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Biomedical subjects

W Seifert

Publications and source records attributed to W Seifert.

At least 73 records · Page 4Linked to original sources
PubMed1984

Simultaneous measurement of 2':3' cyclic-nucleotide 3' phosphodiesterase and RNase activities in sera and spinal fluids of multiple sclerosis patients.

The enzymes 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and RNase were simultaneously measured in the sera and CSF of multiple sclerosis (MS) and non-MS patients. No evidence of increased activity for these enzymes could be found regardless of pathology in either fluid source. Discrepancies between the present results and those from two previous studies that reported significant increases in CNPase activity in the CSF of patients with MS were carefully analyzed. It was concluded that the apparent increased CNPase activity correlated with MS in both previous studies was most probably the result of methodological and computational difficulties.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1984

[3 multicenter phase II studies of the treatment of small cell bronchogenic carcinoma (incl. AIO studies BI + BII)].

Between March 1979 und January 1983 122 patients with small-cell carcinoma of the lung were treated with different polychemotherapy regimen. 33 patients received VP-16-213 (etoposid), ifosfamide and vindesine (VPIV). 37 patients were treated with adriamycin, cisplatin and vincristine (APO). A third 3-drug combination, cyclophosphamide, methotrexate and CCNU (CMCC), was given to the remaining 52 patients alternating with the two other regimen. Response rates varied between 61% for the APO regimen and 85% for the VPIV regimen. The median survival was 10 months for patients treated with VPIV or APO and 12 months for patients treated with alternating drug combinations. This difference was not statistically significant. The rate of long-term survivors (longer than 2 years after diagnosis) was 9.9%. Side effects were seen more frequently in the group treated with APO.

Adolescent↗
PubMed1984

Biopterin synthesis defects: problems in diagnosis.

Hyperphenylalaninemia due to a biopterin synthesis defect was detected in an infant with decreased biopterin and increased neopterin levels in plasma and urine. Tetrahydrobiopterin (BH4) administration normalized plasma phenylalanine levels. CSF biopterin and neurotransmitter metabolite levels were normal and with the infant's normal growth and development suggest that the defect in biopterin synthesis did not affect CNS biopterin metabolism. Comparison of plasma and urine pterin levels from this patient with levels reported in patients who have neurologic complications fails to reveal differences that would distinguish patients at risk for neurologic problems. CSF pterin and neurotransmitter levels may correlate with neurologic function in these patients. CSF pterin and neurotransmitter determinations should be performed prior to initiation of neurotransmitter precursor and BH4 replacement therapies in patients who were determined to have biopterin synthesis defect(s).

Biopterins↗
PubMed1983

Pharmacokinetics of canrenone after oral administration of spironolactone and intravenous injection of canrenoate-K in healthy man.

Five healthy male volunteers received canrenoate-K 200 mg (Sincomen pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066 +/- 876 ng/ml was found after 29 +/- 15 min and thereafter the concentration declined with a half-life of 3.7 +/- 1.2 h. Total clearance was 4.2 +/- 1.7 ml/min . kg. After oral ingestion, the maximum concentration of 177 +/- 33 ng/ml was observed at 4.4 +/- 0.9 h. The absolute bioavailability of canrenone was 25 +/- 9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9 +/- 1.8 h (i.v.) and 3.9 +/- 1.2 h (p.o.).

Administration, Oral↗
PubMed1983

Pharmacokinetics of the new aldosterone antagonist, spirorenone, in healthy volunteers after single and repeated daily doses.

The plasma concentrations of spirorenone in two groups of male volunteers have been determined after single and 14 daily doses of spirorenone 10 and 40 mg. Independent of the dose and pretreatment, spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction were observed after prolonged treatment. In one test subject given spirorenone 40 mg, the concentration of an active metabolite, 1,2-dihydrospirorenone, was measured. This compound accumulated considerably after multiple dosing and the area under the plasma concentration-time curve increased from 16 to 52% relative to that of spirorenone itself.

Adult↗
PubMed1983

Characterization and partial purification of a ganglioside-associated mitogen.

A nonganglioside factor(s) present in Sigma types II and III mixed bovine brain ganglioside preparations synergises with suboptimal amounts of serum to induce proliferation specifically in nondividing B 103 neuroblastoma cultures. The active substance is nondialysable and soluble in water as well as in chloroform-methanol mixtures of 1:1-4:1 (vol/vol). It is completely insoluble in ether and acetone at room temperature. Biological activity survives heating to 70 degrees C in the presence of 0.1 M HCl for 1 h as well as boiling at neutral pH. Loss of activity occurs on heating to 70 degrees C for 1 h with 1 M HCl or 1 M NaOH. The activity is insensitive to digestion with neuraminidase, trypsin, pronase, and phospholipases A2 and C. The factor cochromatographs with gangliosides on Dowex AG 50W and Sephadex G100 and is partially recovered with GM1 on DEAE-Sepharose, but may be isolated in a ganglioside-free fraction by sequential chromatography on Sephadex LH20 and silicic acid columns. The substance(s) has the properties of a water-soluble proteolipid protein, the amino acid composition being reported. It is not immunologically cross-reactive with antibodies to GM1 ganglioside or the major proteolipid protein of myelin.

Amino Acids↗
PubMed1982

A neurotrophic factor (NTF) released from primary glial cultures supports survival and fiber outgrowth of cultured hippocampal neurons.

A nearly pure neuronal culture from embryonic rat brain (hippocampus) has been established in order to observe individual neurons during their in vitro development. This neuronal culture has been used as a test system for a neurotrophic factor (NTF) which is released into a serum-free defined medium, presumably by astrocytes, the dominant cell type in a primary glial culture from rat brain. NTF is essential for the development of the hippocampal neurons in cell culture. The number of neurons responding to NTF by neurite extension is highly dependent on the concentration of the factor in the culture medium. The amount of factor in serum-free glial conditioned medium can be estimated in a rapid (20-hour) bioassay.

Animals↗
PubMed1982

Human tissue distribution of platinum after cis-diamminedichloroplatinum.

Using X-ray fluorescence spectrometry, platinum concentrations were determined in autopsy tissue samples from 12 patients who had received cis-diamminedichloroplatinum (DDP) 20-120 mg/m2 up to 6 months antemortem. Tissue platinum concentrations were highest in liver (0.5-3.7 micrograms/g wet weight), prostate (1.6-3.6 micrograms/g), and kidney (0.4-2.9 micrograms/g), somewhat lower in bladder, muscle, testicle, pancreas, and spleen, and lowest in bowel, adrenal, heart, lung, cerebrum, and cerebellum, Platinum concentrations in tumors were generally somewhat lower than the concentration in the organ in which the tumor was located, with the exception of intracerebral tumors. Different metastatic sites in the same patient had substantially different platinum concentrations and hepatic metastases had the highest concentrations. Intra-arterial administration of drug may augment tissue concentrations of platinum. In a patient undergoing therapeutic abortion 4 days after treatment, the platinum concentration was 0.5 micrograms/g in the placenta and 0.3 micrograms/g in the fetus. The data suggest that for in vitro sensitivity testing, DDP concentrations of less than or equal to 7 micrograms/ml should be used.

Autopsy↗
PubMed1982

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) activity in cultured nerve cell lines from central nervous system: comparison of proliferating and resting growth states and cell cycle-dependent activity changes.

1. The present communication is concerned with the expression and cell cycle-dependent regulation of the enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in cultured nerve cell lines derived from the rat central nervous system (CNS). 2. The enzyme activity was measured in relation to two reversible serum-controlled growth states (exponentially growing/quiescent) including a comparison of the enzyme activities in cell lines of neuronal and glial origin as well as in fibroblasts. CNPase is present in all cell types tested, but the enzyme activity is very sensitive to changes in the cellular growth state. Nerve cell lines in exponentially growing cultures express a 3 to 15 times higher specific CNPase activity than the nonneural cell types. In serum-starved quiescent cultures, the differences in specific enzyme activity between the nerve cell lines and the fibroblasts are enlarged even more up to a ratio of about 50 to 150, indicating a specific function of this enzyme within the central nervous system. 3. Neuron-like B104 cells could be stimulated to synchronized growth by serum readdition to quiescent cultures. A series of ordered activity changes of CNPase has been observed after the reinitiation of cell growth. The enzyme is stimulated at two particular stages during the cell cycle, leading to a biphasic activity profile. Maximum stimulation of CNPase correlates with the G1 phase. 4. Hydroxyurea-induced blockage of synchronized B104 cells to traverse the S phase also prevents the subsequent stimulation of CNPase activity. Therefore, we conclude that a correlation exists between the periodic activity changes of CNPase and particular phases of the B104 cell cycle.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1982

Development of oligodendrocytes and Schwann cells studied with a monoclonal antibody against galactocerebroside.

We have generated a hybridoma cell line secreting a monoclonal antibody that specifically binds to the surfaces of oligodendrocytes and Schwann cells, the cells involved in myelin formation in the central and peripheral nervous systems, respectively. Binding studies using purified sphingolipids showed that this antibody reacts strongly with galactocerebroside (GalC), the major galactosphingolipid of myelin. The antibody was used in conjunction with rabbit antisera against sulfatide, the sulfated form of GalC, to examine the developmental appearance of these lipids on the surfaces of oligodendrocytes and Schwann cells. In addition, the loss of GalC and sulfatide from freshly dissociated Schwann cells was compared. These studied showed that GalC is expressed on the cell surface prior to sulfatide on both of these cell types in vivo and in vitro. Conversely, dissociated Schwann cells lose their cell surface sulfatide more rapidly than they lose their surface GalC under nonmyelinating conditions.

Aging↗
PubMed1981

Intracellular localization of 2',3'-cyclic nucleotide 3'-phosphodiesterase in a neuronal cell line as examined by immunofluorescence and cell fractionation.

The enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, EC 3.1.4.37) occurs not only in myelin fractions and glial cells, but can also be shown to be present in a CNS cell line of neuronal origin (B104). Direct immunofluorescence microscopy of B104 cells with fluorescein isothiocyanate-conjugated rabbit anti-CNPase antibodies shows a discrete and specific intracytoplasmic location of CNPase. Fractionation of the cells was performed by differential centrifugation of a cell homogenate and continuous sucrose density-gradient centrifugation. As monitored by marker enzyme activities, CNPase seems to be associated with endoplasmic reticulum membranes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1981

Characterization of 2':3'-cyclic nucleotide 3'-phosphodiesterase: rapid isolation, native enzyme analysis, identification of a serum-soluble activity, and kinetics.

The enzyme 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) was isolated from bovine brain white matter by a rapid (72 h) procedure. The minimum molecular weight (MW) of the enzyme was approximately 52,500 as estimated by sucrose density gradient analysis. When this isolated enzyme was stimulated with bovine serum albumin (BSA), the peak of activity was shifted to approximately 90,000 MW. Prior treatment by trypsin blocked the expression of the higher MW form of CNPase, but not the BSA activation of the enzyme. If the trypsin digestion was allowed to progress, the MW was gradually lowered to a broad peak sedimenting between 20,000 and 50,000 MW. An apparently soluble form of CNPase found in serum is described. Kinetic and MW comparisons between the serum soluble enzyme and CNPase isolated from bovine brain, as well as an analysis of substrate specificity, were made and it was concluded that the two enzymes were identical.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1981

Characterization of 2':3'-cyclic nucleotide 3'-phosphodiesterase: limited proteolytic digestion, plant lectin affinity chromatography, and immunological identification.

Purified bovine brain 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) migrates as a protein double band in SDS-polyacrylamide gel electrophoresis. The positions of the two protein bands correspond to approximate molecular weights (MW) of 56,000 and 53,000. Limited protease treatment of isolated CNPase leads to subsequent degradation of the enzyme into smaller polypeptides having MWs of approximately 40,000, 30,000, and 20,000. During proteolytic digestion CNPase remains enzymatically active. Binding studies with several immobilized plant lectins as well as periodic acid-Schiff reagent (PAS) staining of SDS gels indicate that CNPase is a glycoprotein. An antiserum against purified CNPase, prepared in rabbits, was used to confirm the immunological identity of various CNPase preparations obtained in our laboratory.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1980

Effects of detergents, proteins, and lipids on 2':3'-cyclic-nucleotide 3'-phosphodiesterase activity.

The myelin marker 2':3'-cyclic-nucleotide 34'-phosphodiesterase (CNPase) was isolated to a lipid- and phosphate-free stage. The effects of exogenously added lipids were tested on this preparation and compared to the known stimulation of the enzyme by detergents and proteins. CNPase could be stimulated 2-3 fold by these various agents which appeared to be additive in their effect. Enzyme-protein and enzyme-lipid interactions and possible medical use of the improved assay conditions for CNPase employed in the study are discussed.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗