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Biomedical subjects

John Lowe

Publications and source records attributed to John Lowe.

At least 19 recordsLinked to original sources
PubMed2006

Transitional B cell fate is associated with developmental stage-specific regulation of diacylglycerol and calcium signaling upon B cell receptor engagement.

Functional peripheral mature follicular B (FoB) lymphocytes are thought to develop from immature transitional cells in a BCR-dependent manner. We have previously shown that BCR cross-linking in vitro results in death of early transitional (T1) B cells, whereas late transitional (T2) B cells survive and display phenotypic characteristics of mature FoB cells. We now demonstrate that diacylglycerol (DAG), a lipid second messenger implicated in cell survival and differentiation, is produced preferentially in T2 compared with T1 B cells upon BCR cross-linking. Consistently, inositol 1,4,5-triphosphate is also produced preferentially in T2 compared with T1 B cells. Unexpectedly, the initial calcium peak appears similar in both T1 and T2 B cells, whereas sustained calcium levels are higher in T1 B cells. Pretreatment with 2-aminoethoxydiphenylborate, an inhibitor of inositol 1,4,5-triphosphate receptor-mediated calcium release, and verapamil, an inhibitor of L-type calcium channels, preferentially affects T1 B cells, suggesting that distinct mechanisms regulate calcium mobilization in each of the two transitional B cell subsets. Finally, BCR-mediated DAG production is dependent upon Bruton's tyrosine kinase and phospholipase C-gamma2, enzymes required for the development of FoB from T2 B cells. These results suggest that calcium signaling in the absence of DAG-mediated signals may lead to T1 B cell tolerance, whereas the combined action of DAG and calcium signaling is necessary for survival and differentiation of T2 into mature FoB lymphocytes.

Animals↗
PubMed2006

Tobacco use, cessation advice to patients and attitudes to tobacco control among physicians in Ukraine.

To examine the relationship between physicians' smoking behaviors and their attitudes toward tobacco use by their patients and tobacco control in the Ukraine, a 70-item questionnaire was administered to 799 general practitioners (287 men and 512 women) working in both rural (278 physicians) and urban (521 physicians) areas of three regions of Ukraine. In all, 13.9% of physicians were current smokers and 21.6% reported being past smokers, with significantly (P<0.001) more men than women being current or past smokers. Odds ratios from logistic regression analysis reveal that physicians who are heavy smokers are 26% less likely to record tobacco use by patients than medium smokers. Heavy smokers devote significantly less effort to providing cessation information to patients and are 36% less likely to support the complete prohibition of smoking in the physician's workplace. Older physicians, female physicians and physicians working in urban areas are significantly more likely than younger, male and rural physicians to advise their patients on smoking. The provision of smoking cessation to patients by general practitioners in Ukraine is influenced by several factors, a major one being the smoking status of the physician. If smoking among physicians declines, this will encourage the patient to consider a serious quit attempt in several ways, most notably: (1) physicians act as societal role models and can promote non-smoking as a norm and (2) the likelihood that a patient will be provided smoking cessation counseling increases.

Adult↗
PubMed2005

Potential novel application of dual time point SUV measurements as a predictor of survival in head and neck cancer.

OBJECTIVES: To examine the potential of pre-treatment dual time point [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a tool for improving the assessment of head and neck cancer. Two main areas were investigated: (a) optimum time to start FDG scanning post-injection and (b) potential of SUV obtained from dual time point scanning as a prognostic indicator of survival. METHODS: Twelve patients with advanced head and neck cancer were prospectively studied. Each patient was scanned using a Siemen's Ecat Exact-47 PET scanner at 1 h and 2 h post-injection. Maximum tumour uptake (SUVt) and ratio of maximum tumour/normal tissue uptake (SUVt/n) were recorded. The optimal time to initiate scanning was investigated by comparing SUVt and SUVt/n with the decision made by two experienced observers as to which scan they preferred to report from, given the choice of the 1 h and 2 h scan in each patient. RESULTS: A significant difference between 1 h and 2 h SUVt (P<0.004, paired t-test) and between 1 h and 2 h SUVt/n (P<0.0003, paired t-test) was observed. All 2 h SUVt and SUVt/n were greater in magnitude than their respective 1 h SUVt and SUVt/n counterparts. The two observers reported an identical number of lesions from the 1 h and 2 h scans but preferred the 2 h data. CONCLUSIONS: Tumour stage and the percentage difference in 1 h and 2 h SUVt showed potential as prognostic indicators of long-term survival.

Female↗
PubMed2005

Being influenced: a Cherokee way of mentoring.

This article reports research findings related to how the Cherokee male achieves self-reliance and how health care professionals can facilitate and incorporate the Cherokee concept of self-reliance into heath care of the Cherokee. Self-reliance to the Cherokee has been defined as a cultural domain with a composite of the three categories: (a) being responsible, (b) being disciplined, and (c) being confident (Lowe, 2002, 2003). Two sample groups of 12 to 14 Cherokee adults were interviewed and observed. The results reveal that mentor-type relationships influenced the participants in the development of Cherokee self-reliance.

Adult↗
PubMed2004

Predictors of sun protection in northern Australian men with a history of nonmelanoma skin cancer.

BACKGROUND: It is important to understand what predicts regular use of sun protection in men susceptible to skin cancer. METHODS: A questionnaire survey of men with previous nonmelanoma skin cancer (n = 300) was conducted. RESULTS: Participants who typically used sunscreen tended to be younger, have fewer excised skin lesions, work indoors, and have spent most of their life in the tropics. Predictors of wearing a long-sleeved shirt with a wide-brimmed hat were not enjoying sun exposure, not having barriers to using sun protection, having more skin lesions previously excised, working for a company with a mandatory policy of sun protection, attitudes that the benefits of a suntan do not outweigh the risks and that skin cancers cannot be easily treated, and age over 50. CONCLUSIONS: Men who adequately protect themselves from the sun and who have better attitudes to sun exposure were more often those with a high level of negative experience with skin cancer. Therefore, the sun protection attitudes and behaviors of some men may only improve after significant sun damage. This study recommends that the use of appropriate sun protective clothing should be made mandatory for all who work outdoors in high-sun-exposure occupations.

Australia↗
PubMed2003

B cell receptor directs the activation of NFAT and NF-kappaB via distinct molecular mechanisms.

BCR engagement initiates intracellular calcium ([Ca2+]i) mobilization which is critical for the activation of multiple transcription factors including NF-kappaB and NFAT. Previously, we showed that Bruton's tyrosine kinase (BTK)-deficient (btk-/-) B cells, which display a modestly reduced calcium response to BCR crosslinking, do not activate NF-kappaB. Here we show that BTK is also essential for the activation of NFAT following BCR engagement. Pharmacological mobilization of [Ca2+]i in BTK-deficient DT40 B cells (DT40.BTK) does not rescue BCR directed activation of NF-kappaB and only partially that of NFAT, suggesting existence of additional BTK-signaling pathways in this process. Therefore, we investigated a requirement for BTK in the production of diacylglycerol (DAG). We found that DT40.BTK B cells do not produce DAG in response to BCR engagement. Pharmacological inhibition of PKC isozymes and Ras revealed that the BCR-induced activation of NF-kappaB requires conventional PKCbeta, whereas that of NFAT may involve non-conventional PKCdelta and Ras pathways. Consistent with an essential role for BTK in the regulation of NFAT, B cells from btk-/- mice display defective expression of CD5, a gene under the control of NFAT. Together, these results suggest that BCR employs distinct BTK-dependent molecular mechanisms to regulate the activation of NF-kappaB versus NFAT.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2003

Prevalence of complicated carotid atheroma as detected by magnetic resonance direct thrombus imaging in patients with suspected carotid artery stenosis and previous acute cerebral ischemia.

BACKGROUND: It is recognized that complicated plaque largely accounts for the morbidity and mortality from atherosclerosis. Ideally, investigation of symptomatic and asymptomatic patients would identify atheromatous plaques independently of stenosis. We have previously shown that a magnetic resonance direct thrombus imaging (MRDTI) technique demonstrates complicated atheroma as high signal within the carotid arterial wall. We used this technique to examine the prevalence of complicated carotid plaque in vivo in the ipsilateral arteries of recently symptomatic patients with suspected carotid artery stenosis and to compare this with their contralateral arteries and with those of healthy age- and sex-matched controls. METHODS AND RESULTS: The carotid arteries of 120 patients with suspected severe carotid artery stenosis and previous acute cerebral ischemia were imaged using MRDTI, as were 28 control arteries. High signal was not seen in any control artery. However, there was a 60% prevalence of high signal, suggestive of complicated plaque in the patients' ipsilateral arteries. The prevalence of high signal was significantly greater in the patients' ipsilateral vessels compared with the contralateral, asymptomatic side (60% versus 36%, chi2 P<0.001), particularly for vessels of only moderate stenosis. CONCLUSIONS: MRDTI high signal suggestive of complicated plaque is prevalent in the ipsilateral carotid arteries of patients with carotid stenosis and recent cerebral ischemic events. MRDTI has a potential role in identifying "at risk" plaque, studying atherogenesis and the effects of plaque-modifying strategies.

Brain Ischemia↗
PubMed2003

Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia.

BACKGROUND: Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high-risk plaque would therefore be beneficial. High-risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens. METHODS AND RESULTS: Sixty-three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false-positive and 7 false-negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (kappa=0.75) and intraobserver (kappa=0.9) agreement for reading MRDTI scans was good. CONCLUSIONS: MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease.

Aged↗
PubMed2003

Benefits of electronic vision enhancement systems (EVES) for the visually impaired.

PURPOSE: To examine whether objective performance of near tasks is improved with various electronic vision enhancement systems (EVES) compared with the subject's own optical magnifier. DESIGN: Experimental study, randomized, within-patient design. METHODS: This was a prospective study, conducted in a hospital ophthalmology low-vision clinic. The patient population comprised 70 sequential visually impaired subjects. The magnifying devices examined were: patient's optimum optical magnifier; magnification and field-of-view matched mouse EVES with monitor or head-mounted display (HMD) viewing; and stand EVES with monitor viewing. The tasks performed were: reading speed and acuity; time taken to track from one column of print to the next; follow a route map, and locate a specific feature; and identification of specific information from a medicine label. RESULTS: Mouse EVES with HMD viewing caused lower reading speeds than stand EVES with monitor viewing (F = 38.7, P <.001). Reading with the optical magnifier was slower than with the mouse or stand EVES with monitor viewing at smaller print sizes (P <.05). The column location task was faster with the optical magnifier than with any of the EVES (F = 10.3, P <.001). The map tracking and medicine label identification task was slower with the mouse EVES with HMD viewing than with the other magnifiers (P <.01). Previous EVES experience had no effect on task performance (P >.05), but subjects with previous optical magnifier experience were significantly slower at performing the medicine label identification task with all of the EVES (P <.05). CONCLUSIONS: Although EVES provide objective benefits to the visually impaired in reading speed and acuity, together with some specific near tasks, some can be performed just as fast using optical magnification.

Aged↗
PubMed2002

Bruton's tyrosine kinase targets NF-kappaB to the bcl-x promoter via a mechanism involving phospholipase C-gamma2 following B cell antigen receptor engagement.

Disruption of Bruton's tyrosine kinase (BTK) function leads to x-linked immunodeficiency (xid) in mice. BTK-deficient (btk(-/-)) B cells are defective for survival. Prior studies show that BTK is required for the induction of Bcl-x(L) following B cell antigen receptor (BCR) engagement. However, the mechanism underlying Bcl-x(L) induction in response to BCR ligation remains unresolved. We now demonstrate that BTK regulates bcl-x expression by transcriptional control in response to BCR engagement. BTK targets nuclear factor-kappaB (NF-kappaB) to activate the bcl-x promoter via a phospholipase C-gamma2 (PLC-gamma2)-dependent mechanism. Perturbation of the BTK/PLC-gamma2/NF-kappaB signaling axis likely contributes to the defective expression of bcl-x and compromised survival of xid B cells.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2002

Transitional type 1 and 2 B lymphocyte subsets are differentially responsive to antigen receptor signaling.

Mature B-lymphocytes develop sequentially from transitional type 1 (T1) and type 2 (T2) precursors in the spleen. To elucidate the mechanisms that regulate the developmental fate of these distinct B cell subsets, we investigated their biochemical and biological responses following stimulation through the B-cell antigen receptor (BCR). As compared with the T1 subset, T2 cells are more responsive to BCR engagement, as evidenced by their robust induction of activation markers, expression of the prosurvival protein Bcl-x(L), and enhanced proliferation. BCR stimulation of T2 cells leads to the appearance of B cells with mature phenotypic characteristics, whereas T1 cells die. All of these T2 responses are dependent on the BCR signal transducer Bruton's tyrosine kinase, which is dispensable for the T1 to T2 transition. Furthermore, the serine/threonine kinases ERK, p38 MAPK, and Akt are predominantly activated in T2 compared with T1 B cells following BCR cross-linking. We conclude that T1 and T2 B cells respond differentially to BCR engagement via the induction of stage-specific signaling pathways. In turn, these signaling pathways probably govern the development and selection processes that are critical for the formation of the mature B cell compartment.

Animals↗
PubMed2002

Enhanced tumor killing by Apo2L/TRAIL and CPT-11 co-treatment is associated with p21 cleavage and differential regulation of Apo2L/TRAIL ligand and its receptors.

Apo2L/TRAIL exhibits enhanced apoptotic activity in tumor xenograft models when used in combination with the topoisomerase 1 inhibitor CPT-11. To investigate the cellular mechanisms involved in this increased tumor-killing activity, a series of in vitro experiments were conducted using the human colon carcinoma cell line (HCT116). Apo2L/TRAIL induced a transient upregulation of DR5 mRNA, while CPT-11 increased both death and decoy receptor expression. Upregulation of decoy receptors by CPT-11 was partially inhibited by co-administration of Apo2L/TRAIL. CPT-11 treatment resulted in accumulation of cells at G(2)M-phase and correlated with a substantial increase in the protein levels of the cyclin-dependent kinase inhibitor p21. However, cells co-treated with CPT-11 and Apo2L/TRAIL, or pretreated with CPT-11 for up to 24 h followed by 2 h Apo2L/TRAIL, resulted in a caspase-dependent degradation of p21, reversal of G(2)-M phase arrest with a concomitant increase in apoptosis. The sequential treatment produced the greatest induction of DR5 and DR4, caspase-3-like cleavage/activation and p21 degradation, as well as increased apoptosis. These data indicate that the up-regulation of Apo2L/TRAIL ligand and its death receptors as well as cleavage of p21 protein in the Apo2L/TRAIL plus CPT-11 treatment contributes to the positive cooperation between these agents in enhancing tumor cell apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Balance and harmony through connectedness: the intentionality of Native American nurses.

This article describes how Native American nurses facilitate and promote harmony and balance through connectedness. According to the Conceptual Framework of Nursing in the Native American Culture, connectedness is at the core of intentionality of Native American nurses. Connectedness occurs through the dynamics of an interdependent and interrelated relationship between the nurse and client. The worldview of Native Americans is illuminated and illustrated within the context of culturally congruent nursing interventions.

Cultural Characteristics↗
PubMed2002

Sun-related behaviors of outdoor working men with a history of non-melanoma skin cancer.

The present study describes sun exposure and sun protection behaviors of northern Australian outdoor workers with previous non-melanoma skin cancer (NMSC). In 1999 a cross-sectional study of northern Australian men with previous NMSC was conducted by self-administered questionnaire. Compared to other men, outdoor workers spent more time in the sun on average working days and days off (P < 0.0001, respectively), and outdoor workers with sun-sensitive skin reported that more skin lesions had been removed (P = 0.0461). The workplace did not reinforce sun-safe practices of 36.8% of workers who spent half their time or more outdoors. Sun-protective behaviors were not different between in- and outdoor workers. Outdoor workers experienced high levels of sun exposure, however, sun-protective behavior was similar to other workers. Workplaces should be targeted to reinforce sun-safe policies.

Analysis of Variance↗
PubMed2002

Cherokee self-reliance.

This qualitative study was conducted using ethnography to identify how (a) self-reliance is conceptualized by the Cherokee; (b) the adult male Cherokee perceives, achieves, and demonstrates self-reliance; and (c) nurses can incorporate the Cherokee concept of self-reliance into health care of the Cherokee. The goal of self-reliance was included in the following mission statement of the 1976 Cherokee Nation constitution: "The mission of the government of the Cherokee Nation is to promote and sustain the self-reliance of its members" (Resolution No. 28-85, 1976). The conceptualization and perspective of self-reliance by the Cherokee must be understood to assist effectively in the development and promotion of self-reliance in the Cherokee, especially the male Cherokee. The cultural domain of self-reliance that emerged from the data is a composite of three categories that include being responsible, being disciplined, and being confident. Cutting across all three categories are the two themes of being true to onself and being connected.

Adolescent↗
PubMedDate not supplied

Randomized, controlled trial of three levels of critical incident stress intervention.

BACKGROUND: Stress debriefing following exposure to a critical incident is becoming more prevalent. Its aim is to prevent or minimize the development of excessive stress response symptoms that lead to loss of productivity or effectiveness in the workplace or at home. There is little evidence that any form of psychological debriefing is effective. This study evaluated the effectiveness of three intervention strategies, and attempted to correlate the symptoms with the severity of the incident and level of intervention. METHODS: A randomized, controlled trial of three levels of critical stress intervention was conducted in the British Columbia Ambulance Service (BCAS), in British Columbia, Canada, among paramedics and emergency medical technicians (EMTs), reporting critical incident stress. Outcomes were measured at one week (Stanford Acute Stress Reaction Questionnaire (SASRQ), the Life Impact Score (LIS), and Schedule of Recent Events (SRE)), and at three months and six months following the intervention (Impact of Events (IE), Coping Mechanisms, LIS, and SRE). RESULTS: Fifty calls were received during the 26-month study period (<1 per 10,000 BCAS response calls): 23 were by third parties, but the involved EMT did not call; nine were placed by crew unwilling to participate in the study; 18 subjects enrolled, but six completed no forms. No correlation was found between severity of the incident and scores on the SASRQ, IE, or LIS, or between any of these scores. There was no consistent pattern in the stress scores over time. CONCLUSION: Requests for critical incident stress intervention were uncommon. The need for intervention may not be as great as generally is assumed. Further randomized trials, ideally multicenter studies, are indicated.

British Columbia↗
PubMedDate not supplied

Nursing in the Native American culture and historical trauma.

Historical trauma is a significant fact in the Native American community, a fact affecting both health status and social milieu. Mental health nurses and other persons working in the mental health professions will be confronted over and over with historical trauma when working with Native American peoples and communities. To heal historical trauma, culturally appropriate strategies derived from the ancient knowledge, philosophy, and world view of Native America are needed. One tool mental health care providers can use when encountering historical trauma is the Conceptual Framework of Nursing in the Native American Culture.

Female↗