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Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 181 records · Page 10Linked to original sources
PubMed1990

Cognitive deficits associated with human immunodeficiency virus encephalopathy.

The encephalopathy associated with direct nervous system infection by the human immunodeficiency virus (HIV) has been recognized as one of the major debilitating aspects of the acquired immunodeficiency syndrome (AIDS) and of pre-AIDS conditions. A comprehensive neuropsychological examination of symptomatic HIV-infected subjects without opportunistic cerebral disease demonstrated a distinctive pattern of cognitive deficits marked by prominent attentional impairment. Evidence of organizational and reasoning impairments also was observed, but language, visual-spatial, and memory consolidation abilities were relatively preserved. The findings suggest a profile of impairment similar to other cognitive syndromes involving dysfunction of predominantly anterior brain structures and projections and suggest a rationale for psychostimulant drug treatment.

AIDS Dementia Complex↗
PubMed1990

An adaptation of the Miller patient classification system for the postanesthesia care unit at Children's Hospital of Eastern Ontario.

Using the Miller Patient Classification framework, a descriptive three-phase study was carried out in order to develop a classification system specifically for the PACU of the Children's Hospital of Eastern Ontario. This study contributes further understanding of the complexities of developing a reliable classification system for the pediatric PACU.

Hospitals, Pediatric↗
PubMed1989

A consensus sequence for substrate hydrolysis by rhinovirus 3C proteinase.

Kinetic constants were determined for the hydrolysis of a series of synthetic peptide substrates by recombinant rhinovirus (HRV 14) 3C proteinase. Systematic removal or replacement of individual residues indicated that the minimum sequence required for effective cleavage by the viral cysteine proteinase was P5-Val/Thr-P3-P2-Gln-Gly-Pro.

3C Viral Proteases↗
PubMed1989

X-ray studies of aspartic proteinase-statine inhibitor complexes.

The conformation of a statine-containing renin inhibitor complexed with the aspartic proteinase from the fungus Endothia parasitica (EC 3.4.23.6) has been determined by X-ray diffraction at 2.2-A resolution (R = 0.17). We describe the structure of the complex at high resolution and compare this with a 3.0-A resolution analysis of a bound inhibitor, L-364,099, containing a cyclohexylalanine analogue of statine. The inhibitors bind in extended conformations in the long active-site cleft, and the hydroxyl of the transition-state analogue, statine, interacts strongly with the catalytic aspartates via hydrogen bonds to the essential carboxyl groups. This work provides a detailed structural analysis of the role of statine in peptide inhibitors. It shows conclusively that statine should be considered a dipeptide analogue (occupying P1 to P1') despite lacking the equivalent of a P1' side chain, although other inhibitor residues (especially P2) may compensate by interacting at the unoccupied S1' specificity subsite.

Amino Acids↗
PubMed1989

Activation of CD4 cells by fibronectin and anti-CD3 antibody. A synergistic effect mediated by the VLA-5 fibronectin receptor complex.

In this study, fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system. The cell-adhesive domain plus additional regions of the fibronectin molecule are involved in this synergy. Anti4B4(CDw29) antibody blocked the activation of CD4 cells in this system. Furthermore, it is the VLA-5 protein within the set of molecules recognized by anti-4B4 that serves as a fibronectin receptor on the CD4 lymphocytes. The VLA-5 fibronectin receptor was mainly expressed on CD4+ CD45R-CDw29+ cells and may in part contribute to the unique function of these cells.

Antibodies, Monoclonal↗
PubMed1989

Inhibition of the aspartic proteinase from HIV-2.

Kinetic constants were determined for the interaction of the HIV-2 aspartic proteinase with a synthetic substrate and a number of inhibitors at several pH values. Acetyl-pepstatin was more effective towards HIV-2 proteinase than the renin inhibitor, H-261; this effect is exactly the opposite from that observed previously for the proteinase from the HIV-1 AIDS virus.

Aspartic Acid Endopeptidases↗
PubMed1989

Inhibition of aspartic proteinases by alpha 2-macroglobulin.

The effect of alpha 2-macroglobulin, one of the major antiproteinases in the plasma of vertebrates, on the action of the aspartic proteinases chymosin, cathepsin D and cathepsin E towards peptide and protein substrates at pH 6.2 was examined. Activities towards protein substrates were blocked, thus demonstrating that alpha 2-macroglobulin can inhibit aspartic proteinases, in addition to serine proteinases, cysteine proteinases and metalloproteinases.

Cathepsin D↗
PubMed1989

Effective blocking of HIV-1 proteinase activity by characteristic inhibitors of aspartic proteinases.

Inhibitory constants (Ki) between 5 and 35 nM were derived (under different conditions of pH and ionic strength) for the interaction of HIV-1 proteinase with acetyl-pepstatin and H-261, two characteristic inhibitors of aspartic proteinases. Thus this enzyme, essential for replication of the AIDS virus, may be classified unequivocally as belonging to this proteinase family.

Aspartic Acid Endopeptidases↗
PubMed1989

Stabilisation of cathepsin E by ATP.

The hydrolysis of 3 distinct substrates by cathepsin E from human red blood cells and gastric mucosa was measured in the presence and absence of physiologically relevant concentrations of ATP. At pH values below about 5.0, the nucleotide was without effect. However, at pH 5.8, whereas cathepsin E was virtually inactive by itself, it was restored to full activity (kcat) by ATP and the non-hydrolysable methylene-ATP analogue. At still higher pH values, kcat progressively diminished but significant levels of cathepsin E activity were readily detectable at pH 7.0. The specificity of this stabilisation effect was examined.

Adenosine Triphosphate↗
PubMed1989

Face processing and name retrieval in an anomic aphasic: names are stored separately from semantic information about familiar people.

Recent models of face recognition have proposed that the names of familiar people are accessed from a lexical memory store that is distinct from the semantic memory store that holds information about such things as a familiar person's occupation and personality. Names are nevertheless retrieved via the semantic system. If such models are correct, then it should be possible for a patient to have full access to semantic information about familiar people while being unable to name many of them. We report this pattern in an anomic aphasic patient, EST, whose inability to recall the names of familiar people occurred in the context of a general word-finding problem. EST showed a preserved ability to access semantic information from familiar faces, voices, and spoken and written names and to process facial expressions, but he was unable to name many familiar faces. These findings are compatible with current models of face processing and challenge models which propose that names are stored alongside semantic information in a general-purpose long-term memory store.

Anomia↗
PubMed1989

Hemorrhagic shock and encephalopathy: clinical, pathologic, and biochemical features.

To further define the clinical, pathologic, and biochemical features of hemorrhagic shock and encephalopathy syndrome, we studied 25 affected children (aged 3 months to 14 years) admitted to a single center between 1982 and 1985. A prodromal illness comprising vomiting, diarrhea, listlessness, and fever was present in 84% of the cases. Acute onset of shock, convulsions and coma, bleeding (or laboratory evidence of disseminated intravascular coagulation), elevated plasma activity of hepatic enzymes, acidosis, and impaired renal function was present in every case. Twenty patients died, and all the survivors are neurologically damaged. At postmortem examination, intravascular microthrombi coexisting with hemorrhages and petechiae were found in most organs. Centrilobular liver necrosis and cerebral edema were prominent features. No microbiologic cause for the disorder was identified, but decreased plasma levels of the protease inhibitors alpha 1-antitrypsin and alpha 2-macroglobulin, together with increased levels of circulating proteolytic enzymes, were frequently present. An overrepresentation of the uncommon variant phenotypes of alpha 1-antitrypsin was found in first-degree relatives of affected patients (four had the MZ phenotype, and one each the MS or MC phenotype, of 19 relatives studied). Abnormal accumulation of alpha 1-antitrypsin was detected immunohistochemically in the livers of six of the patients. Defective protease inhibitor production or release may be involved in the pathogenesis of the disorder.

Adolescent↗
PubMed1989

Attribution of control in psychiatric residents.

At quarterly intervals in 1986-87, attribution of control and subjective symptom ratings were assessed among the 42 general psychiatry residents in the University of Cincinnati's training program. Within each of the four groups of residents (that is, the residents in each postgraduate year), ratings remained stable over time. Between-group differences were significant for ratings of internal locus of control, but the external locus of control ratings showed no corresponding fluctuation. The internal locus of control scores were inversely correlated with psychological distress as reported in the Brief Symptom Inventory.

Humans↗
PubMed1989

Hydrolysis of a series of synthetic peptide substrates by the human rhinovirus 14 3C proteinase, cloned and expressed in Escherichia coli.

The 3C proteins of several picornaviruses, including poliovirus, foot-and-mouth disease virus (FMDV) and encephalomyocarditis virus (EMCV), have been demonstrated to be cysteine-type proteinases, involved in the processing of the respective polyproteins expressed by the monocistronic RNA genome. Nucleotide sequencing data have indicated that the human rhinovirus 14 (HRV-14) RNA genome encodes a homologous 3C protein. The HRV-14 3C protein was purified to homogeneity from Escherichia coli expressing the cloned 3C genomic fragment. The enzyme was assayed against peptides corresponding to those residues, predicted (by nucleotide sequencing data) to occur at authentic cleavage sites within the polyprotein. The peptides representing the 1B/1C, 2A/2B, 2C/3A, 3A/3B, 3B/3C and 3C/3D cleavage sites, where proteolysis was predicted to occur at a Gln-Gly junction, were all cleaved by the 3C proteinase. The hydrolysis was shown (by reverse phase fast protein liquid chromatography and amino acid analysis) to occur specifically at the Gln-Gly bond in each of the peptides. The ready availability of such convenient substrates facilitated the further characterization of the 3C proteinase. By contrast, peptides corresponding to the predicted 2B/2C and 1C/1D cleavage sites, where the processing was presumed to occur at a Gln-Ala or Glu-Gly bond respectively, were not cleaved by the 3C proteinase. The ability of the HRV-14 3C proteinase to hydrolyse the synthetic peptides was inhibited if a Cys----Ser(146) mutation was introduced into the protein. Studies with known proteinase inhibitors substantiated the conclusion that the HRV-14 3C protein appears to be a cysteine proteinase and that the Cys residue at position 146 may be the active site nucleophile. The HRV-14 3C proteinase probably plays an important role, analogous to that implied for the poliovirus 3C proteinase, in the replication of the virus and thus represents a potential target for antiviral chemotherapy.

3C Viral Proteases↗
PubMed1989

Influence of lung inflation reflex on vascular capacitance in the systemic circulation.

The effects of sustained lung inflation on systemic vascular capacitance (SVC), systemic vascular resistance (SVR), and cardiac sympathetic efferent nerve activity (SENA) were investigated in anesthetized dogs. By use of a total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10, 15, and 20 mmHg. Tracheal pressures of 10, 15, and 20 mmHg increased system vascular capacitance by 1.4, 3.1, and 4.3 ml/kg and decreased systemic vascular resistance by 0.11, 0.15, and 0.16 mmHg.kg.min-ml-1, respectively, at low carotid sinus pressure (CSP) of 41 mmHg. SENA showed a concomitant decrease. Bilateral vagotomy attenuated the change in SVR by 69%, SVC by 62%, and SENA by 97% when lungs were inflated to a tracheal pressure of 20 mmHg at a low CSP. These results indicate that lung inflation causes a reflex induced increase in SVC as well as a decrease in both SVR and SENA. The lung inflation reflex is mediated primarily through vagal afferent nerve fibers with a small contribution from other afferent nerve pathways.

Animals↗
PubMed1989

Simultaneous measurement of lung clearance rates for Tc- and In-DTPA in normal and damaged lungs.

We investigated the relative clearance rates for 99mTc-labeled diethylenetriamine-pentaacetate (Tc-DTPA) and 113mIn-labeled DTPA (In-DTPA) when they were inhaled and deposited together within the lungs of same animal. Submicronic aerosols containing Tc-DTPA and In-DTPA were simultaneously generated by different nebulizers and collected within the same anesthetic bag. The combined aerosols were insufflated into piglets. Clearances for both compounds were measured simultaneously in normal lungs and when the lungs were damaged by intravenous oleic acid or by a presumed oxidant agent, intravenous or intratracheal phorbol myristate acetate (PMA). A medium-energy collimator and a computer-assisted gamma camera were used to calculate clearances. Correction was made for downscatter from the In photopeak into the Tc window. Marked lung injury occurred as evidenced by increases in lung water content and decreases in arterial PO2. The clearance of In-DTPA was slightly but significantly slower than for Tc-DTPA in each group of animals. The correlation (r = 0.93) between clearances for Tc-DTPA and In-DTPA was good, even though in vitro studies demonstrated that Tc-DTPA, but not In-DTPA, slowly dissociated at room and body temperatures. Oleic acid increased, but surprisingly, PMA had no effect on clearance rates for both In-DTPA and Tc-DTPA. We recommend continued use of Tc-DTPA for these measurements in view of its lower cost, requirement for only low-energy collimation, better imaging characteristics, and widespread availability. The overlap between control and injured lungs and the lack of increased clearance rates after PMA suggest this technique does not always detect acute lung injury.

Aerosols↗