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Biomedical subjects

G King

Publications and source records attributed to G King.

At least 19 recordsLinked to original sources

Promoting safer sex among HIV-positive youth with haemophilia: theory, intervention, and outcome.

The goal of the project was to develop and evaluate theory-based interventions designed to change sexual behaviour and promote safer sex practices of HIV seropositive young men and adolescents with haemophilia to prevent transmission to sexual partners and offspring. Safer sex was defined as abstinence, consistent condom use, or 'outercourse' (intimate, non-intercourse sexual behaviour). This project utilized the Transtheoretical Model developed by Prochaska and DiClemente, which describes behaviour change as an incremental, stage-based process. The 1-year intervention protocol consisted of two individual sessions and two peer-centred activities. One hundred and four adolescents, residing in 22 states, participated. Pre- and post-intervention evaluations were conducted to measure stage progression for participants. The number who were in the action or maintenance stage of change for safer sex was significantly greater at post-test than at pre-test (79 vs. 62%, P < 0.0001). Participants also reported an increased use of outercourse. In addition, significant increases in self-efficacy and knowledge regarding safer sex were demonstrated. Following these stage-based interventions, participants were significantly more likely to be engaging in safer sex behaviours than they were previously. These intervention activities can be adapted for use with other adolescent populations and for other behaviour change goals in adolescents with haemophilia.

Adolescent↗

Airway smooth muscle cell proliferation is increased in asthma.

UNLABELLED: Increased airway smooth muscle (ASM) within the bronchial wall of asthmatic patients has been well documented and is likely to be the result of increased muscle proliferation. We have for the first time been able to culture ASM cells from asthmatic patients and to compare their proliferation rate with that of nonasthmatic patients. Asthmatic ASM cell cultures (n = 12) were established from explanted lungs and endobronchial biopsies. Nonasthmatic ASM cells (n = 10) were obtained from explanted tissue from patients with no airway disease, emphysema, carcinoma, and fibrosing alveolitis. Cell counts, tritiated thymidine incorporation, and cell cycle analysis were conducted over 7 d. Asthmatic ASM cell numbers at Days 3, 5, and 7 were significantly higher than corresponding values for nonasthmatic cells (p < 0.05). Tritiated thymidine incorporation was increased 3.2-fold in asthmatic cells compared with nonasthmatic cells within the first 24 h (p = 0.026). Flow cytometric analysis of DNA content on Days 1 and 2 revealed that a significantly greater percentage of asthmatic ASM cells were in the G2 + M phase (p < 0.05). This study shows for the first time that proliferation of ASM cells is increased in patients with asthma and provides evidence for an intrinsic abnormality in the ASM cell in this disease. KEYWORDS: asthma; human airway smooth muscle; cell culture; cell proliferation; hyperplasia

Adolescent↗

Double trouble: impact of inappropriate use of asthma medication on the use of health care resources.

BACKGROUND: There is considerable controversy about the regular use of short-acting beta-agonists for the treatment of asthma. Although case-control studies have suggested that excessive use of these drugs may worsen asthma control and increase the risk of fatal or near-fatal asthma, the controversy remains unresolved because of the confounding that exists among disease control, disease severity and the use of short-acting beta-agonists. Whatever the cause-and-effect relation between the use of short-acting beta-agonists and disease severity, we hypothesized that their excessive use, in conjunction with underuse of inhaled corticosteroids, would be a marker for poorly controlled asthma and excessive use of health care resources. METHODS: To characterize the pattern of health services utilization among asthmatic patients taking various doses of inhaled beta-agonists and corticosteroids in British Columbia, we linked the relevant health administrative databases. All patients between 5 and 50 years of age for whom a prescription for a short-acting beta-agonist was filled in 1995 and whose prescription data were captured through the provincial drug plan were included in a retrospective analysis of prescriptions for asthma drugs, physician prescribing patterns and health services utilization. Patients' use of asthma medication was classified as appropriate (low doses of short-acting beta-agonist and high doses of inhaled corticosteroid) or inappropriate (high doses of short-acting beta-agonist and low doses of inhaled corticosteroid), and the 2 resulting groups were compared, by means of logistic, Poisson and gamma regression, for differences in prescribing patterns, physician visits and use of hospital resources. RESULTS: A total of 23,986 patients were identified as having filled a prescription for a short-acting beta-agonist (for inhalation) in 1995. Of these, 3069 (12.8%) filled prescriptions for 9 or more canisters of beta-agonist, and of this group of high-dose beta-agonist users, 763 (24.9%) used no more than 100 micrograms/day of inhaled beclomethasone. On average, those with inappropriate use of beta-agonists visited significantly more physicians for their prescriptions (1.8 v. 1.4), and each of these physicians on average wrote significantly more prescriptions for asthma medications per patient than the physicians who prescribed to appropriate users (5.2 v. 2.5 prescriptions). Patients with inappropriate use were more likely to be admitted to hospital (adjusted relative risk [RR] 1.68, 95% confidence interval [CI] 1.25-2.26), were admitted to hospital more frequently (adjusted RR 1.81, 95% CI 1.41-2.32) and were more likely to require emergency admission (adjusted RR 1.93, 95% CI 1.35-2.77). INTERPRETATION: Despite the widespread distribution of guidelines for asthma pharmacotherapy, inappropriate use of asthma medications persists (specifically excessive use of inhaled short-acting beta-agonists combined with underuse of inhaled corticosteroids). Not only are patients who use medication inappropriately at higher risk for fatal or near-fatal asthma attacks, but, as shown in this study, they use significantly more health care resources than patients with appropriate medication use.

Administration, Inhalation↗

Vesicle-associated proteins and transmitter release from sympathetic ganglionic boutons.

A method is reported for introducing peptides derived from SNARE proteins that control exocytosis of vesicles at boutons formed by sympathetic ganglion cells in tissue culture. These peptides were coupled to the DNA binding domain of the Drosophila transcription factor antennapedia, called penetratin. This facilitated the passage of peptides across the bouton membrane. FM1-43 was used to monitor the exocytosis of transmitter from depolarized boutons after their exposure to the penetratin-peptide sequences IETRHNEIIKLETSIRELHD of syntaxin and KGFLSSLFGGSSK of alpha-SNAP, both of which blocked secretion, whereas the peptide sequences SELDDRA-DALQAGASQFETSAAKLKRK of synaptobrevin did not. This report introduces a readily applicable method for determining the effect of different peptide sequences of vesicle-associated proteins on secretion at vertebrate boutons and presents an account of the effects of a selection of such peptides on exocytosis.

Amino Acid Sequence↗

Toxicology information resources at the Environmental Protection Agency.

Article presents toxicology information resources available to the public from the United States Environmental Protection Agency (EPA). This includes digital information directly usable or downloadable from their web site, or referrals as to where the resource can be obtained. Contents include advice on effective search strategies, a 'guided tour' of the web site and its main categories, and concludes with an extensive annotated bibliography of toxicological databases.

Information Services↗

Cheilanthane sesterterpenes, protein kinase inhibitors, from a marine sponge of the genus Ircinia.

Four cheilanthane sesterterpenoids, 25-hydroxy-13(24),15,17-cheilanthatrien-19,25-olide (1), 13,16-epoxy-25-hydroxy-17-cheilanthen-19,25-olide (2), 25-hydroxy-13(24),17-cheilanthadien-16,19-olide (3), and 16,25-dihydroxy-13(24),17-cheilanthadien-19,25-olide (4), were isolated from the marine sponge Irciniasp. Compounds 1, 3, and 4 are new natural products. The four compounds inhibit MSK1 (mitogen and stress activated kinase) and MAPKAPK-2 (mitogen activated protein kinase activated protein kinase), two protein kinases involved in mitogen and stress signal transduction.

Animals↗

Dysregulated cytokine production in human cystic fibrosis bronchial epithelial cells.

Although pulmonary inflammation is an important pathologic event in cystic fibrosis (CF), the relationship between expression of the CF gene and the inflammatory response is unclear. We studied tumor necrosis factor (TNF) alpha and IL-1beta stimulated production of IL-6 and IL-8 by CF, corrected CF, and normal human bronchial epithelial cells in culture. During the first 24 hours of TNFalpha stimulation, CF cells produced significantly more IL-8 than normal or corrected CF cells. In the second 24 hours of TNFalpha stimulation, IL-6 and IL-8 generation ceased in normal and corrected CF cells but accelerated in CF cells, resulting in marked IL-6 and IL-8 accumulation in CF cells. Similar results were found when cells were stimulated with IL-1beta. Finally, when CF cells were grown at 27 degrees C (a culture condition which results in transport of CF transmembrane conductance regulator, CFTR, to the cell membrane and normalization of chloride conductance) TNFalpha-stimulated production of IL-6 and IL-8 reverted to normal. We conclude that dysregulation of cytokine generation by CF bronchial epithelial cells is directly related to expression of mutant CFTR and these observations provide a potential mechanism for persistence of airway inflammation in CF.

Bronchi↗

Perceptions of intentional wrongdoing and peer reporting behavior among registered nurses.

How a person perceives a wrongdoing being committed by a coworker will affect whether the incident is reported within the organization. A significant factor that may influence the decision to report a wrongdoing is the perceived intentionality of the wrongdoer. This study sought to examine if differences in perceptions of a wrongdoing could affect the disclosure of unethical behavior. Three hundred seventy-two registered nurses (N=372) responded to a survey consisting of both intentional and unintentional wrongdoings that could occur by a nurse. Results of a paired t-test were as predicted. More wide ranging revelations found that respondents were more likely to discuss the unintentional wrongdoings with the wrongdoer in lieu of officially reporting to an immediate supervisor, or a member of upper management. Discussion, limitations, and suggestions for future research are provided.

Data Collection↗

Interleukin 1 upregulates ovarian prostaglandin endoperoxide synthase-2 expression: evidence for prostaglandin-dependent/ceramide-independent transcriptional stimulation and for message stabilization.

We have recently documented a marked dependence of ovarian prostaglandin endoperoxide synthase (PGS)-2 transcripts, proteins, and activity on interleukin (IL) 1, a putative intermediary in the ovulatory cascade. The purpose of the present study was to characterize the cellular and molecular mechanisms underlying the ability of IL-1beta to upregulate the steady-state levels of ovarian transcripts corresponding to PGS-2. Results of studies designed to enrich or deplete nitric oxide strongly suggest that the stimulatory effect of IL-1beta on ovarian PGS-2 expression is independent of nitric oxide. Utilization of a series of agents designed to simulate or enhance transduction via the sphingomyelin ceramide cycle suggests that the long-term stimulatory effect of IL-1beta on ovarian PGS-2 gene expression is independent of ceramide. In contrast, inhibition of prostaglandin biosynthesis with a series of distinct inhibitors suggests that the ability of IL-1beta to upregulate ovarian PGS-2 transcripts is due, if only in part, to the generation of endogenous prostaglandin estradiol-17beta (E(2)). Inhibition of protein biosynthesis suggested that the IL-1beta-induced PGS-2 gene expression required de novo protein biosynthesis. Our findings revealed substantial IL-1beta-mediated stabilization of PGS-2 transcripts, as assessed by a threefold increase in the half-life of the message. We have also observed the ability of IL-1beta to upregulate the transcription of PGS-2 promoter constructs subjected to transient transfection into whole-ovarian dispersates (twofold increase as assessed by activation of the luciferase reporter gene). Taken together, these findings suggest that the stimulatory effect of IL-1beta on PGS-2 expression is 1) independent of nitric oxide as well as ceramide, 2) dependent on prostaglandin E(2), 3) contingent on de novo protein biosynthesis, and 4) accounted for by both increased transcription and message stabilization. These observations provide indirect support for the hypothesis that IL-1beta, acting in part through PGS-2 (an obligatory ovulatory principal), may constitute a key intermediary in the ovulatory cascade.

Animals↗

Aids knowledge and risk behaviors among Midwest migrant farm workers.

The objectives of this study were to investigate the AIDS/HIV knowledge of Latino adolescent and adult migrant farm workers in Michigan, to determine risk behaviors related to HIV, and to determine differences in generational norms regarding sexual activity. For the most part, the Latino migrant population seemed knowledgeable about sexual modes of HIV transmission, although casual contact, through kissing and going to school or work with an infected individual, was also seen as a possible route of transmission for some. Several condom beliefs were identified that may be barriers to use, including the beliefs that condoms are only for use with prostitutes (35 % agreed) and that condoms are only for gay men (54% agreed). Only a small proportion (10%) agreed that condoms were good protection from AIDS. Most respondents knew what condoms were, although only 51% of the sample knew friends who used them. Adolescent females in the camps generally disapproved of premarital sex, while males and older females were more accepting. All these factors make it pertinent to implement HIV/AIDS education programs that are culturally sensitive, gender-specific, and effective in both generations.

Adolescent↗

Smoking in Maywood: the unhealthy southern migrant hypothesis among African Americans.

OBJECTIVES: This paper examines the "unhealthy Southern migrant" hypothesis with regard to cigarette smoking among African Americans. METHODS: Using data collected in 1992 from a sample of 1,518 African Americans in Maywood, Illinois, as part of the International Collaborative Study of Hypertension in Blacks, logistic regression analysis was conducted to examine and compare smoking behavior and sociodemographic characteristics of Southern and Midwestern-born respondents. RESULTS: African Americans born in the South were less likely (OR = .69, CI = 95%, 0.53, 0.90) to be smokers than those born in the Midwest, after controlling for other sociodemographic variables, prior smoking status, and age of arrival to Maywood. CONCLUSIONS: The results do not support the "unhealthy Southern migrant" hypothesis, with regard to cigarette smoking, and indicate the need to identify factors that protect Southern-born African-American migrants from smoking.

Adult↗

The perceived effects of parent-led support groups for parents of children with disabilities.

Parent-led support groups for parents who have children with disabilities are voluntary organizations with goals to provide social support and information and to foster advocacy. The purpose of this study was to explore parents' perceptions of the effect of parent-led support groups in providing parents with support and knowledge and in improving parents' ability to deal with childhood disability issues. Qualitative methods were used to examine the experiences of members of nine parent-run support groups. From these groups, 20 parents were interviewed about the benefits and limitations of participation in support group. Information was also collected by observing support group meetings and reviewing group documents. Interview, observation, and document data were analysed to identify emerging themes. Results of the study indicated that the effects of belonging to a parent-led parent support group were substantial. Through these groups, parents gain increased skills, an increased sense of power and a sense of belonging. Participants are able to connect with each other and provide support and skills to deal with the day-to-day issues of raising a child with disabilities.

Adolescent↗

Oestrogen receptor alpha in female fetal, infant, and child mammary tissue.

Oestrogen receptor alpha (ER alpha) expression was studied in female mammary tissue from a series of 35 samples obtained post-mortem, ranging from fetuses of 13 weeks' gestation to prepubertal children of 12 years. Immunocytochemistry was performed on formalin-fixed tissue after microwave antigen retrieval. ER alpha was present in epithelial cell nuclei from the 30th week of gestation onwards and was markedly up-regulated shortly after birth. For up to 3 months thereafter, progesterone receptor was also expressed, indicative that the ER alpha was functional. During this period, ER alpha was also present in epithelial cell cytoplasm. From this perspective of the developing breast, it is suggested that an early postnatal component should be added to the prenatal oestrogen hypothesis; further, the significance of ER alpha cytoplasmic staining in the adult breast also merits review.

Adult↗

Expression of CD44v6 but not E-cadherin or beta-catenin influences prognosis in primary pulmonary adenocarcinoma.

Primary pulmonary adenocarcinoma was studied, looking for relationships between the expression of cell adhesion molecules (CAMs) E-cadherin, beta-catenin and CD44v6, and clinicopathological tumour parameters and patient post-operative survival. Formalin-fixed, paraffin-embedded tissue from 120 primary lung adenocarcinomas, including 23 poorly differentiated tumours, 17 of probable bronchial origin, and 29 with a prominent bronchioloalveolar pattern, together with nodal metastatic tumour from 34 of these patients was stained using monoclonal antibodies and immunohistochemistry. Sections were scored either high level (>10% cells positive) or low level (<10% positive). High level expression of CD44v6 was retained in 28.4% (34/120) of tumours, while high levels of E-cadherin (57.5%, 69/120) and beta-catenin (80. 8%, 97/120) were more frequent. For all CAMs, staining levels did not correlate with nodal status, stage or tumour type. The apical or basal staining seen in normal bronchial and alveolar epithelium was often seen in papillary, glandular, and bronchioloalveolar areas of tumour, while solid invasive tumour more often showed pericellular staining. When the staining for each CAM in 34 nodal metastases was compared with that in the corresponding primary tumour, a high degree of concordance was found, with no tendency for metastases to show less staining than the primary tumour. Expression of E-cadherin and beta-catenin in the primary tumour had no influence on post-operative survival, but patients whose tumours had low level CD44v6 expression had a poorer post-operative survival than those with high levels of CD44v6 (p=0.0014 for all patients, p=0.0012 for stage I patients only). In primary pulmonary adenocarcinoma, the levels of expression of E-cadherin, beta-catenin, and CD44v6 are not associated with lymph node metastases or tumour stage but the staining pattern is associated with tumour morphology. Low levels of CD44v6 expression predict a poor post-operative survival, independently of stage, while there is no such relationship with the expression of E-cadherin or beta-catenin.

Adenocarcinoma↗

Opinions among mandated reporters toward child maltreatment reporting policies.

OBJECTIVE: This study investigates the opinions of social workers, pediatricians, and physician assistants in their support for the existing child maltreatment mandated reporting policy and an alternative reporting policy. Differences in professional training, age, gender, reporting behavior, attitudes towards reporting, and level of certainty needed to report were considered in determining which group of mandated reporters was most likely to support either the existing or an alternative policy. METHOD: A total of 382 social workers, pediatricians, and physician assistants in Connecticut and Massachusetts completed a self-report questionnaire. This sample represented an overall adjusted response rate of 76%. RESULTS: There was slightly more support for the existing reporting policy compared to the alternative policy. After controlling for age, attitudinal variables, and reporting behavior, social workers were significantly more likely to favor an alternative child maltreatment reporting policy than pediatricians or physician assistants. Also, those mandated reporters who had not consistently reported all suspected cases of maltreatment were significantly more likely to favor the alternative policy than consistent reporters. CONCLUSIONS: Because the majority of mandated reporters do not consistently report all suspected cases of maltreatment and support for an alternative reporting policy varies among different groups, consideration of alternative strategies and policies that address the concerns of different types of professionals may be appropriate.

Adult↗

Immune cell infiltrates and prognosis in primary carcinoma of the lung.

The prognostic significance of immune cell infiltrates in surgically resected human lung cancer was investigated in 710 patients. Lymphoid infiltrates were quantified on both standard H&E stained sections and, in a subset of 95 cases, using immunohistochemistry and antibodies to CD3, CD8, CD57, CD68, CD79a and S100 to identify various immune cell types. Subjective grading (low, moderate, high) of lymphoid cell infiltrates on H&E sections of tumour and measurement, using image analysis, of overall level of tumour infiltration by any of the immunohistochemically labelled specific immune cell types of the stained sections showed no prognostic significance. However, when a distinction between peritumoural and intratumoural infiltration by particular cell types was made, intratumoural infiltration by high levels of CD3+ and S100+ cells was associated with longer post-operative survival (P = 0.02 and P = 0.045, respectively). In lung cancer, subjective assessment of tumour lymphoid infiltration and overall levels of infiltration by particular immune cell types carries no prognostic significance. Intratumoural infiltration by relatively high numbers of CD3+ T-lymphocytes and Langerhans cells (S100+) is associated with a better patient outcome.

Adult↗