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Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 163 records · Page 9Linked to original sources
PubMed1991

The influence of the curriculum in psychiatry residency education.

Extraordinary economic forces are influencing graduate medical education in this country. Federal, state, and third party cost containment efforts, managed care, medical student loan indebtedness, and decreasing governmental and industry enthusiasm to support residency training are producing significant external pressures on academic health centers, recruitment into psychiatry, and on the practice of psychiatry. Other pressures on the psychiatry residency curriculum are being generated from the rapid expansion in our scientific knowledge base in clinical psychiatry and the influence of subspecialization. The future psychiatrist will be trained for a life long career in continuing education to accommodate for the explosive scientific contributions to our field. The residency training program will promote the ability to think scientifically, to teach others, to administrate and lead, and to achieve clinical competence in a more rigorous fashion. Regardless of the number and forms of emerging practice settings, it is best to train our residents for flexibility through emphasizing fundamental clinical and scientific excellence.

Cost Control↗
PubMed1991

Use of tricyclic antidepressants in recipients of heart transplants.

Cardiac transplantation has become an accepted treatment for certain endstage cardiac disease patients. Depression and significant psychosocial stress among heart transplant recipients are not uncommon, but published reports about the use of antidepressants in these persons are very rare. The authors of this study report on a group of nine heart transplant recipients treated with antidepressant medicines. Seven patients achieved clinical remissions of their depression, and only two were unable to tolerate the noncardiac side effects of the medication. Indicators of autonomic, electrocardiographic, and hemodynamic functions showed no adverse effects. Although the study is based on a small sample, it appears that tricyclic antidepressants are safe and effective in heart transplant recipients.

Adaptation, Psychological↗
PubMed1990

Generation of human endothelin by cathepsin E.

Highly-purified cathepsin D processed human big endothelin1-38 into endothelin-like fragments but did not appear to generate endothelin1-21 under the conditions employed. By contrast, human cathepsin E specifically cleaved human big endothelin into endothelin1-21 and the C-terminal fragment under identical conditions but did not degrade either product further.

Amino Acid Sequence↗
PubMed1990

Sub-site preferences of the aspartic proteinase from the human immunodeficiency virus, HIV-1.

A series of synthetic, chromogenic substrates for HIV-1 proteinase with the general structure Ala-Thr-His-Xaa-Yaa-Zaa*Nph-Val-Arg-Lys-Ala was synthesised with a variety of residues introduced into the Xaa, Yaa and Zaa positions. Kinetics parameters for hydrolysis of each peptide by HIV-1 proteinase at pH 4.7, 37 degrees C and u = 1.0 M were measured spectrophotometrically and/or by reverse phase FPLC. A variety of residues was found to be acceptable in the P3 position whilst hydrophobic/aromatic residues were preferable in P1. The nature of the residue occupying the P2 position had a strong influence on kcat (with little effect on Km); beta-branched residues Val or Ile in this position resulted in considerably faster peptide hydrolysis than when e.g. the Leu-containing analogue was present in P2.

Amino Acid Sequence↗
PubMed1990

Rational design of peptide-based HIV proteinase inhibitors.

A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.

Amino Acid Sequence↗
PubMed1990

The expression of a synthetic rainbow trout metallothionein gene in E. coli.

A synthetic gene for rainbow trout metallothionein was constructed and inserted into a dual origin plasmid where expression was induced by a temperature shift in a proteinase-deficient strain of Escherichia coli. The recombinant protein was purified to homogeneity, and a partial amino acid sequence was determined to confirm its identity. Its immunochemical characteristics were similar to those of native metallothionein from rainbow trout. The amounts of recombinant metallothionein produced were quantified in soluble cell extracts by ELISA. Low concentrations were detected when growth was performed either in L-broth or defined (GMM-II) medium. Supplementation of the medium with zinc or copper had no effect on the amount of metallothionein produced. By contrast, when cadmium was included in either L-broth or GMM-II medium, much higher concentrations of the protein within the cells (approx. 13 micrograms/mg soluble cell protein) were detected. This stabilisation of the protein by metal reconstitution in vivo is considered in relation to the selective uptake/exclusion of metals by the cells and its significance for the scavenging of certain precious or toxic heavy metals is discussed.

Amino Acid Sequence↗
PubMed1990

In vitro inhibition of HIV-1 proteinase by cerulenin.

Retroviruses encode proteinases necessary for the proteolytic processing of the viral gag and gag-pol precursor proteins. These enzymes have been shown to be structurally and functionally related to aspartyl proteinases such as pepsin and renin. Cerulenin is a naturally occurring antibiotic, commonly used as an inhibitor of fatty acid synthesis. Cerulenin has been observed to inhibit production of Rous sarcoma virus and murine leukaemia virus by infected cells, possibly by interfering with proteolytic processing of viral precursor proteins. We show here that cerulenin inhibits the action of the HIV-1 proteinase in vitro, using 3 substrates: a synthetic heptapeptide (SQNYPIV) which corresponds to the sequence at the HIV-1 gag p17/p24 junction, a bacterially expressed gag precursor, and purified 66 kDa reverse transcriptase. Inhibition of cleavage by HIV-1 proteinase required preincubation with cerulenin. Cerulenin also inactivates endothiapepsin, a well-characterised fungal aspartyl proteinase, suggesting that the action of cerulenin is a function of the common active site structure of the retroviral and aspartic proteinases. Molecular modelling suggests that cerulenin possesses several of the necessary structural features of an inhibitor of aspartyl proteinases and retroviral proteinases. Although cerulenin itself is cytotoxic and inappropriate for clinical use, it may provide leads for the rational design of inhibitors of the HIV proteinase which could have application in the chemotherapy of AIDS.

Amino Acid Sequence↗
PubMed1990

Identification of primary tumour site by immunolocalization of progastricsin in metastatic adenocarcinoma.

The aspartic proteinase zymogen, progastricsin, which occurs in normal gastroduodenal mucosa and prostate, has been localized by the immunogold-silver method in formalin-fixed, paraffin-embedded sections of metastatic adenocarcinoma in lymph nodes and liver, the primary site being known in each case. Progastricsin was demonstrated in 16 of 84 lymph node metastases, including 7 of 17 from stomach, 2 of 2 from prostate, and 7 of 65 from other sites. Progastricsin was also found in 19 of 98 hepatic metastases, including 8 of 22 from stomach, 6 of 24 from pancreas, and 5 of 52 from other sites. The presence of progastricsin in a metastasis correlated well with a primary tumour in the stomach or prostate or, less significantly, pancreas. Immunolocalization of progastricsin in a histological section of metastatic adenocarcinoma may help to locate the primary site.

Adenocarcinoma↗
PubMed1990

A prospective survey of reactions to blood tests by children and adolescents.

A sample of 171 children and adolescents aged 3-17 years requiring venepuncture for blood sampling were asked to report on their pain and anxiety and were observed immediately before and during blood drawing. Depending on the measures used, 36-64% of children from 3 to 6 years old experienced moderate to severe distress from blood drawing. Multiple regression analysis revealed that age and the parents' prediction of how upset the child would feel before the blood test was a significant predictor of the observed distress and the self-report of pain. Experience with previous needle procedures did not add significantly to the prediction of distress. Identification of children at high risk to respond poorly to painful medical procedures is discussed.

Adolescent↗
PubMed1990

Immunological distinction between piscine and mammalian metallothioneins.

1. Separate antisera to metallothioneins (MT) from rainbow trout and horse were produced in mice and their reactivity with the respective immunogen was confirmed using an ELISA. 2. The ELISA, used in a competitive mode, revealed that the anti-horse MT serum did not cross-react with trout MT. Reciprocally, the anti-trout MT serum did not show any reactivity with horse MT. 3. The anti-rainbow trout MT serum was shown to cross-react totally with MTs from plaice, flounder, turbot, perch, salmon and pike, but exhibited no reactivity towards MTs from human, mouse, rat, worm or crab. Partial reactivity with the proteins isolated from oyster and mussel was demonstrated. 4. The anti-horse MT serum cross-reacted totally with MTs from human, rat and rabbit but no reactivity was demonstrable when MT from either plaice or worm was tested. 5. The behaviour of apo-, holo- and recombinant rainbow trout MTs, in which the metal content was different, indicated that reactivity with anti-MT antibodies was not dependent on the presence or nature of the metals bound in the protein. 6. The patterns of reactivities were analysed in relation to the known amino acid sequences of MT.

Amino Acid Sequence↗
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↗