid association with the separated strands. Helicase I unwinds in the 5'-3' direction of the bound strand. Observations so far indicate that the enzyme exploits the single strand at the initial DNA-binding site for orienting its action, and not the complementary, completely base-paired strand.

Binding Sites↗

[Prenatal diagnosis].

There is probably no other medical field which has undergone such rapid development during the past 20 years as prenatal diagnosis. The number of women who desire this assistance is steadily increasing and more and more techniques have become available which enable a growing number of genetic defects to be diagnosed with certainty prior to birth. Prenatal diagnosis is a significant tool of genetic counselling.

Amniocentesis↗

Glutamic-acid-decarboxylase-and parvalbumin-like-immunoreactive structures in the olfactory bulb of the human adult.

This study examines the distribution and morphological characteristics of glutamic-acid-decarboxylase-like (GAD)- and parvalbumin-like (PA)-immunoreactive structures in the olfactory bulb of the human adult. GAD-immunoreactive somata occurred in the glomerular layer, the external granule cell layer, the more superficial portion of the external plexiform layer, and the internal granule cell layer. The cells were small- to medium-sized. Demonstration of lipofuscin pigment revealed the presence of unpigmented as well as pigmented neurons, thus suggesting the existence of two subpopulations of GAD-positive neurons. GAD-immunoreactive puncta and/or fibers were mainly seen in the periglomerular region and the internal granule cell layer. All other layers of the bulb, as well as the intrabulbar portion of the anterior olfactory nucleus, displayed considerably less of these puncta and/or fibers. The olfactory nerve layer remained practically clear of immunoreactive material. PA-immunoreactive somata occurred in the glomerular layer and both the external and internal granule cell layer. Only a small number of immunoreactive nerve cells were encountered within the white matter or the olfactory tract. Most PA-positive neurons displayed characteristics of short axon cells whereas a few others resembled van Gehuchten cells. All of the PA-immunoreactive neurons were devoid of lipofuscin pigment. Immunoreactive puncta and fibers were present in all layers though predominating in the periglomerular region, the olfactory nerve layer, and the internal granule cell layer. The intrabulbar portions of the anterior olfactory nucleus did not show any immunoreactive structures.

Adult↗

Acute bleeding into a filum terminale ependymoma.

We present a case of a 63-year-old male patient who was admitted to our hospital due to an acute compression syndrome of the cauda equina. He had complained about a sciatica for at least one year. CT-diagnosis appeared to be negative, whereas a lumbar myelogram revealed a complete block at L2/3. Emergency surgery was performed, and an ependymoma of the filum terminale was removed into which it had bled massively. The case is compared to the literature findings. These relate ependymomas in the described region with acute onset more often to symptoms caused by subarachnoid bleeding. Mechanical and/or histopathological factors are discussed as the cause of acute bleeding. Spinal ependymomas represent a rare event compared to other neurosurgical diseases. Even more seldom are tumors of this kind causing an acute cauda equina compression syndrome.

Acute Disease↗

Long-term follow-up of infratentorial pilocytic astrocytomas.

We present the data of 99 patients operated on for infratentorial pilocytic astrocytoma from 1955 to 1980 at the Neurosurgical Department of the University of Hamburg/West Germany. Twenty-two patients had died. From 56 patients long-term follow-up was obtained. A comparison was done for patients either operated on until 1969 or since 1970, the time when microscopes had been introduced into the operation theatre. The mortality rate clearly dropped with the beginning of the "microsurgical era", certainly due to other improvements as well, e. g. neurosurgical intensive care. The drop in mortality was not accompanied by an improvement in outcome. Future perspectives of possibly further improving the therapy of pilocytic astrocytomas are outlined.

Astrocytoma↗

Sr-90 transfer factors for rye in podzolic soils: dependence on soil parameters.

The transfer factor (TF) for Sr-90 was studied in 10 rye fields with podzolic soils near Bremen. Values between 0.10 and 0.30 were obtained with a mean of 0.18. The TF was correlated with various soil parameters (pH, organic matter, K, Ca and P content). Negative correlations were found between TF and pH-value, Ca and P content. However, the content of organic matter in the soils was positively correlated with soil and grain activity (Bq/kg).

Biological Transport↗

Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS.

Fourteen examples of non-Hodgkin's lymphoma (NHL) and four of Hodgkin's disease in patients with AIDS as well as lymph nodes exhibiting changes related to the lymphadenopathy syndrome (LAS) from 11 HIV-positive individuals were studied for the presence of Epstein-Barr virus (EBV) genome both by in situ DNA hybridization and blotting techniques. Both methods were performed using formalin-fixed paraffin-embedded material. All the NHLs were of high malignancy and all but one were of the B-cell type. Of the four examples of Hodgkin's disease, two were lymphocytic predominant, one of mixed cellularity and one of the nodular sclerosing variety. The lymph nodes of patients with LAS were mostly stage I with marked follicular hyperplasia. In 7 of the 14 NHLs the presence of EBV-DNA was clearly demonstrated by dot-blotting and by in situ hybridization. All lymph nodes from the patients with LAS and AIDS-related Hodgkin's disease were negative for EBV by dot-blot and in situ hybridization assays. We conclude that EBV plays a role in the development of AIDS-related lymphomas, but the fact that half these lymphomas are EBV-negative suggests that other mechanisms such as polyclonal stimulation of B-cells by HIV products may also be important.

AIDS-Related Complex↗