Normal Healthy Control Subjects Research Articles

Changes in red nucleus after pyramidal tract injury in patients with cerebral infarct

We investigated red nucleus (RN) changes in patients with a cerebral infarct, using diffusion tensor imaging (DTI). Forty-nine consecutive stroke patients with pyramidal tract(PT) injury (mean age, 62.1 years; range, 41 to 75) and 46 age-matched normal healthy control subjects (mean age, 58.9 years; range, 41 to 75) with no history of neurologic disease were recruited. DTI was performed using a 1.5-T system during the early stage, after cerebral infarct (8-l21 days after onset). DTIs were acquired using a sensitivity-encoding head coil at 1.5 T. We measured fractional anisotropies (FAs) and apparent diffusion coefficients (ADCs) of RNs in the upper midbrain, and assessed the motor function of affected extremities. Mean FA of RNs in affected hemispheres was higher than in unaffected hemispheres (P < 0.05), however, no difference was observed between the unaffected control hemispheres (P> 0.05). However, mean ADC values of RNs were no different between control hemispheres and a patient's affected and unaffected hemispheres (P> 0.05). It appears that RN in affected hemispheres show elevated levels of neuronal activity during the early stage in patients with a corona radiata infarct, which suggests that RNs in affected hemispheres are used to compensate for PT injury.

Association of High Sensitivity C-reactive Protein with Hyperuricemia in Taiwanese Patients with Gout

Objective: To analyze the relationship between high sensitivity C-reactive protein (hsCRP) and hyperuricemia in gout patients in a Taiwan population. Methods: Forty gout patients and 25 normal healthy control subjects were recruited. The serum hsCRP, uric acid, and erythrocyte sedimentation rate (ESR) levels of each participant were measured. The disease duration, visual analogue scale (VAS) pain score and presence or absence of tophi were recorded. The correlations between hsCRP levels and clinical features or laboratory profiles in gout patients were analyzed. Results: The findings demonstrated statistical significance in hsCRP levels in gout patients compared with normal healthy control individuals (p＜0.001). HsCRP correlated with serum ESR (r=0.549, p＜0.001), uric acid (r=0.381, p=0.020) and the VAS pain score (r=0.385, p=0.014), but not with disease duration and presence of tophi. Conclusion: HsCRP was associated with hyperuricemia, high ESR levels and high VAS pain scores in gout patients in Taiwan, suggesting increased hsCRP may be an indicator of uncontrolled hyperuricemia or gouty arthritis.

Analysis of E‐Selectin S128R gene polymorphism in pancreatic cancer

E-selectin, an intercellular adhesion molecule that plays important roles in metastasis of tumor cells, has a polymorphism in exon 4 that results in the substitution of a serine by an arginine within the extracellular domain of the receptor, which increases its affinity for ligands. No evidence exist on the role of E-selectin polymorphism in pancreatic cancer. Eighty pancreatic cancer patients and 160 cases of normal healthy control subjects were investigated for genotype and allelic frequencies of S128R polymorphism of E-selectin gene by PCR-RFLPs. The frequencies for "AA," "CA," and "CC" genotypes were 46.25%, 50%, and 3.75% in patients, and 63.75%, 26.9%, and 9.4% in healthy subjects, respectively. The "C" carriers group of patients ("CA + CC" genotype) and the "C" allele were over-represented among the pancreatic cancer cases (P = 0.012 and 0.096, respectively). Advanced T stage, the presence of lymph node and other adverse pathologic characteristics were not significantly correlated with either the "CA + CC" genotype group of patients or the presence of "C" allele. E-selectin S128R "C" allele may confer an increased susceptibility to pancreatic cancer development, while its carriage status does not appear to be related to the aggressive features of this malignancy.

Analysis of the stromal cell-derived factor 1-3'A gene polymorphism in pancreatic cancer

Stromal cell derived factor-1 (SDF-1), a CXC chemokine that plays an important role in the tumor growth, angiogenesis and metastasis of tumor cells, has a polymorphism at position 801 of its 3'-untranslated region, known as SDF1-3'A. The SDF1-3'A polymorphism has been investigated in various types of cancer, but no information is currently available on its role in pancreatic cancer. In this study, 80 pancreatic cancer patients and 160 normal healthy control subjects were investigated for the genotype and allelic frequencies of the SDF-1 gene using PCR-RFLP. The genotype frequencies for GG, GA and AA were 21.25, 77.5 and 1.25% in patients, and 42.5, 55 and 2.5% in healthy subjects, respectively. The A carrier group (GA+AA genotype) and the A allele were overrepresented among the patients with pancreatic cancer (p=0.015 and p=0.031, respectively). The GA+AA genotype was statistically correlated with an advanced T stage and the presence of lymph node metastasis, and displayed a clear trend towards significance in relation to the presence of distant metastatic disease (p=0.061). Only T stage was significantly related to A allele frequency (p=0.004). SDF1-3' A allele carriers were more prevalent among cancer patients than among normal subjects. SDF1-3' A allele carrier status may imply a higher risk of pancreatic cancer, while the presence of the A allele in pancreatic cancer patients may be related to aggressive features of this malignancy.

Proteolytic degradation by cathepsin D of glycated hemoglobin from diabetes patients gives rise to hemorphin-7 peptides

Previous studies showed a significantly reduced level of hemorphins in the serum of diabetes patients. In order to elucidate the biochemical mechanisms responsible for this anomaly, the influence of hemoglobin glycation on hemorphin generation was studied. The glycation of hemoglobin occurs in the blood of diabetes patients and this could modify its enzymatic digestion and the resulting proteolytic products. Several samples of hemoglobin were obtained from the blood of type 1 diabetes patients ( n = 8) and normal healthy control subjects ( n = 2). The glycated hemoglobin samples were classified on the basis of their HbA1c values expressed as a percentage of total hemoglobin. Four solutions of glycated hemoglobin characterized by HbA1c values of 6%, 9.1%, 10.7% and 12.1% were treated with cathepsin D and the hemorphins obtained following the proteolysis were compared to controls. It was found that hemorphins were produced whatever the level of glycation of hemoglobin and also that the degree of glycation had no effect on the quantity of hemorphins released. Thus the alteration of hemoglobin does not seem to be the essential reason for the decrease in hemorphin concentrations in the sera of diabetic patients.

T−786C polymorphism of the endothelial nitric oxide synthase gene and neuralgia-inducing cavitational osteonecrosis of the jaws

We hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO). In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender. Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender-matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13). The eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.

Significant Correlation Between Association of Polymorphism in Codon 10 of Transforming Growth Factor-β1 T (29) C With Type 1 Diabetes and Patients With Nephropathy Disorder

Type 1 diabetes is an autoimmune disease that is caused by destruction of pancreatic beta-cells. Type 1 diabetes is a heterogenic disease with environmental factors as well as genetic components. It is well established that environmental factors can exert their effects only on genetically susceptible patients. There is increasing evidence that genes outside the major histocompatibility complex (MHC) region contribute to the pathogenesis of type 1 diabetes. Cytokines, due to their role in immune regulation, seem to play a crucial role in the pathogenesis of the disease. In order to investigate the immunosuppressive action of transforming growth factor-beta1 (TGF-beta1) in type 1 diabetes, 388 patients with type 1 diabetes and 229 normal controls were genotyped for the TGF-beta1 T (29) C gene polymorphism. The TGF-beta1 T (29) C gene polymorphism was amplified using ARMS-PCR. Practical part of this work was conducted in Molecular Medicine Research Group, Peninsula Medical School, Plymouth, UK. However, statistical analyses were performed in Department of pathology, Salmaniya Medical Complex, Kingdom of Bahrain. From three different genotypes of TT, TC, and CC of the TGF-beta1 T (29) C, the TC frequency increased in patients with type 1 diabetes compared to normal controls, P value = 0.00001. The TC frequency was significantly higher in patients with diabetic nephropathy (DN) in comparison with diabetic control, P value = 0.007. Further, the CC frequency was significantly less in patients compared to healthy normal control subjects, P value = 0.005. Genetic variation at the TGF-beta1 gene polymorphism T (29) C located in codon 10 is likely to confer significant susceptibility to advanced DN in patients with T1D. This is a small case-control study in Caucasians to investigate the role of the TGF-beta1 gene polymorphism T (29) C located in codon 10 in the genetic predisposition to T1D and DN. To our knowledge, this is the first genetic report highlighting the dual effects of TGF-beta1 in the onset of T1D as well as type 1 DN and can be a good model for extensive studies.

Five Serum Proteins Identified Using SELDI-TOF-MS as Potential Biomarkers of Gastric Cancer

The aims of this study were to detect serum proteomic patterns in gastric cancer serum samples using Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry ProteinChip array technology, to screen biomarker candidates, to build diagnostic models and to evaluate their clinical significance. Serum samples from patients with gastric cancer and normal healthy control subjects (n = 125) were analysed using surface-enhanced laser desorption/ionization technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peak clustering and classification analyses were established using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. The diagnostic models were developed and validated by discriminant analysis. In addition, the results of the surface-enhanced laser desorption/ionization model were compared with the biomarkers carcinoembryonic antigen and carbohydrate antigen 199 in a subset of samples using a microparticle enzyme immunoassay. Five protein peaks at 2046, 3179, 1817, 1725 and 1929 m/z were automatically chosen as components of the best biomarker pattern for diagnosis of gastric cancer. In addition, we identified a single protein peak at 4665 m/z, which could distinguish between stage I/II and stage III/IV gastric cancer with a specificity and sensitivity of 91.6% (11/12) and 95.4% (21/22), respectively. When this biomarker was validated in the second set of samples, the specificity and sensitivity were 91.7% (11/12) and 86.3% (19/22), respectively. The present results suggest that serum surface-enhanced laser desorption/ionization protein profiling can distinguish patients with gastric cancer, and in particular stage I/II patients, from normal subjects with a relatively high sensitivity and specificity. Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry is a potential new diagnostic tool for the screening of gastric cancer.

Abstract B45: Identification of chromosome aberration of oral squamous cell carcinoma patients in southern India

Abstract Oral squamous cell carcinoma (OSCC) is the most frequent cancer and constitutes a major health problem in India, representing the leading cause of death. The aim of the present investigation was to study the major chromosomal aberrations (CA) like deletion, translocation, inversion and mosaic in OSCC patients of South India. Genetic factors play an important role in the etiology of OSCC. Totally 300 oral sumucosa fibrosis symptoms patients were chosen from various hospitals from southern india by advent screening like Toluidine blue staining and brush biopsy. Finally 103 severely affected OSCC patients were selected. 5ml of peripheral blood samples were taken from affected patients. Equal numbers of normal healthy control subjects were chosen after signing a consent form. Cytogenetic studies were performed by using Giemsa-banding technique and finally the results were ensured by spectral karyotyping (SKY) technique. In the present investigation, major CA like deletion, translocation, inversion and mosaic were identified in experimental subjects. Results showed frequent CA in chromosomes 3p, 3q, 8p, 7p, 9p, 11q, 17p, 19q and X. In comparison with experimental subjects, the control subjects exhibited very low levels of major CA (P&amp;lt;0.05). In the present study, the high frequency of centromeric rearrangements indicates a potential role for mitotic irregularities associated with the centromere in OSCC tumorigenesis, interesting chromosomal regions which may harbor susceptibility genes. Identification of chromosome alterations may be helpful in understanding the molecular basis of the disease in a better manner. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B45.

Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population

The transcription factor 7-like 2 gene (TCF7L2) rs7903146 T allele is constantly associated with Type 2 diabetes in various populations and ethnic groups. Nevertheless, this has not been observed in two studies involving Arab populations. The aim of the present study was to investigate the association between TCF7L2 rs7903146 in an Iranian population. Type 2 diabetes patients (N = 258) and normal healthy control subjects (N = 168) from the same area, were examined. The ARMS- PCR (Amplification Refractory Mutation System) technique, subsequently validated by direct sequencing, was used for genotyping. Allele and genotype frequencies were significantly different between patients and controls TT vs. CT + CC [p 0.0081 OR 3.4 95%CI (1.27-11.9)] and T vs. C allele [p 0.02 OR 1.4 95%CI (1.03-1.9)]. Our data thus confirm the association between the rs7903146 T allele and T2D in an Iranian population, contrary to previous reports in Arab populations. This can possibly be attributed to differences in ethnic background or the effects of environmental factors.

Platelet Serotonin Transporter Function and Heart Rate Variability in Patients with Panic Disorder

Many studies showed abnormal serotonin transporter (5-HTT) function and heart rate variability (HRV) in panic disorder patients. The present study investigated the relationship between HRV power spectral analysis findings and platelet serotonin uptake in panic disorder patients. Short-term HRV over 5 min and platelet serotonin transporter uptake parameters (Vmax and Km) were measured both in 45 patients with panic disorder and in 30 age-matched normal healthy control subjects. Low frequency power (LF) normalized unit (nu) and LF/high frequency power (HF) were significantly higher, whereas HF and HF nu were lower in the patient group than in the control group. Vmax and Km were all significantly lower (i.e., reflects decreased 5-HTT function) in patients with panic disorder than in normal controls. In the patient group, Km was negatively correlated with LF/HF and LF nu whereas no such correlations between them were found in the control group. By multivariate analysis based on multiple hierarchical linear regression, a low Km independently predicted an increased LF nu even after controlling for age, sex, and body mass index in the patient group. These results suggest that impaired 5-HTT function is closely related to dysregulation of autonomic nervous system in panic disorder.

Corticospinal tract injury in patients with diffuse axonal injury: A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can be useful in detecting corticospinal tract (CST) injury at the subcortical white matter level. In the current study, we attempted to investigate the incidence and distribution of CST injury in patients with diffuse axonal injury (DAI), using DTI. Fourteen patients who showed motor weakness without any specific lesion along the CST pathway on conventional brain MRI, and twelve age-matched, normal healthy control subjects were recruited. DTI was performed using 1.5 T with a synergy-L Sensitivity Encoding (SENSE) head coil. Fractional anisotropy was measured using the region of interest method. A CST injury was defined as the FA value of a certain area being decreased two standard deviations below that of normal controls. All 14 patients had more than one lesion at the CST injury, and the mean number of CST injuries was 3.6 (range: 2-7). The CSTs were involved at the following locations: the pons (61%), the cerebral peduncle (39%), the corona radiata (21%), the medulla (14%), and the posterior limb (11%). The pons was the most prevalent area of CST injury in patients with weakness caused by DAI at the subcortical level. We found that DTI is a useful technique for detecting a DAI of the CST at the subcortical level.

Splice Variant JAK2 Transcript Deleting Exon 14 in Patients with Chronic Myeloproliferative Neoplasms.

Abstract 2161Poster Board II-138The JAK2 V617F mutation in exon 14 is the most common mutation in chronic myeloproliferative neoplasms (MPNs). While other point mutations and small deletions and insertions in exons 12, 13, and 14 have been reported in the JAK2 JH2 domain, deletion of the entire exon 14 is rarely detected in patients with MPNs. In a series of >10,000 samples from patients with suspected MPNs tested for JAK2 mutations by direct sequencing of mRNA, we detected a complete exon 14 (88 bp) deletion mutation in <1% of those with JAK2 mutation. This appears to be an alternative splicing mutation, not detectable with DNA-based testing, leading to a frameshift deletion in the JAK2 JH2 domain and the expression of a truncated protein (S593I fsX8). Although this mutation was present at detectable levels (>15% of total JAK2 transcript) in a small proportion of MPN cases, we decided to investigate the possibility it may be expressed at low levels (<15% of JAK2 transcript) in patients with MPNs. Using a sensitive reverse transcription-PCR—based fluorescent fragment analysis method to quantify the percentage of truncated (minus exon 14) JAK2 mRNA as compared to wild-type, we tested 61 patients with confirmed MPN; 183 patients with suspected MPNs (93 V617F positive, 90 V617F negative); and 46 healthy normal control subjects. The wild-type PCR product was 273 bp, while the exon 14 splice mutant displayed a 185-bp peak. All samples with a splicing mutant expression to wild-type ratio >15% were confirmed by direct sequencing. The JAK2 exon 14 splice mutation was detected at low levels in 9 of the 61 MPN patients (15%), accounting for 3.96% to 33.85% (mean=12.04%) of JAK2 transcript in these individuals. Among the 183 suspected MPN patients, the exon 14 splice variant was detected in 20 of the 93 (21.5%) with V617F (mean expression level relative to wild type=5.41%, range=2.13%-26.22%) and 31 of the 90 (34.4%) without V617F (mean expression=3.88%; range=2.08%-12.22%). All 46 normal individuals were considered negative for the alternatively spliced transcript. In conclusion, the expression of an alternatively spliced JAK2 mRNA with deletion of exon 14, leading to a truncated JAK2 protein, is a common abnormality in patients with MPNs. This alternatively spliced transcript is more common in MPN patients without V617F mutation and might contribute to the leukemogenesis in these patients. Low levels of JAK2 exon 14 splice mutation may also contribute to the effects of the V617F mutation in patients with MPNs. However, this mutation is missed if DNA and not the RNA is used for testing for JAK2 mutations. Disclosures:No relevant conflicts of interest to declare.

Sulfasalazine and Mesalamine Modulate Beryllium-Specific Lymphocyte Proliferation and Inflammatory Cytokine Production

Occupational exposure to beryllium (Be) results in Be sensitization (BeS) that can progress to pulmonary granulomatous inflammation associated with chronic Be disease (CBD). Be-specific lymphocytes are present in the blood of patients with BeS and in the blood and lungs of patients with CBD. Sulfasalazine and its active metabolite, mesalamine, are clinically used to ameliorate chronic inflammation associated with inflammatory bowel disease. We tested whether sulfasalazine or mesalamine could decrease Be-stimulated peripheral blood mononuclear cell (PBMC) proliferation in subjects with CBD and BeS and Be-induced cytokine production in CBD bronchoalveolar lavage (BAL) cells. CBD (n = 25), BeS (n = 12) and healthy normal control (n = 6) subjects were enrolled and ex vivo proliferation and cytokine production were assessed in the presence of Be and sulfasalazine or mesalamine. Be-stimulated PBMC proliferation was inhibited by treatment with either sulfasalazine or mesalamine. Be-stimulated CBD BAL cell IFN-γ and TNF-α cytokine production was decreased by treatment with sulfasalazine or mesalamine. Our data suggest that both sulfasalazine and mesalamine interfere with Be-stimulated PBMC proliferation in CBD and BeS and dampens Be-stimulated CBD BAL cell proinflammatory cytokine production. These studies demonstrate that sulfasalazine and mesalamine can disrupt inflammatory pathways critical to the pathogenesis of chronic granulomatous inflammation in CBD, and may serve as novel therapy for human granulomatous lung diseases.

Breast Cancer Risk Associated With Polymorphisms of IL-1RN and IL-4 Gene in Indian Women

Interleukins and cytokines are important regulator of the aetio-pathogenesis of the majority of cancers. Mechanistic role of IL-1RN and IL-4, particularly in breast carcinogenesis, is well documented. However, the role of polymorphisms of IL-1RN and IL-4 combinations associated with risk of breast cancer is not reported. The IL-1RN and IL-4 gene polymorphisms were genotyped with VNTR-PCR in 100 patients (benign tumor n = 32 and breast cancer n = 68) and 200 normal healthy control subjects with normal mammogram. Genotype distribution and allelic frequencies between patients and controls were compared and odds ratios (OR) with 95% confidence intervals (CI) were calculated using SPSS software (version 12.0). There were no significant differences in the genotype distributions of both IL-1RN and IL-4 polymorphisms between cases and controls. Similarly, subgroup analysis showed that there is no significant association for pre- and postmenopausal women. However, BB genotype of IL-1RN significantly differs among benign and malignant stages of breast cancer. IL-1RN and IL-4 polymorphisms alone or in combination are not associated with risk of breast cancer in Indian patients. The association of IL-1RN with malignant stages may indicate its possible role in progression of breast cancer. Further studies in other population are needed to confirm our findings and to elucidate the role of IL-1RN in progression of breast cancer.

A study of apolipoproteins E and A-I in cutaneous amyloids

Background Apolipoprotein E (apoE) is present in a variety of biochemically different amyloid deposits, including Alzheimer's disease, systemic amyloidosis and primary cutaneous amyloidosis (PCA). Among the three closely related alleleic forms of apoE, the ε4 allele is linked to Alzheimer's disease. Apolipoprotein A‐I (apoA‐I), another apolipoprotein, is also found in senile plaques of Alzheimer's disease and in amyloid of aortic atherosclerotic plaques. Furthermore, apoA‐I has recently been found to be associated with hereditary cutaneous and cardiac amyloidosis. Objectives To determine whether the apoE ε4 allele is associated with increased risk of PCA and whether apoE and apoA‐I are present in PCA and common secondary cutaneous amyloidosis (SCA) (i.e. basal cell carcinoma, Bowen's disease and seborrhoeic keratosis). Methods We examined the apoE genotype in 57 Chinese patients with PCA and 58 normal healthy control subjects of similar age. In addition, immunohistochemical staining was performed to determine the localization of apoE and apoA‐I in skin tissues from 15 patients with SCA and 15 with PCA. Results The frequency of the ε4 allele in the PCA group was not significantly higher than that in the control group (8·8% vs. 6·9%, P > 0·05). ApoE was present in amyloid deposits in both PCA and SCA, but apoA‐I was not detected in these cutaneous amyloid deposits. Conclusions ApoE is also a component of amyloid deposits in SCA. Although the genetic susceptibility of certain apoE isoforms may not be a crucial factor in the development of PCA and, although apoA‐I is not associated with amyloid deposits of PCA and SCA, the role of apolipoproteins in amyloidogenesis deserves further scrutiny.

Modulation of Lymphocyte Proliferation by Antioxidants in Chronic Beryllium Disease

Occupational exposure to beryllium (Be) can result in chronic granulomatous inflammation characterized by the presence of Be-specific CD4+ T cells. Studies show that oxidative stress plays a role in the pathogenesis of chronic inflammatory disorders. We hypothesized that Be-induced oxidative stress modulates the proliferation of Be-specific CD4+ T cells. Thirty-three subjects with chronic beryllium disease (CBD), 15 subjects with beryllium sensitization, and 28 healthy normal control subjects were consecutively enrolled from the Occupational and Environmental Health Clinic of the National Jewish Medical and Research Center. All studies were performed with Ficoll-Hypaque-isolated peripheral blood mononuclear cells from subsets of the study subjects. Decreased intracellular levels of the thiol antioxidants, glutathione and cysteine, were observed in peripheral blood mononuclear cells from subjects with beryllium sensitization and CBD, as compared with healthy control subjects. Beryllium stimulation decreased intracellular thiol antioxidants by more than 40%, accompanied by increased reactive oxygen species levels and the proliferation of Be-specific blood CD4+ T cells from subjects with CBD. Be-induced T-cell proliferation was inhibited by treatment with the thiol antioxidant N-acetylcysteine or the catalytic antioxidant manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP). MnTBAP treatment also inhibited T-cell proliferation in response to the unrelated, MHC class II-restricted antigen tetanus toxoid. Treatment of CBD blood lymphocytes, but not antigen-presenting cells, with MnTBAP decreased Be-induced T-cell proliferation by more than 40%. Beryllium can mediate a thiol imbalance leading to oxidative stress that may modulate the proliferation and clonal expansion of Be-specific blood CD4+ T cells. These data suggest that Be-induced oxidative stress plays a role in the pathogenesis of granulomatous inflammation in CBD.

HLA-Class II Alleles in Egyptian Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is linked to environmental, dietary, and life style factors. Its incidence and distribution vary widely among ethnic groups, sex, and geographic regions. HBV and HCV Infection, liver cirrhosis, male gender, and old age are important risk factors of HCC. Variability in outcome following exposure, and the clustering of HCC within families raise the possibility that genetic factors are also involved in susceptibility to HCC. The Major Histocompatibility Complex (MHC) plays a key role in anti-virus and tumor defense. HLA polymorphism is implicated in conferring genetic susceptibility to a large number of immune-mediated diseases, including some cancers. The association between HLA class II antigen and HCC in different ethnic populations that has been reported is controversial. Therefore, the aim of this work was to study the association between HLA class II-DRB1 and DQB1 polymorphism and HCC in Egyptian patients and to investigate their role as risk factors for the development of HCC. Methods: HLA-class II (DRB1 and DQB1) typing was done by SSP for 100 subjects; 50 patients suffering from HCC (45 males and 5 females) with age range 40–64 years (51.16 years (y) ± 6.16); and 50 normal healthy control subjects. Results: 1. A significantly increased frequency of DRB1*04, and DQB1 *02 in HCC patients versus control group (p = 0.016, and 0.032, respectively) was found; 2. A significantly decreased frequency of DQB1*06 (p = 0.032) was found; 3. A significantly increased frequency of DRB1*07 (odds ratio (OR) = 4.929) was found; and 4. A significantly decreased frequency of DRB1*15 (OR = 0.316) was seen. In conclusion, while some alleles are significantly associated with HCC (DRB1*04, DQB1*02) and others are not associated (DQB1*06); therefore, it can be concluded that the DRB1*04 and DQB1*02 alleles might be risk factors for the occurrence of HCC (OR = 4.373 and 3.807, respectively), and DQB1*06 may be a protective allele (OR = 0.259).

Polymorphisms of Human Leukocyte Antigen Genes in Korean Children with Kawasaki Disease

BackgroundKawasaki disease is a leading cause of acquired heart disease in children. The prevalence rate varies in different ethnic groups. Recently, with the clinical application of molecular genetic technology, human leukocyte antigen (HLA) polymorphisms associated with several diseases have been identified by DNA analysis. This study aimed to assess the association of HLA alleles with susceptibility and complications of Kawasaki disease in Korean children.MethodsIn this study, DNA was extracted from 74 children with a diagnosis of Kawasaki disease. The polymorphisms of the HLA-A, -B, -C, and -DRB1 alleles of patients with Kawasaki disease were determined by polymerase chain reaction (PCR)–amplification refractory mutation system (ARMS) and PCR–sequence-specific primer (SSP) analysis. The polymorphisms identified were compared with those of 159 normal healthy control subjects.ResultsThere was a significant increase in the frequencies of the HLA-B35, -B75, and -Cw09 alleles in patients with Kawasaki disease compared with the healthy control group. There was no increase in the frequency of HLA-DRB1 alleles among the Kawasaki disease patients compared with a healthy control group. When the patients with Kawasaki disease were divided into two subgroups, with or without coronary complications, the Kawasaki disease patients with coronary complications showed a significantly increased frequency of the HLA-DRB1*11 allele compared with the healthy control group and increased frequency of HLA-DRB1*09 in a comparison of the subgroups.ConclusionsThis study suggests that polymorphisms in some alleles of B and C in HLA class I genes are associated with Kawasaki disease in Korean children.

N200 latency and P300 amplitude in depressed mood post-traumatic brain injury patients

In order to examine the independent and combined effects of depressive symptoms and traumatic brain injury on event-related potential (ERP) components, we classified traumatic brain injury (TBI) patients as depressed and non-depressed mood according to their scores on the Zung Self-rating Depression Scale (SDS). Non-depressed mood post-traumatic brain injury patients (NondepTBI, n = 9), depressed mood post-traumatic brain injury patients (DepTBI, n = 26), and normal healthy control subjects (HC, n = 10) were assessed for N100, N200, and P300 latencies and amplitudes by the auditory “oddball paradigm”. DepTBI subjects had significantly prolonged N200 latency and low P300 amplitude compared with the NondepTBI and HC groups. A longer P300 latency in the NondepTBI and DepTBI than in the HC groups was found. A prolongation of N200 latency accompanied by low P300 amplitude may be a characteristic of post-traumatic brain injury patients with depressed mood. Prolonged P300 latency may be more closely associated with TBI than with depression, as it was significantly greater in both the DepTBI and NondepTBI, than in the HC group.