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Biomedical subjects

John B Lowe

Publications and source records attributed to John B Lowe.

At least 19 recordsLinked to original sources
PubMed2006

Significant decrease in alpha1,3-linked fucose in association with increase in 6-sulfated N-acetylglucosamine in peripheral lymph node addressin of FucT-VII-deficient mice exhibiting diminished lymphocyte homing.

Lymphocyte homing is mediated by binding of L-selectin on lymphocytes with L-selectin ligands present on high-endothelial venules (HEV) of peripheral and mesenteric lymph nodes. L-selectin ligands are specific O-linked carbohydrates, 6-sulfo sialyl Lewis X, composed of sialylated, fucosylated, and sulfated glycans. Abrogation of fucosyltransferase-VII (FucT-VII) results in almost complete loss of lymphocyte homing, but structural analysis of carbohydrates has not been carried out on FucT-VII null mice. To determine whether functional losses seen in FucT-VII null mice are caused by structural changes in carbohydrates, we elucidated the carbohydrate structure of GlyCAM-1, a major L-selectin counter-receptor. Our results show that most alpha1,3-fucosylated structures in 6-sulfo sialyl Lewis X are absent and 6-sulfo N-acetyllactosamine is increased in the mutant mice. Surprisingly, the amount of 6'-sulfated galactose (Gal) that bound to Sumbucus nigra agglutinin column was also increased. We found that structures of those oligosaccharides containing 6'-sulfated Gal are almost identical to those synthesized by keratan sulfate sulfotransferase (KSST). We then showed that overexpression of KSST suppresses the expression of sialyl Lewis X on Chinese hamster ovary (CHO) cells engineered to express sialyl Lewis X. Moreover, KSST expression in those cells suppressed lymphocyte rolling compared with mock-transfected CHO cells expressing 6-sulfo sialyl Lewis X. 6'-Sulfo sialyl Lewis X can neither be found in GlyCAM-1 from CHO cells expressing both KSST and FucT-VII nor be found in GlyCAM-1 from HEV of mice. These results combined together suggest that KSST competes with FucT-VII for the same acceptor substrate and downregulates the synthesis of L-selectin ligand by inhibiting alpha1,3-fucosylation.

Acetylglucosamine↗
PubMed2006

What motivates men age > or =50 years to participate in a screening program for melanoma?

BACKGROUND: The screening behavior and screening outcomes of men age > or =50 years was investigated within a randomized controlled trial of a community-based intervention of screening for melanoma, consisting of a community education program, an education program for medical practitioners, and the provision of dedicated skin-screening clinics. METHODS: Data from cross-sectional telephone surveys before (559 completed interviews), at the end (591 completed interview), and at 2 years after the intervention (445 completed interviews) were analyzed. In addition, the authors analyzed data from skin-screening clinics within the intervention program (3355 men age > or =50 years participated). RESULTS: During the intervention period men age > or =50 years increased both their screening behavior and intention to screen. Those men age > or =50 years who reported a past history of removal of a mole as well as other risk factors for skin cancer and positive attitudes toward screening were more likely to participate in skin screening across time. Men age > or =50 years accounted for 20.5% of all skin-screening clinic attendees, 31.3% of those referred for a suspicious lesion, 48.5% of melanomas, and 45% of all keratinocyte carcinomas diagnosed within the screening program, respectively. CONCLUSIONS: The intervention program successfully motivated men age > or =50 years to attend screening for skin cancer, resulting in the highest yield of skin cancer within this subgroup of the population. Messages addressing skin cancer risk factors and attitudes toward skin cancer and screening could be used to target a screening program for melanoma toward men age > or =50 years.

Attitude to Health↗
PubMed2006

Abrogation of functional selectin-ligand expression reduces migration of pathogenic CD8+ T cells into heart.

CD8+ T cells are involved in autoimmune and infectious myocarditis and cardiac allograft rejection. The role of selectins in cardiac recruitment of CD8+ T cells is not understood. In this study, the contribution of T cell selectin ligands to effector CD8+ T cell recruitment into the heart was examined using a model of myocarditis, which depends on transfer of OVA peptide-specific CD8+ T cells (OT-I) into mice (CMy-mOva) that express OVA in the heart. alpha-(1,3)-Fucosyltransferase (FucT)-VII-deficient OT-I cells displayed over a 95% reduction in their ability to interact with P-selectin under flow conditions in vitro, compared with wild-type OT-I cells. Interaction of FucT-VII-deficient OT-I cells with E-selectin was reduced approximately 50%. FucT-VII-deficient OT-I cells were also less efficiently recruited into a dermal site of Ag and adjuvant injection. Significantly, FucT-VII-deficient OT-I cells were also impaired in their ability to migrate into CMy-mOva hearts, compared with wild-type OT-I cells. Transfer of FucT-VII-deficient T cells caused less severe early myocarditis and myocyte damage than transfer of wild-type T cells. Combined FucT-IV/VII-deficient OT-I cells displayed a more profound reduction in E-selectin interactions in vitro compared with FucT-VII-deficient T cells, and the FucT-IV/VII-deficient T cells also showed less early recruitment and pathogenicity in the CMy-mOva myocarditis model. These results identify a prominent role for selectin ligands in contributing to effector CD8+ T cell recruitment into the myocardium and indicate that selectin-dependent T cell recruitment is relevant to other tissues besides the skin.

Adoptive Transfer↗
PubMed2006

Increase in skin cancer screening during a community-based randomized intervention trial.

Survival from cutaneous melanoma is mainly dependent on the thickness of the lesion at diagnosis. Skin screening may increase detection of thin lesions and hence improve survival. Within a community-based randomized controlled trial of a population screening program for melanoma in Queensland, Australia, 9 communities were randomly assigned to the 3-year intervention and 9 communities to the control group. Skin screening prevalence was monitored by cross-sectional surveys at baseline, 1, 2 and 3 years into the intervention and 2 years later. At baseline, prevalence of whole-body clinical skin examination was similar in intervention and control communities. In intervention communities, the prevalence of whole-body skin examinations increased to 29.2%, an absolute difference of 18% from baseline, with a peak of 34.8% 2 years after baseline, and began to decline again at the end of the intervention period. The largest increases were seen in men and women > or =50 years. Uptake of screening did not differ according to melanoma risk factors; however, the decline in screening was less in participants who reported a number of melanoma risk factors. The prevalence of skin self-examination remained stable during the intervention program. No changes were observed in the control communities. These results indicate that the intervention program significantly increased the prevalence of whole-body clinical skin examinations in intervention communities. Once the intervention program ceased, and particularly after skin clinics ceased, levels of skin screening began to decline. The provision of specialized skin screening clinics may be needed to achieve sufficient screening rates should population based screening for skin cancer be considered.

Adult↗
PubMed2006

Who attends skin cancer clinics within a randomized melanoma screening program?

BACKGROUND: Screening may reduce morbidity and mortality associated with melanoma, although in the absence of randomized-controlled trials, this remains unproven. METHODS: As part of a randomized community-based trial of melanoma screening in Queensland, Australia, sociodemographic characteristics, skin cancer risk factors and attitudes towards skin cancer associated with attendance at screening clinics and reasons for attendance or non-attendance were examined. A telephone survey was conducted among 743 attendees and 298 non-attendees. RESULTS: After adjustment, the following factors were associated with clinic attendance: age 40-49 years, having fair skin, a personal history of skin cancer or melanoma or concern about a specific spot or mole, and no recent whole-body skin examination by a doctor. The main reasons for attendance were "to see if I have melanoma", "to have a suspicious mole checked" or "to have a whole-body skin examination". The main reasons for non-attendance were lack of knowledge about the clinics, no time or being away while the clinics were held and having had a skin check in the recent past. Overall, 77% of non-attendees compared to 65% of attendees stated they planned to participate in future screening. CONCLUSIONS: The results suggest that we were able to attract both men and women equally to a skin screening clinic, along with those at all levels of education and indicate the importance of using well-designed promotional materials to attract community members to skin screening clinics. Future work should test strategies to remove barriers to participation in skin screening identified in this study.

Adult↗
PubMed2006

Selectin ligand-independent priming and maintenance of T cell immunity during airborne tuberculosis.

Immunity to Mycobacterium tuberculosis infection is critically dependent on the timely priming of T effector lymphocytes and their efficient recruitment to the site of mycobacterial implantation in the lung. E-, P-, and L-selectin counterreceptors control lymphocyte homing to lymph nodes and leukocyte trafficking to peripheral sites of acute inflammation, their adhesive function depending on fucosylation by fucosyltransferases (FucT) IV and VII. To address the relative importance of differentially glycosylated selectin counterreceptors for priming of T cell effector functions in a model of mycobacteria-induced granulomatous pulmonary inflammation, we used aerosol-borne M. tuberculosis to infect FucT-IV-/-, FucT-VII-/-, FucT-IV-/-/FucT-VII-/-, or wild-type control mice. In lymph nodes, infected FucT-IV-/-/FucT-VII-/- and, to a lesser extent, FucT-VII-/- mice had severely reduced numbers of T cells and reduced Ag-specific effector responses. By contrast, recruitment of activated T cells into the lungs was similar in all four groups of mice during infection and expression of T cell, and macrophage effector functions were only delayed in lungs of FucT-IV-/-/FucT-VII-/- mice. Importantly, lungs from all groups expressed CXCL13, CCL21, and CCL19 and displayed organized follicular neolymphoid structures after infection with M. tuberculosis, which suggests that the lung served as a selectin ligand-independent priming site for immune responses to mycobacterial infection. All FucT-deficient strains were fully capable of restricting M. tuberculosis growth in infected organs until at least 150 days postinfection. Our observations indicate that leukocyte recruitment functions dictated by FucT-IV and FucT-VII-dependent selectin ligand activities are not critical for inducing or maintaining T cell effector responses at levels necessary to control pulmonary tuberculosis.

Animals↗
PubMed2006

Measuring the intrapersonal component of psychological empowerment: confirmatory factor analysis of the sociopolitical control scale.

The Sociopolitical Control Scale (SPCS) is a widely used measure of the intrapersonal component of psychological empowerment. Confirmatory factor analyses (CFA) were conducted with data from two samples to test the hypothesized structure of the SPCS, the potential effects of method bias on the measure's psychometric properties, and whether a revised version of the scale (SPCS-R) yielded improved model fit. Sample 1 included 316 randomly selected community residents of the Midwestern United States. Sample 2 included 750 community residents of the Northeastern U.S. Results indicated that method bias from the use of negatively worded items had a significant effect on the factor structure of the SPCS. CFA of the SPCS-R, in which negatively worded items were rephrased so that all statements were positively worded, supported the measure's hypothesized two-factor structure (i.e., leadership competence and policy control). Subscales of the SPCS-R were found reliable and related in expected ways with measures of community involvement. Implications of the study for empowerment-based research and practice are described, and strategies to further develop the SPCS are discussed.

Adolescent↗
PubMed2006

Do centralised skin screening clinics increase participation in melanoma screening (Australia)?

OBJECTIVE: To compare during the first 12 months of a 3-year randomised community-based trial of population screening for melanoma three methods of screening delivery: skin screening within day-to-day primary care (Group A); screening in dedicated skin screening clinics either organised privately by local physicians (Group B); or organised centrally with participants referred back to their physicians for definitive diagnosis and management (Group C). METHODS: The trial involved 18 regional communities in Queensland, Australia. Of the nine communities randomised to the intervention group, three communities were allocated to each of the Groups A, B or C. All intervention communities received a community education programme and an education and support programme for primary care physicians. The self-reported prevalence of clinical skin examination was assessed by surveying 3,110 residents (66.9% participation rate) aged > or = 30 years by telephone at baseline, and 14,060 residents (70.9% participation rate) by self-administered mailed questionnaire at 12-month follow-up. RESULTS: At baseline the prevalence of skin screening did not differ between intervention and control communities. At 12-month follow-up, participants within intervention communities reported skin screening significantly more frequently (20.9% versus 10.9%; p < 0.001). Within intervention communities, the prevalence of clinical skin examinations in Group A was similar to that of control communities (12.6% and 10.9%; p = 0.33). Communities in Group B (16.5%; p = 0.001) and Group C (27.1%; p < 0.001) reported significantly higher prevalence of clinical examinations than the control group. CONCLUSIONS: The provision of centrally organised skin screening clinics significantly increases skin screening rates and may have relevance for future melanoma control programmes.

Adult↗
PubMed2006

A population survey--would Australian general practice be the first point of contact during an anthrax bioterrorism event?

BACKGROUND: Anthrax bioterrorism is a new threat to Australians. How they would respond to an anthrax bioterrorism event is unknown. METHOD: A national telephone survey of Australian adults. RESULTS: We successfully interviewed 1001 Australian adults (response rate 63%). The threat of anthrax bioterrorism was of medium to high concern to 57% of survey participants. In the event of an anthrax bioterrorism event, the first point of care would be GPs for 60% of survey participants, and 71% were confident in their doctor's ability to recognise anthrax. Most would accept vaccination if anthrax bioterrorism cases were reported locally, or even elsewhere in Australia. DISCUSSION: Australian GPs should be included in any bioterrorism planning to respond to such threats.

Anthrax↗
PubMed2005

Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment.

Natural killer (NK) cells are known to reject certain tumors in vivo; however, the ability of NK cells to prevent metastasis of tumors into secondary lymphoid organs has not been addressed. Here, we report that in tumor-bearing hosts, NK cells are recruited to regional lymph nodes in wild-type mice, but not in mice deficient for L-selectin or L-selectin ligands. By adoptive transfer and complete Freund's adjuvant stimulation experiments, we demonstrated that L-selectin on NK cells and L-selectin ligands on endothelial cells are essential for NK cell recruitment to lymph nodes. Furthermore, freshly isolated resident lymph node NK cells lysed tumors efficiently, and metastasis of B16 melanoma cells to draining lymph nodes was suppressed in wild-type or Rag-1-deficient mice, but not when NK cells were depleted. Although L-selectin-deficient NK cells efficiently lysed tumor cells in vitro, NK cell-dependent suppression of tumor metastasis was diminished in mice deficient for L-selectin or L-selectin ligands because of insufficient NK cell recruitment to lymph nodes. Moreover, tumor metastasis was substantially inhibited in L-selectin-deficient mice reconstituted with wild-type NK cells. These findings indicate that L-selectin-mediated NK cell recruitment plays a crucial role in the control of tumor metastasis into secondary lymphoid organs.

Adoptive Transfer↗
PubMed2005

Clinical outcomes from skin screening clinics within a community-based melanoma screening program.

BACKGROUND: Within a randomized trial of population screening for melanoma, primary care physicians conducted whole-body skin examinations and referred all patients with suspect lesions to their own doctor for further treatment. OBJECTIVE: Our aim was to describe characteristics of skin screening participants, clinical screening diagnoses, management following referral, and specificity and yield of screening examinations. METHODS: Information collected from consent forms, referral forms, and histopathological reports of lesions that had been excised or undergone biopsy was analyzed by means of descriptive statistics. RESULTS: A total of 16,383 whole-body skin examinations resulted in 2302 referrals (14.1% overall; 15.5% men, 18.2% > or = 50 years of age) for 4129 suspect lesions (including 222 suspected melanoma, 1101 suspected basal cell carcinomas [BCCs], 265 suspected squamous cell carcinomas [SCCs]). Histopathologic results were available for 94.8% of 1417 lesions excised and confirmed 33 melanomas (23 in men; 24 in participants > or = 50 years of age), 259 BCCs, and 97 SCCs. The probability of detecting skin cancer of any type within the program was 2.4%. The estimated specificity of whole-body skin examinations for melanoma was 86.1% (95% confidence interval = 85.6-86.6). The positive predictive value (number of confirmed/number of lesions excised or biopsied x 100) for melanoma was 2.5%, 19.3% for BCC, and 7.2% for SCC (overall positive predictive value for skin cancer, 28.9%). LIMITATIONS: Follow-up of participants with a negative screening examination has not been conducted for the present investigation. CONCLUSIONS: The rate of skin cancer detected per 100 patients screened was higher than previously reported and men and attendees older than 50 years more frequently received a referral and diagnosis of melanoma. The specificity for detection of melanoma through whole-body skin examination by a primary care physician was comparable to that of other screening tests, including mammography.

Adult↗
PubMed2005

N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules.

Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.

Animals↗
PubMed2005

The relationship between active living and health-related quality of life: income as a moderator.

This study used a moderator model to examine the relationship between active living and the physical components of health-related quality of life [i.e. overall physical component of quality of life (PQOL), physical functioning and ability to fulfill physical role] among a randomly selected sample of rural residents (n = 407) from the Midwestern US. Results showed that active living was associated with greater increases in health-related quality of life for those reporting lower income. The effect size of the relationship between active living and the PQOL for the low-income group was over 2 times the effect size for the high-income group. For physical functioning, the effect size of active living for the low-income group was greater than 3 times the effect size for the high-income group. Although active living behaviors have been demonstrated to be less prevalent among those of low socioeconomic status, this group may have the most to gain from these activities. Findings highlight the need for increased and specifically targeted promotion of active living interventions.

Adult↗
PubMed2005

Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo.

Regulatory T cells (Tregs) play a fundamental role in the suppression of different immune responses; however, compartments at which they exert suppressive functions in vivo are unknown. Although many groups have described the presence of Tregs within inflammatory sites, it has not been shown that inflamed tissues are, indeed, the sites of active suppression of ongoing immune reactions. Here, by using alpha(E)+ effector/memory-like Tregs from fucosyltransferase VII-deficient animals, which lack E/P-selectin ligands and fail to migrate into inflamed sites, we analyzed the functional importance of appropriate Treg localization for in vivo suppressive capacity in an inflammation model. Lack of suppression by Tregs deficient in E/P-selectin ligands demonstrates that immigration into inflamed sites is a prerequisite for the resolution of inflammatory reactions in vivo because these selectin ligands merely regulate entry into inflamed tissues. In contrast, control of proliferation of naive CD4+ T cells during the induction phase of the immune response is more efficiently exerted by the naive-like alpha(E)-CD25+ Treg subset preferentially recirculating through lymph nodes when compared with its inflammation-seeking counterpart. Together, these findings provide the first conclusive evidence that appropriate localization is crucial for in vivo activity of Tregs and might have significant implications for anti-inflammatory therapies targeting recruitment mechanisms.

Animals↗
PubMed2005

Efficient recruitment of lymphocytes in inflamed brain venules requires expression of cutaneous lymphocyte antigen and fucosyltransferase-VII.

Lymphocyte migration into the brain represents a critical event in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the mechanisms controlling the recruitment of lymphocytes to the CNS via inflamed brain venules are poorly understood, and therapeutic approaches to inhibit this process are consequently few. In this study, we demonstrate for the first time that human and murine Th1 lymphocytes preferentially adhere to murine inflamed brain venules in an experimental model that mimics early inflammation during EAE. A virtually complete inhibition of rolling and arrest of Th1 cells in inflamed brain venules was observed with a blocking anti-P-selectin glycoprotein ligand 1 Ab and anti-E- and P-selectin Abs. Th1 lymphocytes produced from fucosyltransferase (FucT)-IV(-/-) mice efficiently tethered and rolled, whereas in contrast, primary adhesion of Th1 lymphocytes obtained from FucT-VII(-/-) or Fuc-VII(-/-)FucT-IV(-/-) mice was drastically reduced, indicating that FucT-VII is critical for the recruitment of Th1 cells in inflamed brain microcirculation. Importantly, we show that Abs directed against cutaneous lymphocyte Ag (CLA), a FucT-VII-dependent carbohydrate modification of P-selectin glycoprotein ligand 1, blocked rolling of Th1 cells. By exploiting a system that allowed us to obtain Th1 and Th2 cells with skin- vs gut-homing (CLA(+) vs integrin beta(7)(+)) phenotypes, we observed that induced expression of CLA on Th cells determined a striking increase of rolling efficiency in inflamed brain venules. These observations allow us to conclude that efficient recruitment of activated lymphocytes to the brain in the contexts mimicking EAE is controlled by FucT-VII and its cognate cell surface Ag CLA.

Adjuvants, Immunologic↗
PubMed2005

Tobacco outlet density and demographics at the tract level of analysis in Iowa: implications for environmentally based prevention initiatives.

This study assessed the geographic association between tobacco outlet density and three demographic correlates-income, race, and ethnicity-at the tract level of analysis for one county in the Midwestern United States. Data for residential census tracts in a Midwestern U.S. county were derived from year 2003 licenses for 474 tobacco outlets. Demographic variables were based on 2000 census data. Census tracts with lower median household income, higher percent of African American residents, and higher percent of Latinos residents had greater density of tobacco selling retail outlets. Areas characterized by lower income and disproportionately more African Americans and Latinos have greater physical access to tobacco products. Physical access to tobacco is a critical public-health issue because, given that smokers have been shown to be price sensitive, lowering access costs (e.g., reduced travel time) is likely to increase consumption. Findings also suggest the need for structural or environmental interventions, i.e., tobacco outlet zoning laws, to mitigate the health consequences associated with tobacco use in certain populations and geographic regions.

Censuses↗
PubMed2005

Test-retest of self-reported exposure to artificial tanning devices, self-tanning creams, and sun sensitivity showed consistency.

OBJECTIVE: Exposure to ultraviolet radiation has consistently been linked to an increased risk of melanoma. Epidemiologic studies are susceptible to measurement error, which can distort the magnitude of observed effects. Although the reliability of self-report of many sun exposure factors has been previously described in several studies, self-report of use of artificial tanning devices and self-tanning creams has been less well characterized. STUDY DESIGN AND METHODS: A mailed survey was re-administered 2-4 weeks after completion of the initial survey to 76 randomly selected participants in a case-control study of melanoma. Cases and controls were individuals diagnosed in 1999 and 2000 who were ascertained from the Iowa Cancer Registry in 2002. We assessed the consistency of self-reported use of sunlamps and self-tanning creams, sun sensitivity, and history of sunburns. RESULTS: There was substantial reliability in reporting the use of sunlamps or self-tanning creams (cases: Kappa (kappa)=1.0 for both exposures; controls: kappa=0.71 and 0.87, respectively). kappa estimates of 0.62-0.78 were found for overall reliability of several sun sensitivity factors. CONCLUSION: Overall, the survey instrument demonstrated substantial reproducibility for factors related to the use of sunlamps or tanning beds, self-tanning creams, and sun sensitivity factors.

Adult↗