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Biomedical subjects

T Meyer

Publications and source records attributed to T Meyer.

At least 397 records · Page 22Linked to original sources
PubMed1987

Enhancement of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA amplification in a Simian virus 40-transformed Chinese hamster cell line by 3-aminobenzamide.

A Simian virus 40-transformed Chinese hamster cell line (CO 60) amplifies integrated viral DNA sequences as a response to treatment with a variety of carcinogens. To study a possible involvement of poly(ADP-ribose) synthesis, DNA amplification was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), an alkylating carcinogen that strongly stimulates poly(ADP-ribose) synthesis. In the presence of 3-aminobenzamide (3AB) (2 mM), a competitive inhibitor of poly(ADP-ribose) polymerase, MNNG-induced amplification was increased two to six times the level induced by MNNG alone. Concomitantly, 3AB reduced cellular poly(ADP-ribose) levels and increased MNNG-induced cytotoxicity, as expected. The effect of 3AB on MNNG-induced amplification depended both on the concentration of 3AB and the duration of its presence after MNNG treatment. By contrast, 3-aminobenzoic acid, a noninhibitory structural analogue of 3AB, had no influence on amplification induced by MNNG. These data strongly suggest an involvement of poly(ADP-ribose) in the process of DNA amplification, as it is shown that inhibition of carcinogen-stimulated poly(ADP-ribose) synthesis by 3AB is correlated with an enhancement of inducible DNA amplification in this cell line.

Animals↗
PubMed1987

Echocardiographic and hemodynamic correlates of diastolic closure of mitral valve and diastolic opening of aortic valve in severe aortic regurgitation.

Acute severe aortic regurgitation (AR) is characterized by a steep increase in left ventricular end-diastolic pressure, exceeding left atrial pressure and occasionally equilibrating with aortic diastolic pressure. These pressure phenomena correlate with the M-mode echocardiographic (echo) findings of diastolic closure of the mitral valve (DCMV) and diastolic opening of the aortic valve (DOAV). Six men, aged 23 to 48 years, with recent-onset, severe AR were evaluated by M-mode echo and pressures at cardiac catheterization. DCMV was seen in all 6 patients and DOAV in 4. Near-constant time intervals from the preceding R wave of the electrocardiogram to DCMV and DOAV were seen, even in 3 patients with varying RR intervals (1 with atrial fibrillation and 2 with asynchronous and demand atrial pacing). When the RR intervals were shorter than these intervals, DCMV and DOAV did not occur. Increasing the heart rate in the 2 patients by atrial pacing resulted in a marked decrease in left ventricular end-diastolic pressure. In conclusion, DCMV and DOAV have a near constant relation to the preceding R wave of the electrocardiogram, DCMV with competence of the mitral valve must be present for DOAV to occur, DOAV indicates that the diastolic blood pressure equals left ventricular end-diastolic pressure, and heart rate is an important factor influencing the hemodynamic and echocardiographic parameters in recent-onset, severe AR.

Adult↗
PubMed1986

The lipophilic muramyltripeptide MTP-PE, a biological response modifier, is an activator of protein kinase C.

The lipophilic immunomodulator MTP-PE is able to activate purified protein kinase C (PKC) by substituting phosphatidyl-serine (PS) or the synthetic diacylglycerol, DiC8, in the assay system. In addition, MTP-PE inhibited [3H]-phorbol-12, 13-dibutyrate ([3H]-PDBu) binding to PKC in a reconstituted receptor system as well as on intact cells (MCF-7). Furthermore, MTP-PE was also able to reduced the epidermal growth factor binding of MCF-7 cells to an extent similar to that found with DiC8 or PDBu. These data indicate that MTP-PE is able to compete for the phorbol ester binding site on PKC both in vivo and in vitro. The components of the MTP-PE molecule, MTP (muramyl-tripeptide) and PE (phosphatidylethanolamine) exerted only marginal effects on PKC activity, did not affect the phorbol ester binding of PKC and the EGF binding of intact MCF-7 cells. Our results suggest that only the complete molecule of the immunomodulator MTP-PE is able to interact with PKC.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Production of anti-(ADP-ribose) antibodies with the aid of a dinucleotide-pyrophosphatase-resistant hapten and their application for the detection of mono(ADP-ribosyl)ated polypeptides.

Previous attempts to produce anti-(ADP-ribose) antibodies by immunization of rabbits with ADP-ribose conjugated to serum albumin had resulted in the production of 5'AMP-specific antibodies [Bredehorst et al. (1978) Eur. J. Biochem. 82, 105-113]. To obtain true anti-(ADP-ribose) antibodies an antigen was constructed that was resistant to enzymic degradation at the pyrophosphate group. The enzymically active beta-methylene derivative of NAD (NAD[CH2]) was synthesized from ADP containing a methylene bridge (CH2) instead of an oxygen in the diphosphate group. NAD[CH2] was converted to its N6-[(2-carboxyethyl)thiomethyl] derivative and hydrolyzed to the corresponding ADP[CH2]-ribose derivative which was then coupled to bovine serum albumin. The antibodies obtained with this antigen were specific for free or protein-bound ADP-ribose groups, except for a cross-reaction with FAD, AMP, ADP, ATP or poly(ADP-ribose) interfered with [3H]ADP-ribose tracer binding only at higher concentrations. No interference was observed with poly(A), RNA and DNA at 6000-fold excess. The antibodies were purified on a novel type of affinity matrix. This was formed from NAD and guanidinobutyrate by a cholera-toxin-catalyzed reaction and the product, ADP-ribosyl guanidinobutyrate, was bound to Affi Gel by carbodiimide-aided condensation. The purified antibodies allowed the detection of ADP-ribose conjugated to polypeptides in amounts lower than 1 pmol as demonstrated by immunoblotting of [14C]ADP-ribosylated elongation factor 2. They also could be used to observe in situ, by indirect immunofluorescence, the increased mono(ADP-ribosyl)ation of nuclear proteins in dimethyl-sulfate-treated cells, and to show that histone H2B was the principal histone acceptor of single ADP-ribose groups in alkylated 3T3 cells.

Adenosine Diphosphate Ribose↗
PubMed1986

Antagonism of interferon induction in spleen and adherent peritoneal cells of mice by the lipophilic antiviral muramyl peptide MTP-PE.

The immunomodulator muramyl tripeptide-phosphatidylethanolamine (MTP-PE) has been shown to enhance host resistance against a variety of experimental infections and to cure influenza virus infection in mice when given in a single dose, even at a late stage of the disease. Tests of its capacity to induce alpha/beta- and gamma-interferon (IFN-alpha/beta and -gamma) in vitro demonstrated that it is neither an inducer nor a primer of IFN synthesis. On the contrary, we found that it inhibits the induction of IFN-alpha/beta and -gamma by poly(rI:rC), Newcastle disease virus, lipopolysaccharide, or concanavalin A in adherent cells from the peritoneal cavity and spleen of mice. The antiviral activity of already induced or exogenously added murine IFN was, however, not impaired.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

[CEA studies in squamous cell carcinomas of the head and neck].

The serum CEA levels of 134 patients with squamous cell carcinoma of the head and neck were studied at the time of diagnosis, at the end of primary therapy and every three months during the follow-up period. Since such patients are mostly nicotine and alcohol addicts, only CEA concentrations above 5 ng/ml were regarded as abnormal. At the time of diagnosis 30% of the patients had clearly abnormal CEA values, more commonly in oropharyngeal and hypopharyngeal tumours than for oral and laryngeal carcinomas. The incidence of pathological CEA concentrations also increased with increasing tumour extension, to a greater extent in well-differentiated than in undifferentiated squamous cell carcinomas. After termination of the primary therapy we found no correlation between success of treatment and serum CEA concentration. Studies of the course of CEA values in tumour-free patients revealed both rising and falling serum values during the period of observation. It was not possible to diagnose tumour recurrence early with the aid of increasing CEA concentrations. CEA exhibits only moderate sensitivity towards squamous cell carcinomas of the head and neck. As correlations between the course of the disease and CEA concentrations in serum could only rarely be observed, the usefulness of this tumour marker for following the course of head and neck squamous cell carcinoma must be regarded as rather low.

Adult↗
PubMed1984

NAD[S], an NAD analogue with reduced susceptibility to phosphodiesterase. Chemical synthesis and enzymic properties.

The chemical synthesis of adenosine(5') [alpha-thio]diphospho(5')ribofuranosyl-nicotinamide (NAD[S]) is described. The product occurs as a pair of diastereomers with different configuration at the sulfur-bearing phosphorus atom. The diastereomers were separated by high-performance liquid chromatography and their absolute configuration was determined after chemical degradation to the ADP[alpha S] diastereomers and chromatographic comparison with enzymically synthesized ADP[alpha S] diastereomers of known absolute configuration. Additional support for this assignment is based on different rates in the phosphodiesterase-catalyzed hydrolysis. Furthermore the synthesis of [14C]NAD[S] is described. The coenzyme activity of NAD[S] in the reaction with alcohol dehydrogenase from baker's yeast and lactate dehydrogenase from pig heart is very similar to that of beta-NAD. Also, NAD and NAD[S] serve equally well as substrates for NAD glycohydrolase from calf spleen. In contrast, no reaction was detected with NAD pyrophosphorylase, and hydrolysis of the separated NAD[S] diastereomers with snake venom phosphodiesterase showed a 26-fold and a 33-fold slower reaction rate than that of NAD. Nucleotide pyrophosphatase was less sensitive to the S substitution, hydrolyzing NAD[S] 14-times slower than NAD. Poly(ADP-ribose) polymerase from Ehrlich ascites tumor cell nuclei accepted NAD[S] as a substrate but the reaction was significantly slower and approached saturation at much lower values than with NAD. Alkaline hydrolysis of the products insoluble in trichloroacetic acid yielded AMP[S] as the main derivative. It is concluded that with NAD[S] as a substrate the nuclear acceptors were nearly exclusively mono(ADP-ribosyl) ated .

Alcohol Dehydrogenase↗
PubMed1984

Lupus erythematosus with erythema multiforme (Rowell's syndrome). A case report.

A patient who presented with erythema multiforme on clinical and histological examination but who subsequently developed fatal, fulminant systemic lupus erythematosus is reported. The prognostic significance of the development of erythema multiforme-type lesions in lupus erythematosus is discussed with reference to cases reported by Rowell et al. and Provost et al. The term 'Rowell's syndrome' is best avoided.

Adult↗
PubMed1984

Combined action of mouse alpha and beta interferons in influenza virus-infected macrophages carrying the resistance gene Mx.

In mice, the combined action of alpha and beta interferons (IFNs) against influenza viruses is modulated by the host gene Mx. High concentrations of IFN fail to prevent efficiently the replication of influenza A virus in cultured macrophages lacking the gene Mx, whereas cultured macrophages carrying Mx develop strong antiviral activity even at low concentrations of IFN. Several steps in the replication cycle of influenza virus were compared in Mx/Mx and +/+ mouse macrophages treated with IFN-alpha + beta. Uncoating was not affected. A twofold reduction in the accumulation of primary transcripts was observed in IFN-treated macrophages at the highest concentration of IFN regardless of the genetic constitution of the host cell. No evidence was obtained for inhibition of influenza virus translation in macrophages which lacked Mx when treated with IFN-alpha + beta. In contrast, a marked shut-off of influenza virus polypeptide synthesis occurred in Mx-bearing macrophages treated with these IFNs, although the primary transcripts were active in directing the synthesis of viral polypeptides in a cell-free system. We concluded that a specific inhibitory mechanism for influenza virus translation was induced by IFN-alpha + beta in macrophages bearing the resistance gene Mx.

Animals↗
PubMed1984

Molecular structure and biochemical activity of 3,5,3'-triiodothyronamine.

The thyroid hormone decarboxylation product, 3,5,3'-triiodothyronamine (T3AM), has been shown to inhibit the cAMP production stimulated by isoproterenol in turkey erythrocytes. This adrenergic receptor binding inhibition was not shown by the thyroid hormones nor by tyramine, but was observed for 3,5-diiodotyramine, 3,5-diiodothyronamine, and thyronamine. T3AM also inhibits prolactin secretion in cultured pituitary cells as well as domperidon binding in rat corpora striata membranes. T3AM has no thyromimetic activity at the nuclear level. The molecular structure of T3AM, determined as a borosalicylate salt by X-ray diffraction techniques, is the first report of a decarboxylated thyroid hormone analogue.

Animals↗
PubMed1983

Ethanol interaction with propoxyphene and norpropoxyphene metabolism in isolated rat hepatocytes.

Suspensions of isolated rat hepatocytes (approximately 7.5 X 10(5) cells/ml) metabolized added propoxyphene and norpropoxyphene rapidly. At 2 microM, the metabolism of both drugs obeyed first-order elimination kinetics. Increasing propoxyphene concentrations (1, 2, 4 and 8 microM) gradually increased the medium concentrations of norpropoxyphene. The total propoxyphene metabolism was the same at 4 and 8 microM. The effect of ethanol (10 and 60 mM) on propoxyphene (2 microM) and norpropoxyphene (2 microM) metabolism in suspensions of isolated rat hepatocytes was studied. The half-lives of propoxyphene were 7.1 +/- 5.5 min in absence and 6.7 +/- 2.8 min in presence of 10 mM ethanol, but increased to 10.7 +/- 5.8 min in presence of 60 mM ethanol (p less than 0.05). The half-lives of added norpropoxyphene increased from 17.9 +/- 4.1 min to 26.0 +/- 7.3 min at 10 mM ethanol (p less than 0.05) and 29.3 +/- 5.9 min at 60 mM ethanol (p less than 0.05). Ethanol (60 mM) reduced the elimination rate constant of propoxyphene and norpropoxyphene by 31 +/- 25% and 38 +/- 15%, respectively.

Animals↗
PubMed1983

Triiodothyronamine--a beta-adrenergic metabolite of triiodothyronine?

Triiodothyronamine (Triam) is a potential metabolite of triidothyronine (T3), resulting from decarboxylation of the side-chain. In an attempt to elucidate the physiological properties of Triam we have investigated the binding of Triam to beta-adrenergic receptors, using turkey-erythrocytes and performing binding studies with ( (-)(3H)-dihydroalprenolol) ( (-)(3H)-DHA) as a specific beta-adrenergic ligand. The inhibition constant Ki for Triam was determined as 5 X 10(-6) M, compared to dopamine (Ki = 1,3 X 10(-2) M), norepinephrine (Ki = 3 X 10(-4) M), epinephrine (Ki = 5 X 10(-5) M) and isoproterenol (Ki = 3 X 10(-6) M). The inhibition of ( (-)(3H)-DHA)-binding by Triam was further compared with other iodothyronines thyroxine (T4), T3, 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2). It is concluded that Triam binds to beta-adrenergic receptors like naturally occurring amines but different from typical circulating iodothyronines.

Animals↗