Association of HLA class I antigens and HLA class II alleles with vitiligo in a Turkish population

As is the case with many other autoimmune diseases, there is an association between vitiligo and HLA complex. HLA subtypes vary with racial/ethnic background. The purpose of this study was to determine which HLA class I antigens and HLA class II alleles are associated with Turkish vitiligo patients. Forty-one patients with vitiligo and 61 healthy control subjects were typed for HLA class II alleles. Thirty-three out of 41 patients with vitiligo and 100 healthy transplant donors were typed for HLA class I antigens. HLA DNA typing was performed by polymerase chain reaction/sequence specific primer method for class II. HLA typing for class I was performed by serological method. The frequency of HLA DRB1*03 was 0.6340 in patients compared to 0.2950 in controls (P = 0.0014). The frequency of HLA DRB1*04 was found to be 0.6830 in patients compared to 0.2950 in controls (P = 0.00026). The allele HLA DRB1*07 was present in 0.390 of patients compared to 0.0820 of the controls (P = 0.0004). A preventive antigen for the manifestation of vitiligo has not been identified in this study. Our findings suggest that DRB1*03, DRB1*04 and DRB1*07 alleles are genetic markers for general susceptibility to vitiligo in a Turkish population.     

Biotransformation of racemic diisophorone by <Emphasis Type="Italic">Cephalosporium aphidicola</Emphasis> and <Emphasis Type="Italic">Neurospora crassa</Emphasis>

Racemic diisophorone (500 mg) was converted by Cephalosporium aphidicola and Neurospora crassa over 10 days at 25 °C to 8β-hydroxydiisophorone in yields of 10% (52 mg) and 20% (103 mg), respectively. The structure was established by IR, specific rotation, mass spectral, 1D and 2D-NMR studies.Revisions requested 2 March 2005 and 21 April 2005; Revisions received 8 April 2005 and 10 May 2005     

A simple technique for collecting blood of testicular origin: application to in vivo studies on testicular steroidogenesis in rats and Macaca fascicularis

A technique for rapidly collecting blood of testicular origin is described, one which can provide sufficient plasma amounts to investigate some steps of testicular steroid biogenesis in vivo in 2 species. In adult male rats, testosterone (T), androstenedione (4A) and 5-androstenediol (5AD) were determined in pampiniform plexus testicular venous blood (PPTV) and peripheral (PV) blood samples before and 2 h after human Chorionic Gonadotropin (hCG). PPTV concentration of 5AD was 0.83 +/- 0.1 ng/ml (mean +/- SEM) with a PPTV/PV ratio of 7.0 +/- 1.0, comparable to a PPTV/PV ratio for 4A of 5.8 +/- 1.8. After hCG, PPTV concentration of 5AD significantly increased to 1.28 +/- 0.15 ng/ml (P less than 0.05). Those data are in favor of a participation of 5-ene pathway to testicular biogenesis of T associated to a 4-ene pathway which is predominant. In adult male Macaca fascicularis, spermatic vein (SV) concentrations of 5AD and 4A were comparable (3.0 +/- 1.2 vs 4.3 +/- 1.0 ng/ml) as well as SV/PV ratios under basal conditions (3.5 +/- 0.9 vs 5.1 +/- 0.1), as well as 48 h after hCG, confirming in vivo that both 5-ene and 4-ene pathways are involved in testicular T biogenesis. Testicular production of estradiol (E2), estrone (E1) and their sulfates E2S and E1S showed a SV/PV ratio significantly higher than 1 (3.4 +/- 0.6; 2.4 +/- 0.1; 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively).     

The molecular basis of β-thalassemia in Turkey

Summary By using oligonucleotide hybridization, restriction endonuclease analysis and direct sequencing of amplified genomic DNA, we have been able to characterize 18 different mutations in the -globin genes of 161 thalassemia homozygotes and 107 -thalassemia heterozygotes from Turkey (429 -thalassemia chromosomes). Previous studies dealing with -thalassemia in Mediterranean countries have shown that, in most Mediterranean populations, only a few mutations are prevalent. In contrast, -thalassemia in Turkey does not seem to be associated with a few predominant mutations. The six most frequent alleles, IVS-I-110 (GA), IVS-I-6(TC), FSC-8 (-AA), IVS-I-1(GA), -30(TA) and FSC-5 (CT), account for only 69.3% of the disease genes; indeed, all 26 mutations assayed represent 85.8% of the disease genes, confirming the considerable molecular heterogeneity of -thalassemia among Turks, and indicating the possible presence of rare, previously undefined, mutations in the population. Two mutations observed in this study, IVS-I-116 (TG) and Cd44(-C), have not been reported in the Turkish population to date. Since preventive medical services, such as genetic counseling and prenatal diagnosis, are greatly improved by detailed knowledge of the molecular pathology of thalassemia, we strongly believe that the presented data will facilitate the intended establishment of a prenatal diagnosis center, based on DNA analysis, in Turkey.     

Dual Effect of Glucocorticoid-Induced Tumor Necrosis Factor–Related Receptor Ligand Carrying Mesenchymal Stromal Cells on Small Cell Lung Cancer: A Preliminary in vitro Study

Background aims

TNFR family member glucocorticoid-induced tumor necrosis factor–related receptor (GITR/TNFRSF18) activation by its ligand glucocorticoid-induced TNF-related receptor ligand (GITRL) have important roles in proliferation, death and differentiation of cells. Some types of small cell lung cancers (SCLCs) express GITR. Because mesenchymal stromal cells (MSCs) may target tumor cells, we aimed to investigate the effect of MSCs carrying GITRL overexpressing plasmid on the proliferation and viability of a GITR⁺ SCLC cell line (SCLC-21H) compared with a GITR^– SCLC cell line (NCI-H82).

Differential structuring of human populations for homologous X and Y microsatellite loci.

The global pattern of variation at the homologous microsatellite loci DYS413 (Yq11) and DXS8174 and DXS8175 (Xp22) was analyzed by examination of 30 world populations from four continents, accounting for more than 1,100 chromosomes per locus. The data showed discordant patterns of among- and within-population gene diversity for the Y-linked and the X-linked microsatellites. For the Y-linked polymorphism, all groups of populations displayed high FST values (the correlation between random haplotypes within subpopulations, relative to haplotypes of the total population) and showed a general trend for the haplotypes to cluster in a population-specific way. This was especially true for sub-Saharan African populations. The data also indicated that a large fraction of the variation among populations was due to the accumulation of new variants associated with the radiation process. Europeans exhibited the highest level of within-population haplotype diversity, whereas sub-Saharan Africans showed the lowest. In contrast, data for the two X-linked polymorphisms were concordant in showing lower FST values, as compared with those for DYS413, but higher within-population variances, for African versus non-African populations. Whereas the results for the X-linked loci agreed with a model of greater antiquity for the African populations, those for DYS413 showed a confounding pattern that is apparently at odds with such a model. Possible factors involved in this differential structuring for homologous X and Y microsatellite polymorphisms are discussed.     

Mitochondrial criticality: a new concept at the turning point of life or death

A variety of stressors can cause the collapse of mitochondrial membrane potential (DeltaPsi(m)), but the events leading up to this catastrophic cellular event are not well understood at the mechanistic level. Based on our recent studies of oscillations in mitochondrial energetics, we have coined the term "mitochondrial criticality" to describe the state in which the mitochondrial network of cardiomyocytes becomes very sensitive to small perturbations in reactive oxygen species (ROS), resulting in the scaling of local mitochondrial uncoupling and DeltaPsi(m) loss to the whole cell, and the myocardial syncytium. At the point of criticality, the dynamics of the mitochondrial network bifurcate to oscillatory behavior. These energetic changes are translated into effects on the electrical excitability of the cell, inducing dramatic changes in the morphology and the threshold for activating an action potential. Emerging evidence suggests that this mechanism, by creating spatial and temporal heterogeneity of excitability in the heart during ischemia and reperfusion, underlies the genesis of potentially lethal cardiac arrhythmias.     

Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart

Ischemia/reperfusion (I/R) of the heart becomes injurious when duration of the ischemic insult exceeds a certain threshold (approximately ≥20 min). Mitochondrial bound hexokinase II (mtHKII) protects against I/R injury, with the amount of mtHKII correlating with injury. Here, we examine whether mtHKII can induce the transition from non-injurious to injurious I/R, by detaching HKII from mitochondria during a non-injurious I/R interval. Additionally, we examine possible underlying mechanisms (increased reactive oxygen species (ROS), increased oxygen consumption (MVO₂) and decreased cardiac energetics) associated with this transition. Langendorff perfused rat hearts were treated for 20 min with saline, TAT-only or 200 nM TAT-HKII, a peptide that translocates HKII from mitochondria. Then, hearts were exposed to non-injurious 15-min ischemia, followed by 30-min reperfusion. I/R injury was determined by necrosis (LDH release) and cardiac mechanical recovery. ROS were measured by DHE fluorescence. Changes in cardiac respiratory activity (cardiac MVO₂ and efficiency and mitochondrial oxygen tension (mitoPO₂) using protoporphyrin IX) and cardiac energetics (ATP, PCr, ?G_ATP) were determined following peptide treatment. When exposed to 15-min ischemia, control hearts had no necrosis and 85% recovery of function. Conversely, TAT-HKII treatment resulted in significant LDH release and reduced cardiac recovery (25%), indicating injurious I/R. This was associated with increased ROS during ischemia and reperfusion. TAT-HKII treatment reduced MVO₂ and improved energetics (increased PCr) before ischemia, without affecting MVO₂/RPP ratio or mitoPO₂. In conclusion, a reduction in mtHKII turns non-injurious I/R into injurious I/R. Loss of mtHKII was associated with increased ROS during ischemia and reperfusion, but not with increased MVO₂ or decreased cardiac energetics before damage occurs.     

Corneal protein nitration in experimental uveitis

Increased expression of inducible nitric oxide synthase (NOS-2) in inflammatory diseases like uveitis suggests that it contributes to the observed pathological state. The aim of this study was to evaluate corneal expression of NOS-2 and corneal protein nitration in a rat model of uveitis. A single injection of intravitreal lipopolysaccharide was used to induce uveitis. Corneal proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by Coomassie blue staining. Expression of NOS-2 and nitrotyrosine (NO(2)Tyr) formation were determined via immunohistochemistry and Western blot analysis. Total nitrate/nitrite levels in the vitreous were measured by spectral analysis via the Griess reagent. Immunohistochemical analysis revealed increased corneal NOS-2 and NO(2)Tyr immunoreactivity in rats with uveitis compared with controls. NOS-2 and NO(2)Tyr immunoreactivity was observed in and around basal cells in the corneal epithelium. Western blot analysis of corneal lysates showed multiple nitrated protein bands in uveitic rats. Spectrophotometric measurement of total nitrate/nitrite levels in the vitreous affirmed significantly increased levels of nitric oxide generation in uveitis (126 +/-2.63 microM/mg protein) compared with controls (65 +/-6.57 microM/mg protein). The presented data suggests that extensive formation of protein nitration and reactive nitrogen species in the cornea contributes to tissue destruction in uveitis. Hence, selective inhibition of NOS-2 may prevent long-term complications and lead to an improvement in the management of uveitis.     

Frequency and severity of musculoskeletal symptoms in humans during an outbreak of trichinellosis caused by Trichinella britovi

Musculoskeletal symptoms such as myalgia are well-known features in the course of trichinellosis; however, the characteristics of musculoskeletal findings have been described in detail in only 1 study. The present study was aimed to determine the joint and muscle symptoms in subjects diagnosed with acute trichinellosis at our rheumatology unit during a Trichinella britovi outbreak that occurred in Izmir, Turkey, in 2004. In total, 98 patients (55 females, 43 males; mean age 32.3 +/- 10.9 yr) were included in the study. A detailed history and full musculoskeletal examination were obtained in each patient. A self-administered questionnaire developed for recording the musculoskeletal symptoms was completed monthly until all the symptoms were resolved. Pain at the joints, restriction of movements (in shoulders, elbows, wrists, knees, ankles, and temporomandibular joints), myalgia, and muscle weakness (neck and shoulder girdle, muscles of the upper and forearm, back, thigh, and calf muscles) were assessed in every patient. Eosinophil counts, serum levels of creatine kinase, and lactate dehydrogenase also were analyzed. The most frequent musculoskeletal symptoms were muscle pain (86 cases [87.8%]), joint pain (83 [84.7%]), subjective muscle weakness (75 [76.5%]), and restriction of joint movements (63 [64.3%]). Calves, upper arm, neck and shoulder girdle, and forearms were the most affected muscle groups. Muscle pain was reported more frequently in the upper than in the lower extremities and during activity. The most frequent painful joints were shoulders, knees, wrists, and ankles. Upper extremity joints were affected more frequently than the lower extremity joints (77.6 vs. 70.4%). Joint pain occurred more frequently at rest. Both muscle weakness and restriction of joint movements were reported in and around the most frequently affected regions. No evidence of arthritis and objective muscle weakness was noted on physical examination in any patient. Musculoskeletal symptoms in the course of T. britovi infection are frequent but with an excellent prognosis. Joint pain in people suffering from acute trichinellosis may occur more frequently than reported previously.