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Biomedical subjects

J B Lowe

Publications and source records attributed to J B Lowe.

At least 55 records · Page 3Linked to original sources

Comparison of two self-help smoking cessation booklets.

OBJECTIVE: To compare two self-help smoking cessation booklets distributed to callers to a Quitline telephone service in Queensland (Australia). DESIGN: Callers were randomised to receive either a structured 14-day quit programme (Time to quit) or another booklet and described four broad stages of quitting (Can quit). Approximately one month later, these callers were interviewed by telephone. MAIN OUTCOME MEASURES: Self-reported smoking status at one month and recent quit attempts together with process measures. RESULTS: Altogether, 521 callers (78.3%) were interviewed. They were heavier smokers when compared with all Queensland smokers: on average they had smoked for more than 15 years, smoked nearly 25 cigarettes per day, and almost two-thirds had attempted to quit smoking in the past year. In each group, significant proportions either did not begin to use the booklet (50.5-56.0%), or did not complete its use (77.4-82.3%). There were no differences in the self-reported quit rates at one month (17.0% vs 16.1%; p = 0.93). In an ordinal regression modelling procedure involving age, sex, number of recent quit attempts, number of cigarettes smoked per day, smoking status of partner, number of five closest friends who smoke, education, and booklet received, only the number of cigarettes smoked per day was significantly related to smoking status at one month. CONCLUSIONS: Callers to telephone Quit-line services are typically heavier smokers than the general smoking population, and simple strategies, such as self-help booklets, appear to achieve relatively high success. Nevertheless, there is potential to improve the effectiveness of these materials by making a range of materials available and encouraging callers to make a serious attempt to quit smoking.

Adult↗

Evaluation of a three-year school-based intervention to increase adolescent sun protection.

The efficacy of a school-based intervention was evaluated using a randomized controlled trial in Australia. In consecutive grades (8, 9, and 10), students in the intervention group received components of a program that addressed issues related to the need to protect yourself from the sun, behavioral strategies related to using sun-protective measures, personal and social images of having a tan, the use of sun-safe clothing, and how to change their schools through forms of structural change. Pre- and postintervention measures among junior high school students showed greatest improvement in the intervention group's knowledge scores and minimal changes in sun protection behavior from Grade 8 to Grade 9, which were not maintained through Grade 10. Results of the study highlight some limitations of school-based interventions for changing sun protection behaviors.

Adolescent↗

The role of open rhinoplasty in the management of nasal dermoid cysts.

The nasal dermal sinus cyst is one of many midline nasal masses that often pose diagnostic and treatment dilemmas for the plastic and reconstructive surgeon. The differential diagnosis of the midline nasal mass includes both congenital and acquired processes. A thorough understanding of its cause is crucial to treatment. A comprehensive discussion of the pathogenesis, diagnosis, sequelae, and surgical management, and a representative case analysis, of the nasal dermal sinus cyst is presented to delineate the role of open rhinoplasty in optimizing the care of this congenital nasal deformity.

Adolescent↗

The role of open rhinoplasty in the management of nasal dermoid cysts.

The nasal dermal sinus cyst is one of many midline nasal masses that often pose diagnostic and treatment dilemmas for the plastic and reconstructive surgeon. The differential diagnosis of the midline nasal mass includes both congenital and acquired processes. A thorough understanding of its cause is crucial to treatment. A comprehensive discussion of the pathogenesis, diagnosis, sequelae, and surgical management, and a representative case analysis, of the nasal dermal sinus cyst is presented to delineate the role of open rhinoplasty in optimizing the care of this congenital nasal deformity.

Adolescent↗

Alpha(1,3)-fucosyltransferase VII-dependent synthesis of P- and E-selectin ligands on cultured T lymphoblasts.

T lymphocytes up-regulate the synthesis of ligands for E- and P-selectin during proliferative responses in vivo and in vitro. Previous studies from our laboratories indicated that the alpha(1,3)-fucosyltransferase FucT-VII regulates the synthesis of E-selectin ligands and sialylated Lewis(x)-related epitopes (sLe(x)-related epitopes) in human T lymphoblasts. The current report shows that production of both P- and E-selectin ligands is FucT-VII dependent, but peak synthesis of each occurs at different levels of fucosyltransferase activity in intact cells. In brief, FucT-VII mRNA levels were higher in cultured T lymphoblasts expressing sLe(x)-related epitopes and both selectin ligands than in cells expressing P-selectin ligands alone. However, synthesis of the epitopes and both selectin ligands required the FucT-VII enzyme in transfected Molt-4 cells. In contrast, neither constitutive nor transfection-enhanced levels of the FucT-IV enzyme generated active P-selectin ligands in these lines. In addition, targeted deletion of the FucT-VII gene in mice markedly inhibited the synthesis of both P- and E-selectin ligands during blast transformation in vitro. Finally, the optimal synthesis of active P-selectin ligands occurred at lower level of FucT-VII activity than required for synthesis of equally active E-selectin ligands in both cultured T lymphoblasts and FucT-VII transfectants. Consequently, the FucT-VII enzyme is essential for the synthesis of both P- and E-selectin ligands by T lymphoblasts, and its activity determines whether P-selectin ligands are expressed alone or in conjunction with E-selectin ligands and sLe(x)-related epitopes on human T cells.

Animals↗

Endothelial selectins and alpha4 integrins regulate independent pathways of T lymphocyte recruitment in the pulmonary immune response.

The cell adhesion molecules (CAMs) required for T lymphocyte recruitment during pulmonary immune responses have not been defined. Our laboratories recently reported that intratracheal (IT) challenge of sensitized mice with SRBC induced prolonged expression of vascular P-selectin, E-selectin, and VCAM-1, particularly in areas of mononuclear leukocyte infiltration. A surge in the number of circulating T lymphocytes expressing selectin ligands preceded the peak accumulation of T cells in the lung. In addition, a significant percentage of the T cells recovered from the lung expressed selectin ligands as well. The current study demonstrates that cultured T lymphoblasts use both selectin ligands and alpha4 integrins to enter the airspace and interstitium during the response to SRBC. Fluorescently labeled T lymphoblasts, derived via activation on CD3 and growth in low dose IL-2, showed inflammation-specific recruitment into lungs harvested 24 h after cell infusion. Their flux paralleled the accumulation of host lymphocytes in the lung, with both peaking 2 to 4 days after SRBC challenge. Trafficking studies conducted over a 24-h period during peak lymphocyte accumulation in the lungs revealed preferential recruitment of labeled T lymphoblasts expressing P- and E-selectin ligands. In addition, mAb blockade of the alpha4 integrins and targeted deletion of an alpha(1,3)fucosyltransferase essential for selectin ligand synthesis each reduced labeled T lymphoblast trafficking to a significant degree. Furthermore, alpha4 integrin blockade reduced the trafficking of the selectin ligand-deficient cells into the airspace, confirming that its contribution is in part independent from the vascular selectins. These findings imply that both selectin ligands and alpha4 integrins participate in T lymphoblast recruitment during the pulmonary immune response to IT SRBC.

Animals↗

Overlapping functions of E- and P-selectin in neutrophil recruitment during acute inflammation.

Selectin adhesion molecules mediate leukocyte rolling on activated endothelium, a prerequisite to leukocyte accumulation at sites of inflammation. The precise role of each selectin (E-, P-, and L-) in this process is unclear and may vary depending on the particular inflammatory stimulus, vascular bed, leukocyte subset, and species; most data suggest discrete functional roles for each selectin. To define the relative roles of E- and P-selectin in mediating neutrophil accumulation in acute dermal inflammation, mice genetically deficient in E-selectin, P-selectin, or both E- and P-selectin were injected intradermally with zymosan. Luminal endothelial expression of E- and P-selectin in response to zymosan was documented in wild-type mice by intravenous administration of fluorochrome-labeled anti-E- and anti-P-selectin antibodies. In mice deficient in E- or P-selectin, neutrophil accumulation was unchanged or only subtly reduced relative to wild-type control mice. In mice deficient in both E- and P-selectin, neutrophil accumulation was significantly reduced (87% at 4 hours and 79% at 8 hours). These data demonstrate that, in this model of acute inflammation, there is considerable overlap in the functions of E- and P-selectin; loss of both selectins was required to impair neutrophil accumulation.

Animals↗

Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells.

Subsets of mammalian cell surface oligosaccharides contain specific fucosylated moieties expressed in lineage- and/or temporal-specific patterns. The functional significance of these fucosylated structures is incompletely defined, although there is evidence that subsets of them, represented by the sialyl Lex determinant, are important participants in leukocyte adhesion and trafficking processes. Genetic deletion of these fucosylated structures in the mouse has been a powerful tool to address functional questions about fucosylated glycans. However, successful use of such approaches can be problematic, given the substantial redundancy in the mammalian alpha-1,3-fucosyltransferase and alpha-1,2-fucosyltransferase gene families. To circumvent this problem, we have chosen to clone the genetic locus encoding a mammalian GDP-D-mannose-4,6-dehydratase (GMD). This enzyme generates GDP-mannose-4-keto-6-D-deoxymannose from GDP-mannose, which is then converted by the FX protein (GDP-4-keto-6-D-deoxymannose epimerase/GDP-4-keto-6-L-galactose reductase) to GDP-L-fucose. GMD is thus imperative for the synthesis of all fucosylated oligosaccharides. An expression cloning approach and the GMD-deficient CHO host cell line Lec13 were used to generate a population of cDNA molecules enriched in GMD cDNAs. This enriched plasmid population was then screened using a human expressed sequence tag (EST AA065072) with sequence similarity to an Arabidopsis thaliana GMD cDNA. This approach, together with 5'-rapid amplification of cDNA ends, yielded a human cDNA that complements the fucosylation defect in the Lec13 cell line. Northern blot analyses indicate that the GMD transcript is absent in Lec13 cells, confirming the genetic deficiency of this locus in these cells. By contrast, the transcript encoding the FX protein, which forms GDP-L-fucose from the ketosugar intermediate produced by GMD, is present in increased amounts in the Lec13 cells. These results suggest that metabolites generated in this pathway may participate in the transcriptional regulation of the FX protein and possibly the GMD protein. The results also suggest that the genomic structure encoding GMD in Lec13 cells likely has a defect different from a point mutation in the coding region.

Amino Acid Sequence↗

Platelet-endothelial interactions in inflamed mesenteric venules.

The selectins are membrane glycoproteins promoting adhesive events between leukocytes, platelets, and endothelial cells. We have previously demonstrated that platelets roll on P-selectin expressed on stimulated endothelium. In this study, we wished to examine the function of both the platelet and endothelial selectins, P- and E-selectins, in mediating platelet-endothelial interactions during inflammation. We demonstrate, using intravital microscopic examination of venules inflamed with tumor necrosis factor-alpha (TNF-alpha), that resting platelets interact with both P- and E-selectins and that the leukocyte alpha(1,3)fucosyltransferases FucT IV and FucT VII do not provide platelets with selectin ligand activity. We also show that after thrombin activation of wild-type (+/+) platelets, platelet P-selectin can mediate interactions on a TNF-alpha-inducible endothelial ligand. To evaluate the potential role of platelet P-selectin in the recruitment of leukocytes to inflammatory sites, we reconstituted the bone marrow of mice deficient in both P- and E-selectins (P/E-/-) with wild-type (+/+) or P-selectin-deficient (P-/-) bone marrow containing megakaryocytic precursors. Providing +/+ platelets to P/E-/- mice by bone marrow transplantation did not rescue the immunodeficient phenotype, suggesting that platelet P-selectin does not have an active function in the recruitment of leukocytes into inflammatory sites. To participate in inflammatory or hemostatic responses, platelets may use the endothelial selectins.

Animals↗

Complementary acceptor and site specificities of Fuc-TIV and Fuc-TVII allow effective biosynthesis of sialyl-TriLex and related polylactosamines present on glycoprotein counterreceptors of selectins.

The P-selectin counterreceptor PSGL-1 is covalently modified by mono alpha2,3-sialylated, multiply alpha1,3-fucosylated polylactosamines. These glycans are required for the adhesive interactions that allow this adhesion receptor-counterreceptor pair to facilitate leukocyte extravasation. To begin to understand the biosynthesis of these glycans, we have characterized the acceptor and site specificities of the two granulocyte alpha1,3-fucosyltransferases, Fuc-TIV and Fuc-TVII, using recombinant forms of these two enzymes and a panel of synthetic polylactosamine-based acceptors. We find that Fuc-TIV can transfer fucose effectively to all N-acetyllactosamine (LN) units in neutral polylactosamines, and to the "inner" LN units of alpha2,3-sialylated acceptors but is ineffective in transfer to the distal alpha2,3-sialylated LN unit in alpha2,3-sialylated acceptors. Fuc-TVII, by contrast, effectively fucosylates only the distal alpha2,3-sialylated LN unit in alpha2,3-sialylated acceptors and thus exhibits an acceptor site-specificity that is complementary to Fuc-TIV. Furthermore, the consecutive action of Fuc-TIV and Fuc-TVII, in vitro, can convert the long chain sialoglycan SAalpha2-3'LNbeta1-3'LNbeta1-3'LN (where SA is sialic acid) into the trifucosylated molecule SAalpha2-3'Lexbeta1-3'Lexbeta1-3'Lex (where Lex is the trisaccharide Galbeta1-4(Fucalpha1-3)GlcNAc) known to decorate PSGL-1. The complementary in vitro acceptor site-specificities of Fuc-TIV and Fuc-TVII imply that these enzymes cooperate in vivo in the biosynthesis of monosialylated, multifucosylated polylactosamine components of selectin counterreceptors on human leukocytes.

Amino Sugars↗

Regulation of fucosyltransferase-VII expression in peripheral lymph node high endothelial venules.

Binding of L-selectin to the highly glycosylated peripheral lymph node addressins (PNAd) plays a central role in the normal recirculation of lymphocytes between the bloodstream and the lymph node. This interaction requires correct fucosylation of the PNAd, mediated by the recently identified fucosyltransferase-VII (Fuc-TVII). Here we show that during ontogeny Fuc-TVII is absent at the day of birth, barely detectable on day 1, and clearly present from day 2 onwards. PNAd expression as detected by the MECA-79 antibody precedes the expression of Fuc-TVII. Furthermore, we demonstrate that in adult mice antigenic stimulation of peripheral lymph nodes leads to a temporary disappearance of Fuc-TVII at days 2 and 3 after stimulation, followed by a complete reappearance by day 4, while expression of MECA-79 is never completely absent during this period. Finally, occlusion of afferent lymphatics to peripheral lymph nodes resulted in a decreased expression of Fuc-TVII in the high endothelial venules by day 5, and complete disappearance within 8 days. We conclude that the activity of Fuc-TVII in cells of high endothelial venules is directly affected by afferent lymph and activation processes that occur in the lymph node after antigenic stimulation. The expression of Fuc-TVII is therefore yet another level at which the function of high endothelial venules, and thus lymphocyte trafficking, can be regulated.

Animals↗

Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.

Mammalian serine/threonine-linked oligosaccharides (O-glycans) are commonly synthesized with the Golgi enzyme core 2 beta-1,6-N-acetylglucosaminyltransferase (C2 GlcNAcT). Core 2 O-glycans have been hypothesized to be essential for mucin production and selectin ligand biosynthesis. We report that mice lacking C2 GlcNAcT exhibit a restricted phenotype with neutrophilia and a partial deficiency of selectin ligands. Loss of core 2 oligosaccharides reduces neutrophil rolling on substrata bearing E-, L-, and P-selectins and neutrophil recruitment to sites of inflammation. However, the diminished presence of L-selectin ligands on lymph node high endothelial venules does not affect lymphocyte homing. These studies indicate that core 2 oligosaccharide biosynthesis segregates the physiologic roles of selectins and reveal a function for the C2 GlcNAcT in myeloid homeostasis and inflammation.

Animals↗

Quality of measurement of smoking status by self-report and saliva cotinine among pregnant women.

OBJECTIVE: The objectives of this paper were to determine the rate of misclassification of smoking and nonsmoking status by self-reports and saliva continine of pregnant women participating in a smoking cessation trial, determine the relationship of the number of cigarettes smoked per day and saliva continine, and examine whether misclassification was due to an inappropriate saliva continine cutoff point. METHODS: End of pregnancy self-reports of smoking status and saliva continine were used to calculate misclassification rates. RESULTS: The findings revealed that 61 of 441 self-reported smokers had biochemical values inconsistent with smoking status for a smoking misclassification rate of 13.8%. The results also revealed that 28 of 107 self-reported quitters had continine values consistent with smoking status for a nonsmoking misclassification rate of 26.2%. Receiver Operating Characteristic (ROC) curves were then plotted to determine whether misclassification resulted from an inappropriate cutoff point. The continine cutoff point that maximized sensitivity and specificity for all women was 24 ng/ml. Racial ROC comparisons indicated a higher cutoff point for blacks than whites. Use of any of the ROC indicated cutoff points would not change the misclassification rates. CONCLUSIONS: These findings suggest that underreporting of smoking status during pregnancy is high and that social desirability of nonsmoking status may have contributed to the lack of precision in saliva continine to distinguish smoking status in this study.

Adult↗

In vitro and in vivo selectin-blocking activities of sulfated lipids and sulfated sialyl compounds.

There is accumulating evidence that sulfated lipids, sulfated oligosaccharides and other sulfated compounds are reactive with selectins in a manner that interferes with selectin interactions with their natural ligands. In the report we describe the ability of sulfated lipids (sulfatides and gangliosides) and multimeric forms of sulfated sialic acid to block binding of P- and E-selectin-Ig to neutrophils. The in vivo ability of these compounds to block lung injury in rats following i.v. infusion of purified cobra venom factor (CVF), which induces injury that is L- and P-selectin dependent, was also determined as well as effects on recruitment of neutrophils, as measured by lung myeloperoxidase. There was a significant correlation between the ability of sulfated lipids and sialyl compounds to interfere in vitro with P-selectin-Ig binding to neutrophils and to protect against P-selectin-dependent acute lung injury induced by CVF. The biological effects of these sulfated compounds were also associated with diminished accumulation of neutrophils. The protective effects of these compounds may be linked to their ability to interfere with P-selectin binding to counter-receptors on neutrophils.

Animals↗

Evaluation of antenatal smoking cessation programs for pregnant women.

Smoking during pregnancy has been linked to health problems, including the risk of low birthweight, preterm labour, spontaneous abortion and perinatal death. Two trials to investigate the efficacy of self-help materials were undertaken. During the first trial, a self-help booklet developed overseas was evaluated through a randomised controlled design to determine the effects of the booklet alone, compared with the booklet with midwife counselling for the women. We recruited 217 women into the study and followed them up at 20 weeks' gestation to ascertain smoking cessation and to measure process variables. Smoking cessation rates were lower than expected, and process measures indicated that materials were not being used. A second trial was commenced after a comprehensive review of the materials with focus groups of pregnant women and one-to-one interviews of nurses and doctors. Trial 2 was based new materials, and used a magazine-style (smoking cessation) booklet designed by the focus groups. A total of 119 women were randomly allocated into the new-materials group or a usual-care group. The materials were well received, relevant and pertinent, and were used by the women. Smoking cessation rates at 20 weeks' gestation were biochemically validated and indicated that 9 per cent in the intervention group and none in the usual-care group had stopped smoking. The use of overseas programs needs to be approached with caution.

Australia↗

Improving general practitioner clinical records with a quality assurance minimal intervention.

BACKGROUND: Although good medical records have been associated with good care, there is considerable room for their improvement in general practice. AIM: To improve the quality of general practice medical records at minimal cost. METHOD: A total of 150 randomly sampled general practitioners (GPs) in suburban Brisbane, Australia, were randomized in a controlled trial to receive or not receive an intervention. The intervention consisted of 6 to 12 one-hour monthly meetings when the pairs of GPs assessed samples of each other's medical records using a 12-item instrument. This was developed previously by a process of consensus of general practice teachers. Mean scores of 10 medical records selected at random from before the intervention started and one year later were compared. RESULTS: After the intervention, the increase in the total score (for which the maximum possible was 18) for the intervention GPs (from a baseline of 11.5 to 12.3) was not significantly greater than for the controls (from 11.4 to 11.7). Legibility and being able to determine the doctor's assessment of the consultation were significantly improved. The post-intervention increase of 1.06 (9.3%) of the total scores of the 47% of intervention GPs who complied with the intervention was significantly greater than that for the controls. CONCLUSION: The quality assurance activity improved some components of the quality of GPs' clinical records. However, the improvement was small, and the search for activities for Australian GPs that demonstrate an improvement in the quality of their practice must continue.

Family Practice↗