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Biomedical subjects

C Reuter

Publications and source records attributed to C Reuter.

At least 37 records · Page 2Linked to original sources
PubMed1993

Meiotic synapsis of homogeneously staining regions (HSRs) in chromosome 1 of Mus musculus.

About 50 copies of a long-range repeat DNA family with a repeat size of roughly 100 kb and with sequence homology to mRNAs are clustered in the G-light band D of chromosome 1 of the house mouse, Mus musculus. We studied amplified versions of the cluster which are found in many wild populations of M. musculus. They are cytogenetically conspicuous as one or two C-band positive homogeneously staining regions (single- and double band HSRs) which increase the mitotic length of chromosome 1. The double band HSR was phylogenetically derived from a single band HSR by a paracentric inversion. In homozygous condition, such HSRs contribute, albeit not as much as expected from their mitotic length, to the synaptonemal complex (SC) length of chromosome 1. In HSR heterozygous animals an elongation of the SCs was not noticeable. In single band HSR heterozygous males, synapsis proceeds regularly and continuously from the distal telomere towards the centromeric end without forming buckles. Thus, the single band HSR has no adverse effect on pairing. The same straight pairing behaviour was found in the majority of double band HSR heterozygous spermatocytes. This shows that extensive nonhomologous pairing can take place in the earliest phase of synapsis. Synapsis was discontinuous, leaving the central part of the bivalent 1 asynapsed, in only 14.3% of double band HSR heterozygous cells. In such cells the chromosome 1 SC is completed at a later stage of meiosis. The delay is presumably an effect of the inversion that includes one HSR band and the segment between the two HSR bands.

Animals↗
PubMed1992

Differences in the intracellular pharmacokinetics of cytosine arabinoside (AraC) between circulating leukemic blasts and normal mononuclear blood cells.

The increasing insights into the pharmacokinetics and the metabolism of cytosine arabinoside (AraC) have improved the rationale for its application in leukemia therapy and have led to a pharmacologically directed design of antileukemic treatment. The current study aims at adding to this approach by detecting differences in the intracellular metabolism of AraC 5'-triphosphate (AraCTP) between leukemic and normal mononuclear blood cells. Measurements of intracellular AraCTP levels were complemented by determinations of plasma AraC and AraU concentrations and were performed in 32 patients with acute myeloid leukemia undergoing combination therapy including either conventional (100 mg/m2 daily) or high-dose (1.0 or 3.0 g/m2 twice daily) AraC. Plasma AraC concentration showed a linear relationship to the applied AraC dose but did not correlate with intracellular AraCTP levels. During conventional-dose AraC therapy little interpatient variation was observed in AraCTP retention times in leukemic blasts from 5 patients with t1/2 values ranging from 1.70 to 2.50 h (median 2.14 h). In all cases AraCTP levels declined rapidly after the end of the AraC infusion. Substantial differences in AraCTP retention times were revealed, however, during 3 h infusions of either 1.0 or 3.0 g/m2 AraC in leukemic blasts from 10 patients with t1/2 values between 1.60 to 7.63 h (median 2.42 h). In addition, AraCTP levels declined in only one patient by > 10% within the first hour after the end of therapy and remained constant or even increased up to 1.5-fold in a post-treatment period of 1 to 2.5 h in the other nine cases. In contrast, AraCTP retention times were relatively uniform in normal mononuclear blood cells from 11 patients with t1/2 values of 3.34 to 5.29 h (median 3.85 h). More importantly, AraCTP levels dropped by > 10% within the first hour after the end of the high-dose AraC infusion in eight of 11 cases. A post-therapeutic increase > 10% was not observed in any patient. Similar findings emerged after in vitro exposure of normal bone marrow cells from six healthy volunteers to 20 mumol/l AraC for 3 h revealing a > 10% decrease of intracellular AraCTP within the first post-treatment hour in all cases with AraCTP retention times of 2.29 to 8.63 h (median 3.20 h). These differences in AraCTP pharmacokinetics between leukemic and normal blood cells may provide the basis for a modified timing of AraC administration with the aim of selectively maintaining cytotoxic AraCTP levels in leukemic blasts while allowing an intermittent drop of AraCTP levels in normal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗
PubMed1991

Therapeutic activity, clinical and gastric tolerance of 20mg daily dose of droxicam in comparison with piroxicam in patients with degenerative joint disease.

The efficacy and safety of droxicam were compared with piroxicam in a pilot study in twenty patients with degenerative joint disease. After a one week washout period a baseline gastroscopy was carried out. Treatment during the following 4 weeks was randomised to droxicam or piroxicam. Safety and tolerance parameters were monitored at weekly intervals. Pain was evaluated with two visual analogue scales (VAS) (patient and investigator). Affected joints, articular index (AI), patient's status and a daily living activities questionnaire were also evaluated. Another gastroscopy was carried out at the end of the treatment period. Droxicam and piroxicam relieved all symptoms significantly without statistically significant clinical differences. Both groups showed no drug related side effects in the laboratory values. In the gastroscopic examinations two patients of the droxicam group and four of piroxicam group had minor gastric erosions after four weeks of treatment without any accompanying clinical symptoms.

Adult↗
PubMed1991

In vitro and in vivo effects of rh GM-CSF in acute myeloid leukemia (AML).

70% of patients with newly diagnosed and 50% of patients with relapsed acute myeloid leukemia (AML) can achieve a complete remission with intensive chemotherapy. However, the treatment-associated mortality can be as high as 30% increasing with age, previous chemotherapy and intensity of chemotherapy. GM-CSF was first applied in 36 patients with high risk AML after chemotherapy to reduce the time of critical neutropenia. The early death rate was significantly lower in the GM-CSF group compared to 56 patients of a historic control group with similar risk factors and identical chemotherapy (p less than 0.009). The rate of complete remissions was also significantly higher in the GM-CSF group (p less than 0.09). More recently, GM-CSF was used as a priming agent 24 h prior to start of chemotherapy. 25 patients have entered the study up to now. The cell biological effects of GM-CSF in vivo include an immediate increase of leukemic blasts and of normal myeloid cells in the peripheral blood with a median of 2.0, an increase of cells in the S-phase of the cell cycle in bone marrow biopsies, an increase in DNA polymerase activity, an increase in Ara-C cytotoxicity and immunophenotypic changes compatible with differentiation of leukemic blasts along the pathway of normal myeloid progenitors. GM-CSF has a dual effect on normal and leukemic myeloid cells. It can be safely applied in patients with AML. Prospective randomized trials have to be performed to establish its role in reducing treatment toxicity and in improving the overall treatment results.

Acute Disease↗
PubMed1990

Characterization of purified pp60c-src protein tyrosine kinase from human platelets.

Intact pp60c-src, the cellular homologue of the transforming protein of Rous sarcoma virus, was purified from human platelets. The purified fractions also contained small amounts of a 54-kDa proteolytic degradation product of pp60c-src. We investigated some of the biochemical and kinetic properties of pp60c-src protein tyrosine kinase. Maximum kinase activity occurred at pH 6.5 and required a mixture of 2 mM Mn2+/Mg2+ as divalent cations. The enzyme most strongly phosphorylated casein, followed by enolase and alcohol dehydrogenase. The Km value for ATP was 4 microM for substrate phosphorylation and for autophosphorylation. Using casein, we determined a Vmax for substrate phosphorylation by pp60c-src in the range of 1.9-3.4 nmol.min-1.mg-1. Since the Vmax value for the purified 54-kDa fragment of pp60c-src was also included in this value, we conclude that proteolytic degradation of a 6-kDa fragment from the N-terminus of pp60c-src did not affect its kinase activity. Tryptic phosphopeptide analysis identified Tyr-416 as the major autophosphorylation site. Preincubation of purified pp60c-src with ATP increased the amount of autophosphorylation accompanied by an increase in Vmax, whereas the Km values were not altered. Our data directly demonstrate that autophosphorylation at Tyr-416 exerts, in contrast to phosphorylation at Tyr-527, a positive regulatory effect on the pp60c-src kinase activity.

Adenosine Triphosphate↗
PubMed1990

Platelet membrane glycoproteins IIb and IIIa are substrates of purified pp60c-src protein tyrosine kinase.

Human platelet glycoproteins IIb and IIIa form the receptor for fibrinogen, von Willebrand factor and fibronectin. Isolated human glycoproteins IIb-IIIa are phosphorylated by purified pp60c-src protein tyrosine kinase. Analysis of the phosphorylated proteins on SDS-PAGE showed that under reducing conditions both phosphoproteins change their relative molecular masses from 135 to 120 kDa and from 97 to 105 kDa, which are characteristic properties of glycoproteins IIb-IIIa. Phosphorylated proteins could be immunoprecipitated with an antiserum against glycoproteins IIb-IIIa but not by control serum. Some kinetic properties of the glycoprotein phosphorylations are also investigated. How the glycoprotein IIb-IIIa complex acquires its receptor activity in stimulated platelets is unknown; however, phosphorylation could be an important mechanism.

Blood Platelets↗
PubMed1989

Frequency of idiopathic gastric stasis and intestinal transit disorders in essential dyspepsia.

Gastric emptying, mouth-to-cecum transit (MCT), and whole-gut transit of a solid-liquid meal was measured in 30 control subjects and in 43 patients with essential dyspepsia, in whom organic digestive diseases and secondary disorders of gastric emptying had been excluded. The rate of gastric emptying was determined by an anterior gamma camera technique, MCT by the hydrogen breath test, and whole-gut transit by the first appearance of stool makers. Approximately 30% of patients with essential dyspepsia, predominantly women, in whom statistical analysis failed to reveal any specific pattern of symptoms, had significantly delayed gastric emptying suggesting idiopathic gastric stasis. Concerning MCT and whole-gut transit, significant differences between the control and study group could not be detected.

Adolescent↗
PubMed1989

The reducing effects of tazifylline on histamine-induced bronchoconstriction in atopic asthmatics.

Percentage reductions in the peak flow rates to a standardized number of histamine inhalations were compared after 7 days of treatment with 10 mg bd tazifylline and after 7 days of placebo in a randomized crossover study in 11 male seasonal atopic asthmatics. After tazifylline, mean % reductions in peak flow rates were significantly lower than after placebo (p = 0.03). The effects of tazifylline had disappeared within 7 days of stopping treatment. Using a 50% decrease in bronchial reactivity as the criteria of "protection", 7 of the subjects were "protected" by tazifylline only and none by placebo only (p = 0.03).

Adolescent↗
PubMed1988

High-yield purification of a pp60c-src related protein-tyrosine kinase from human platelets.

A protein-tyrosine kinase (PTK, EC 2.7.1.112) from human platelets was purified with high yield. Purification of the enzyme involved sequential chromatography on casein-agarose, tyrosine-agarose, heparin-Sepharose and hydroxylapatite. The procedure resulted in substantially enriched 54/52 kDa polypeptides on SDS-polyacrylamide gel electrophoresis and a yield of about 25% in PTK activity. About 250 micrograms of purified protein could be obtained from 1 g of cell protein. The purification factor varied between 1000 and 1500. Determination of the molecular mass of the purified PTK under nondenaturating conditions by molecular sieve chromatography revealed that the enzyme is a monomer of about 50 kDa. Among various protein substrates tested, casein was most prominently phosphorylated. All substrates were exclusively phosphorylated at tyrosine residues. Autophosphorylation at tyrosine residues of the 54/52 kDa proteins was observed in the presence of Mg2+ or Mn2+. At each purification step, the 54/52 kDa proteins were precipitated by sera from tumor-bearing rabbits immunoprecipitating pp60src, but not by control sera. The amount of the immunoprecipitated purified 54/52 kDa phosphoproteins was directly proportional to the amount of antiserum used. Partial peptide mapping by V8 proteinase showed a 26 kDa tyrosine-phosphorylated fragment for the 54 and the 52 kDa proteins as well as for the pp60c-src molecules of intact platelets. All these data indicated that purified PTK is closely related to pp60c-src of human platelets. Using casein as a substrate for the purified enzyme, the Km for ATP was 4 microM and the Vmax for the reaction was 2.0 nmol/min per mg.

Blood Platelets↗
PubMed1987

Amiloride inhibits the protein tyrosine kinases associated with the cellular and the transforming src-gene products.

Amiloride inhibits a protein tyrosine kinase from rat brain extracts. The kinase activity is characterized by an anti-serum (TBR-serum) which immunoprecipitates pp60c-src, the cellular counterpart of the transforming protein pp60v-src of Rous sarcoma virus. In immunocomplexes, TBR-IgG serves as an artificial but specific phosphate acceptor. The phosphate incorporation into TBR-IgG is a time- and temperature-dependent process. In the presence of amiloride the TBR-IgG phosphorylation is reduced. The drug does not influence the immunocomplexes formed by TBR-IgG and pp60src and no amiloride-activated protein tyrosine phosphatase can be detected in the immunocomplex system. Half-maximal inhibition of the tyrosine kinase occurs at 300 microM amiloride and is competitive with respect to ATP. Viral pp60src kinase of transformed cells is more sensitive to amiloride (IC50: 50-100 microM). Furthermore, normal cellular tyrosine kinases are to a lesser extent inhibited by amiloride as compared to the transforming viral pp60src kinase. These results may indicate different amiloride-sensitive forms of cellular pp60src kinases.

Adenosine Triphosphate↗
PubMed1986

[Operative treatment of asymptomatic carotid stenosis].

Over a period of five-and-a-half years 183 patients with high-grade asymptomatic carotid stenoses in stage I were operated upon. Postoperative mortality was 0.5%; there was no permanent morbidity. Cumulative survival rate after four years was 68%. The proportion of patients without neurological disorders after five years was nearly 100%. Asymptomatic re-stenoses were found in 6% of patients. Principal cause of death during the follow-up period was of cardiac origin (9 of 17).

Adult↗
PubMed1986

Alterations in immunoregulatory T-cell subsets in cigarette smokers. A phenotypic analysis of bronchoalveolar and blood lymphocytes.

Abnormalities in the proportions of immunoregulatory T-lymphocytes in bronchoalveolar lavage fluid have been reported in interstitial pulmonary diseases, yet the effect of cigarette smoking on T-cell subsets in bronchoalveolar lavage fluid from normal subjects has not been investigated. We applied an immunoperoxidase technique performed on glass slides using the monoclonal antibodies, OKT3, OKT4, OKT8, OKIa, and Leu-7 to study T-cell subsets in bronchoalveolar lavage fluid and blood of 11 normal nonsmokers and 12 smokers. In the bronchoalveolar lavage fluid of smokers, a decrease in the percentage of OKT4+ helper/inducer and an increase in OKT8+ suppressor/cytotoxic cells resulted in a markedly decreased OKT4/OKT8 ratio (0.9 +/- 0.4) compared with nonsmokers (1.9 +/- 0.8) (p less than 0.005). These abnormalities of lymphocyte subsets in bronchoalveolar lavage fluid correlated with the cumulative pack-years of smoking history but were not reflected in the peripheral blood. These results suggest that cellular immunoregulation is disturbed in the lungs of cigarette smokers. This may play a role in pulmonary defense mechanisms and tumor immunity.

Adult↗