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Biomedical subjects

K Coates

Publications and source records attributed to K Coates.

10 recordsLinked to original sources
PubMed2001

A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse.

OBJECTIVE: Our aim was to develop a condition-specific, reliable, validated, and self-administered instrument to evaluate sexual function in women with pelvic organ prolapse or urinary incontinence. STUDY DESIGN: The questionnaire was designed after review of the literature and of nonspecific validated instruments. The study was completed in 2 phases. In phase 1 a total of 83 women completed both our questionnaire and the Incontinence Impact Questionnaire-7, with 20 women undergoing test-retest reliability analyses. Item analysis was based on the internal consistency, the correlations with the Incontinence Impact Questionnaire-7, the patient's age and self-rating of satisfaction, and the results of reliability testing. For final validation the questionnaire was administered in phase 2 to 99 women. Factor and item analyses were repeated, results were correlated with the Sexual History Form-12, and comparison was made between patients with high depression scores and those with low depression scores on the Symptom Questionnaire. RESULTS: Factor analysis identified 3 domains, labeled Behavioral/Emotive, Physical, and Partner-Related. Sexual function scores were highly correlated with scores on the Sexual History Form-12 for the questionnaire (r = -0.74; P <.001) and for both the Behavioral/Emotive and the Partner-Related domains (r = -0.79 and -0.5, respectively; P <.001). The Physical domain was correlated with scores on the Incontinence Impact Questionnaire-7 (r = -0.63; P <.001). Women with high depression scores on the Symptom Questionnaire had significantly lower scores on the final questionnaire, in comparison with women without depression (P <.001). CONCLUSION: We developed a condition-specific, validated, and reliable instrument, containing 31 items divided into 3 domains, to evaluate sexual functioning in women with urinary incontinence or pelvic organ prolapse.

Adult↗
PubMed1999

The value of an evaluation framework for telehealth initiatives.

Healthcare managers and policy makers will, in the immediate and near future, make major decisions about the allocation of scarce healthcare resources for telehealth 'solutions'. In our haste to capitalize on what technology can do we may be obscuring discussion and research about what technology should do. For example, currently much attention is being paid to standardization for technological aspects of telehealth. In contrast few efforts have been made to seek standardization in regards to a broad evaluation framework for telehealth. A body of opinion believes that missing in our rush into the on-line world is a systematic approach to research into the human, social, cultural, economic, and political factors associated with healthcare. As a result we lack the tools and experience necessary to assess the true value and implications of telehealth 'solutions'. Developing general guidelines for an evaluation framework, from needs assessment through integrated research to post-study assessment, would greatly enhance the quality of decision making by healthcare managers and policy makers. We propose a model--the Telehealth Integrated Research Model (TIRM)--as the first step in encouraging discussion and development of an internationally accepted standardized telehealth evaluation framework.

Data Collection↗
PubMed1997

Protein kinase C-mediated phosphorylation of HIV-I nef in human cell lines.

Stable human cell lines expressing the human immunodeficiency virus type I (HIV-I) Nef protein from inducible promoters were used to analyze the phosphorylation status of Nef in vivo. Nef phosphorylation in both HeLa and Jurkat cells was stimulated by phorbol ester treatment. Phosphoamino acid analysis revealed a predominance of phosphoserine with a small proportion of phosphothreonine. Treatment of cells with selective protein kinase inhibitors revealed that Nef phosphorylation was markedly reduced by bisindolylmaleimide, an inhibitor of protein kinase C, but was unaffected by inhibitors of mitogen-activated protein kinase kinase or cAMP-dependent kinase. These data implicate protein kinase C in Nef phosphorylation in vivo, and thus confirm and extend earlier in vitro data. Phosphorylation of a nonmyristoylated Nef mutant was impaired, suggesting that membrane targeting of Nef was required for phosphorylation. This was expected given that activated protein kinase C translocates from the cytosol to the plasma membrane. However, analysis of the subcellular localization of phosphorylated wild-type Nef revealed that both the cytosolic and membrane-associated pools of Nef were phosphorylated to an equivalent extent. Thus the significance of myristoylation for Nef function may be in influencing protein conformation, although these data could be explained by a transient and dynamic interaction between myristoylated Nef and the plasma membrane.

Cytosol↗
PubMed1997

Abdominal sacral colpoperineopexy: a new approach for correction of posterior compartment defects and perineal descent associated with vaginal vault prolapse.

OBJECTIVE: Our purpose was to assess a modification of abdominal sacral colpopexy in 19 patients. STUDY DESIGN: The rectovaginal space was dissected to the superior aspect of the posterior vaginal fascia still contiguous with the perineal body. Mersilene (Ethicon, Somerville, N.J.) mesh was sutured to this fascia and along the entire posterior vaginal wall. Patients with vault prolapse, perineal descent, and associated rectoceles or enteroceles are reported. Outcome measures included bowel symptoms and pelvic organ prolapse staging. Defecography was performed in three patients. Wilcoxon signed rank analysis was used for comparison of prolapse measures. RESULTS: Mean follow-up was 11 weeks. Bowel symptoms improved in 8 of 11 women. No subjects had greater than stage II prolapse postoperatively and median improvement in stage was 3 (range 2 to 4). The mean decrease in the genital hiatus measurement was 3.13 +/- 1.25 (range 2 to 6) cm. Postoperative defecography documented correction of rectoceles and enteroceles and improvement in perineal descent with straining. CONCLUSIONS: Abdominal sacral colpoperineopexy is effective surgery for vaginal vault prolapse associated with perineal descent and posterior vaginal defects.

Adult↗
PubMed1997

Regulated expression vectors demonstrate cell-type-specific sensitivity to human immunodeficiency virus type 1 Nef-induced cytostasis.

The nef gene product of both human and simian immunodeficiency viruses is critically important for virus replication and disease progression in vivo. However, the precise biological function of Nef remains poorly characterized in vitro, with previous reports suggesting that Nef might be either cytotoxic or cytostatic. As a result of difficulties encountered by several groups in establishing cell lines constitutively expressing Nef, we have developed two inducible systems resulting in stable Nef expression in various mammalian cell lines. Tetracycline-regulated Nef expression was achieved in HeLa cells but could not be established in human T cell lines. Jurkat E6-1 T cell and RAW264.7 murine macrophage cell lines expressing a regulated nef gene were generated using a system in which Nef expression was controlled by a mutated version of the heavy metal-inducible human metallothionein IIA promoter. Induction of high levels of Nef expression in HeLa-Nef and Jurkat-Nef cells resulted in a moderate (2-fold) and a dramatic (10-fold) retardation of cell growth respectively, supporting the contention that Nef may be a cytotoxic or cytostatic factor. This property was also observed at low basal levels of Nef expression in RAW264.7-Nef macrophage clones (5-fold reduction in growth) and was associated with an altered morphological phenotype suggesting that different cell types may be more susceptible to the cytostatic activity of Nef. The regulated Nef-expression systems provide tools for investigating the molecular basis of Nef function, including Nef-mediated cytopathogenicity, CD4 down-regulation and enhancement of virus infectivity.

Animals↗
PubMed1995

The human immunodeficiency virus type 1 Nef protein functions as a protein kinase C substrate in vitro.

The human immunodeficiency virus type 1 Nef protein was expressed in Escherichia coli as a C-terminal fusion with glutathione S-transferase (GST). The ability of GST-Nef to act as a substrate for cellular kinases in vitro was examined by incubation of purified GST-Nef fusion proteins, immobilized on glutathione-agarose beads, with cytoplasmic extracts from a number of human cell lines. In the presence of [gamma32P]ATP, phosphorylation of Nef occurred predominantly on serine residues. Studies with protein kinase inhibitors suggested that protein kinase C (PKC) was involved in Nef phosphorylation. This was supported further by the demonstration that purified PKC was also able to phosphorylate Nef in the absence of cell extract. Serine/threonine phosphorylation of Nef was also observed in vivo when Nef was expressed with a C-terminal GST or 6-histidine tag in Spodoptera frugiperda insect cells by recombinant baculoviruses. In extracts from Jurkat T cells and U937 monocyte/macrophages Nef also associated with a 57 kDa cellular protein that was itself phosphorylated in vitro. Phosphorylation of this Nef-associated protein was inhibited by heparin and is thus likely to be mediated by casein kinase II. The observation that PKC can phosphorylate Nef in vitro raises the possibility that PKC might play a role in regulating both Nef function and the physical interactions between Nef and cellular components.

Animals↗
PubMed1993

Identification of cellular proteins that bind to the human immunodeficiency virus type 1 nef gene product in vitro: a role for myristylation.

The human immunodeficiency virus (HIV) type 1 nef gene product was expressed as an N-terminal fusion protein with glutathione-S-transferase (GST) in the baculovirus system. The resulting nefGST fusion protein was found to be authentically myristylated at the N terminus and could be purified to homogeneity by one-step affinity chromatography on immobilized glutathione. The high affinity of nefGST for glutathione was exploited to develop an assay to identify cellular proteins capable of interacting with nef. Several such proteins were identified in extracts from the Jurkat human T cell line. The interaction between nef-binding proteins and immobilized nefGST could be specifically competed by the addition of soluble nef. Cell fractionation showed that nef-binding proteins were present in both cytosolic and membrane-associated fractions. A non-myristylated derivative failed to bind to the membrane-associated proteins but was able to bind to the cytosolic group, albeit with reduced affinity. In addition, a single protein present in both soluble and membrane-associated fractions exhibited myristylation-independent binding to nef. By analogy with other myristylated proteins such as MARCKS (myristylated alanine-rich C kinase substrate) and the Rous sarcoma virus transforming protein, src, the membrane-associated proteins that bind only to myristylated nef may represent a specific membrane target for nef. The cytosolic proteins that interact with nef may constitute soluble components of an as yet unidentified signal transduction pathway which is the target of nef action in the HIV-1-infected cell.

Acylation↗
PubMed1982

Cerebral malaria in children: a retrospective study of admissions to Madang Hospital, 1980.

A review was undertaken of sixty-eight children admitted with cerebral malaria to Madang Hospital, Madang, Papua New Guinea (PNG) in 1980. Children with cerebral malaria were significantly older than those with uncomplicated malaria, and older than children admitted with other conditions causing fits or coma. The nutritional status of children with cerebral malaria did not differ from that of children admitted with other diagnoses. The cerebrospinal fluid was normal in 80% of children with cerebral malaria, and in 20% mildly elevated protein or leukocytes were noted. Of the 68 children with cerebral malaria, four died (5.9%). This is a low mortality rate in comparison wih other centres in PNG and with reports from other countries.

Brain Diseases↗