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Biomedical subjects

R Koch

Publications and source records attributed to R Koch.

At least 217 records · Page 12Linked to original sources
PubMed1989

[Experiences with 169 mechanical colorectal anastomoses (1981-1984)].

An account is given of 169 rectal anastomosis performed with the EEA-stapler between 1981 and 1984 in the Municipal Hospital Waid of Zurich. The average age of the patients was 63.8 years. 71.6% of the operations have been performed because of a rectosigmoidal carcinoma (50.4% of them with lymph node metastasis) and 28.4% because of a benign rectal disease. 44.4% of the anastomosis were localized at 3.5 to 7 centimeter, 34.9% between 7.5-11 and 20.7% higher than 11 centimeter above the anus. We used the biggest loading unit of 31 millimeter diameter in 89% of all cases. A primary anastomotic insufficiency was discovered intraoperatively in 6.5% (anastomosis sutured or redone). 3.1% of the patients had a temporary colostomy. We found a 4.3% rate of secondary anastomotic insufficiency. All those colo-cutaneous fistula healed spontaneously. Non specific complications as thromboembolism, urinary or wound infection and others were detected in 31.3% of the cases. We found a perioperative mortality rate of 2.5% with no intraoperative deaths. 91.4% of the patients had a follow-up over 2-5 years. There was a need of dilatation of anastomotic stenosis in 2.5% of the cases within the first 4-8 postoperative months. 40.2% of the cancer patients died during their follow-up, two thirds of them within the first two years. The local recurrence rate after 2-5 years of the cancer patients who were operated curatively was 22.3% and 10.7% for distant metastasis. 60.2% were disease free. 54.5% of the recurrent disease was found in patients with primary tumors stage Dukes C2 and D.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Primary extranodular non-Hodgkin's lymphomas--observations on etiopathogenesis, histology and prognosis].

The total non-Hodgkin's lymphoma-population treated between 1978 and 1986 by means of radiotherapy or combined chemo/radiotherapy was analysed as to primary extranodular manifestation. 39 cases, 16 women and 23 men, were observed (stage IE 12, stage IIE 22 and stage IIIE 5). Immunoblastic (10), lymphoblastic (9) and centroblastic (6) lymphomas are the most frequent with respect to histology. Gastroenteron (16) and otorhinolaryngological region (13) are in the lead with regard to localisation. 5-year-survival-rates are determined in dependence on clinical stage: IE 65.8%, IIE 39.2% (low, connected with the proportion of high-malignant histology) and IIIE 25.0%. The 5-year-survival-rate of primary gastrointestinal manifestation amounted to 51.5%. With respect to aetiopathogenesis of primary extranodular lymphomas gut-, mucosa- and bronchial-associated lymphoid tissue, aberrant lymph-nodes and the influence of viral- and immunologic factors seem to be important.

Adult↗
PubMed1988

Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line.

The influence of memantine on several properties of a neuronal cell line was tested. The aim was to get some insight into possible mechanisms of action of this drug which is therapeutically applicable in treatment of spasticity, Parkinson's disease, and cerebral coma. In neuroblastoma X glioma hybrid cells, memantine, at micromolar concentrations, blocked the depolarization induced by iontophoretically applied serotonin (5-hydroxytryptamine, 5-HT). In the hybrid cells, receptors of the 5-HT3 type mediated the depolarization, which was frequently accompanied by a series of action potentials. The inhibition by memantine of the serotonin response occurred fast and was completely reversible, irrespective of whether the cell showed a stable membrane potential or spontaneous action potentials. However, memantine did not alter spontaneous or electrically evoked action potential activity in the hybrid cells, and apparently did not block the underlying ionic conductances. Furthermore memantine did not affect either the cation permeability activated by substance P in the hybrid cells or the K+ channel triggered by bradykinin in a glioma cell line. Thus, memantine appears specifically to suppress the ion channel opened by serotonin in the hybrid cells. The interaction of memantine with serotonin receptors and the associated ion channels reported here, might give an important clue, as to a site of action of memantine in the nervous system.

Amantadine↗
PubMed1988

Characterization of the protein which binds insulin-like growth factor in human serum.

The binding of the 125I-labelled insulin-like growth factors I and II (125I-IGF I and 125I-IGF II) to the high-molecular-mass binding protein of human serum was characterized. With diluted human serum both growth factors showed optimal specific binding at 4 degrees C and pH 5-6. When 0.1% Triton X-100 was present in the incubation buffer an increase in the affinity of the IGF-binding protein was induced, which produced an enhanced binding of IGF I and IGF II. Competition experiments with various peptide hormones revealed that the native IGF-binding protein complex binds both the IGF I and IGF II with high specificity. Analysis of binding data according to the method of Scatchard resulted in linear plots for IGF I and IGF II respectively, indicating that in human serum only a single class of non-interacting binding sites is present. At optimal binding conditions the dissociation constants were determined to be 0.28 x 10(-9) M for IGF I binding and 0.66 x 10(-9) M for IGF II. Human serum was gel-filtered on Sepharose CL-6B at neutral pH and the eluate was assayed for binding activity with both IGF I and IGF II. One peak with an apparent molecular mass of 175 kDa and a Stokes radius of 4.8 nm was determined for both growth factors. Thus, our data suggest that human serum contains one class of high-molecular-mass binding protein with comparable binding characteristics for IGF I and IGF II.

Binding Sites↗
PubMed1988

In vitro estrogenic actions in rat and human cells of hydroxylated derivatives of D16726 (zindoxifene), an agent with known antimammary cancer activity in vivo.

A series of 2-phenyl-1-ethyl-3-methylindoles with or without a hydroxyl group in the para position of the phenyl ring and the 5 or 6 position of the indole nucleus were compared with 17 beta-estradiol in the stimulation of (a) prolactin production in rat pituitary cells in primary culture, (b) progesterone receptor synthesis in MCF-7 cells, and (c) proliferation of MCF-7 cells. All compounds were less active than estradiol but all derivatives including D15414, the hydroxylated metabolite of D16726 (zindoxifene, a known antitumor agent against mammary cancer) were fully estrogenic. Hydroxyl groups at the para position of the phenyl ring and 6 position of the indole nucleus conferred the highest estrogen potency [ED50 (drug concentration producing 50% of maximum activity) in all assays around 10(-10) M]. Moving or eliminating the hydroxyl on the indole ring markedly reduced the estrogen potency; however, an even more dramatic reduction in estrogenic activity was produced by removing the hydroxyl of the phenyl ring.

Animals↗
PubMed1988

Genetic effects of chlorinated ethylenes in the yeast Saccharomyces cerevisiae.

The chlorinated ethylenes 1,1-dichloroethylene (vinylidene chloride), trans-1,2-dichloroethylene, trichloroethylene, and tetrachloroethylene (perchloroethylene) were assayed for their ability to induce mitotic gene conversion and point mutation as well as mitotic aneuploidy in diploid strains of the yeast Saccharomyces cerevisiae. From strain D7 late logarithmic-phase cells grown in 20% glucose liquid medium, containing a high level of cytochrome P-450, as well as stationary-phase cells combined with an exogenous metabolic activating system (S9) were used, in order to activate the chlorinated compounds and to produce electrophilic mutagenic intermediates. Only 1,1-dichloroethylene exhibited a dose-dependent genetic activity, while the other ethylenes did not. The 2 ways of metabolic activation were compared and were found to cause approximately the same effect. In contrast to the findings with strain D7, vinylidene chloride, trans-1,2-dichloroethylene, and trichloroethylene induced, without metabolic activation, mitotic chromosomal malsegregation in strain D61.M. The presence of liver homogenate as an activating system did not enhance the respective frequencies of chromosome loss. In the case of tetrachloroethylene, sufficient data have not become available, since this compound showed a highly toxic effect towards yeast cells, decreasing the rate of surviving cells to less than 30% at a concentration of 9.8 mM.

Biotransformation↗
PubMed1988

Phenylalanine hydroxylase expression in liver of a fetus with phenylketonuria.

The expression and activity of phenylalanine hydroxylase was studied in the liver of a fetus aborted after prenatal diagnosis of phenylketonuria. No phenylalanine hydroxylase enzymatic activity or immunoreactive protein was detectable in the PKU liver specimen, though both enzymatic activity and immunoreactive protein were detectable in control specimens of similar gestational age. Phenylalanine hydroxylase messenger RNA of normal size was present in the PKU fetal liver at normal abundance. These results confirm the genetic diagnosis of PKU in this fetus and indicate that the mutations in this fetus affect translation or stability of the phenylalanine hydroxylase protein.

Abortion, Induced↗
PubMed1988

Interaction of memantine with cholecystokinin receptors in mouse brain.

The effect of memantine on CCK receptors in mouse brain has been investigated using particles of dissected cortex and striatum. Total binding of radio-labelled CCK33 was one-half maximal within 10 min of incubation and reached a maximum after 30 to 60 min when either cortex or striatum was used. Non-specific binding (presence of 100 microM unlabelled CCK8) was 50 to 80% of total binding at steady state conditions. CCK8 inhibited specific binding of radiolabelled CCK33 in a dose-dependent manner; the IC50 (half-maximal inhibitory concentration) was in the range 3 to 4 nM. Memantine increased CCK binding in a concentration-dependent manner, though at high concentrations. The EC50 (half-maximal effective concentration) of this effect was less than 100 microM. The memantine effect is not due to an inhibition of labelled CCK degradation in the medium. The effect of memantine on CCK binding is unique for brain since it was not observed in pancreatic acinar membranes. These data, therefore, suggest a modulatory effect of memantine on CCK receptors in mouse brain (cortex and striatum) particles.

Amantadine↗
PubMed1988

Ligand interaction at the estrogen receptor to program antiestrogen action: a study with nonsteroidal compounds in vitro.

The estrogenic and antiestrogenic actions of the geometric isomers of tamoxifen and 4-hydroxytamoxifen were determined in a PRL synthesis assay using primary cultures of dispersed immature rat pituitary gland cells. 4-Hydroxytamoxifen was 100 times more potent as an antiestrogen than tamoxifen. The cis isomer of tamoxifen was a weak estrogen, but the cis isomer of 4-hydroxytamoxifen was converted to the trans isomer during the 6-day assay. This made an accurate determination of the properties of cis-(E)4-hydroxytamoxifen impossible. A series of fixed ring derivatives of the compounds were evaluated in the PRL synthesis assay in vitro to determine their estrogenic and antiestrogenic activities. The fixed ring derivatives of tamoxifen, cis-tamoxifen and trans-(Z)4-hydroxytamoxifen all had properties that were the same as those of the original triphenylethylenes. The fixed ring derivative of the cis-(E) isomer of 4-hydroxytamoxifen was a weak competitive antagonist of estrogen action with only very slight estrogenic properties. This contrasted with the other cis isomers of triphenylethylenes. We propose that the hydroxyl group on the molecule may orient the ligand at the binding site of the estrogen receptor to place the alkylaminoethoxy side-chain in a position to produce antiestrogen action.

Animals↗
PubMed1988

ADP-ribosyl proteins formed by pertussis toxin are specifically cleaved by mercury ions.

Various types of ADP-ribosyl protein conjugates were synthesized and their chemical stability was compared with that of cysteine-linked ADP-ribosyl groups as formed by incubation of transducin or Gi/Go proteins with NAD and pertussis toxin. Treatment with 0.1 mM HgCl2 specifically cleaved the cysteine-linked conjugates. This may provide a tool for the quantitation of modified Gi/Go proteins as well as of other acceptors modified by ADP-ribose at cysteine residues in the presence of other ADP-ribosyl proteins.

Adenosine Diphosphate Ribose↗
PubMed1988

Diagnostics of septicaemia in childhood by coagulation parameters.

The diagnostic importance of coagulation parameters was tested in 438 children with septicaemia by discriminant analysis. The values of 756 patients with other diseases had been analysed for comparison. After the selection of the parameters by multivariate analyses discriminant functions were calculated for different subgroups. The best discriminant functions were found for septic newborns up to the age of 3 days. Their use may be helpful for diagnostics in practice. A more weak discrimination power was evident in newborns beyond the 3rd day of life. A simultaneous comparison of 7 subgroups of newborns with different illnesses by 3 discriminant functions led to lower sensitivity rate and don't suit for practice. Beyond the postnatal period the diagnostic importance of coagulation parameters for septicemia is even lower. The low reparation capacity of thrombopoiesis in neonates may be a cause for the good discriminant functions for septicaemia. The reason for the better discrimination in the newborns up to the 3rd day could be the more profound defects in the coagulation system.

Blood Coagulation Tests↗
PubMed1988

[Combination hormone-chemotherapy versus hormone therapy alone in the initial treatment of advanced prostate carcinoma--a prospective cooperative study].

The effectiveness of orchiectomy plus an antigonadotropic therapy alone (ethinylestradiol sulfonate), of orchiectomy plus a combined hormone and chemotherapy (ethinylestradiol sulfonate plus vincristine/vinblastine, cyclophosphamide, methotrexate) and of orchiectomy plus chemotherapy (vincristine/vinblastine, cyclophosphamide, methotrexate) alone for the initial treatment of advanced (stage IV) carcinoma of the prostate was compared. The cumulative 4-year survival rate was better after combined hormone and chemotherapy. Our results do not justify the administration of combined hormone and chemotherapy in previously untreated advanced carcinoma of the prostate.

Antineoplastic Combined Chemotherapy Protocols↗