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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

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↗

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↗

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↗

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↗

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↗

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↗

Selective impairment of the retrieval of people's names: a case of category specificity.

Recent cases of 'proper names anomia' have been interpreted as arising from a category-specific recall deficit that is mediated either by the effects of 'uniqueness', or 'meaningfulness'. However, an alternative account is suggested by the report of a patient whose difficulties in naming familiar people arise from a selective learning impairment. The current case study presents data that are inconsistent with a learning interpretation of difficulties in naming people. We conclude that a dissociation exists between selective deficits affecting the learning and recall of people's names.

Aged↗

Emotional distress, coping, and adjustment in human immunodeficiency virus infection and acquired immune deficiency syndrome.

Fifty-seven ambulatory, human immunodeficiency virus (HIV)-infected patients at various stages of disease progression and 17 HIV seronegative controls were examined in a cross-sectional study with self-administered measures of emotional distress, coping, and adjustment to illness. All infected and control subjects were homosexual or bisexual and free of acute medical illness. The findings indicated that both uninfected and infected subjects had enhanced emotional distress in a variety of domains. However, while somatic and cognitive-ruminative complaints were greater in symptomatic subjects relative to controls, depression and anxiety were not. Professed coping strategies were heterogeneous and not particularly related to HIV diagnostic status, with the exception of planful problem solving which was decreased for acquired immune deficiency syndrome subjects. Disruption in several aspects of daily life adjustment was markedly increased in symptomatic subjects. The findings suggest that both HIV seropositive status and perceived risk for infection produce a sustained level of generalized psychological distress. Even in the absence of current medical illness, patients with advanced disease progression are concerned primarily with anticipated medical implications and cognitive effectiveness.

Acquired Immunodeficiency Syndrome↗

I recognize your face but I can't remember your name: is it because names are unique?

Burton & Bruce (1992), and Cohen (1990a), offer alternative accounts of the differences in 'normal' and neurologically impaired subjects' abilities to recall people's names and other pieces of biographical information. Cohen claims that the principal difference between names and other biographical information is in their relative meaningfulness, while Burton & Bruce argue that uniqueness is the crucial variable. As yet existing empirical evidence cannot be explained within the framework of either of these accounts, although the Burton & Bruce (1992) proposal has the advantage of being implemented as an interactive activation model. This paper describes the case of a patient who, following a stroke, retained the ability to access 'unique' semantic information for familiar people she is no longer able to name. It is argued that this pattern of performance provides difficulties for the Burton & Bruce model. However, it can be accounted for by Cohen's account, and a modified version of Burton & Bruce's model (Bruce, Burton & Walker, 1994).

Aged↗

Do both paternal and maternal smoking influence the prevalence of childhood asthma? A study into the prevalence of asthma in children and the effects of parental smoking.

Asthma is one of the commonest of chronic illnesses affecting children. Parental smoking has been considered to have an effect on this. In an attempt to clarify the relationship between parental smoking and the prevalence of childhood asthma we interviewed parents of 97.5% of the children aged 3-11 years registered with a large urban British general practice. We found a lifetime prevalence of asthma of 19.6%, 23.2% of boys and 15.9% of girls. Asthma was more common, 37.6%, in children who also had eczema. Parental smoking appeared to increase the prevalence of asthma. This was more marked when both parents smoked.

Absenteeism↗

Adolescent sexuality in Saint Petersburg, Russia.

OBJECTIVES: To describe adolescent knowledge, attitudes and behavior relevant to sexuality and the prevention of AIDS in Saint Petersburg, Russia. SUBJECTS AND METHODS: A cross-sectional descriptive study was designed, taking a random sample of 10th grade students at 14 Saint Petersburg grade schools, which were stratified by socio-economic district. A total of 185 female and 185 male students completed a self-administered 46-item questionnaire, with a response rate of 94%. RESULTS: From the questionnaires, 20% of females and 31% of males reported having had sexual intercourse and 25% of females and 12% of males reported being sexually abused. These adolescents displayed much misinformation about sexual matters and AIDS prevention. Only 25% of the females and 34% of the males believed that condoms should be used just once, and 38% of each sex believed that if washed, they could be used multiple times. Many respondents, especially males, rated their knowledge about sexual matters as high or adequate. Support for sex education was strong, especially among females, and respondents generally saw sex education as improving sexual pleasure. Most information sources about sexual activity were either not considered very credible, or not adequately accessible. CONCLUSIONS: Substantial reported rates of sexual abuse, sexual experience and much misinformation and unwarranted attitudes toward condoms, safer sexual practices and HIV/AIDS suggest the need for vigorous sex education programs for Russian youth. The early and sustained education of girls is especially important. Sex education should be introduced at an early age so that children can be taught how to reduce the risks of sexual abuse, HIV infection and other sexually transmitted diseases, and to improve their sexual experiences as responsible adults.

Acquired Immunodeficiency Syndrome↗

High level expression and characterisation of Plasmepsin II, an aspartic proteinase from Plasmodium falciparum.

DNA encoding the last 48 residues of the propart and the whole mature sequence of Plasmepsin II was inserted into the T7 dependent vector pET 3a for expression in E. coli. The resultant product was insoluble but accumulated at approximately 20 mg/l of cell culture. Following solubilisation with urea, the zymogen was refolded and, after purification by ion-exchange chromatography, was autoactivated to generate mature Plasmepsin II. The ability of this enzyme to hydrolyse several chromogenic peptide substrates was examined; despite an overall identity of approximately 35% to human renin, Plasmepsin II was not inhibited significantly by renin inhibitors.

Amino Acid Sequence↗

Interactions of substrates and inhibitors with a family of tethered HIV-1 and HIV-2 homo- and heterodimeric proteinases.

Genes were constructed to encode single-chain tethered human immunodeficiency virus HIV-1/HIV-1 and HIV-2/HIV-2 homodimeric proteinases and two HIV-1/HIV-2 heterodimers which differed in the nature of the interface strands. All four constructs under the control of a heat-inducible promoter were expressed in E. coli and the resultant proteinases were purified therefrom. Kinetic parameters (Km, kcat and kcat/Km) were derived for the interaction of the tethered homo and heterodimeric proteinases with two distinct substrates at a variety of pH values. All four enzymes were comparably active toward one substrate. With the second substrate at pH 4.7, the kcat/Km value was best for the HIV-1/1 tethered homodimer, 15-fold lower for the two heterodimeric proteinases, and was reduced by an additional 6-fold for the HIV-2/2 homodimer. From the Ki values determined for the interactions of the four tethered dimer proteinases with a systematic series of synthetic inhibitors, a parallel trend was observed. Whereas several inhibitors were equipotent against all four enzymes, two were discriminatory in that they inhibited strongly the HIV-1/1 homodimer and the two heterodimeric proteinases but had little effect on the HIV -2/2 tethered homodimer (or its untethered wild-type counterpart from HIV-2). The significance of these findings for active site interaction with HIV-proteinases is considered.

Amino Acid Sequence↗

Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum.

A clone encoding the aspartic proteinase (PFAPD) from Plasmodium falciparum strain HB3 was obtained during the course of a project designed to sequence and identify the protein coding regions of the parasite's genome. The protein encoded by the clone contains a sequence identical to the N-terminal sequence determined for an aspartic proteinase isolated from the digestive vacuole of P. falciparum and demonstrated to participate in the hemoglobin digestive pathway (D. Goldberg, personal communication). The translated polypeptide sequence encompasses a number of features characteristic of aspartic proteinases, having > 30% identity and > 50% similarity overall to human cathepsin D, cathepsin E and renin. A model of the three-dimensional structure of PFAPD was constructed using rule-based procedures. This confirms that the primary sequence may be folded as a single chain into a three dimensional structure closely resembling those of other known aspartic proteinases. It includes a lengthy prosegment, two typical-hydrophobic-hydrophobic-Asp-Thr/Ser-Gly motifs and a tyrosine residue positioned in a beta-hairpin loop. The distribution of hydrophobic residues throughout the active site cleft is indicative of a likely preference for hydrophobic polypeptide substrates. The recombinant form of this enzyme expressed using the pGEX2T vector in Escherichia coli is active in digesting hemoglobin at acidic pH and in hydrolyzing a synthetic peptide corresponding to the putative initial cleavage site in hemoglobin. Activity is inhibited completely by pepstatin, confirming the identity of PFAPD as a member of the aspartic proteinase family. Specific mRNA for PFAPD is expressed in the erythrocytic stages of the life cycle.

Amino Acid Sequence↗