Aspartic proteinases from the human malaria parasite Plasmodium falciparum.
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Biomedical subjects
Publications and source records attributed to J Kay.
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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.
A survey was carried out using the Canterbury Alcohol Screening Test (CAST) and clinical criteria for risk of alcohol withdrawal of 2000 randomly selected hospital in-patients in order to determine the prevalence of alcohol-related problems, the work-load for a specialist alcohol withdrawal service and the target group for early intervention. Patients at risk of alcohol withdrawal were followed prospectively.The major findings were: 14.3% of patients had a positive CAST and 8% were at risk of alcohol withdrawal; the prevalence of positive clinical criteria was greatest in men under the age of 30 years (OR 3.6) and very low (OR 0.34) in women over 60 years. In addition, patients who were too sick or refused to complete the questionnaire had high rates of being at risk for alcohol withdrawal. The prevalence of CAST positivity was greatest in men under the age of 40 years (OR 3.7) and lowest in women over 70 years (OR 0.2). It is concluded that 15-20% of in-patients have alcohol problems and 8% are at risk of withdrawal; questionnaires will produce underestimates of the order of 25%; and female in-patients over the age of 60 years are extremely unlikely to have problems with alcohol.
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.
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).
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.
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.
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.
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.
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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.
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.
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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.
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.
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.
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.