Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 127 records · Page 7Linked to original sources

PubMed1994

Quality assurance in the management of alcohol withdrawal in a general hospital.

We have shown previously that a standardized protocol is effective in the management of alcohol withdrawal in a general hospital. In this study a Quality Assurance (QA) approach was used to determine whether all patients at risk were detected and treated correctly in time. A total of 500 episodes were monitored, 82% of patients at risk were identified, and 89% of patients were seen within 24 h (median 4 h). The protocol was followed correctly in 86% of cases but was inappropriately applied in 7.2%. Medication was given in 242 cases, on 93% of occasions according to guidelines. In all, 11.8% of episodes became complicated by seizure, hallucinations or confusion and two patients had terminal respiratory failure which worsened after sedation. A standardized protocol for alcohol withdrawal can be used in a general hospital with high rates of detection of at risk patients, a high rate of compliance with treatment guidelines and a low rate of complications.

Adolescent↗

PubMed1994

Enhancement of human monocyte beta-glucan receptors by glucocorticoids.

Glucocorticoids are potent and diverse in their effects on mononuclear phagocytes, ranging from suppression to stimulation. To determine whether glucocorticoids affected functions mediated by monocyte beta-glucan receptors, human mononuclear cells (MNC) were incubated for 20 hr at 37 degrees with 20-2000 nM dexamethasone or hydrocortisone, and the monocytes were subsequently assayed for their ingestion of purified yeast glucan particles. Prior treatment with dexamethasone or hydrocortisone enhanced monocyte phagocytosis of glucan particles in a dose-dependent manner and both steroids effected a twofold increase at 200 nM. Monocytes from three different donors were assessed for secretion of beta-N-acetylglucosaminidase, and all were increased by exposure to 200 nM dexamethasone for 20 hr and subsequent stimulation with glucan particles for 2 hr; the average percentage net release was 16.2%. The enhancement in monocyte phagocytosis of glucan particles did not result by culture of MNC with beta-oestradiol, progesterone, testosterone or spironolactone, indicating a specificity for corticosteroids with glucocorticoid activity. The increases in phagocytic activity by monocytes that had been exposed during culture to either 200 nM dexamethasone or 200 nM hydrocortisone were both reduced by 40-50% by pretreatment of monocytes with the anti-idiotype (anti-Id) that recognizes beta-glucan receptors. Exposure of cells to 200 nM dexamethasone for 2 hr and washing before continued incubation for 18 hr in steroid-free media resulted in stimulation of monocyte beta-glucan receptors, whereas similar exposure without subsequent culture or with the addition of cycloheximide for the final 18 hr did not. Thus, glucocorticoids enhance monocyte functions mediated by beta-glucan receptors, and this stimulation is dependent on proteins that are newly synthesized during culture.

Adult↗

PubMed1993

Analysis of regulatory elements flanking metallothionein genes in Cd-tolerant fish (pike and stone loach).

From genomic libraries constructed for both pike and stone loach, clones were isolated containing the metallothionein genes from these two species of cadmium-tolerant fish. A single copy metallothionein gene was identified in each species by Southern blot analysis. Sequencing revealed that each gene consisted of three exons followed by polyadenylation signals at the 3' end. In the 5' flanking region, putative metal responsive elements were identified both close to the transcription start site and clustered distally approx. 500 bp upstream. Neither gene locus showed any homology with the glucocorticoid or interferon responsive elements that have been identified in mammalian species. The significance of the absence of such responsive elements and their replacement by additional metal responsive elements in the same location of the 5'-flanking region of the MT genes is discussed in relation to the organisation of the MT gene loci in (the Cd-sensitive) rainbow trout and higher mammalian species.

Animals↗

PubMed1993

Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation.

To understand the differences in the binding specificities within the aspartic proteinase family of enzymes, we have carried out studies to determine the inhibition constants of a set of related compounds with various members of the human enzyme family. The inhibition constants (Ki values) were determined by competitive inhibition of the hydrolysis of chromogenic octapeptide substrates in the pH range of 3-5. For comparison, inhibition of monkey renin was studied by RIA at pH 6.0. All inhibitors were based on the general structure 4-(morpholinylsulfonyl)-L-Phe-P2-(cyclohexyl)Ala psi[isostere]-P1'-P2'. The isosteric replacements of the scissile peptide bond included difluorohydroxyethylene, 1,2-diols, 1,3-diols, and difluoroketones. Side chain substituents in P2 include hydrogen, allyl, ethylthio, (methoxycarbonyl)methyl, N-methylthiouridobutyl, imidazolylmethyl, and 4-amino-2-thiazolylmethyl. Our measurements have identified potent and selective inhibitors which are useful in evaluating the differences in the specificities among selected enzymes of this family.

Amino Acid Sequence↗

PubMed1993

Human cathepsin E produced in E. coli.

A cDNA for procathepsin E was generated from human gastric adenocarcinoma (AGS) cells, amplified by PCR and inserted into the T7 dependent vector pET 22b for expression in E. coli. Purification of the resultant product was accomplished simply, without the need to resort to column chromatography. The recombinant protein displayed comparable properties to those of its naturally occurring counterpart. The yield of homogeneous active enzyme obtained was approximately 3 mg per 40 g of cells. This is sufficient to permit crystallisation and structural analysis to begin and a mutagenesis programme to examine structure/activity relationships now to be undertaken.

Adenocarcinoma↗

PubMed1993

Presence and possible significance of immunocytochemically demonstrable metallothionein over-expression in primary invasive ductal carcinoma of the breast.

Metallothioneins (MTs) are ubiquitous low-molecular-weight proteins with a high affinity for heavy metal ions such as zinc, copper and cadmium. MT over-expression has been associated with resistance against anticancer drugs. In the present study we investigated 86 cases (45 cases of tumour category pT1 and 41 of category pT2) of routinely fixed and paraffin-embedded primary breast carcinomas immunohistochemically with a monoclonal antibody to an epitope of MT shared by its I and II isoforms. Immunohistochemically demonstrated MT over-expression was found in the invasive components of 7 of 32 pT1 and 17 of 28 pT2 invasive ductal carcinomas, whereas all 26 invasive lobular carcinomas gave weak or negative results. Fourteen of 17 pT2 and 2 of 7 pT1 invasive ductal carcinomas with MT over-expression developed metastases during follow-up with poor prognostic outcome. In contrast only 3 of 11 pT2 and none of the 25 pT1 cases without MT over-expression had a poor clinical course (P < 0.001). It is concluded that MT over-expression is associated with significantly poor prognosis particularly in pT2 invasive ductal breast carcinomas.

Adult↗

PubMed1993

Medical student abuse: perceptions and experience.

A questionnaire containing 18 vignettes of common clinical educational situations with potentially abusive treatment of medical students and a 10-item attitude assessment about abusive behaviour were administered to the first- and fourth-year medical students at a mid-west US university medical school. The first- and fourth-year groups did not differ significantly on perceived abusiveness of most of the vignettes, although several of the individual vignettes were perceived significantly differently by the two groups. As hypothesized, the fourth-year students had experienced such situations more frequently. Attitudes towards abusive behaviour did not differ between the two groups. The authors contrast teaching interactions perceived as educationally useful and not abusive with those seen as abusive and not useful and offer explanations for the differences observed. Finally, the possible implications of the results for medical education are discussed.

Attitude↗

PubMed1993

Clinical epidemiology of childhood abdominal migraine in an urban general practice.

The present study examined the epidemiology of abdominal migraine among 1104 children registered with a general practice. There was a similar prevalence of recurrent abdominal pain as in other studies (8.4 per cent). The prevalence of headache was higher among children with recurrent abdominal pain and significantly so among girls. Migrainous headache was not significantly more prevalent in children with recurrent abdominal pain. The prevalence of abdominal migraine with and without migrainous headache was 0.7 and 1.7 per cent, respectively. The peak prevalence of abdominal migraine without migrainous headache was between five and seven years for both sexes. When associated with migrainous headache, it peaked at five to seven years in girls and seven to nine years in boys. The syndrome was associated with travel sickness and was more common among girls and those with a maternal history of migraine. Many children were photo- and phonophobic during an attack.

Abdominal Pain↗

PubMed1993

The prevalence of headache and migraine in atopic children: an epidemiological study in general practice.

The lifetime prevalence of headache and migraine was assessed in an unselected sample of atopic (asthma, eczema or rhinitis) children in a general practice population of known socio-economic and age/sex composition. Maternal migraine was also recorded. The prevalence of both headache and migraine was significantly and proportionally higher in children with atopic disorders compared to those without. Childhood migraine was associated with atopy and the association was strongest with rhinitis. Rhinitis in children was associated with maternal migraine. A history of atopy (especially rhinitis) supports the diagnosis of migraine in young children with paroxysmal headaches.

Child↗

PubMed1993

Analysis of latent forms of renin using antibodies raised against the propart segment of human prorenin: validation with representative samples of ovarian cyst and follicular fluids.

Antisera were raised against synthetic peptides from the prosegment of human prorenin. The use of each of these for detection of the appropriate prosegment region of prorenin was validated by development of an ELISA protocol standardised with recombinant prorenin present in culture medium conditioned by myeloma cells transfected with a prorenin expression plasmid. Detection of the respective epitopes in the prosegment required prior exposure of the prorenin in the medium to acid pH in order to partially unfold the prorenin molecule by dislodging the prosegment from the main body of the protein. By these ELISA protocols, the form of latent renin present in representative samples from ovarian cyst and follicular fluids was analysed; one follicular cyst fluid was found to contain full-length prorenin whereas the fluid from a benign cyst and ovarian follicular fluid samples contained the precursor in truncated form.

Amino Acid Sequence↗

PubMed1993

An economic appraisal of alternative pre-natal screening programmes for Down's syndrome.

The objective of this study was to evaluate economically a screening programme within the Oxford Regional Health Authority for Down's syndrome, based on maternal serum alpha fetoprotein, unconjugated oestriol and human chorionic gonadotrophin as well as maternal age (the triple test) against maternal age alone. The design of the study involved cost-effectiveness analysis of the triple test relative to the maternal age screening programme, and the main outcome measure was the cost per Down's birth avoided. It was found that the triple test is more cost-effective over a wide range of assumptions concerning detection rates and procedure costs. Indirect costs are important in considering the cost-effectiveness of the screening programmes. The most efficient detection rate is around 58 per cent for which the cost per Down's birth avoided is approximately 29,600 pounds if only direct costs are evaluated, 20,100 pounds if all NHS costs are considered and -49,800 pounds if all resource consequences are analysed. It may be concluded that screening for Down's syndrome using the triple test is cost-effective over a wide range of assumptions concerning detection rate and procedure costs. If all resource costs are considered, the programme is highly cost-effective in comparison with other health care interventions.

Abortion, Therapeutic↗

PubMed1993

Lyme disease.

Explore the source record for details and available documents.

Adult↗

PubMed1993

The development of a tool to assess neonatal pain.

The objectives of this study were to (1) develop a behavioral assessment tool for the measurement of pain in the preterm and full-term neonate; (2) establish the construct and concurrent validity, interrater reliability, and internal consistency of the tool; and (3) examine the relationship between the pain scores and infant characteristics. Thirty-eight infants contributed to the 90 procedures videotaped for the study. The Neonatal Infant Pain Scale (NIPS) was used to score behavioral responses before, during, and after each intrusive procedure. The significant difference in NIPS scores over time indicates that the scale provides a measurement of intensity of infant responses to intrusive procedures. Concurrent validity was established by correlations, ranging from .53 to .84, between NIPS scores at each minute of observation and scores on the Visual Analogue Scale. Interrater reliability was high: Pearson correlations ranged from .92 to .97 across successive minutes of observation. The six component scores of the NIPS had high internal consistency: Cronbach's alphas were .95, .87, and .88 for before, during, and after the procedures, respectively. Although gestational age and five-minute Apgars were positively associated with NIPS scores over time, there was no association between these factors and responsiveness to pain, as measured by change in NIPS scores from before to during the procedure. Results are discussed in terms of the use of the NIPS in clinical trials and its clinical application in a neonatal intensive care unit.

Apgar Score↗

PubMed1992

Intrinsic activity of precursor forms of HIV-1 proteinase.

The wild-type -Phe*Pro- bond located at the N-terminus of the mature aspartic proteinase of HIV-1 was replaced by -Ile-Pro- or -Val-Pro-. By this means, processing at this cleavage junction was prevented and so, extended or precursor forms of HIV-proteinase were generated. These constructs were expressed in Escherichia coli, purified therefrom, and their specificity, activity at different pH values and susceptibility to the potent inhibitor, Ro31-8959, was assessed. A hitherto unobserved cleavage junction (at approximately Ala-Phe*Leu-Gln approximately) in the frame-shift region of the gag-pol viral genome was identified and confirmed by demonstrating cleavage of a synthetic peptide corresponding to this region. The implications for viral replication of self-processing at neural pH by proteinase whilst still present (in a precursor form) as a component of the polyprotein are considered; such reactions, however, are still blocked even at pH values as high as 8.0 by Ro31-8959.

Amino Acid Sequence↗

PubMed1992

Different requirements for productive interaction between the active site of HIV-1 proteinase and substrates containing -hydrophobichydrophobic- or -aromaticpro- cleavage sites.

The sequence requirements for HIV-1 proteinase catalyzed cleavage of oligopeptides containing two distinct types of junctions (-hydrophobic*hydrophobic- or -aromatic*Pro-) has been investigated. For the first type of junction (-hydrophobic*hydrophobic-) the optimal residues in the P2 and P2' positions were found to be Val and Glu, respectively, in accord with recent statistical analysis of natural cleavage sites [Poorman, R. A., Tomasselli, A. G., Heinrikson, R. L., & Kézdy, F. J. (1991) J. Biol. Chem. 266, 14554-14561]. For the -aromatic*Pro- type of junction, in the specific sequence context studied here, the value of Glu in the P2' position was again observed. An explanation for the inefficient cleavage observed for peptides with the sequence -Val-Tyr*Pro- has been provided from molecular modeling of the putative enzyme-substrate complex. A significant effect upon cleavage rates due to the amino acid in the P5 position has also been documented. While lysine in the P5 position in one sequence of the -hydrophobic*hydrophobic- type produces a peptide cleaved very efficiently (kcat greater than 15 s-1 for Lys-Ala-Arg-Val-Nle*p-nitrophenylalanine-P2'-Ala-Nle-NH2, for P2' = Glu, Gln, Ile, Val, or Ala), for substrates of the -aromatic*Pro- type, the P5 residue can exert either a positive or negative effect on cleavage rates. These results have again been interpreted in light of molecular modeling. We suggest that interaction of the substrate sequence on the periphery of the active site cleft may influence the match of the enzyme-substrate pair and, hence, control the efficiency of catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1992

Kinetic parameters for the generation of endothelins-1,-2 and -3 by human cathepsin E.

The specific conversion of human endothelin (ET) precursors big ET-1, big ET-2 and big ET-3 into their respective ET by cathepsin E was examined. Comparable pH optima were obtained for ET-1 and ET-2 generation, whereas effective conversion of big ET-3 into ET-3 necessitated a lower pH value. Determination of kinetic parameters (Km, kcat.) for all three conversions indicated that the precursors were efficiently bound by cathepsin E. The significance of the values obtained for the catalytic-centre activities and the effect of a specific inhibitor are discussed.

Amino Acid Sequence↗

PubMed1992

Sequestration of cadmium and copper by recombinant rainbow trout and human metallothioneins and by chimeric (mermaid and fishman) proteins with interchanged domains.

A family of synthetic genes was constructed encoding a rainbow trout metallothionein (MT), a human MT, and two chimeric molecules which contained respectively (i) the N-terminal (or head) domain of human MT followed by the C-terminal (or tail) domain of a fish MT (termed mermaid MT) and (ii) the head domain of fish MT fused with the tail domain of human MT (denoted fishman MT). These were expressed in Escherichia coli and the four recombinant proteins were purified to homogeneity therefrom. All four were found to bind 7 g atoms of Cd(II) per mol; at pH 7.0, but not at pH 8.6, four Cd(II) ions were sequestered preferentially in the tail (or alpha) domain. Reciprocally, copper was found to bind preferentially in the head (or beta) domain. The human and fishman MTs displayed a stoichiometry of 12 g atoms of Cu(I) per mol, while rainbow trout and mermaid MTs bound only 10. The significance of these findings is discussed in relation to the different positional organization of cysteine residues close to the N and C termini of mammalian and piscine metallothioneins.

Amino Acid Sequence↗

PubMed1992

Musculoskeletal manifestations in beta 2-microglobulin amyloidosis. Case discussion.

The cases presented illustrate some of the typical (case 1) and less common (case 2) clinical features of beta 2m amyloidosis. The accumulation of beta 2m amyloid in tissues is a potentially severe complication of dialysis-treated chronic renal failure. Beta 2m amyloidosis has been shown to have distinct clinical, radiologic, and pathologic features. The pathogenesis of this condition is not yet clearly understood, and recommendations for the clinical management of these patients at present are limited to recognition of the disease and symptomatic treatment. Further insights into the biology of this disease should lead to new strategies for prevention and treatment.

Aged↗