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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 379 records · Page 21Linked to original sources
PubMed1989

Critical issues in chemotherapy with tiazofurin.

Some of the current critical issues in the tiazofurin treatment of end-stage leukemia were presented and discussed. 1. Tiazofurin infusions (daily X 10 to 15) provided remissions in 50% of end-stage leukemic patients. The remissions, of 1 to 10 months' duration, varied from antileukemic effect or hematologic improvement to complete response and complete remission. The total survival of the responding patients was from about 1 to 15 months. 2. Our administration of tiazofurin in a 60-min infusion by pump decreased the incidence and severity of toxicity. 3. It was shown that tiazofurin dose does not need to be escalated at each relapse. Depending on the biochemical and hematological response in this novel protocol, 2,200 to 4,400 mg/m2 tiazofurin appeared to be sufficient to provide remissions. 4. A new role was identified for allopurinol, originally given to decrease uric acid in the plasma. Allopurinol markedly increased plasma hypoxanthine concentrations which competitively inhibited the activity of the salvage enzyme, guanine phosphoribosyltransferase, in the blast cells. Thus, the elevated hypoxanthine plasma levels inhibited guanine salvage. To maintain high hypoxanthine levels allopurinol (100 mg) was given every 4 to 6 hr. This provided combination chemotherapy with tiazofurin which inhibited IMP dehydrogenase activity and blocked the de novo biosynthesis of guanylates in the blast cells. 5. Preliminary evidence was obtained in the patients that tiazofurin induced differentiation of the bone marrow. Recent studies also showed that tiazofurin down-regulated the expression of the c-Ki-ras oncogene in K562 erythroleukemic cells. Therefore, tiazofurin treatment provides an impact by chemotherapy, induced differentiation, and, if applicable, through down-regulation of the ras oncogene. 6. Novel aspects of tiazofurin treatment include rational targeting and a continuously monitored trial by measurement of the activity of IMP dehydrogenase and of GTP and TAD concentrations in blast cells and of tiazofurin and hypoxanthine in plasma. 7. Since tiazofurin has not yet achieved lasting remissions in patients nor terminal differentiation of leukemic cells it probably will be advantageous to combine tiazofurin with other drugs to provide synergism. In preclinical tissue culture studies in HL-60 cells synergy was observed with retinoic acid. This may be of interest because retinoic acid also caused differentiation and down-regulation of the myc oncogene.

Adult↗
PubMed1989

IMP dehydrogenase: inhibition by the anti-leukemic drug, tiazofurin.

Tiazofurin through its active metabolite thiazole-4-carboxamide adenine dinucleotide (TAD) inhibits IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis. IMP dehydrogenase activity in human leukemic cell extracts (33.4 +/- 0.1 nmol/h/mg protein) was increased 11-fold compared to normal leukocytes (3.1 +/- 0.5). Km values for IMP and NAD+ of leukemic IMP dehydrogenase were 22.7 and 44.0 microM, respectively. XMP inhibited competitively with IMP and noncompetitively with NAD+. NADH exerted mixed type inhibition with respect to both IMP and NAD+. The inhibitory pattern of TAD was quite similar to that of NADH; however, the affinity of TAD to leukemic IMP dehydrogenase (Ki = 0.1 microM) was three orders of magnitude higher than the natural product NADH (Ki = 150 microM). These results contribute to an understanding of the mechanism of action of tiazofurin in the treatment of leukemia.

Adenine Nucleotides↗
PubMed1989

Intraoperative balloon angioplasty.

Since 1981 intraoperative balloon dilatation has been performed in 78 patient suffering from occlusive arterial disease of the lower extremities. The indications were claudication in 32, and limb salvage in 46 patients. In most of the 34 patients in whom a proximal iliac stenosis was dilated in association with a femoro-popliteal bypass (10 patients), endarterectomy (19 patients) or profundoplasty (5 patients), the ankle arm index returned to near normal immediately after the procedure. In 44 patients, the femoro-popliteal segment distal to an ilio-femoral reconstruction was dilated. The follow-up period ranged from 1 to 60 months with an accumulated patency rate of 97.6% in aortoiliac and 60.2% in femoro-popliteal segment at 5 years. Fourteen patients were dead at five years after the intervention from concurrent cardiac disease. Balloon angioplasty is a valuable adjunct to vascular surgery either to improve inflow or outflow in association with surgical reconstruction.

Adult↗
PubMed1989

3,4-Dihydro-2H-1-benzopyran-2-carboxylic acids and related compounds as leukotriene antagonists.

Evaluation of a series of 3,4-dihydro-2H-1-benzopyran-2-carboxylic acids linked to the 2-hydroxyacetophenone pharmacophore present in the standard peptidoleukotriene antogonist FPL 55712 (1) has led to the discovery of Ro 23-3544 (7), an antagonist possessing greater potency and duration of action vs LTD4 than the standard (aerosol route of administration, guinea pig bronchoconstriction model). Interestingly, this compound also potently inhibited bronchoconstriction induced by LTB4 whereas 1 did not. Attempts to establish structure--activity relationships in this series involved modifications in the 2-hydroxyacetophenone moiety, the linking chain, and the chroman system. All variations produced analogues which were either inactive or possessed reduced potency relative to acid 7. Optical resolution of 7 was achieved by two methods. Absolute configurations of the enantiomers were determined via X-ray crystallographic analyses of an intermediate as well as a salt of the S enantiomer. Although the enantiomers exhibited similar potencies in in vitro assays and in vivo when administered intravenously, significant differences were observed in the guinea pig bronchoconstriction model vs LTC4 and LTD4 when administered by the aerosol route (S antipode 15-fold more potent). The properties of 7 have been compared with several recently reported leukotriene antagonists.

Animals↗
PubMed1989

Relationship of serum selenium levels to tumor activity in acute non-lymphocytic leukemia.

Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in patients than in controls (0.082 +/- 0.033 micrograms/ml versus 0.097 +/- 0.035 micrograms/ml, P less than 0.01). Pretreatment serum Se correlated inversely with the absolute peripheral blast cell count (R = -0.62, P less than 0.001) and other measurements of the tumor burden. Seven days after the initiation of chemotherapy, serum Se increased significantly in proportion to the initial tumor burden (P less than 0.01). Thereafter, serum Se levels remained essentially normal in patients entering a complete remission while decreasing gradually in failures. In conclusion, these data do not lend support to the hypothesis that a low selenium status enhances the risk of developing ANLL, but indicate that serum Se levels in patients with acute leukemia are mostly dependent on tumor activity.

Female↗
PubMed1989

The controversy about a sexual dimorphism of the human corpus callosum.

A sexual dimorphism of the splenium corporis callosi in man was reported in 1982. The authors described the posterior part of the female corpus callosum to be larger and more bulbous than its male counterpart. From the lateralization research, it has previously been stated that the female brain is less well lateralized for visuospatial functions than the male. The authors postulated that a larger splenium implies a larger number of fibers and that the number of interhemispheric fibers correlates inversely with lateralization of function. However, their sample was very small and not adequately matched for sex. Therefore, we reinvestigated this question. A standardized computer assisted program will be presented. With this program the "classical" parameters have been evaluated and the "rotatory diameter measurement" was performed. No differences between the sexes were seen either for the splenium corporis callosi or for the other parts of the corpus callosum.

Adult↗
PubMed1989

[UV-inactivation of microorganisms in water].

UV-Inactivation of Escherichia coli, Bacillus subtilis spores, Staphylococcus-Phage A 994, Poliovirus type Mahoney and Rotavirus SA 11 was tested under controlled physical conditions. B. subtilis-spores were found to be the most resistant of these microorganisms, followed by Rotavirus, Bacteriophage and Poliovirus. E. coli required the lowest irradiation dose for inactivation. Causes and meaning of these dose-survival-reactions are discussed.

Bacillus subtilis↗
PubMed1989

[Psychoanalysis and psychotherapy management in Austria].

In a study on the psychotherapeutic provision in Austria the participation of the psychoanalysts was also researched. All over Austria there is a lack of psychotherapists in numbers and regionally. Long term psychotherapy except for a few special institutions are free of charge for the client. In private practice however the patients have to pay heavily. Non-medical psychotherapists are not eligible for refunds by the health insurance system. Almost 4/5 of all psychotherapists belong to a non-medical profession (e.g. psychologists). Only about 1/5 are medical doctors who work as psychotherapists on the basis of a therapeutic training. Psychoanalysts in Austria primarily work as psychoanalytic oriented psychotherapists and to a lesser extent as psychoanalysts.

Austria↗
PubMed1989

Influence of CDP-choline administration on the aortic wall lesions in dietically hypercholesterolaemic rabbits: a morphometric evaluation.

In New Zealand rabbits subjected for a 2 month period to a 1% or 2% hypercholesterolic diet, larger intimal involvement and histologically heavier lesions were observed in the animals on a hypercholesterolic diet. The intimal involvement was larger in the aortic arch. In groups of rabbits simultaneously subjected to similar diets and to i.v. CDP-choline injections, the intimal involvement appeared reduced (p less than 0.01) both in the arch and in the descending tract of the thoracic aorta.

Animals↗
PubMed1989

[Report of 2 cases of isolated, primary amyloidosis of the male urethra and urinary bladder of a female].

Primary localized amyloidosis of the bladder and urethra is a rare condition. Two cases of isolated primary amyloidosis, of the urethra in a man and of the bladder in a woman, are reported. The clinical specificity of the location and the specific therapy are discussed. We draw attention to the extended, palette of diagnostic investigations now available and the new classification made possible by the introduction of immunohistochemistry and immunoelectron microscopy.

Aged↗
PubMed1989

[Osteopenia in premature children: an emerging problem].

Osteopenia of preterm newborns is a condition of undermineralization which arises during the first years of life in very low birth-weight infants. The pathogenesis of disease is multifactorial, even if its main mechanism is the inadequate mineral intake (overall the inadequate phosphorus intake). A wide spectrum of signs and symptoms may be observed ranging from overt rickets to asymptomatic conditions. Diagnosis is usually based on either photon or biochemical findings (hypophosphoremia, hyper calciuria, hypophosphaturia). There is not agreement about the prevention and the treatment and about the benefit of any form of mineral supplementation. The aim of our study is a review of the recent studies concerning the osteopenia of prematurity to focus this new problem.

Bone Diseases, Metabolic↗
PubMed1989

Hepatocyte iron release in rats.

Hepatocyte iron release was studied in vivo in rats. After the injection of iron 59-labeled ferritin, hemoglobin, or human asialotransferrin, the proportions of the radioactive iron returned to the plasma and incorporated into stores were determined under various conditions. Iron 55-labeled rat transferrin was injected at the same time as the 59Fe-labeled compound, and storage iron release was calculated from the cumulative incorporation of the two isotopes in the red cell mass over 2 weeks. The various 59Fe-labeled compounds were processed differently by the hepatocyte, but the radioactive iron was incorporated in the same iron stores. About 6% of the hepatocyte storage iron was released daily in normal rats, but a pool of iron that is not mobilized spontaneously was clearly identified in iron overload. Iron turnover in the hepatocyte was regulated by the rate of erythropoiesis and iron status of the animal, and inflammation blocked hepatocyte iron release. A strong correlation between hepatocyte iron release and plasma transferrin receptor levels was observed (p less than 0.001), suggesting that plasma transferrin receptors could mediate the regulation of hepatocyte iron mobilization in rats.

Animals↗