Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 127 records · Page 7Linked to original sources

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↗

PubMed1992

Utility of high-resolution ultrasound for the diagnosis of dialysis-related amyloidosis.

OBJECTIVE: To evaluate the utility of real-time, high-resolution ultrasound of the shoulder in the diagnosis of dialysis-related amyloidosis. METHODS: We performed a case series study of 2 groups of patients seen at a referral-based clinic in a tertiary care hospital. The shoulders of 13 patients with normal renal function and of 38 patients receiving long-term hemodialysis were studied by real-time, high-resolution ultrasound. All hemodialysis patients were evaluated clinically for the presence of dialysis-related amyloidosis. Surgical specimens of joints were available for all 13 patients with normal renal function and for 17 of the 38 hemodialysis patients. These specimens were evaluated for the presence of beta 2-microglobulin (beta 2m) amyloid by Congo red and immunohistochemical staining. RESULTS: Two ultrasonographic findings were selectively observed in the dialysis patients with clinical and histologic evidence of beta 2m amyloid in comparison with patients with normal renal function and no evidence of amyloid: rotator cuffs greater than 8 mm in thickness and echogenic pads between muscle groups of the rotator cuff. The presence of at least 1 of these 2 findings corresponded to the presence of clinically and histologically evident beta 2m amyloid with a sensitivity of 79% and a specificity of 100%. When additional patients without surgical specimens for histologic confirmation of amyloidosis were included, the sensitivity of these 2 sonographic findings was 72% and the specificity was 97%. CONCLUSION: Real-time, high-resolution ultrasound is a relatively sensitive and highly specific noninvasive adjunct to the clinical diagnosis of beta 2m amyloidosis in patients receiving long-term hemodialysis.

Adult↗

PubMed1992

Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E.

Proteolytic degradation (processing) of antigen by antigen-presenting cells is a major regulatory step in the activation of a T lymphocyte immune response. However, the enzymes responsible for antigen processing remain largely undefined. In this study we show that cathepsin E, and not the ubiquitous lysosomal cathepsin D, is the major aspartic proteinase in a murine antigen-presenting cell line, A20. This enzyme is localized to a non-lysosomal compartment of the endosomal system in these cells. Functional studies using a highly specific inhibitor of cathepsin E show that this enzyme is essential for the processing of ovalbumin by this cell line. Thus, cathepsin E, whose function was hitherto unknown, may play a major role in antigen processing.

Animals↗

PubMed1992

Inhibition of aspartic proteinases by synthetic peptides derived from the propart region of human prorenin.

1. Five synthetic peptides which together spanned the propart segment of human prorenin were tested for their ability to interact with human renin, pepsin, gastricsin, cathepsin D, cathepsin E, calf chymosin and the aspartic proteinase from Endothia parasitica. 2. While two peptides showed no significant effect with any of the enzymes, a further two were cleaved by several enzymes. 3. Only one (corresponding to the 32P-43P residues in the propart sequence) acted as a weak competitive inhibitor of most of the enzymes.

Amino Acid Sequence↗

PubMed1992

Does letter-by-letter reading involve the spelling system?

Warrington and Shallice (Brain 103, 99-112, 1980) proposed that letter-by-letter readers can no longer access the visual word-form system, and read by using the spelling system 'in reverse'. Contrary to their suggestion, this paper presents the case of a letter-by-letter reader who appears to use quite different strategies in word reading and spelling. Reading and spelling are both impaired, but they appear to be impaired in different ways. Most strikingly, the patient's spelling errors consist largely of phonological regularizations--indeed there is little evidence that he has any lexical spelling knowledge available--whereas there are virtually no regularizations amongst his reading errors. These are largely visual paralexias and letter misidentifications. It is suggested that this pattern is more easily explained in terms of compensatory mechanisms that access the reading lexicon than by use of the spelling system 'in reverse'.

Adult↗

PubMed1992

Childhood migraine in general practice: clinical features and characteristics.

Previous studies have evaluated the clinical features and characteristics of migraine in selected children attending hospital clinics. There have, however, been no community studies on the prevalence and characteristics of migraine in children aged 3-11 years in British general practice. In this study, a total of 1,083 children (from 1,104 registered with a general practice) and their parents were interviewed. Possible migraine sufferers took part in an extended interview that assessed various characteristics of the patients and their attacks. The survey showed that migraine attacks started in infancy, and migrainous children were more likely to have mothers with migraine. Some clinical features were found to be age-dependent. Compared with similar hospital surveys there was a lower frequency of attacks recorded but the prevalence of aura was similar to that found in previous studies.

Age Factors↗