Biomedical subjects

E Widmark

Publications and source records attributed to E Widmark.

28 records · Page 2Linked to original sources

PubMed1985

Comparison of the effects of forskolin and isoprenaline on tracheal, cardiac and skeletal muscles from guinea-pig.

Forskolin, a potent activator of adenylate cyclase, and isoprenaline, an unselective beta-adrenoceptor agonist, were studied in vitro on tissues from guinea-pig with respect to relaxation of the carbachol-contracted trachea, increase in the force of contraction of the papillary muscle and depression of subtetanic contractions of the soleus muscle, three well-characterized beta-adrenoceptor-mediated effects. Forskolin and isoprenaline relaxed the trachea and increased the force of contraction of the papillary muscle. Isoprenaline but not forskolin caused a depression of the subtetanic contraction of the soleus muscle. Forskolin did not seem to potentiate the effects of isoprenaline on the tissues studied; the combined effects appeared to be a mere addition. Forskolin did not increase the efficacy of the partial agonist prenalterol either. It is concluded that there is no simple relation between c-AMP generation and the functional response to beta-adrenoceptor agonists. Forskolin should not be used uncritically to probe beta-adrenoceptor-mediated effects.

Animals↗

PubMed1985

Gene duplications in the TL region of the mouse major histocompatibility complex.

We have isolated a class I gene from the TL region of the A/J mouse. The gene, T2A, is a homologue of the C57BL/10 mouse gene T2. In the process of mapping this gene we screened a number of BALB/c class I cosmid clusters with a T2A flanking probe. Several of the hybridizing clusters were found to contain identical DNA segments and could therefore be linked together into one single BALB/c TL region which appears to be identical to the TL region of the C57BL/10 mouse. However, two of the hybridizing clusters do not overlap with the C57BL/10 TL region. It appears that these two clusters represent a partial duplication of the TL region in the BALB/c mouse.

Animals↗

PubMed1985

Intron sequences reveal evolutionary relationships among major histocompatibility complex class I genes.

The multigene family of the class I histocompatibility antigens is unusual in that allelic and intergenic differences often are of equal magnitude. It has been suggested that this is due to gene conversion events, which would produce allelic variation but at the same time reduce intergenic differences. We compared the sequences of 11 class I genes in an attempt to elucidate the evolutionary history of this gene family. Our analysis shows that the intron sequences can be used to establish the order of divergence of various class I genes from each other. The results obtained agree with the order of divergence deduced from major insertion and deletion events. It appears that certain genes in the murine TL antigen-encoding region diverged very early from the H-2 and Qa-2,3 genes. The latter can be subgrouped as H-2 and Qa-2,3 genes by both sequence homology and insertion patterns. In contrast to the introns, exon sequences provide less information on evolutionary relationships. Thus, these analyses are consistent with the view that concerted evolution due to gene conversion occurs preferentially in exons.

Animals↗

PubMed1985

Steric aspects of agonism and antagonism at beta-adrenoceptors: experiments with the enantiomers of clenbuterol.

The enantiomers of clenbuterol, a beta 2-selective adrenoceptor agonist with partial agonistic activity, were examined with respect to their ability to react in vitro on adrenoceptors in the trachea (mostly beta 2), the soleus muscle (beta 2) and in the papillary muscle of the left ventricle (beta 1) from the guinea-pig. (-)-Clenbuterol relaxed the carbachol contracted trachea and depressed the subtetanic contractions of the soleus muscle in a concentration-dependent manner. (+)-Clenbuterol was at least 1,000 times less potent in this respect. Both isomers inhibited competitively the effect of isoprenaline on the trachea, the (-)-isomer being about 100 times more active than the (+)-isomer. None of the isomers showed any detectable positive inotropic effect on the papillary muscle but both inhibited competitively the response to isoprenaline. Also in this respect (-)-clenbuterol was more potent than (+)-clenbuterol. It is concluded that the beta 2-agonistic as well as the beta 1-antagonistic effect of clenbuterol resides in the (-)-isomer and that the (+)-isomer does not seem to contribute to the pharmacological effects displayed by racemic clenbuterol.

Animals↗

PubMed1984

Molecular map of the human HLA-SB (HLA-DP) region and sequence of an SB alpha (DP alpha) pseudogene.

The human major histocompatibility complex contains the genes for at least three different types of class II antigens, DR, DC and SB (DR, DQ and DP). They are all composed of an alpha and a beta chain. We have cloned a chromosomal region of 70 kb containing the SB (DP) gene family in overlapping cosmid clones. This segment contains two alpha genes and two beta genes, located in the order SB alpha 1, SB beta 1, SB alpha 2 and SB beta 2. The orientation of the alpha genes is reversed compared with that of the beta genes. This organisation suggests that the SB region has arisen by duplication of a chromosomal segment encompassing one alpha and one beta gene. Partial nucleotide sequences of the SB alpha 1 and SB beta 1 exons demonstrate that the genes correspond to SB alpha and beta cDNA clones. Consequently these genes are expressed. In contrast nucleotide sequence determination of the SB alpha 2 gene shows that it is a pseudogene.

Amino Acid Sequence↗

PubMed1983

The complete nucleotide sequence of the I-E alpha d immune response gene.

We have isolated and sequenced the complete murine I-E alpha immune response gene of the H-2db haplotype. The I-E alpha d gene consists of 5300 basepairs and is organized into five or possibly six exons that correspond to different domains of the alpha chain. The amino acid sequence deduced from the I-E alpha gene shows 75% homology to its human counterpart, the HLA-DR alpha chain. The absence of I-E antigen in H-2 mice is due to lack of E alpha chain synthesis. We show here that this defect is caused by a deletion in the 5' end of the I-E alpha b gene.

Amino Acid Sequence↗

PubMed1982

Alpha chain of HLA-DR transplantation antigens is a member of the same protein superfamily as the immunoglobulins.

Four cDNA clones, pDR-alpha-1, pDR-alpha-2, pDR-alpha-3 and pDR-alpha-4, corresponding to the alpha chain of HLA-DR antigens, have been sequenced. Restriction maps and sequences suggest that all clones are identical apart from a single-base substitution present in pDR-alpha-1. Amino acid sequence data, together with the nucleotide sequence data, allowed the complete amino acid sequence to be predicted. The alpha chain is composed of 229 amino acids, of which 191 are exposed on the outside of the plasma membrane. The membrane-embedded portion of the chain consists of 23 hydrophobic amino acids. The succeeding 15 amino acids form the cytoplasmically localized hydrophilic tail. The extracellular portion, with carbohydrate moieties linked to Asn78 and Asn118, seems to be organized into two domains. The second domain, which contains the only disulfide bond of the alpha chain, displays amino acid sequence homology to immunoglobulin constant regions, to the second domain of the beta chain of a class II antigen, to the third domain of heavy chains of class I antigens and to beta 2-microglobulin. Thus the subunits of immunoglobulins, class I antigens and class II antigens are related evolutionarily.

Amino Acid Sequence↗

PubMedDate not supplied

Neuropeptides in guinea pig trachea: distribution and evidence for the release of CGRP into tracheal lumen.

The airways of the guinea pig are richly innervated by peptide-containing nerve fibers. Among the most abundant neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are stored in nerve fibers located predominantly within and beneath the epithelium, and vasoactive intestinal peptide (VIP), which is located in fibers running mainly among smooth muscle bundles and seromucous glands. Sensory denervation (capsaicin treatment) of adult guinea pigs caused an almost total disappearance of CGRP- and SP-containing nerve fibers, while the density of VIP-containing nerve fibers located in smooth muscle seemed to increase. In the isolated trachea, perfused luminally, CGRP was found to appear in the intraluminal fluid after exposure to capsaicin but not after electrical vagal stimulation. CGRP concentrations in the tracheal wall did not change significantly. Luminally applied CGRP did not affect smooth muscle tension, measured as intraluminal volume changes.

Animals↗

PubMedDate not supplied

Isolation of a cDNA clone coding for an SB beta-chain.

Class II antigens of the major histocompatibility complex (MHC) consist of a family of closely related cell surface-expressed glycoproteins. These antigens, which are genetically polymorphic, control important aspects of the immune response. At least three types of human class II antigens, namely, DR, DC and SB (refs 2-4), have been identified. All class II antigens are heterodimers composed of one alpha- and one beta-chain. The genes for both types of subunits are encompassed within the MHC. The general features of the DC and DR antigens have recently been elucidated. Much less is known, however, about the SB molecules. Here we describe the isolation of a cDNA clone as well as a genomic clone encoding a beta-chain whose amino acid sequence is compatible with the partial amino-terminal sequence of SB beta-chains.

Amino Acid Sequence↗

PubMedDate not supplied

The interaction of ephedrine with beta-adrenoceptors in tracheal, cardiac and skeletal muscles.

Three beta-adrenoceptor mediated effects were measured in vitro on tissues from guinea-pig: (a) relaxation of the trachea (mainly beta 2), (b) increase in the force of contraction of the papillary muscle (beta 1), and (c) depression of the subtetanic contractions of the soleus muscle (beta 2). The relaxant effect of ephedrine on the trachea was weak but was resistant to reserpine pretreatment. There was no appreciable agonistic effect of ephedrine on the soleus muscle. Ephedrine per se had a marked positive inotropic effect on the papillary muscle with a pD2 of about 6.0. This effect disappeared completely after pretreatment with reserpine. Ephedrine inhibited the response to isoprenaline. The apparent pA2 was about 4.8 in all tissues studied.

Animals↗