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Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 109 records · Page 6Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

The prevalence of childhood atopic eczema in a general population.

BACKGROUND: Atopic eczema has become more common during recent decades, but few studies have looked at its prevalence in the general community. OBJECTIVE: Our purpose was to ascertain the prevalence of atopic eczema, its age of onset, and its relationship to breast-feeding and ear piercing in a general practice population. METHODS: Children (N = 1104), aged 3 to 11 years, were identified from a computerized register in a socially and ethnically mixed English general practice population of 13,314. Of these, 1077 children (97.6% recruitment) were interviewed with parents or guardians, and the resultant data were recorded on a survey form. RESULTS: The lifetime occurrence of atopic eczema was 20% in boys (12% in the past year) and 19% in girls (11% in the past year). Prevalence in the past year was 10% to 14% in boys aged 3 to 11 years but fell in girls from 15% at 3 to 5 years to 8% at 9 to 11 years. Atopic eczema developed in the first 12 months of life in 60% of the children who had the condition, and it developed in the first 6 months of life in three quarters of these children. Ear piercing had been performed in 35% of girls and 3% of boys and was most prevalent in social classes 3, 4, and 5. More than half the girls aged 9 to 11 years had pierced ears. Breast-feeding did not affect the prevalence of atopic eczema. CONCLUSION: The lifetime prevalence of atopic eczema was 20% in children aged 3 to 11 years. There was no evidence that ear piercing perpetuated eczema in this age group. Breast-feeding did not protect against the development of atopic eczema.

Asthma↗
PubMed1994

Medical students' perceptions of patient-initiated sexual behavior.

BACKGROUND: Sexual behavior in the context of the doctor-patient relationship has potentially devastating effects on health care and the psychological well-being of patients. METHOD: To investigate the exposure of medical students to patient-initiated sexual behaviors (defined as any kind of sexual remarks or behaviors directed toward students by patients), 253 third- and fourth-year students and 1992 graduates of Wright State University School of Medicine were surveyed in the summer of 1992. The instrument used was a 16-item self-administered questionnaire, which solicited data on each respondent's age and gender as well as responses to patient-initiated sexual behavior, various aspects of the clinical settings in which such behavior occurred, and the effects of this behavior on the respondent's education and future practice. RESULTS: Of the 253 students and graduates surveyed, 155 (61%) responded (73 women and 82 men.) Fifty-two (71%) of the women and 24 (29%) of the men reported at least one instance of inappropriate sexual behavior by a patient. Frequently students had encountered inappropriate behavior more than once. CONCLUSION: Even assuming that all the nonrespondents had not experienced inappropriate sexual behavior, the proportion of students and graduates who did report such behavior is considerable. Understanding the extent and nature of patient-initiated sexual behavior experienced by physician trainees is hampered by differing definitions of inappropriate sexual behavior, subjective reporting, and variable perceptions of situations dependent on previous experience. Since patient-initiated sexual behavior can cause physicians to distance themselves from their patients and can put patients at risk for sexual exploitation, training in medical school is necessary to help students effectively manage such complex behavior.

Adult↗
PubMed1994

Irregular distortion of the erythrocytes (acanthocytes, spur cells) in senile dementia.

An excess of irregularly distorted red cells with spiked forms (acanthocytes, spur cells) has been found in a substantial minority of patients with senile dementia of Alzheimer type (7 of 50 patients, 3 of 21 men and 4 of 29 women). Of 100 control patients, 42 men and 58 women), 5 (3 men and 2 women) showed comparable distortion, but, of these, one man may well have incipient dementia and the others had serious organic diseases which may be associated with comparable erythrocytic changes. The cause of the distortion is not yet clear, but the presence of occasional giant erythrocytes in the absence of general macrocytosis suggests a possible abnormality of cell-membrane synthesis. This distortion may be a useful marker in patients with loss of memory. Whether it is a manifestation of a haemopoietic clone or a constitutional anomaly associated with Alzheimer's disease remains to be seen.

ABO Blood-Group System↗
PubMed1994

Statistical models for PET and SPECT data.

This article outlines the statistical developments that have taken place in emission tomography during the past decade or so. We discuss the statistical aspects of the modelling of the projection data and define the additive Poisson regression model. This leads to the use of the method of maximum likelihood as a means of estimating the underlying isotope concentration within a given region of a patient's body, and to the use of the EM algorithm to compute the reconstruction. The need for the regulation of the maximum likelihood solution is tackled using Bayesian techniques. A number of algorithms for the computation of regularized solutions are outlined. The issue of parameter estimation is discussed and some open issues are mentioned.

Algorithms↗
PubMed1994

Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects.

Epidural steroids (ESI) are often used for the treatment of low back pain but their effects on the endocrine system have not been determined. We studied the hypothalamic-pituitary adrenal (HPA) axis in 14 patients by measuring plasma adrenocorticotropin (ACTH) by sensitive two-site immunoradiometric assay and by evaluating the acute cortisol response to cosyntropin. We also evaluated the additional impact of sedation with midazolam before ESI on the degree of suppression of the HPA axis. Plasma ACTH and cortisol were significantly suppressed 7 days after the first ESI; the group receiving midazolam was more suppressed. By 14 days after the first ESI (7 days after the second ESI), plasma ACTH was more suppressed in the group receiving midazolam and plasma cortisol was markedly suppressed in both groups. At 48 days after the first ESI (34 days after the third ESI), plasma ACTH and cortisol were significantly suppressed only in the group that had received midazolam before each ESI. At 48 days, the plasma cortisol response to cosyntropin was blunted (< 500 nmol/L) in 5 of 14 patients. All patients had a normal cortisol response to cosyntropin by 3 mo after the last ESI. Weekly ESI over 3 wk caused a dramatic acute and chronic suppression of the HPA axis. Median suppression was less than 1 mo, and all patients had recovered by 3 mo. Sedation with midazolam accentuated the suppression of the HPA axis. Exogenous steroid coverage during this potentially vulnerable period should be considered in patients undergoing major stress especially if the adrenocortical response to ACTH is subnormal.

Adrenocorticotropic Hormone↗
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↗