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Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 91 records · Page 5Linked to original sources
PubMed1997

The EM algorithm in medical imaging.

This article outlines the statistical developments that have taken place in the use of the EM algorithm in emission and transmission tomography during the past decade or so. We discuss the statistical aspects of the modelling of the projection data for both the emission and transmission cases and define the relevant probability models. This leads to the use of the method of maximum likelihood as a means of estimating the relevant unknown parameters within a given region of a patient's body and to the use of the EM algorithm to compute the reconstruction. Various different types of EM algorithm are discussed, including the SAGE algorithms of Fessler and Hero. The limitations of the EM algorithm, per se, are covered and the need for regularization is stressed. A number of different methods for penalizing the likelihood are described and a number of algorithms for the computation of the penalized EM reconstruction are discussed.

Algorithms↗
PubMed1997

Brief psychodynamic psychotherapies. Past, present, and future challenges.

The future educational and research needs of brief psychodynamic psychotherapy are discussed. Specific shortcomings of current education and training in brief dynamic therapies are elucidated. Many of these are relevant to psychotherapy instruction in graduate medical education in nondynamic treatments as well. Educational and technological recommendations are suggested to remedy these shortcomings.

Forecasting↗
PubMed1997

Extremely low awareness of AIDS, sexually transmitted diseases and condoms among Dai ethnic villagers in Yunnan province, China.

OBJECTIVE: To assess the awareness of AIDS, other sexually transmitted diseases (STDs), condoms, sources of health information and HIV-related societal risks among Dai villagers in southern Yunnan Province, China. SUBJECTS AND METHODS: In November-December 1994, a cross-sectional descriptive study, comprising a questionnaire-based survey and focus group discussions, was conducted in three Dai villages in Mengla county; a total of 177 Dai villagers were interviewed in the survey and eight focus group discussions were held. Ethnographic observations provided a composite picture of HIV risks in the area. RESULTS: Only 18% of respondents had heard of AIDS, and only 25 and 28%, respectively, had heard of STDs or condoms. Furthermore, among these more aware groups, the level of knowledge was low and misconceptions were common. An ability to understand the official language (Mandarin) was the most important predictor of awareness of AIDS, other STDs or condoms. The sources of information in the three Dai villages sampled included TV, videos, radio and magazines, but only TV and videos had a large audience. Even so, these media were mostly in Mandarin and were not used in AIDS education. Travel outside of China was frequent; most villagers (77%) had traveled to Laos and 9% had traveled to Thailand. Societal risks of HIV transmission, such as an increasing incidence of STDs and an active sex industry, were observed in this area. CONCLUSIONS: Dai villagers in southern Yunnan Province had an extremely low awareness and knowledge of AIDS, other STDs and condoms. Given the high mobility of ethnic villagers to neighboring countries in Southeast Asia and the societal risks of HIV transmission in this area, there is an urgent need to provide accessible education about AIDS and other STDs. Suggestions regarding such health education and the implications of HIV policy-making are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Expression, characterisation and mutagenesis of the aspartic proteinase from equine infectious anaemia virus.

The gene encoding the proteinase from equine infectious anaemia virus (EIAV) was cloned and expressed in Escherichia coli. The recombinant EIAV proteinase was purified to homogeneity and shown to have the ability to process polyprotein and synthetic peptide substrates of human immunodeficiency virus (HIV) origin with an efficiency that can approach that exhibited by HIV proteinase. EIAV proteinase, however, was not susceptible to inhibition by a wide variety of inhibitors of HIV-1 proteinase, including those which have been licenced as anti-AIDS drugs. In this respect, EIAV proteinase behaves like an extreme case of a drug-resistant mutant of HIV-1 proteinase that has arisen under selective drug pressure. Only one potent inhibitor (HBY-793) of HIV-1 proteinase showed comparable efficiency against the EIAV enzyme; the compounds A-77003 and A-76889, which differ only in their stereochemistry and which are otherwise structurally identical to HBY-793 from residues P2 to P2' [nomenclature of Schechter, I. & Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162], were not effective inhibitors of EIAV proteinase. Mutant forms of EIAV proteinase (Thr30-->Asp and Ile54-->Gly) were generated and their ability to interact with substrates and inhibitors was characterised. HBY-793 inhibited [Gly54]proteinase as effectively as the wild-type proteinase but was tenfold less potent against [Asp30]proteinase. Data interpretations are presented, based on the structure solved for the complex between HBY-793 and EIAV [Gly54]proteinase [Gustchina A., Kervinen, J., Powell, D. J., Zdanov, A., Kay, J. & Wlodawer, A. (1996) Protein Sci. 5, 1453-1465].

Amino Acid Sequence↗
PubMed1996

Regulation of cathepsin E expression during human B cell differentiation in vitro.

Cathepsin E is an aspartic proteinase which has been implicated in antigen processing in the class II major histocompatibility complex pathway. In this study we show that cathepsin E, measured at both the protein and message level, is up-regulated late in human B cell activation. The implications of this observation in terms of cathepsin E function are discussed.

Adolescent↗
PubMed1996

Structure of equine infectious anemia virus proteinase complexed with an inhibitor.

Equine infectious anemia virus (EIAV), the causative agent of infectious anemia in horses, is a member of the lentiviral family. The virus-encoded proteinase (PR) processes viral polyproteins into functional molecules during replication and it also cleaves viral nucleocapsid protein during infection. The X-ray structure of a complex of the 154G mutant of EIAV PR with the inhibitor HBY-793 was solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.136. The molecule is a dimer in which the monomers are related by a crystallographic twofold axis. Although both the enzyme and the inhibitor are symmetric, the interactions between the central part of the inhibitor and the active site aspartates are asymmetric, and the inhibitor and the two flaps are partially disordered. The overall fold of EIAV PR is very similar to that of other retroviral proteinases. However, a novel feature of the EIAV PR structure is the appearance of the second alpha-helix in the monomer in a position predicted by the structural template for the family of aspartic proteinases. The parts of the EIAV PR with the highest resemblance to human immunodeficiency virus type 1 PR include the substrate-binding sites; thus, the differences in the specificity of both enzymes have to be explained by enzyme-ligand interactions at the periphery of the active site as well.

Amino Acid Sequence↗
PubMed1996

Reading speed in pure alexia.

This study investigated possible causes of differences in reading speed between two alexic patients who read words letter by letter. As both patients appeared to rely on serial left-to-right processing of letters within words, the difference in reading speed did not seem to be related to any differences in the extent to which the patients could recognize letters in words in parallel or 'ends-in'. Differences in reading speed also seemed to be unrelated to the patients ability to identify individual letters since their letter recognition accuracy was very similar. Furthermore, although patient PD was significantly slower at reading words aloud than patient DC, PD was in fact significantly quicker than DC on a test that has previously been used to assess letter recognition skills in letter-by-letter readers. It is therefore concluded that PD reads words more slowly because of an additional impairment at the level of the word form system. The results therefore reinforce the distinction between Type 1 and Type 2 letter-by-letter readers that was first drawn by Patterson and Kay.

Adult↗
PubMed1996

The Safety of Ethanol-Tagged Glycine for Monitoring Fluid Absorption During Hysteroscopy

We assessed the value of expired breath ethanol as a marker of 1% ethanol-tagged 1.5% glycine irrigating fluid absorption during hysteroscopic surgery in a prospective analysis of 48 women. Expired breath ethanol and venous blood samples were taken before and at 10-minute intervals during surgery. Volumetric absorption of irrigating fluid was checked at the same time. There was a linear positive correlation (r = 0.86, p <0.001) between direct absorption of the irrigating fluid and expired breath ethanol concentration. Prediction can be given with 95% confidence that if the alcohol meter reading is below 0.45 mg/ml, the volume of irrigating fluid absorbed is below 2000 ml. There was no significant correlation between expired breath ethanol and indirect fluid absorption. As it is not possible to distinguish direct and indirect fluid absorption during hysteroscopic surgery, the measurement of expired breath ethanol is insufficient to assess overall fluid balance, and continuous volumetric assessment is still required.

Journal Article↗
PubMed1996

Measures for investigating the contextual modulation of information transmission.

The aim of this paper is to show how information theoretic measures can be used to analyse and interpret the results of psychophysical experiments designed to search for conditions under which information from one source modulates the transmission of information from another source. We therefore use measures of mutual and conditional information to analyse systems with two inputs. The information transmitted by such a system can be split into three components depending on whether it is shared between the two inputs or is specific to each. We are concerned here with distinguishing systems that use one input to modulate transmission of information about the other from systems that simply add both inputs, and show how the three components provide evidence for distinguishing between additive and modulatory effects. We also report numerical simulations of the sampling biasses and variances of these measures as a function of the sample size and propose minimum sample sizes that should be used to overcome the bias.

Journal Article↗
PubMed1996

Cloning, expression and characterization of the proteinase from human herpesvirus 6.

After the U53 gene encoding the proteinase from human herpesvirus 6 (HHV-6) was sequenced, it was expressed in Escherichia coli, and the activity of the purified, recombinant HHV-6 proteinase was characterized quantitatively by using synthetic peptide substrates mimicking the release and maturation cleavage sites in the polyprotein precursors of HHV-6, human cytomegalovirus (CMV), murine CMV, and Epstein-Barr virus. Despite sharing 40% identity with other betaherpesvirus proteinases such as human CMV proteinase, the one-chain HHV-6 enzyme was distinguished from these two-chain proteinases by the absence of an internal autocatalytic cleavage site.

Amino Acid Sequence↗
PubMed1996

Performance characteristics of a dialysis-related amyloidosis questionnaire.

To evaluate the effects of beta-2 microglobulin amyloidosis on functional status, a 19-item self-administered questionnaire exploring two major domains-symptoms and disability-was developed as part of this study. Fifteen patients with dialysis-related amyloidosis (DRA) were identified and compared with 15 age-matched control subjects who had been on hemodialysis for less than 24 months. Demographic data, Charlson comorbidity scores, and other clinical and laboratory variables were recorded. Total dialysis-related amyloidosis questionnaire (DRAQ) score (52.1 +/- 16.3 versus 24.4 +/- 6.2, P < 0.0001) and the scores of the symptom (24.5 +/- 7.0 versus 11.5 +/- 2.3, P < 0.0001) and disability (27.5 +/- 10.8 versus 12.9 +/- 4.0, P < 0.0001) subscales were markedly increased among patients with DRA. Baseline characteristics among case and control subjects were similar, except for serum creatinine concentration, which tended to be lower among patients with DRA (8.9 +/- 2.6 versus 11.5 +/- 2.3 mg/dL, P = 0.07). Instrument reliability and internal consistency were high. With a total DRAQ score of 30 or more, the sensitivity and specificity of the instrument were 93% and 80%, respectively. The DRAQ is a reliable, internally consistent, and valid instrument that may be suitable for population screening and clinical practice.

Activities of Daily Living↗
PubMed1996

New challenges to the faculty in the education of psychiatrists.

Significant social and economic pressures on academic medicine to become more cost conscious and scientifically accountable have led to new tensions in psychiatric residency training. Failure to distinguish between changes in practice derived from scientific advances and those derived from other sources has major implications for the education of future psychiatrists. After providing a conceptual framework for understanding current forces that affect residency training, the author proposes a new role for the psychiatric faculty, who should protect the curriculum and the trainee from shortsighted demands that could lower the quality of residency education and make psychiatry a less attractive specialty.

Career Choice↗
PubMed1995

Monomeric human cathepsin E.

Cathepsin E is a homodimer, consisting of two monomers linked by an inter-molecular disulphide bond. The cysteine residue involved is located near to the N-terminus of the mature proteinase. By mutating this residue to alanine, a monomeric form of human cathepsin E was engineered and purified. The activity of the resultant enzyme was not altered significantly (in terms of its ability to hydrolyse two chromogenic peptide substrates; and its susceptibility to inhibition by pepstatin). However, the stability of the mutant enzyme to alkaline pH and to temperature was markedly reduced.

Amino Acid Sequence↗
PubMed1995

Exploring the binding preferences/specificity in the active site of human cathepsin E.

Aspartic proteinases are produced in the human body by a variety of cells. Some of these proteins, examples of which are pepsin, gastricsin, and renin, are secreted and exert their effects in the extracellular spaces. Cathepsin D and cathepsin E on the other hand are intracellular enzymes. The least characterized of the human aspartic proteinases is cathepsin E. Presented here are results of studies designed to characterize the binding specificities in the active site of human cathepsin E with comparison to other mechanistically similar enzymes. A peptide series based on Lys-Pro-Ala-Lys-Phe*Nph-Arg-Leu was generated to elucidate the specificity in the individual binding pockets with systematic substitutions in the P5-P2, and P2'-P3' based on charge, hydrophobicity, and hydrogen bonding. Also, to explore the S2 binding preferences, a second series of peptides based on Lys-Pro-Ile-Glu-Phe*Nph-Arg-Leu was generated with systematic replacements in the P2 position. Kinetic parameters were determined for both sets of peptides. The results were correlated to a rule-based structural model of human cathepsin E, constructed on the known three-dimensional structures of several highly homologous aspartic proteinases; porcine pepsin, bovine chymosin, yeast proteinase A, human cathepsin D, and mouse and human renin. Important specificity-determining interactions were found in the S3 (Glu-13) and S2 (Thr-222, Gln-287, Leu-289, Ile-300) subsites.

Amino Acid Sequence↗