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Biomedical subjects

D Doyle

Publications and source records attributed to D Doyle.

At least 55 records · Page 3Linked to original sources
PubMed1992

[The intermittent "warm" blood cardioplegia].

Even today, a plethora of cardioplegic solutions are in clinical use. In the study presented here, sixty-six consecutive coronary bypass procedures received normothermic (37 degrees C) blood cardioplegia (NBC) intermittently. This group of patients was compared to an historical group of 68 patients having received cold crystalloid cardioplegia (CCC), and a second group of 41 patients having received cold blood (10 degrees C) cardioplegia (CBC). The number of patients, as well as their age, sex, functional class, ejection fraction and urgency of intervention were comparable between the three groups. The preoperative use of inotropic drugs was less prevalent in the normothermic blood cardioplegia group (NBC 24% v. CCC 52% and CBC 51%, p < 0.05), as was the use of a pacemaker (NBC 8% v. CCC 52% and CBC 51%, p < 0.02). Finally, the rates of myocardial infarction and mortality were comparable between the three groups. These results suggest that normothermic blood cardioplegia is efficient in reducing the demand in O2, by inducing the electromechanical arrest of the heart and, that intermittent normothermic blood cardioplegia can be safe and effective.

Aged↗
PubMed1991

A Fischer rat substrain deficient in dipeptidyl peptidase IV activity makes normal steady-state RNA levels and an altered protein. Use as a liver-cell transplantation model.

Dipeptidyl peptidase IV (DPPIV) is a serine exoproteinase expressed at high levels in epithelial cells of kidney, liver and small intestine. Recently Watanabe, Kohima & Fujimoto [(1987) Experientia 43, 400-401] and Gossrau et al. [(1990) Histochem. J. 22, 172-173] reported that Fischer 344 rats are deficient in this enzyme. We have examined DPPIV expression in Fischer 344 rats available from U.S. and German suppliers and find that livers of the U.S. Fischer rats, in contrast with their German counterparts, express active DPPIV (D+). Northern analysis of liver RNA showed comparable levels of 3.4 kb and 5.6 kb DPPIV transcripts in both D+ rats from the U.S. and German (D-) rats. Monoclonal antibody (MAb) 236.3 to DPPIV immunoprecipitated at 150 kDa enzymically active (105 kDa, denatured) protein from surface-labelled D+ hepatocytes and reacted with canalicular and sinusoidal membranes (as shown by immunofluorescence microscopy). MAb 236.3 failed to immunoprecipitate a labelled peptide from D- cell extract or to stain D- liver sections. Polyclonal antibody (PAb) specific for DPPIV immunoprecipitated an enzymically active peptide from D+ hepatocyte extracts and a smaller, inactive peptide from D- hepatocyte extracts. Peptide maps of DPPIV immunoprecipitated from D+ extracts with MAb 236.3 and PAb were identical, but differed from that of the D- hepatocyte component recognized by PAb. The molecular basis of the DPPIV deficiency in the D- rats thus appears to be the translation of an enzymically inactive protein missing the epitope recognized by MAb 236.3. We have exploited these D- rats as hosts for syngeneic transplantation of liver cells from D+ Fischer rats. DPPIV expression is stable in the transplanted cells and allows them to be readily distinguished from the surrounding D- tissue.

Animals↗
PubMed1991

Pituitary apoplexy and its effect on vision.

A series of 15 patients with a clinical diagnosis of pituitary apoplexy is reviewed. Clinical features are highlighted, with stress on the defects of visual function and ocular motility, and the associated endocrine abnormalities are described. Potential diagnostic errors and their significance are considered. The incidence of this complication in a large series of pituitary adenoma patients is measured, and the radiological and pathological findings are recorded. The results of treatment by surgery and/or radiotherapy and/or bromocriptine are assessed, particularly in relation to visual consequences, and compared with previous reports in the literature, which are reviewed.

Adult↗
PubMed1991

Characterization of an oxytetracycline-resistance gene, otrA, of Streptomyces rimosus.

The sequence of a 2657 bp DNA fragment containing the coding and regulatory regions of the oxytetracycline (OTC)-resistance gene, otrA, from the OTC producer Streptomyces rimosus was determined. The predicted amino acid sequence of OtrA had extensive identity with tetracycline-resistance genes from other bacteria which mediate resistance via non-covalent ribosomal modification. The N-terminal domain had extremely high identity with the GTP-binding sites of elongation factors, such as EF-G and EF-Tu, suggesting that binding and hydrolysis of GTP is important to the function of the protein. Significant identity with EF-G was present throughout the polypeptide. Transcriptional activity upstream of the otrA coding region was investigated. An Escherichia coli-type promoter, otrAp1, was identified. Transcriptional readthrough of otrA from the upstream gene (otcZ) was also detected in S. rimosus cultures. A divergent promoter activity was identified with subclones of the OtrA fragment in promoter probe vectors analysed in Streptomyces lividans. However, this activity was not identified in a subclone containing more than half of the otrA coding sequence in S. lividans or at all in S. rimosus, indicating that OtrA negatively regulates the expression of the divergent transcript. The data are consistent with regulation of antibiotic production by OtrA to prevent 'suicide'.

Amino Acid Sequence↗
PubMed1991

Biologically active conformations of thymopentin. Studies with conformationally restricted analogs.

Four cyclic analogs of thymopentin were synthesized and evaluated for biological activity on the human T cell line CEM. Three of these conformationally restricted analogs were biologically active. The one analog which most closely mimicked the conformation predicted from NMR and theoretical energy minimization calculations proved to be inactive. These studies establish that the biologically active conformations of thymopentin differ from the most probable conformation predicted from solution NMR and theoretical energy minimization studies.

Amino Acid Sequence↗
PubMed1991

Morphine: myths, morality and economics.

It is a tragedy that morphine is scarcely available for between 1.3 and 2.5 billion people whilst 3.5 million cancer patients suffer needlessly. In only 10 countries is its consumption rising, in many more only codeine consumption shows an increase, and in many areas even in the Western world prescribing is grossly limited, fears of psychological addiction persist, professional education of doctors and nurses in analgesia remains minimal and too much importance is attached to expensive sophisticated methods of administration. Doctors have a professional and a moral responsibility to press for improved morphine availability in the most useful and economical forms worldwide.

Humans↗
PubMed1990

Mouse asialoglycoprotein receptor cDNA sequence: conservation of receptor genes during mammalian evolution.

The asialoglycoprotein receptor internalizes galactose-terminated glycoproteins into mammalian hepatocytes for degradation in lysosomes. We report the cloning and sequencing of one murine asialoglycoprotein receptor cDNA which exhibits homology with rat and human receptor forms. Conserved regions may correlate with functional domains. The membrane-bound M (mouse) HL polypeptide does not contain a cleavable N-terminal signal sequence and is probably anchored to the membrane via an internal insertion sequence.

Amino Acid Sequence↗
PubMed1990

Pain control.

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Analgesics↗
PubMed1990

Assembly of a heterooligomeric asialoglycoprotein receptor complex during cell-free translation.

We have translated RNAs for the two rat asialoglycoprotein receptor polypeptides together in a cell-free system containing dog pancreatic microsomes and immunoprecipitated the products with antibodies that distinguish the two proteins. In this system the proteins oligomerize, as judged by their coprecipitation with either of the subunit-specific antisera. Oligomerization does not occur between subunits synthesized without microsomes or between subunits synthesized on separate microsomes mixed during detergent solubilization. Thus, oligomerization occurs within the microsomal membrane. We calculate that oligomerization proceeds with an efficiency of approximately 85%. The receptor complex appears to represent a specific oligomer because it excludes a third membrane glycoprotein synthesized in the same reaction. Oligomerization of the asialoglycoprotein receptor in vitro should provide a useful system to study the assembly of a membrane-protein complex.

Animals↗
PubMed1990

Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPPIV) is a membrane glycoprotein with a type II orientation in the plasma membrane. As shown in a cell-free translation system, the amino-terminal 34 amino acids of rat DPPIV are involved in translocating nascent polypeptide across the membrane of microsomes and in anchoring the translocated polypeptide in the microsomal membrane. The amino-terminal sequence performing this dual function is composed of: a central hydrophobic core of 22 amino acid residues; 6 amino-terminal residues preceding the hydrophobic core (MKTPWK); and 6 residues following the hydrophobic core. The six residues preceding the hydrophobic core are exposed on the outside (cytoplasmic side) of the microsomal membrane. Site-directed mutagenesis studies show that deletion of this cytoplasmic domain, excluding the amino-terminal initiating methionine, does not affect translocation of nascent DPPIV polypeptide, but does affect significantly anchoring of the translocated polypeptide in the microsomal membrane. In contrast, changing the two cytoplasmic Lys to Glu residues or shortening of the hydrophobic core from 22 to 15 residues or converting the last 11e of the shortened hydrophobic core into Ala affects neither translocation across nor anchoring of the DPPIV polypeptide in the microsomal membrane. These and other structural features of the DPPIV amino-terminal signal-anchor sequences are discussed along with other types of sequences for their role in targeting nascent polypeptides to the RER.

Amino Acid Sequence↗
PubMed1990

The role of coronary angioplasty in patients with associated noncardiac medical and surgical conditions.

Percutaneous transluminal coronary angioplasty was performed in 22 patients with associated significant medical or surgical conditions. It was successful in 22 patients. Two had procedure-related complications: one femoral hematoma and one small myocardial infarction. The patients were divided into a 'medical' group (12 patients) and a 'surgical' group (10 patients). In the medical group, mean coronary artery stenosis decreased from 87 +/- 5% to 20 +/- 13% and mean coronary artery stenosis decreased from 57 +/- 2% to 16 +/- 7%. In the surgical group coronary artery stenosis decreased from 83 +/- 9% to 18 +/- 9% and the gradient from 49 +/- 16 to 16 +/- 6 mmHg. Percutaneous transluminal coronary angioplasty allowed the safe management of underlying conditions in all patients so that medical treatment could be continued and noncardiac surgery performed.

Adult↗
PubMed1989

Expression of enzymatically active rat dipeptidyl peptidase IV in Chinese hamster ovary cells after transfection.

Dipeptidyl peptidase IV (DPPIV) is a cell surface membrane glycoprotein expressed in many tissues. We have subcloned the coding region of a full-length cDNA for DPPIV into the inducible eukaryotic expression vector pMSG. The resulting construct was used to transfect Chinese hamster ovary (CHO) cells. Stable transformants were found to express DPPIV, and the expression is enhanced by dexamethasone. Metabolic labeling of the transfected cells with [35S]Met followed by immunoprecipitation revealed the presence of two specific products of apparent Mr 100,000 (100-kDa form) and 110,000 (110-kDa form), respectively. Pulse-chase experiments demonstrated that the 100-kDa form can be chased into the 110-kDa form, suggesting the 100-kDa form is the precursor of the 110-kDa form. Further studies with endo H treatment demonstrated that the carbohydrate structures are of the high-mannose type, and of the complex type for the 100- and 110-kDa forms, respectively. The 110-kDa form is present at the cell surface as shown by its accessibility to cell surface iodination. The DPPIV expressed on the cell surface is resistant to digestion by relatively high concentrations of trypsin. Studies also demonstrated that the surface DPPIV is fairly stable with a half-life for turnover of about 40 h. Furthermore, the DPPIV produced in the transfected cells displays specific dipeptidyl peptidase activity. The stably transfected cells that express enzymatically active DPPIV in an inducible manner will provide an excellent system for further biochemical, functional, and cell biological characterizations of DPPIV.

Animals↗
PubMed1989

Cloning and analysis of cDNA clones for rat kidney alpha-spectrin.

We have isolated a 3922-base pair (bp) cDNA clone for rat nonerythroid alpha-spectrin from a rat kidney lambda gt11 cDNA library. Sequence analysis revealed that this cDNA contains an open reading frame of 3090 bp encoding for the C-terminal 1030 amino acid sequence of rat kidney alpha-spectrin. The 3'-untranslated region (including a 38-bp poly(A+) tail) contains an 832-bp sequence. A single mRNA of about 8 kilobase pairs was detected in rat liver, kidney, brain, heart, intestine, lung, testis, stomach, spleen, and muscle with varying abundances, which is consistent with and further confirms the presence of spectrins in nonerythroid tissues as demonstrated previously by immunoblot analysis. Southern blot analysis suggested that there is a single gene for nonerythroid alpha-spectrin. The derived amino acid sequence contains sequence from the spectrin 106-residue internal repeat 12 to the C terminus of rat kidney alpha-spectrin. Sequence comparison with human and chicken nonerythroid alpha-spectrin showed that nonerythroid alpha-spectrin is well conserved during evolution. The rat kidney alpha-spectrin sequence, when compared to rat brain alpha-spectrin, contains an extra 76-amino-acid sequence at the C terminus. Sequence comparison of all the internal repeats available revealed that the internal repeat 3, 4, 5, 6, 7, and 8 has highest sequence similarity with internal repeat 12, 13, 14, 15, 16, and 17, respectively. Therefore, internal repeats 3-8 and 12-17 are most likely derived from an ancestral gene through gene duplication, suggesting that the spectrin gene is derived from a half-spectrin gene by gene duplication and divergence during evolution.

Amino Acid Sequence↗