Breaking the shackles of the genetic code: engineering retroviral proteases through total chemical synthesis.
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Biomedical subjects
Publications and source records attributed to J Elder.
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Decreased acid secretion, due to therapy or disease, predisposes to increased bacterial counts in gastric juice. As bacterial numbers increase, the number of nitrate-reducing strains and the concentration of luminal nitrite usually also increase. However, there is controversy (mainly because of assay problems) about whether decreased acid increases generation of N-nitroso compounds: these may be produced by acid or by bacterial catalysis, and the relative contributions of each are still uncertain. Other potentially important factors include ascorbate secretion (can prevent nitrite conversion to nitroso compounds) and the particular spectrum of nitroso compounds produced. Nitrosation of several histamine H2-receptor antagonists has been demonstrated experimentally, but under conditions that are very unlikely to be encountered clinically. Some acid suppressant therapies have been claimed to aid eradication of Helicobacter pylori, but more work is needed to evaluate this. If ulcer treatment regimens do not also address eradication of H. pylori (when present), gastritis will progress, and the recently documented association between H. pylori and gastric carcinoma needs to be considered. Enteric flora probably also increase if acid secretion is markedly reduced: this does not appear to have nutritional consequences but probably reduces the resistance to occasional infections, of which cholera is the best documented.
Interventions to improve child health depend, at least implicitly, on changing maternal knowledge and behaviour and a reallocation of maternal time. There have been few studies, however, of the time cost involved in the adoption of new health technologies and even fewer that examine changes in maternal activities in response to child illness. The present study examines maternal daytime activities and investigates changes that occur when children are ill. We examine the impact of acute childhood diarrhoea episodes on the activity patterns of the mother/caretaker in this setting. The results show that mothers alter their usual activity patterns only slightly in response to acute diarrhoea episodes in their children. They continue to perform the same variety of activities as when the children are healthy, although they are more likely to perform them with the child 'carried' on their back. There is some indication that diarrhoea perceived to be more severe did result in the mother acting as caretaker more frequently. These findings have important implications for health interventions that depend on changing the amount of maternal or caretaker time spent for child health technologies, but the implications may vary depending on the reasons for the observed lack of changes in caretaker activities.
Snoring is a very common problem but there are few publications on the histological findings of the soft palate/uvula and these lack consistency. The relative proportions of tissue types in the base of the uvula removed from 17 adults who underwent uvulopalatopharyngoplasty for heavy snoring were therefore compared with 14 cadaveric specimens. The mean percentage of muscle from the snoring group was 12.1% compared with 7.2% in the control group (P < 0.05). The percentage of fibrous tissue was greater in the cadavers (52.8% vs 45.5% in the snorers, P < 0.05). The percentage of muscle was inversely related to the percentage of fibrous tissue in the snoring group (P < 0.02). We hypothesize that these changes are a consequence of the repetitive forces on the soft palate during snoring rather than being related to the pathogenesis of snoring.
Compañeros en la Salud (Partners in Health) is a 3-year project funded by the National Cancer Institute to conduct a church-based health promotion program whose aim is to reduce the risk of breast, cervical, and diet-related cancers in Latino/Hispanic women by increasing their knowledge of preventive behaviors, motivating healthy behavior change, and increasing their access to and utilization of preventive health services. From a systems perspective, churches serve as miniature, dynamic communities that present an opportunity for developing and implementing a program of health promotion. An analysis of church, Promotora (peer health worker), and participant characteristics from the preintervention base-line data revealed a naturally occurring segmentation of churches by congregation size and denomination. The Catholic churches almost exclusively were larger, whereas the Protestant churches almost exclusively were smaller. An analysis of the psychosocial characteristics of the various Latino women, when stratified by church congregation size, revealed that the women from the smaller, Protestant churches were poorer, had a lower level of acculturation, and had lower lifetime rates of clinical breast examinations. These results suggested greater resource deficits and a relatively higher need for Promotora outreach services for women from the smaller, Protestant churches. Implications are presented for differential approaches to effective health promotion among various types of churches.
OBJECTIVE: To investigate the variability in serum pepsinogen levels in an asymptomatic population. DESIGN: Cross-sectional survey of 420 men aged 18-63 years, without symptoms or a history of gastric disease, recruited from four factories in Stoke-on-Trent. METHODS: During an interview, data on history of gastric health, 'lifestyle' and occupation were collected, blood samples were taken for measurement of serum pepsinogen and anti-Helicobacter pylori antibody levels and height and weight were measured. RESULTS: Extreme (low/high) levels of pepsinogens A and C, indicative of chronic gastritis, were found in 24 (5.7%) and 61 (14.5%) of the participants, respectively. Low A-C ratios, indicative of moderate or severe gastric atrophy, were found in 13 (3.1%) participants. Of the variables examined, Helicobacter pylori serology had the strongest influence on serum pepsinogen levels. Serum pepsinogen A and C levels were significantly higher in the 33.6% of participants who were seropositive. The effect was more marked for pepsinogen C; thus, A-C ratios were lower in seropositive individuals. In seronegative participants, both pepsinogen A and pepsinogen C levels increased with increasing age; pepsinogen A levels increased with increasing height and were higher in smokers, but decreased with increasing weight. The effect of smoking on pepsinogen A levels was also detectable in seropositive individuals, but was considerably less marked. Among seronegative participants, those employed on the 'shop-floor' in manual jobs had higher serum pepsinogen C levels and lower A-C ratios than office-based workers. CONCLUSION: H. pylori serology was a major source of variation in serum pepsinogen levels, but causes of gastritis other than H. pylori were indicated. Independent of these effects, serum pepsinogen levels may also vary with age, height and weight. Screening of serum pepsinogen levels in the general population may identify 5-15% who require further investigation. Other 'filters' may be required in conjunction with serum pepsinogen levels to identify those needing investigation for significant gastric pathology.
OBJECTIVES: To relate the prevalence of infection with Helicobacter pylori in adults to their living conditions in childhood to identify risk factors for infection. DESIGN: Prevalence study of IgG antibodies to H pylori (> 10 micrograms IgG/ml, determined by enzyme linked immunosorbent assay (ELISA)) and reported living conditions and other socioeconomic factors in childhood. SETTING: Three factories in Stoke on Trent. SUBJECTS: 471 male volunteers aged 18 to 65 years. MAIN OUTCOME MEASURES: Seroprevalence and variables in childhood. RESULTS: Seroprevalence of H pylori increased with age (22/74 (29.7%) at < 30 years v 29/46 (63%) at 55-65 years; P < 0.001 for trend) and was related to manual occupation (14/65 (21.5%) for non-manual v 162/406 (39.9%) for manual; P = 0.003). After data were adjusted for age and occupation subjects from large families, whose childhood homes were crowded or who regularly shared a bed in childhood, were significantly more likely to be seropositive (adjusted odds ratio (95% confidence interval) 2.15 (1.41 to 3.30) for crowding and 2.13 (1.38 to 3.30) for sharing a bed), but there was no relation with possession of a bathroom, inside toilet, refrigerator, or household pets in childhood. CONCLUSIONS: Close person to person contact in childhood is an important determinant of seroprevalence of H pylori in adulthood, suggesting that the infection is transmitted directly from one person to another and may be commonly acquired in early life.
In images of real visual scenes, contours are often fragmented by occlusion, shadows and low reflectance contrast. In order to infer shape from contour, the human visual system must selectively integrate fragments projecting from a common object while keeping fragments from different objects separate. In a previous paper we showed that contour closure has a strong influence on the speed of this process. In this paper we employ a visual search method to evaluate potential measures for the perceptual closure of fragmented shapes. We show that while certain intuitive measures are psychophysically inconsistent, a measure based on a sum of squares of the lengths of contour gaps is appropriate for both polygonal and smooth shapes in that response time can be expressed as a function of this measure. This L2 measure is shown to emphasize large gaps relative to small, and to embody a principle of perceptual regularity.
Nuclear protein binding sites in the long terminal repeat (LTR) of feline immunodeficiency virus (FIV) were identified by the method of DNase I footprinting. Using nuclear protein extracts from a feline T lymphoma cell line, several discrete footprints were generated upstream of the transcriptional initiation site (-50 to -150). The specificity of protein binding was examined by competition with oligonucleotides representing consensus DNA binding sites for known transcription factors. Binding to AP-1 (-124) and ATF (-58) motifs was observed, with cross-competition between these sites. A strong footprint signal was also detected over a tandemly repeated C/EBP motif (-94, -86) and an adjacent weaker footprint was found to be specific for an NF1 motif (-72/-63). The effect on FIV LTR promoter activity of progressively deleting these nuclear factor binding sites was examined by linking LTR deletion mutants to the chloramphenicol acetyltransferase (CAT) gene. Deletion of the AP-1 site caused a 10- to 25-fold loss of CAT activity whereas deletion past the ATF site reduced activity virtually to background levels. The effects of deleting the C/EBP and NF1 sites were less marked and varied according to cell type. Transactivation of the LTR was assayed using constructs linked to a CAT reporter gene. The full-length FIV LTR was not significantly trans-activated. However, the expression of a deleted LTR construct lacking the AP-4/AP-1 site but retaining C/EBP and ATF sites was partially restored by co-infection with FIV or by co-transfection with an infectious molecular clone of FIV (FIV-PPR). These results show that host transcription factors responsive to cellular activation have a major role in regulating FIV expression, and suggest that virus-coded trans-activators acting through U3 may play a role in some cellular environments.
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An outline drawing often serves as an excellent depiction of a visual scene. Somehow, our visual system can form two- and three-dimensional percepts solely from one-dimensional contour information. In mathematics, contour closure plays a key role in bridging this dimensional gap, however in perception the link between closure and shape is unclear. To better understand this relationship, we devised a set of visual search experiments in which subjects discriminate outline figures by means of their two-dimensional shape. By modulating the degree of closure of the outlines, we show that two-dimensional shape processing is rapid for closed stimuli but slow for open stimuli. We further show that search can be characterized as a smooth, monotonic function of the degree of closure, supporting the notion of a perceptual closure continuum.
Epidermoid cyst of the testis is a rare, benign intratesticular tumor in children. Four patients 4 to 15 years old with epidermoid cysts were managed by tumor excision with salvage of the testis. Preoperative ultrasound, tumor marker status and intraoperative findings were suggestive of a benign neoplasm. Under these circumstances epidermoid cysts may be safely treated by excision in prepubertal patients.
A 73-year-old woman with cholangitis due to stricture of the bile duct and the presence of stones was treated by the placement of a biliary endoprosthesis. However, 8 weeks later the lower end of the stent had retracted into a duodenal diverticulum and penetrated its inferior wall. The patient was readmitted to hospital for treatment of a retroperitoneal abscess.
The Escherichia coli mannitol permease is an integral membrane protein that catalyzes the concomitant transport and phosphorylation of D-mannitol and also acts as the chemoreceptor for chemotaxis of E. coli to this hexitol. At least 4 aminoacyl residues in this protein have been suggested to be important in these activities: His-195, His-256, Cys-384, and His-554. Previous evidence has implicated His-554 and Cys-384 as residues that are covalently phosphorylated, in sequence, as intermediates in phosphotransfer to mannitol. We have constructed a number of site-specific mutants of the mannitol permease at these positions. The properties of proteins in which His-554 or Cys-384 has been changed are consistent with their essential roles in phosphorylation. We also used these mutants to show that intermolecular phosphotransfer between His-554 and Cys-384 can occur in vivo in membrane-bound heterodimers consisting of different mutant subunits. The properties of proteins with mutations at position 195 suggest an important role for this residue involving hydrogen bonding, while His-256 performs no significant function in the mannitol permease. Finally, the phosphorylation and chemoreception activities for each mutant protein were each roughly in the same proportion to these activities in the wild-type protein, showing that these functions of the mannitol permease are tightly coupled under normal physiological conditions.
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METHODS. A randomly selected sample of Californian adults was surveyed by telephone to assess their knowledge, attitudes, and behaviors with respect to tobacco use and its control. The questions asked of this sample were whether they had recently (in the past 12 months) asked someone not to smoke in certain situations and whether they would ever consider doing such a thing. RESULTS. Results of the survey indicated that 59.1% of nonsmokers and 44.4% of smokers had asserted themselves within the past 12 months, while another 28.2 and 29.1% of the nonsmokers and smokers, respectively, indicated that they would consider asking someone not to smoke. Only 12.7% of the nonsmokers and 26.4% of the smokers indicated that they would not consider doing such a thing. Those more likely to object publicly to tobacco smoke are generally younger, are more educated, and have anti-tobacco attitudes related to either a specific health belief or social influence.
A study was undertaken to determine the rate of viral transmission among naive specific-pathogen-free (SPF) cats living in close contact with feline immunodeficiency virus (FIV)-infected cats. Twenty SPF cats were housed in the same rooms with experimentally FIV-infected seropositive and virus culture-positive cats for 2 to 4 years and were monitored for the presence of FIV nucleic acids and antibodies. Only 1 of the 20 cats became seropositive and virus culture positive and developed signs of disease. Genomic DNA from bone marrow and peripheral blood mononuclear cells (PBMC) of 10 of 19 healthy-appearing seronegative cats became positive for FIV DNA by the polymerase chain reaction. Twenty-eight SPF cats housed as groups in separate quarters and never exposed to FIV-infected cats were uniformly negative for FIV DNA. FIV RNA transcripts were detected in concanavalin A-stimulated PBMC cultures from 4 of 10 FIV DNA-positive, seronegative cats by in situ hybridization. PBMC from three of four naive SPF cats acquired FIV nucleic acids after the cats were transfused with blood and bone marrow from FIV genome-positive, seronegative donors. Three of five FIV-seronegative cats housed for years with naturally FIV-infected cats in a private household were also found to harbor FIV DNA, indicating that the same phenomenon occurred in the field. These findings demonstrate that cats living in close contact with FIV-infected seropositive cats can acquire FIV nucleic acids without developing detectable levels of serum antibodies or disease.
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