Home About us Contact
|
Home About us Contact | ||
|
|
||
Normal Healthy Individuals (normal + healthy_individual)
Selected AbstractsIn vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cellsEXPERIMENTAL DERMATOLOGY, Issue 6 2003Bo Bang Abstract:,In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after a single dose of UVB irradiation. Normal healthy individuals were irradiated with three minimal erythema doses (MED) of UVB on forearm or buttock skin. Suction blisters from unirradiated and irradiated skin were raised, and Fas, FasL, and apoptosis of epidermal cells were quantified by flow cytometry. Clustering of Fas was demonstrated by confocal laser scanning microscopy on cryostat sections from skin biopsies. Soluble FasL in suction blister fluid was quantified by ELISA. Flow cytometric analysis demonstrated increased expression intensity of Fas after irradiation, with 1.6-, 2.2- and 2.7-fold increased median expression at 24, 48 and 72 h after irradiation, respectively (n = 4). Apoptosis was demonstrated by the TUNEL reaction, and the maximum of apoptotic cells was detected at 48 h after irradiation. Double-staining for Fas and TUNEL showed that apoptosis was restricted to the Fas-positive epidermal subpopulation, but there was no correlation between the intensities of Fas expression and TUNEL reaction. Median expression intensity of FasL-positive cells transiently decreased to 0.9- and 0.8-fold of the preirradiation respective level after 24 h and 48 h, respectively, and returned to the respective preirradiation level at 72 h after irradiation (n = 4). Concentrations of soluble FasL in suction blister fluid from UVB-irradiated skin did not differ from those in unirradiated skin (n = 5). Confocal laser scanning microscopy showed a rapid clustering of Fas within 30 min after irradiation. A simultaneous clustering of the adapter signalling protein FADD suggested that Fas clustering has a functional significance. Our results are in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure. [source] CD4 T,cell activation by myelin oligodendrocyte glycoprotein is suppressed by adult but not cord blood CD25+ T,cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003Kajsa Wing Abstract Regulatory T,cells expressing CD25 have been shown to protect rodents from organ-specific autoimmune diseases. Similar CD25+ cells with a memory phenotype exerting suppressive function after polyclonal or allogeneic stimulation are also present in adult human blood. We demonstrate that adult human CD25+ cells regulate the response to myelin oligodendrocyte glycoprotein (MOG), as depletion of CD25+ cells increases responses of PBMC and the addition of purified CD25+ cells suppresses MOG-specific proliferation and IFN-, production of CD4+CD25, T,cells. In contrast, cord blood CD25+ cells do not inhibit responses to self antigens, and only a small subpopulation of cord CD25+ cells expresses the typical phenotype of adult regulatory T,cells (CD45RA, and GITR+) enabling suppression of polyclonal responses. We conclude that activation of self-reactive T,cells in normal healthy individuals is prevented by the presence of self-antigen-specific CD25+ regulatory T,cells and that the majority of these cells mature after birth. [source] Are Nonresorbing Osteoclasts Sources of Bone Anabolic Activity?,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2007Morten A Karsdal PhD Abstract Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that osteoclasts are the source of anabolic signals for osteoblasts. In normal healthy individuals, bone formation is coupled to bone resorption in a tight equilibrium. When this delicate balance is disturbed, the net result is pathological situations, such as osteopetrosis or osteoporosis. Human osteopetrosis, caused by mutations in proteins involved in the acidification of the resorption lacuna (ClC-7 or the a3-V-ATPase), is characterized by decreased resorption in face of normal or even increased bone formation. Mouse mutations leading to ablation of osteoclasts (e.g., loss of macrophage-colony stimulating factor [M-CSF] or c- fos) lead to secondary negative effects on bone formation, in contrast to mutations where bone resorption is abrogated with sustained osteoclast numbers, such as the c-src mice. These data indicate a central role for osteoclasts, and not necessarily their resorptive activity, in the control of bone formation. In this review, we consider the balance between bone resorption and bone formation, reviewing novel data that have shown that this principle is more complex than originally thought. We highlight the distinct possibility that osteoclast function can be divided into two more or less separate functions, namely bone resorption and stimulation of bone formation. Finally, we describe the likely possibility that bone resorption can be attenuated pharmacologically without the undesirable reduction in bone formation. [source] p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjectsAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2006Stenio Fernando Pimentel Duarte Several genes play a major role in obese phenotypes, and studies suggest that genetic variations among individuals, as well as their lifestyles, may bring about different body compositions. Among these genes, LEP, which codifies leptin, and the LEPR gene encoding its receptor were extensively studied for variants that could explain the obese phenotype. The LEPR p.Q223R gene polymorphism was analyzed in a sample of obese and nonobese individuals from Brazil to evaluate the role of this polymorphism in the obese phenotype in the population. Two hundred obese patients (60 males, 140 females, body mass index (BMI) >30 kg/m2) were screened, together with 150 lean or normal healthy individuals (63 males, 87 females, BMI <24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction (PCR). PCR products were digested with the restriction of endonuclease MspI, and separated by electrophoresis through an 8% polyacrilamide gel stained with silver nitrate. There was a significant difference in LEPR p.Q223R polymorphism frequency when comparing obese and lean subjects, with an odds ratio of 1.92 and a 95% confidence interval of 1.15,3.22 (P = 0.013). There is a strong association of the LEPR p.Q223R gene polymorphism with obesity in Brazil. Am. J. Hum. Biol. 18:448,453, 2006. © 2006 Wiley-Liss, Inc. [source] Association of vitamin-D receptor (Fok-I) gene polymorphism with bladder cancer in an Indian populationBJU INTERNATIONAL, Issue 4 2007Rama D. Mittal OBJECTIVE To explore the association of vitamin-D receptor (VDR) genotypes and haplotypes (variants at the Fok-I, and Taq-I sites) with the risk of bladder cancer, as vitamin D is antiproliferative and reported to induce apoptosis in human bladder tumour cells in vitro. PATIENTS, SUBJECTS AND METHODS A case-control study using polymerase chain reaction-restriction fragment length polymorphism was conducted in 130 patients with bladder cancer and 346 normal healthy individuals in a north Indian population. Patients were also categorized according to grade and stage of tumour. RESULTS There was a significant difference in genotype and allelic distribution of VDR (Fok-I) polymorphism in the patients (P = 0.033 and = 0.017, respectively). The FF genotype was associated with twice the risk for bladder cancer (odds ratio 2.042, 95% confidence interval, CI, 0.803,5.193). There was no significant difference in genotypic distribution or allelic frequencies of the VDR (Taq-I) polymorphism (P = 0.477 and 0.230) when compared with the controls. The stage and grade of the bladder tumours had no association with VDR (Fok-I and Taq-I) genotypes. There was a significant difference in the frequency distribution of the haplotypes FT and fT (P < 0.001); these haplotypes had a protective effect in the control group (odds ratio 0.167, 95% CI 0.096,0.291, and 0.079, 0.038,0.164). CONCLUSION These data suggest that VDR (Fok-I) polymorphism is associated with the risk of bladder cancer. Further, the results for the haplotype FT and fT indicate that patients with this haplotype have a lower risk of developing bladder cancer than those with other haplotypes. [source] Microbiological effect of photodynamic therapy (PDT) in healthy volunteers: a comparative study using methyl aminolaevulinate and hexyl aminolaevulinate creamCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007A. Yung Summary Background., Acne vulgaris is a common skin problem that affects up to 90% of adolescents. Colonization of the duct with Propionibacterium species is one of the factors implicated in the development of acne. Owing to the increasing incidence of antibiotic resistance, there has been an greater interest in the development of new methods to treat acne. Early studies have shown that photodynamic therapy (PDT) with aminolaevulinic acid (ALA) can lead to prolonged improvement in acne. Newer derivatives of ALA such as methyl aminolaevulinate hydrochloride (MAL) and hexyl aminolaevulinate hydrochloride (HAL) have been developed for use in PDT, with the potential benefits of higher lipophilicity and penetration potential. Objectives., To determine the microbiological effect and tolerability of a single application of HAL-PDT and to compare it with MAL-PDT in healthy volunteers. Methods., This was a randomised double-blind study to examine the microbiological effects and safety of a single application of MAL-PDT and HAL-PDT on normal skin in 18 healthy volunteers. Bacterial skin samples for Propionibacterium spp. and Micrococceae were obtained at baseline and 2, 4, 7 and 14 days. Results., Following PDT with MAL and HAL, a statistically significant transient reduction in mean density of Propionibacterium spp. 2 days after treatment using each agent (P < 0.05 for both) was found. There were no significant changes in mean number of Micrococceae for the duration of the study period. Treatment with HAL-PDT and MAL-PDT was well tolerated. Overall, HAL-PDT was associated with fewer side-effects compared with MAL-PDT (P < 0.01) over the 14 day study period. Conclusion., HAL-PDT and MAL-PDT transiently reduce density of Propionibacterium spp. density to a similar degree in normal healthy individuals. The transient reduction in Propionibacterium spp. suggests that the prolonged antiacne effect of PDT relies on factors independent of bacterial density. HAL-PDT appears to be better tolerated than MAL-PDT. [source] Comparisons of cutaneous blood flow reactivity to norepinephrine and sodium nitroprusside between patients with heart transplantation and healthy subjectsCLINICAL TRANSPLANTATION, Issue 1 2001Ying-Tai Wu Heart transplant patients are reported to have impaired regulation of the microvasculature. The purpose of this study was to investigate the cutaneous blood flow and its reactivity to sodium nitroprusside (vasodilator, Nipride 0.1%) and norepinephrine (vasoconstrictor, Levophed 0.1%) in patients after heart transplantation in comparison to normal healthy individuals. Eighteen patients after heart transplantation and 16 healthy, nonsmoking individuals served as subjects of the study. Sodium nitroprusside and norepinephrine were introduced by iontophoresis to the skin of the right and left forearms, respectively. After measuring cutaneous blood flow reactivity in the pre-exercise state by laser Doppler flowmetry, subjects were then asked to close and open their fists for 2 min. The same measurements were repeated after exercise. Comparisons between the groups were carried out by the Wilcoxan signed rank test. The Mann,Whitney U -test was used for comparison between pre-exercise and post-exercise states. The results demonstrated that sodium nitroprusside significantly increased forearm cutaneous perfusion at rest but produced only a mild increase after exercise. This reactivity was significantly lower after exercise with no significant differences between groups. Norepinephrine decreased cutaneous blood flow at rest. The transplant patients were significantly less sensitive to norepinephrine before but not after exercise. The changes in norepinephrine reactivity with exercise were significantly different between groups (p<0.05). [source] | ||||||||||