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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 73 records · Page 4Linked to original sources

Human herpesvirus 8-encoded thymidine kinase and phosphotransferase homologues confer sensitivity to ganciclovir.

Human herpesvirus 8 (HHV-8) sensitivity to the nucleoside analog ganciclovir (GCV) suggests the presence of a virally encoded kinase that catalyzes the initial phosphorylation of GCV. Analysis of the HHV-8 genome identified two candidate kinases: proteins encoded by open reading frame (ORF) 21, with homology to the herpesvirus thymidine kinases (TK), and ORF 36, with homology to the herpesvirus phosphotransferases (PT). Experiments presented here show that both ORF 21 and ORF 36 encode GCV kinase activities as demonstrated by GCV phosphorylation and GCV-mediated cell death. In both regards the PT homologue ORF 36 was more active than the TK homologue ORF 21. ORF 21, but not ORF 36, weakly sensitized cells to killing by penciclovir. Neither ORF sensitized cells to killing by (E)-5-(2-bromovinyl)-2'-deoxyuridine.

Amino Acid Sequence↗

Regional assignment and expression analysis of 29 expressed sequence tags mapped to chromosome 3.

Of 311 expressed sequenced tags (ESTs) mapped to single human chromosomes by analysis of a monochromosome somatic cell hybrid panel, 29 were localized to chromosome 3. Analysis of somatic cell hybrid lines containing different regions of chromosome 3 has enabled the regional assignment of these 29 ESTs to 13 of 23 intervals covering chromosome 3. Northern analysis of 25 of the EST clones has provided information on the pattern of expression of potential genes represented by these transcripts in 16 human tissue types. Nine of the clones hybridized solely to a transcript(s) in the testis, 12 hybridized to transcripts in testis and other tissues, and 4 hybridized with transcripts in testis and other tissues but in addition have testis-specific transcript sizes. These ESTs will provide useful markers throughout chromosome 3 for the development of physical and transcription maps. In addition, they provide candidate genes for disease loci mapping to the intervals defined by the chromosome 3 deletion panel.

Chromosome Mapping↗

Stem cell factor as a single agent induces selective proliferation of the Philadelphia chromosome positive fraction of chronic myeloid leukemia CD34(+) cells.

The interaction between p145(c-KIT) and p210(bcr-abl) in transduced cell lines, and the selective outgrowth of normal progenitors during long-term culture of chronic myeloid leukemia (CML) cells on stroma deficient in stem-cell factor (SCF) suggests that the response of CML cells to SCF may be abnormal. We examined the proliferative effect of SCF(100 ng/mL), provided as the sole stimulus, on individual CD34(+) cells from five normal donors and five chronic-phase CML patients. Forty-eight percent of isolated single CML CD34(+) cells proliferated after 6 days of culture to a mean of 18 cells, whereas only 8% of normal CD34(+) cells proliferated (mean number of cells generated was 4). SCF, as a single agent, supported the survival and expansion of colony-forming unit-granulocyte-macrophage (CFU-GM) from CML CD34(+)CD38(+) cells and the more primitive CML CD34(+)CD38(-) cells. These CFU-GM colonies were all bcr-abl positive, showing the specificity of SCF stimulation for the leukemic cell population. Coculture of CML and normal CD34(+) cells showed exclusive growth of Ph+ cells, suggesting that growth in SCF alone is not dependent on secretion of cytokines by CML cells. SCF augmentation of beta1-integrin-mediated adhesion of CML CD34(+) cells to fibronectin was not increased when compared with the effect on normal CD34(+) cells, suggesting that the proliferative and adhesive responses resulting from SCF stimulation are uncoupled. The increased proliferation may contribute to the accumulation of leukemic progenitors, which is a feature of CML.

Adult↗

Comparison of four commercial urinary albumin (microalbumin) methods: implications for detecting diabetic nephropathy using random urine specimens.

The results of four urinary albumin methods used to identify patients with early diabetic renal disease were compared using random urine samples from healthy and diabetic patients. These methods were the Beckman Array and Behring BNAI immunonephelometric methods, the Dade aca particle-enhanced turbidimetric inhibition immunoassay method, and the INCSTAR SPQ immunoturbidimetric method. The albumin/creatinine ratio reference interval was found to be 2-20 mg albumin/g creatinine (mg/g) for the Array and 3.5-27.5 mg/g for the aca method. All four methods were compared using urines from a group of diabetic and nondiabetic patients. The BNAI, SPQ and Array methods compared well with one another while the aca demonstrated a positive bias of almost 60% at the 30 mg/g and 300 mg/g levels with certain lots of reagent and calibrator. Calibrator cross-over experiments demonstrated that some of the positive bias of the aca method could be accounted for by calibrator differences.

Albuminuria↗

Compliance with universal precautions among pediatric residents.

BACKGROUND: There are few data on the rate of compliance with universal precautions among pediatricians. We hypothesized that compliance in pediatrics would be poor because of the intrinsic difficulties in performing invasive procedures in small subjects. DESIGN: Prospective, observational study. SETTING: Tertiary care children's hospital. STUDY PARTICIPANTS: A convenience sample of pediatric house staff. MAIN OUTCOME MEASURES: Pediatric house staff members were observed while performing invasive procedures. Procedure type, number of attempts required, and patient's age and diagnosis were recorded. Degree of compliance with universal precautions was judged by means of Centers for Disease Control and Prevention guidelines. Comparisons between the compliant and noncompliant groups were analyzed by chi2 and 2-tailed t test. RESULTS: A total of 128 procedures performed by 43 house officers, 4 advanced medical students, and 3 chief residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were performed correctly according to universal precaution guidelines. Rate of compliance did not appear to be influenced by small patient size, as judged by the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years among those in whom universal precautions were properly used vs 4.9+/-5.4 years among patients in whom precaution guidelines were breached; P=.96). Moreover, the number of attempts required in compliant procedures (1.31+/-0.53) was almost identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally, compliance did not improve with advanced level of training. CONCLUSIONS: Failure of compliance among pediatricians has no apparent association with procedure difficulty, and compliance rates continue to be poor through the course of pediatric training. These findings underline the need for effective education concerning universal precautions throughout pediatric residency, and they suggest that such efforts will not be precluded by obstacles intrinsic to performing invasive procedures on young subjects.

Humans↗

Phase I study of oral JM216 given twice daily.

JM216 [bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an oral platinum complex that is currently in phase II trials in ovarian cancer and lung cancer on a daily-times-5 schedule. This trial examined an alternative schedule of two doses given 12 h apart, which may be better tolerated by patients. A total of 19 patients were given 50 cycles of treatment at doses ranging from 150 to 350 mg/m2 b.i.d. The study was stopped before the MTD was reached due to non-linear pharmacokinetics. Toxicity was similar to that encountered in previous phase I studies, with nausea, vomiting and diarrhoea being seen at all dose levels, although this was generally mild and short-lived, and grade 3 and 4 myelosuppression being seen at dose levels ranging from 250 to 350 mg/m2. There was no nephro-, oto-, or neurotoxicity, but one patient had an allergic reaction at 300 mg/m2 on the fifth and sixth cycles. No response was seen, but two patients with mesothelioma had stable disease and received six cycles. There was considerable interpatient variability in plasma pharmacokinetics at all dose levels. There was no relationship between dose and AUC (dose 1 and dose 2) or Cmax after dose 1. In a limited number of patients the first dose was given in the morning rather than in the evening, apparently resulting in lower AUC, Cmax and Tmax values at the 250-mg/m2 dose level, but this was not seen in one patient at 300 mg/m2. This study confirms that the pharmacokinetics of JM216 is non-linear and highly variable due to saturable absorption and that the daily times 5 schedule is the optimal schedule for further phase II trials.

Adult↗

Multivalent pneumococcal capsular polysaccharide conjugate vaccines employing genetically detoxified pneumolysin as a carrier protein.

A genetically detoxified pneumolysin, pneumolysoid (PLD), was investigated as a carrier protein for pneumococcal capsular polysaccharide (CPS). Such a CPS-PLD conjugate might provide additional protection against pneumococcal infections and resultant tissue damage. A single point mutant of pneumolysin was selected, which lacked measurable haemolytic activity, but exhibited the overall structural and immunological properties of the wild type. PLD conjugates were prepared from CPS serotypes 6B, 14, 19F, and 23F by reductive amination. The structural features of free PLD, as well as the corresponding CPS-PLD, as assessed by circular dichroism spectroscopy, were virtually indistinguishable from the wild type counterpart. Each of the CPS monovalent and tetravalent conjugate formulations were examined for immunogenicity in mice at both 0.5 and 2.0 micrograms CPS per dose. Tetanus toxoid (TT) conjugates were similarly created and used for comparison. The resultant conjugate vaccines elicited high levels of CPS-specific IgG that was opsonophagocytic for all serotypes tested. Opsonophagocytic titres, expressed as reciprocal dilutions resulting in 50% killing using HL-60 cells, ranged from 100 to 30,000, depending on the serotype and formulation. In general, the lower dose and tetravalent formulations yielded the best responses for all serotypes (i.e., either equivalent or better than the higher dose and monovalent formulations). The PLD conjugates were also generally equivalent to or better in CPS-specific responses than the TT conjugates. In particular, both the PLD conjugate and the tetravalent formulations induced responses for type 23F CPS that were approximately an order of magnitude greater than that of the corresponding TT conjugate and monovalent formulations. In addition, all the PLD conjugates elicited high levels of pneumolysin-specific IgG which were shown to neutralize pneumolysin-induced haemolytic activity in vitro. As a result of these findings, PLD appears to provide an advantageous alternative to conventional carrier proteins for pneumococcal multivalent CPS conjugate vaccines.

Animals↗

Rapid improvement teams.

BACKGROUND: Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. SUGGESTIONS: Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. CONCLUSIONS: Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

Benchmarking↗

Nurse perceptions of ostomy patients & their ostomy care competence.

The nursing role of caring for ostomy patients has evolved from the bedside nurse to an enterstomal therapist (ET) or a nurse clinical specialist with ostomy care experience. Routine practice calls for staff nurses and physicians to refer patients with a new ostomy or patients with stoma problems to these specialists. The responsibility for successful outcomes typically falls on these specialized nurses.

Adult↗

Australian and South African undergraduates' HIV-related knowledge, attitudes, and behaviors.

To understand safe sex behavior in two countries which have been differentially affected by the HIV/AIDS epidemic, the present study compared the AIDS-related knowledge, attitudes, and behaviors of 920 heterosexual undergraduate students in Australia and 228 heterosexual undergraduate students in South Africa. South African students were found to have significantly less knowledge about HIV/AIDS, and significantly less favorable attitudes toward safe sex behavior than their Australian counterparts. They were also more likely to report that they have avoided various groups of people for fear of contracting AIDS. Experience from Australia over the period 1986-1995 suggests that significant improvements in the AIDS-related knowledge, attitudes, and behaviors of South African undergraduates are achievable.

Acquired Immunodeficiency Syndrome↗

Collagen biosynthesis by neointimal smooth muscle cells cultured from rabbit aortic explants 15 weeks after de-endothelialization.

Extracellular matrix (ECM) accumulation in arterial neointima, developed in response to de-endothelialization, is a prolonged process. In this study, we examined the relationship between increased collagen accumulation and synthetic activity of neointimal smooth muscle cells (SMCs) derived from aortic explants fifteen weeks after balloon catheter injury. Freshly confluent SMCs, derived either from normal aorta or from aortic neointima, were used in this study. The newly synthesized collagen was analysed by measuring [3H]-proline incorporation; and the mRNA expression for two major types of collagen, collagen type I and type III, was studied by Northern blot analysis. Our results indicated a three fold increase in protein (collagen) synthesis by neointimal SMCs. At the same time, the steady-state mRNA for procollagen I and procollagen III was elevated five and three times, respectively. These data indicate that persistent synthesis contributes to collagen accumulation in the arterial neointima and both transcriptional and post-transcriptional regulation take part in this process.

Animals↗

Safe sex or safe love: competing discourses?

The way in which sex may be constructed as safe through its relationship with 'love' is the concern of this study. Interviews with 112 heterosexual women and men from discos and bars in Melbourne, Australia, catering to single adults revealed the pervasive construction of sex within the discourses of 'love' and 'romance'. The relationship of these discourses to unsafe practices is discussed and the article presents an analysis of the normative function of the sex-as-love/sex-as-desire opposition in terms of safe sex and HIV/AIDS prevention. We conclude that health messages which emphasize that 'sex is unsafe' may be counterproductive. We illustrate how women and some men construct casual sex as a strategy for obtaining the possibility of 'love'. For these women and men, 'safe sex' as 'unprotected sex' is viewed as a strategy for maximizing the possibility that the casual encounter will result in a longer term relationship. On the other hand, 'unsafe sex' as 'unprotected sex' is viewed as a strategy that is more likely to interrupt the construction of romance in the causal encounter thus risking the possibility of love as the desired outcome.

Adult↗

Correlation between two clinical balance measures in older adults: functional mobility and sensory organization test.

BACKGROUND: Functional mobility of older adults has been shown to correlate with stance stability to various extents. This variability could be due to the difference in the way sensory information is processed in these two types of balance tests. Correlations between functional mobility and stance stability under altered sensory conditions, such as those in the Sensory Organization Test (SOT), are needed to test this possibility. The present study investigated the correlation between the performance of older adults on a newly developed Sensory-Oriented Mobility Assessment Instrument (SOMAI) and on the various sensory conditions of the SOT. METHODS: Twenty-seven community-dwelling older adults (76 +/- 7 years) underwent tests of the six SOT conditions and 10 SOMAI mobility maneuvers performed under normal- and focal-vision (peripheral vision eliminated) conditions. Behavioral performance in the two SOMAI conditions and the amounts of postural sway in the six SOT conditions were ranked among the subjects. Correlations of performance rankings on these two tests were analyzed. RESULTS: Performance on the two SOMAI conditions significantly correlated with that on the SOT conditions in which accurate visual, vestibular, and somatosensory inputs were all present (p < .05). Performance on the focal-vision SOMAI condition was also significantly correlated with that on the SOT condition in which somatosensory input was unreliable for orientation while visual and vestibular inputs were reliable (p < .05). There were no correlations between the SOMAI performance and performance on the no-vision or unreliable-vision SOT conditions. CONCLUSIONS: The ability to use all visual, somatosensory, and vestibular inputs for balance was correlated with functional mobility. The moderate correlations between the performance on the normal-sensory SOT condition and the SOMAI conditions suggest that body systems other than balance senses also contribute to mobility performance.

Aged↗

Balance and muscle strength as predictors of frailty among older adults.

The term frailty is increasingly used in gerontological literature and in practice. However, indicators differentiating frail from nonfrail are not well delineated. Identifying factors discriminating between frail and nonfrail older community-residing adults may lead to more comprehensive clinical assessments and targeted interventions to minimize or prevent frailty. Eighty-four adults, ages 60 to 88 (mean = 74) living independently in the community completed a functional performance questionnaire and a perceived health questionnaire that were combined as measures of frailty. Predictor variables of frailty included four measures of balance and three measures of lower leg strength. Discriminant analysis revealed that one balance score and dorsiflexion correctly classified 65% of group membership, with better prediction of the nonfrail than frail group. This study clarifies that the predictors of frailty include the combination of dorsiflexion strength and balance, specifically the contribution of vision to balance when the support surface is compliant. Recommendations are proposed for conceptualizing and operationalizing frailty and adding variables to enhance discrimination between frailty and nonfrailty. Nursing implications include adding clinical assessments of specific components of balance and ankle strength to develop a more comprehensive evaluation of frailty.

Activities of Daily Living↗