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Biomedical subjects

P Lau

Publications and source records attributed to P Lau.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacy diabetes care program: analysis of two screening methods for undiagnosed type 2 diabetes in Australian community pharmacy.

OBJECTIVE: To compare the efficacy and cost-effectiveness of two methods of screening for undiagnosed type 2 diabetes in Australian community pharmacy. METHODS: A random sample of 30 pharmacies were allocated into two groups: (i) tick test only (TTO); or (ii) sequential screening (SS) method. Both methods used the same initial risk assessment for type 2 diabetes. Subjects with one or more risk factors in the TTO group were offered a referral to their general practitioner (GP). Under the SS method, patients with risk factors were offered a capillary blood glucose test and those identified as being at risk referred to a GP. The effectiveness and cost-effectiveness of these approaches was assessed. RESULTS: A total of 1286 people were screened over a period of 3 months. The rate of diagnosis of diabetes was significantly higher for SS compared with the TTO method (1.7% versus 0.2%; p=0.008). The SS method resulted in fewer referrals to the GP and a higher uptake of referrals than the TTO method and so was the more cost-effective screening method. CONCLUSIONS: SS is the superior method from a cost and efficacy perspective. It should be considered as the preferred option for screening by community based pharmacists in Australia.

Australia↗
PubMed2005

A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors.

Oligodendrocyte development is controlled by a number of survival and migratory factors. The present study shows that signaling of CXCR4 receptor by the chemokine CXCL12 regulates survival and migration of neural precursors (NP) as well as oligodendrocyte progenitors (OP). CXCR4 is expressed by E14 striatal NP and OP generated by neurospheres. In CXCR4-defective mice, the number of NP in neurosphere outgrowth was twofold less than in wild-type (WT) mice; NP radial cell migration was also decreased. In contrast, the addition of CXCL12 to WT NP increased radial migration from the sphere in a dose-dependent manner with a maximal response at 200 nM. When oligodendrocytes differentiated in neurosphere outgrowth, CXCR4 was downregulated. OP isolated from newborn brain coexpressed CXCR4 with platelet-derived growth factor receptor-alpha (PDGFR alpha) or chondroitin sulfate proteoglycan; receptor expression also decreased during differentiation in vitro. Neonatal OP showed a peak migratory response to 20 nM of CXCL12 in chemotactic chambers, a migration inhibited by a CXCR4 antagonist and anti-CXCL12 antibody. In the embryonic spinal cord, the number of OP-expressing PDGFR alpha was reduced more than twofold in CXCR4-defective mice compared with WT and the ratio of ventral to dorsal OP was significantly increased. This indicates a defect in OP survival and their dorsal migration from the ventral cord region, probably because CXCR4(-/-) OP are unable to respond to CXCL12 made by vascular endothelia and the pia mater. We propose that CXCR4 signaling regulate survival and outward chemotactic migration of OP during embryonic and postnatal CNS development.

Animals↗
PubMed2005

Complementary role of adjunctive breast magnetic resonance imaging and scintimammography in patients of all ages undergoing breast cancer surgery.

The aims of this study were to assess breast MRI and scintimammography (SMM) for the detection of breast cancer, and to determine any complementary role of these tests to each other and conventional imaging. Seventy-two patients (age 35-81 years) with a suspicious breast mass were investigated by mammography, breast ultrasound, breast MRI and SMM before undergoing surgical excision of the breast mass. Sensitivity, specificity and area under receiver operator characteristic curves were calculated for each test. Of the 72 patients, there were 66 proven malignant tumours, including two patients with bilateral breast cancer. When comparing the diagnostic sensitivity of breast MRI and SMM for lesion size, both tests showed higher sensitivities for lesions >25 mm in size, particularly for SMM. When these tests were compared for patient age, patients less than 51 years showed higher sensitivities for both tests. This was statistically significant for breast MRI. The overall respective diagnostic sensitivities for mammography, mammography with breast ultrasound, breast MRI and SMM were 56, 67, 86 and 85%. The differences were significant between mammography, mammography/ultrasound and both breast MRI and SMM. Breast MRI and SMM offer incremental diagnostic advantage in the diagnosis of breast cancer. Although improved diagnostic accuracy is seen in patients of all ages, those patients less than 51 years of age receive the greatest diagnostic benefit.

Adult↗
PubMed2003

Suppressor of cytokine signalling gene expression is elevated in breast carcinoma.

Cytokines are important for breast cell function, both as trophic hormones and as mediators of host defense mechanisms against breast cancer. Recently, inducible feedback suppressors of cytokine signalling (SOCS/JAB/SSI) have been identified, which decrease cell sensitivity to cytokines. We examined the expression of SOCS genes in 17 breast carcinomas and 10 breast cancer lines, in comparison with normal tissue and breast lines. We report elevated expression of SOCS-1-3 and CIS immunoreactive proteins within in situ ductal carcinomas and infiltrating ductal carcinomas relative to normal breast tissue. Significantly increased expression of SOCS-1-3 and CIS transcripts was also shown by quantitative in situ hybridisation within both tumour tissue and reactive stroma. CIS transcript expression was elevated in all 10 cancer lines, but not in control lines. However, there was no consistent elevation of other SOCS transcripts. CIS protein was shown by immunoblot to be present in all cancer lines at increased levels, mainly as the 47 kDa ubiquitinylated form. A potential proliferative role for CIS overexpression is supported by reports that CIS activates ERK kinases, and by strong induction in transient reporter assays with an ERK-responsive promoter. The in vivo elevation of SOCS gene expression may be part of the host/tumour response or a response to autocrine/paracrine GH and prolactin. However, increased CIS expression in breast cancer lines appears to be a specific lesion, and could simultaneously shut down STAT 5 signalling by trophic hormones, confer resistance to host cytokines and increase proliferation through ERK kinases.

Breast Neoplasms↗
PubMed2002

A prostaglandin f(2alpha) analog induces suppressors of cytokine signaling-3 expression in the corpus luteum of the pregnant rat: a potential new mechanism in luteolysis.

PRL and placental lactogen (PL) play key roles in maintaining the rodent corpus luteum through pregnancy. Suppressors of cytokine signaling (SOCS) have been shown to decrease cell sensitivity to cytokines, including PRL, and so here we have addressed the issue of whether luteolysis induced by prostaglandin F(2alpha) (PGF(2alpha)) might up-regulate SOCS proteins to inhibit PRL signaling. In d 19 pregnant rats, cloprostenol, a PGF(2alpha) analog, rapidly induced transcripts for SOCS-3 and, to a lesser extent, SOCS-1. We also found increased SOCS-3 protein in the ovary by immunoblot and in the corpus luteum by immunohistochemistry. Increased SOCS-3 expression was preceded by an increase in STAT3 tyrosine phosphorylation 10 min after cloprostenol injection and was maintained for 4 h, as determined by gel shift and immunohistochemistry. Induction of SOCS-3 was accompanied by a sharp decrease in active STAT5, as determined by gel-shift assay and by loss of nuclear localized STAT5. Four hours after cloprostenol administration, the corpus luteum was refractory to stimulation of STAT5 by PRL administration, and this was not due to down-regulation of PRL receptor. Therefore, induction of SOCS-3 by PGF(2alpha) may be an important element in the initiation of luteolysis via rapid suppression of luteotropic support from PL.

Animals↗
PubMed2001

The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes.

The concept that selective transfer of high density lipoprotein (HDL)-derived cholesteryl esters (CE) does not require lipoprotein internalization has been challenged recently by evidence that implicates HDL recycling during the selective uptake process. This has prompted us to examine the role of the low density lipoprotein receptor-related protein (LRP) in selective uptake. LRP is an endocytic receptor for lipoprotein lipase (LpL) and apolipoprotein E (apoE) ligands that are able to mediate selective uptake. We report that molecules that interfere with ligand binding to LRP, such as the receptor-associated protein (RAP), suramin, alpha(2)-macroglobulin, or lactoferrin, inhibit HDL-CE selective uptake by human primary adipocytes and SW872 liposarcoma cells by 35-50%. This partial inhibition of selective uptake from total HDL was not due to preferential inhibition of the HDL(2) or HDL(3) subfractions. Selective uptake by the scavenger receptor BI was not inhibited by RAP, excluding its involvement. Furthermore, in SW872 cells in which LRP was reduced to 14% of control levels by stable antisense expression, selective uptake was attenuated by at least 33%, confirming a role for LRP in this process. RAP, alpha(2)-macroglobulin, lactoferrin, and suramin (individually or in paired combinations) also attenuated selective uptake of HDL-CE by primary human adipocytes by about 40%. On the other hand, human skin fibroblasts express LRP abundantly but lack the capacity for selective uptake, demonstrating that other molecules are required. In SW872 cells, exogenous apoE or LpL can facilitate selective uptake but only the apoE-enhanced uptake can be inhibited by RAP, implicating apoE as a likely co-mediator. We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake.

Adipocytes↗
PubMed2001

4-1BB ligand induces cell division, sustains survival, and enhances effector function of CD4 and CD8 T cells with similar efficacy.

A costimulatory member of the TNFR family, 4-1BB, is expressed on activated T cells. Although some reports have suggested that 4-1BB is primarily involved in CD8 T cell activation, in this report we demonstrate that both CD4 and CD8 T cells respond to 4-1BB ligand (4-1BBL) with similar efficacy. CD4 and CD8 TCR transgenic T cells up-regulate 4-1BB, OX40, and CD27 and respond to 4-1BBL-mediated costimulation during a primary response to peptide Ag. 4-1BBL enhanced proliferation, cytokine production, and CTL effector function of TCR transgenic T cells. To compare CD4 vs CD8 responses to 4-1BBL under similar conditions of antigenic stimulation, we performed MLRs with purified CD4 or CD8 responders from CD28(+/+) and CD28(-/-) mice. We found that CD8 T cells produced IL-2 and IFN-gamma in a 4-1BBL-dependent manner, whereas under the same conditions the CD4 T cells produced IL-2 and IL-4. 4-1BBL promoted survival of CD4 and CD8 T cells, particularly at late stages of the MLR. CD4 and CD8 T cells both responded to anti-CD3 plus s4-1BBL with a similar cytokine profile as observed in the MLR. CD4 and CD8 T cells exhibited enhanced proliferation and earlier cell division when stimulated with anti-CD3 plus anti-CD28 compared with anti-CD3 plus 4-1BBL, and both subsets responded comparably to anti-CD3 plus 4-1BBL. These data support the idea that CD28 plays a primary role in initial T cell expansion, whereas 4-1BB/4-1BBL sustains both CD4 and CD8 T cell responses, as well as enhances cell division and T cell effector function.

4-1BB Ligand↗
PubMed2001

Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection.

BACKGROUND: Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM: To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD: Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS: One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS: The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Types of patients in a psychiatric intensive care unit.

OBJECTIVE: This paper reports the findings of a descriptive study of a patient population over a three-month period on an eight bed psychiatric intensive care unit (PICU) in Western Australia. The report provides a quantitative insight into the profile of patients in PICUs. It provides information on patients' diagnoses, presenting signs, symptoms and/or behaviours, legal codes assigned to patients, treatment interventions and management. METHOD: Data were collected prospectively from August to October 1999. A total of 122 patients were admitted to the PICU during the review period. Data were entered into an Access program then exported to SPSS (Version 9 for Windows) for analysis and frequency distributions were obtained. RESULTS: The results confirmed that the majority of patients admitted to the PICU were assessed as a high level of risk or needed containment. This finding is in line with the admission criteria developed by staff working in the PICU. It also supports the view that staff working in these units require expertise and confidence to communicate with and manage potentially aggressive and highly aroused patients. CONCLUSION: This study demonstrates the importance of ongoing evaluations of patient populations in promoting best practice initiatives in psychiatric care.

Adult↗
PubMed2001

Measurement of body fat using leg to leg bioimpedance.

AIMS: (1) To validate a leg to leg bioimpedance analysis (BIA) device in the measurement of body composition in children by assessment of its agreement with dual energy x ray absorptiometry (DXA) and its repeatability. (2) To establish a reference range of percentage body fat in Hong Kong Chinese children. METHODS: Sequential BIA and DXA methods were used to determine body composition in 49 children aged 7-18 years; agreement between the two methods was calculated. Repeatability for the BIA method was established from duplicate measurements. Body composition was then determined by BIA in 1139 girls and 1243 boys aged 7-16 years, who were randomly sampled in eight local primary and secondary schools to establish reference ranges. RESULTS: The 95% limits of agreement between BIA and DXA methods were considered acceptable (-3.3 kg to -0.5 kg fat mass and -3.9 to 0.6% body fat). The percentage body fat increased with increasing age. Compared to the 1993 Hong Kong growth survey, these children had higher body mass index. Mean (SD) percentage body fat at 7 years of age was 17.2% (4.4%) and 14.0% (3.4%) respectively for boys and girls, which increased to 19.3% (4.8%) and 27.8% (6.3%) at age 16. CONCLUSION: Leg to leg BIA is a valid alternative method to DXA for the measurement of body fat. Provisional reference ranges for percentage body fat for Hong Kong Chinese children aged 7-16 years are provided.

Absorptiometry, Photon↗
PubMed2001

Tissue-specific induction of SOCS gene expression by PRL.

The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary gland of pup-deprived rats. Deprivation of PRL and pups for 48 h allows the mammary gland to induce SOCS genes in response to PRL administration, and this is associated with a decrease in basal SOCS-3 mRNA and protein expression to the level seen in other tissues, suggesting that SOCS-3 induced refractoriness related to filling of the gland. In reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT 5-responsive beta-lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the ovary and adrenal gland. We propose that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3.

Adrenal Glands↗
PubMed2001

Gene flow between natural and domestic populations of Lutzomyia longipalpis (Diptera: Psychodidae) in a restricted focus of American visceral leishmaniasis in Venezuela.

The epidemiology of the visceral leishmaniasis in the Americas is associated with both a natural and a domestic cycle. The existence of reproductively isolated populations of Lutzomyia longipalpis (Lutz & Neiva), and the scarcity of records of this species from natural habitats in areas where it has been associated with domestic habitats indicated that natural populations could be genetically distinct from domestic ones. Therefore, we compared the genetic structure and estimated the gene flow between L. longipalpis from domestic and peridomestic habitat and from an adjacent undisturbed natural environment along a 1.2-km transect. The analyses were performed on electrophoretic data from eight isozyme loci. The absence of fixed differences in the diagnostic loci Ak and Hk indicated that all specimens belonged to one of the two cryptic species identified in Venezuela. The average number of alleles per locus ranged from 2.0 to 2.9 and the average heterozygosity ranged from 7.8 to 13.4%. No differences were detected in the genetic structure of this species from domestic or peridomestic habitats and those trapped as far as 1.2 km from human dwellings. Nm, estimated from Wright's Fst, indicated that at least 208 individuals per generation migrated between the peridomestic habitat and a 1.2-km distant point to maintain the observed similarities in allelic frequencies. This high rate of gene flow indicated that this species has high migration rates between domestic and natural environments, and has the potential to transport for Leishmania from natural to domestic environments.

Adenylate Kinase↗
PubMed2001

Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D.

Lipids that are synthesized de novo in the epidermis, including fatty acids, oxysterols, 1,25-dihydroxyvitamin D(3), and farnesol, can regulate the differentiation of normal human keratinocytes (NHK). Cholesterol sulfate (CS), an epidermal lipid that is produced in the upper nucleated layers of the epidermis coincident with terminal differentiation, has been shown to play a role in the regulation of the late stages of keratinocyte differentiation, including formation of the cornified envelope. In the present study, we determined i) whether CS regulates involucrin (INV), an early keratinocyte differentiation marker, and ii) the mechanism by which CS regulates differentiation. mRNA and protein levels of INV, a precursor protein of the cornified envelope, increased 2- to 3-fold in NHK incubated in the presence of CS. In contrast, cholesterol had no effect on INV protein or mRNA levels. Transcriptional regulation was assessed in NHK transfected with INV promoter-luciferase constructs. CS increased luciferase reporter activity approximately 2- to 3-fold in NHK transfected with a 3.7-kb INV promoter construct. Deletional analysis revealed a CS-responsive region of the INV promoter located between bp --2452 and --1880. A 5-base pair (bp) mutation of the AP-1 site (bp --2117 to --2111) within this responsive region abolished CS responsiveness, suggesting a role for the AP-1 complex in the regulation of INV transcription by CS. Electrophoretic mobility shift analysis demonstrated increased binding of nuclear extracts isolated from CS-treated NHK to AP-1 DNA as compared with vehicle-treated controls. Incubation of the nuclear extract with the appropriate antibodies showed that the AP-1 DNA-binding complex contained Fra-1, Fra-2, and Jun D. Western blots demonstrated that CS treatment increased the levels of Fra-1, Fra-2, and Jun D, and Northern analyses revealed that CS increased mRNA levels for these same AP-1 factors. These data indicate that CS, an endogenous lipid synthesized by keratinocytes, regulates the early stages of keratinocyte differentiation, and may do so through its ability to modulate levels of AP-1 proteins. -- Hanley, K., L. Wood, D. C. Ng, S. S. He, P. Lau, A. Moser, P. M. Elias, D. D. Bikle, M. L. Williams, and K. R. Feingold. Cholesterol sulfate stimulates involucrin transcription in keratinocytes by increasing Fra-1, Fra-2, and Jun D. J. Lipid Res. 2001. 42: 390--398.

Binding Sites↗
PubMed2000

Rate of heart failure and 1-year survival for older people receiving low-dose beta-blocker therapy after myocardial infarction.

BACKGROUND: Many older people do not receive beta-blocker therapy after myocardial infarction or receive doses lower than those tested in trials, perhaps because physicians fear that beta-blockers may precipitate heart failure. We examined the relation between use of beta-blockers, the dose used, and hospital admission for heart failure and 1-year survival in a cohort of all older patients surviving myocardial infarction in Ontario, Canada. METHODS: We collected data on a cohort of 13,623 patients aged 66 years or older who were discharged from hospital after a myocardial infarction and who did not receive beta-blocker therapy or received low, standard, or high doses. We used Cox's proportional-hazards models to study the association of dose with admission for heart failure and survival with adjustment for factors including age, sex, and comorbidity. FINDINGS: Among 8232 patients with no previous history of heart failure, dispensing of beta-blocker therapy was associated with a 43% reduction in subsequent admission for heart failure (adjusted risk ratio 0.57 [95% CI 0.48-0.69]) compared with patients not dispensed this therapy. Among the 4681 patients prescribed beta-blockers, the risk of admission was greater in the high-dose than in the low-dose group (1.53 [1.01-2.31]). Among all 13,623 patients in the cohort, 2326 (17.1%) died by 1 year. Compared with those not dispensed beta-blocker therapy, the adjusted risk ratio for mortality was lower for all three doses (low 0.40 [0.34-0.47], standard 0.36 [0.31-0.42], high 0.43 [0.33-0.56]). INTERPRETATION: Compared with high-dose beta-blocker therapy, low-dose treatment is associated with a lower rate of hospital admission for heart failure and has a similar 1-year survival benefit. Our findings support the need for a randomised controlled trial comparing doses of beta-blocker therapy in elderly patients.

Adrenergic beta-Antagonists↗
PubMed2000

Farnesol stimulates differentiation in epidermal keratinocytes via PPARalpha.

The isoprenoids farnesol and juvenile hormone III (JH), metabolites of the cholesterol biosynthetic pathway, have been shown to stimulate fetal epidermal development in rodents. In this study we determined whether this effect might be attributed to a direct induction of keratinocytes differentiation and examined the mechanisms responsible for these effects. Rates of cornified envelope formation, a marker of keratinocyte terminal differentiation, as well as protein and mRNA levels of two proteins required for cornified envelope formation, involucrin (INV) and transglutaminase, increased 2- to 3-fold in normal human keratinocytes (NHK) treated with either farnesol or JH, even at low calcium concentrations (0.03 mM), which otherwise inhibit differentiation. In contrast, neither cholesterol nor mevalonate affected INV or transglutaminase mRNA levels. Effects of farnesol and JH on INV and transglutaminase mRNA levels were additive with high calcium concentrations (1.2 mM) that independently stimulate keratinocyte differentiation. In contrast, keratinocyte DNA synthesis was inhibited by these compounds. Both farnesol and JH stimulated INV and transglutaminase promoter activity, suggesting regulation at the transcriptional level. A series of truncation and deletion experiments revealed a farnesol-responsive region (-2452 to -1880 base pairs (bp)) in the INV gene. This region contained an AP-1 site. A single base pair mutation of the AP-1 site at -2116 to -2110 bp abolished farnesol responsiveness, identical to effects by peroxisome proliferator-activated receptor (PPARalpha) activators. Farnesoid X-activated receptor mRNA was not detected in NHK, but farnesol treatment increased activities of both a PPAR response element and PPARalpha mRNA levels in NHK. Furthermore, the increase in PPRE activity by farnesol was dependent upon PPARalpha in CV-1 cells. Finally, topical applications of farnesol increased mRNA and protein levels of the differentiation-specific genes, profilaggrin and loricrin, determined by immunohistochemistry and in situ hybridization, in wild-type but not in PPARalpha-/- murine epidermis. These findings suggest a novel role for selected isoprenoid cholesterol intermediates in the regulation of differentiation-specific gene transcription and a convergence of PPARalpha with the cholesterol synthetic pathway.

Animals↗
PubMed2000

Oxysterols induce differentiation in human keratinocytes and increase Ap-1-dependent involucrin transcription.

Ligands and activators of the nuclear hormone receptor superfamily are important in the regulation of epidermal development and differentiation. Previously, we showed that naturally occurring fatty acids, as well as synthetic ligands for the peroxisome proliferator-activated receptor, induce keratinocyte differentiation in vitro. Here we asked whether oxysterols, another class of lipids formed de novo in the epidermis and that activate liver X-activated receptor, regulate keratinocyte differentiation. mRNA and protein levels of involucrin and transglutaminase 1, markers of differentiation, increased 2- to 3-fold in normal human keratinocytes incubated in the presence of 25- or 22R-hydroxycholesterol in low calcium. In high calcium, which alone induces differentiation, mRNA levels were further increased by oxysterols. Rates of cornified envelope formation, an indicator of terminal differentiation, also increased 2-fold with oxysterol treatment. In contrast, the rate of DNA synthesis was inhibited approximately 50% by oxysterols. Transcriptional regulation was assessed in keratinocytes transfected with either transglutaminase 1 or involucrin promoter-luciferase constructs. 22R-hydroxycholesterol increased transglutaminase 1 and involucrin promoter activity 2- to 3-fold. Either deletion of the -2452 bp to -1880 bp region of the involucrin promoter, or mutation of the AP-1 site within this region, abolished oxysterol responsiveness. Moreover, increased AP-1 DNA binding was observed in oxysterol-treated keratinocytes by gel shift analyses. Finally, we demonstrated the presence of liver X-activated receptor alpha and beta mRNAs, and showed that oxysterols stimulate a liver X-activated receptor response element transfected into keratinocytes. These data suggest that oxysterols induce keratinocyte differentiation, in part through increased AP-1-dependent transcription of the involucrin gene, an effect that may be mediated by liver X-activated receptor.

Calcium↗
PubMed2000

A possible role of bats as a blood source for the Leishmania vector Lutzomyia longipalpis (Diptera: Psychodidae).

Some evidence suggests that bats may provide an alternative blood source for Lutzomyia longipalpis, the main vector of American visceral leishmaniasis. Feeding trials were conducted to determine whether L. longipalpis feeds on captive bats. The high feeding success indicated that L. longipalpis is capable of feeding on at least four species of bats. Implications for the epidemiology of leishmaniases are discussed.

Animals↗