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Biomedical subjects

S Heinemann

Publications and source records attributed to S Heinemann.

At least 91 records · Page 5Linked to original sources
PubMed1986

Cardiovascular actions of dihydralazine as modified by dietary linoleic acid.

The experiments were carried out in order to examine whether the hypotensive effect of dihydralazine can be augmented by concomitant ingestion of a diet enriched with linoleic acid. After prefeeding with a linoleic acid rich diet (13.3 J%) an augmented hypotensive dihydralazine effect (11-24 mm Hg) could be observed in acute experiments in conscious (1 mg/kg i.v.) and pentobarbital-anaesthetised (4 mg/kg i.v.) normotensive rats with different duration of the feeding period as well as in conscious (1 mg/kg i.v.) spontaneously hypertensive rats relative to linoleic acid poor (0.5 J%) fed animals. This effect was abolished by pretreatment with the cyclooxygenase inhibitors indomethacin (10 mg/kg i.v.) or acetylsalicylic acid (100 mg/kg i.v.). The chronotropic dihydralazine response was with one exception not different between the two dietary groups. In chronic experiments with spontaneously hypertensive rats the augmentation of the hypotensive dihydralazine effect (1 mg/kg X d, s.c.) after linoleic acid rich diet did not attain statistical significance after a 6-weak prefeeding period. The renovasodilatory action of dihydralazine (3 mg) was increased in isolated kidney preparations of linoleic acid rich fed rats. This effect was accompanied by a shift of the prostaglandin formation toward vasodepressive PGE. We conclude that the altered cardiovascular effects of dihydralazine after linoleic acid rich diet are primarily caused by changes in the formation of prostaglandins and the activity of the sympathetic nervous system.

Animals↗
PubMed1985

Isolation of a clone coding for the alpha-subunit of a mouse acetylcholine receptor.

The mouse cell line BC3H-I synthesizes an acetylcholine receptor (AChR) with the pharmacological properties of a muscle nicotinic cholinergic receptor. We have purified mRNA from this cell line and used the size-fractionated poly(A)+RNA to produce a cDNA library of approximately 50,000 clones. The library was screened with a subclone containing genomic sequences coding for the putative acetylcholine-binding site of the alpha-subunit of chicken AChR. We obtained a plasmid, pMAR alpha 15, with a 1,717-base pair insert. The insert cDNA has 26 nucleotides at the 5'-end which code for a portion of the signal peptide followed by a single open reading frame of 1,311 nucleotides which code for a protein of 49,896 daltons. The insert has 377 bases of 3'-untranslated sequence with 3 polyadenylation sites. Radiolabeled plasmid DNA has been used to identify homologous RNA species of about 2 kilobases in Northern blot analyses of poly(A)+ selected RNA from BC3H-I cells. A similar size mRNA is seen in innervated mouse diaphragm and leg muscle, and both mouse and rat brain. Comparisons of the deduced amino acid sequence of the mouse AChR alpha-subunit with Torpedo marmorata, T. californica, chicken, human, and calf sequences show overall homologies of 80%, 80%, 86%, 96%, and 95%, respectively. More detailed analyses reveal a non-random distribution of amino acid substitutions in several structural domains. Based on the absolute conservation of cysteine residues, a new model for the arrangement of the disulfide bonds in the extracellular portion of the alpha-subunit is proposed.

Amino Acid Sequence↗
PubMed1985

Muscle denervation increases the levels of two mRNAs coding for the acetylcholine receptor alpha-subunit.

The mRNA coding for the alpha-subunit of the acetylcholine receptor was studied in mouse leg and rat diaphragm muscle. We find that denervation of rat diaphragm results in a 7-fold increase in mRNA coding for the alpha-subunit, whereas denervation of mouse leg muscle results in approximately a 50-fold increase in alpha-subunit-specific mRNA. The relationship of the mRNAs purified from innervated and denervated muscle was investigated by SI nuclease mapping. Two mRNA species were found in both innervated and denervated muscle which differ in their 3'-untranslated region. The levels of both these mRNA species increase upon denervation of mouse leg muscle.

Animals↗
PubMed1983

Nucleotide and deduced amino acid sequences of Torpedo californica acetylcholine receptor gamma subunit.

The nucleotide sequence has been determined of a cDNA clone that codes for the 60,000-dalton gamma subunit of Torpedo californica acetylcholine receptor. The length of the cDNA clone is 2,010 base pairs. The 5' and 3' untranslated regions have respective lengths of 31 and 461 base pairs. Data suggest that the putative polyadenylylation consensus sequence A-A-T-A-A-A may not be required for polyadenylylation of the mRNA corresponding to the cDNA clone described in this study. From the DNA sequence data, the amino acid sequence of the gamma subunit was deduced. The subunit is composed of 489 amino acids giving a molecular mass of 56,600 daltons. The deduced amino acid sequence data also indicate the presence of a 17-amino acid extension or signal peptide on this subunit. From these data, structural predictions for the gamma subunit are made such as potential membrane-spanning regions, possible asparagine-linked glycosylation sites, and the assignment of regions of the protein to the extracellular, internal, and cytoplasmic domains of the lipid bilayer.

Amino Acid Sequence↗
PubMed1982

Mutants in the y region of bacteriophage lambda constitutive for repressor synthesis: their isolation and the characterization of the Hyp phenotype.

Bacteriophage lambdahyp mutants have been isolated as survivors of Escherichia coli K-12 bacteria lysogenic for lambda Nam7am53cI857. The hyp mutants are characterized by (i) their localization in the y region very close to the imm lambda/imm434 boundary, (ii) polarity on O gene expression, (iii) immediate recovery of lambda immunity at 30 degrees C after prolonged growth of lambda Nam7am53cI857 hyp lysogens at 42 degrees C even in the presence of an active cro gene product, (iv) ability of phage lambda v2v3vs326 but not lambda v1v2v3 to propagate on lambda cI+hyp lysogens, (v) inability to express lambda exonuclease activity after prophage induction, and (vi) inviability at any temperature of phage carrying the hyp mutation. All these properties are referred to collectively as the Hyp phenotype. We show that the Hyp phenotype is due to cII-independent constitutive cI-gene-product synthesis originating in the y region, which results in the synthesis of anti-cro RNA species, and constitutive levels of cro gene product present even in lambda cI+hyp lysogens. A model is presented which is consistent with all the experimental observations.

Antigens, Viral↗
PubMed1982

Molecular cloning of cDNA coding for the gamma subunit of Torpedo acetylcholine receptor.

From the electric organ of Torpedo californica, we purified mRNA that, when translated in vitro, produces polypeptides immunoprecipitable by antibodies against purified acetylcholine receptor. A novel cloning system [Okayama, H. & Berg, P. (1982) Mol. Cell. Biol. 2, 161-170] was used to produce a cDNA library from this mRNA. This library contained clones with receptor sequences identified by differential hybridization and hybridization-selection. We describe a clone of 2,030 base pairs with sequences appropriate for the amino-terminal amino acids of the gamma subunit of acetylcholine receptor. This clone contains 82 bases 5' of the codon for the amino-terminal amino acid of the mature protein. A portion of this sequence codes for a methionine followed by a 16-amino acid polypeptide that is contiguous to the amino-terminal amino acid of the mature protein and that has the characteristics of a leader peptide. The cDNA insert hybridizes to a 2,100-base RNA present in electric organ but not in the brain of T. californica.

Animals↗
PubMed1981

Phycomycosis as postoperative complication of urologic surgery.

A case of phycomycosis (Mucor) complicating urologic surgery is presented. It is a rare disease that is rapidly fatal, though caused by a usually benign saphophytic fungus. No previous urologic surgical cases have been found in the literature where Mucor has been a postoperative complication.

Aged↗
PubMed1981

Factors affecting the susceptibility of different strains of mice to experimental myasthenia gravis.

Mice immunized with purified AChR (T. californica) invariably form anti-AChR antibodies and often develop a condition of extreme muscular weakness and flaccid paralysis. Pharmacological, physiological, and ultrastructural studies indicate that the pathophysiology of EMG in the mouse closely resembles that of human MG. The single episode of muscular weakness typically found in mouse EMG differs from the acute phase of rat EMG in that macrophages and other phagocytes do not appear to play an active role in the destruction of the neuromuscular junction. The frequency of paralysis in mice immunized with AChR is highly strain dependent and is not attributable to polymorphisms with respect to susceptibility to cholinergic blockade. The incidence of paralysis does not correlate with the magnitude of the humoral response to either T. californica or mouse AChR. Because both paralyzed and nonparalyzed mice form antibodies which are able to increase the rate of both junctional and extrajunctional AChR degradation, the mere presence of antibodies reactive with cell surface antigenic determinants of AChR is not sufficient for the induction of paralysis. While it is still possible that antibody-induced degradation of AChR may be necessary for the induction of paralysis, these studies rule out the possibility that antigenic modulation of AChR is sufficient to account for the induction of paralysis in mouse EMG. In the present studies alleles of the two loci were identified which significantly effect the probability with which mice immunized with AChR can be expected to become paralyzed, the MHC and the IgCH region. Because one genotype, H-2b, Ig-1b segregated with high susceptibility to EMG in four strains derived from three dissimilar backgrounds, these studies strongly suggest that susceptibility to the development of paralysis is a heritable trait determined by regions of the mouse genome which regulate immune responsiveness.

Animals↗
PubMed1979

Acetylcholine receptor degradation in adult rat diaphragms in organ culture and the effect of anti-acetylcholine receptor antibodies.

Acetylcholine receptor located at the neuromuscular synapse of normal innervated adult muscle fibers is extremely stable metabolically. We have studied the kinetics of receptor degradation in both normal innervated and denervated rat diaphragms in organ culture. These studies show that degradation of receptor-bound 125I-alpha-bungarotoxin is a valid measure of junctional receptor degradation. Degradation of junctional receptor is similar or identical to degradation of extrajunctional receptor in many ways: 1) both require energy, 2) both are inhibited by specific lysosomal protease inhibitors, 3) both are inhibited by treatment with colchicine, and 4) both are stimulated by treatment with anti-acetylcholine receptor antibodies. The one important distinction between degradation of junctional and extrajunctional receptor is a 10-fold difference in rate constant for the process.

Acetylcholine↗
PubMed1979

Degradation of acetylcholine receptor in diaphragms of rats with experimental autoimmune myasthenia gravis.

The degradation of acetylcholine receptor observed in denervated and innervated normal rat diaphragms in organ culture is stimulated by exogenous antireceptor serum. In this paper we demonstrate that diaphragms from rats with experimental autoimmune myasthenia gravis contain reduced amounts of acetylcholine receptor. Acetylcholine receptor from myasthenic, but not from normal, rats has antibody bound to it and is degraded at an accelerated rate. We conclude that in the chronic phase of experimental autoimmune myasthenia gravis increased acetylcholine receptor degradation can be accounted for by a mechanism involving antigenic modulation, and that such a process can contribute to the clinical symptoms of impaired neuromuscular transmission.

Acetylcholine↗
PubMed1979

Degradation of junctional and extrajunctional acetylcholine receptors by developing rat skeletal muscle.

We have examined the rate of degradation of the total acetylcholine receptor content of diaphragm muscles of young rats and have found that even in muscles from 1-day-old rats some receptors are metabolically more stable than adult extrajunctional receptors. Further experiments have shown that acetylcholine receptors at junctional regions from young rats are degraded slowly, whereas those in extrajunctional regions are degraded rapidly. The results demonstrate that junctional acetylcholine receptors in rat diaphragm are degraded at a slow rate characteristic of adult junctional receptors at all ages after birth.

Acetylcholine↗
PubMed1978

Biology of cultured nerve and muscle.

Cells from the nervous system can be grown in culture and exhibit many of the biophysical, biochemical, and morphological properties found in vivo. They can be induced to differentiate in culture and perform some of the interactions that occur in the nervous system, including synaptogenesis. A number of important questions relating to nervous system development and function have been approached in culture in ways that cannot be done in vivo. The use of clonal cell lines should lead to rapid progress in the analysis of the nervous system at the chemical level.

Acetylcholine↗
PubMed1977

Cholinergic metabolism and synapse formation by a rat nerve cell line.

The PC12 clone of a rat pheochromocytoma is able to synthesize acetylcholine. The amount of acetylcholine synthesized, and the specific activity of choline O-acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), varies as a function of the culture growth curve and is dependent on cell density. The specific activity of choline acetyltransferase is increased by nerve growth factor, growth-conditioned medium from a variety of cell types, and adenosine 3':5'-monophosphate. Finally, the PC12 cell line is able to form cholinergic synapses with a clonal cell line of skeletal muscle origin.

Acetylcholine↗