Pulmonary tuberculosis in an HIV- and hepatitis C virus-coinfected kidney-pancreas transplant recipient: a case report

Tuberculosis (TB) is a serious infection in immunocompromised patients, such as solid organ transplant recipients and HIV-infected patients. The diagnosis and treatment in this population present several challenges because of the aspecific clinical manifestations, the difficulty in diagnosis, and the choice of the most appropriate therapeutic regimen. Therapeutic challenges arise from drug-related toxicities, interactions between immunosuppressive, antiretroviral, and antituberculous drugs. We present a case of primary TB infection that occurred 3 years after transplantation in a HIV-and hepatitis C virus-coinfected kidney-pancreas recipient. The infection was successfully treated with no hepatotoxicity or rejection with a non-rifampin-containing regimen.     

Graphene as a Buffer Layer for Silicon Carbide-on-Insulator Structures

We report an innovative technique for growing the silicon carbide-on-insulator (SiCOI) structure by utilizing polycrystalline single layer graphene (SLG) as a buffer layer. The epitaxial growth was carried out using a hot-mesh chemical vapor deposition (HM-CVD) technique. Cubic SiC (3C-SiC) thin film in (111) domain was realized at relatively low substrate temperature of 750 °C. 3C-SiC energy bandgap of 2.2 eV was confirmed. The Si-O absorption band observed in the grown film can be caused by the out-diffusion of the oxygen atom from SiO₂ substrate or oxygen doping during the cleaning process. Further experimental works by optimizing the cleaning process, growth parameters of the present growth method, or by using other growth methods, as well, are expected to realize a high quality SiCOI structure, thereby opening up the way for a breakthrough in the development of advanced ULSIs with multifunctionalities.     

Association between TNF-a and IL-1β genotypes vs Helicobacter pylori infection in Indonesia

AIM:To investigate the correlation between the Helicobacter pylori(H.pylori)infection and host genetic background of healthy populations in Indonesia.METHODS:In March 2007,epidemiological studies were undertaken on the general population of a city in Indonesia(Mataram,Lombok).The participants included 107 men and 187 women,whose ages ranged from6 to 74 years old,with an average age of 34.0(±14.4)(±SD).The H.pylori of subject by UBT method determination,and through the polymerase chain reaction with confronting two-pair primers(PCR-CTPP)method parsing the single nucleotide polymorphism of interleukin(IL)-8,IL-4,IL-1β,CD14,tumor necrosis factor(TNF-a)and tyrosine-protein phosphates non-receptor type 11(PTPN11)genotypes.The experimental data were analyzed by the statistical software SAS.RESULTS:The H.pylori infection rates in the healthy Indonesian population studied were 8.4%for men and12.8%for women;no obvious differences were noted for H.pylori infection rates by sex or age.TC genotypes of IL-4,TC and CC genotypes of TNF-a,and GA genotypes of PTPN11,were higher in frequency.Both CC and TC genotype of TNF-a T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of(OR=1.99;95%CI:0.67-5.89)and(OR=1.66;95%CI:0.73-3.76),respectively.C allele of IL-1βT-31C gene locus was at a higher risk(OR=1.11;95%CI:0.70-1.73)of H.pylori infection,but no statistical significance was found in our study.CONCLUSION:We reveal that the association between the TNF-a and IL-1βgenotypes may be the susceptibility of H.pylori in the studied population.     

Familial clear cell renal cell carcinoma (FCRC): clinical features and mutation analysis of the VHL, MET, and CUL2 candidate genes

Familial renal cell carcinoma (RCC) is genetically heterogeneous. Genetic predisposition to clear cell RCC (CCRCC) is a major feature of von Hippel-Lindau (VHL) disease (MIM 193300) and has rarely been associated with chromosome 3 translocations. In addition, familial papillary (non-clear cell) RCC may result from germline mutations in the MET proto-oncogene (MIM 164860). However, rare kindreds with familial CCRCC (FCRC) not linked to the VHL tumour suppressor gene have been described suggesting that further familial RCC susceptibility genes exist. To investigate the genetic epidemiology of FCRC, we undertook a clinical and molecular study of FCRC in nine kindreds with two or more cases of CCRCC in first degree relatives. FCRC was characterised by an earlier age at onset (mean 47.1 years, 52% of cases <50 years of age) than sporadic cases. These findings differ from the only previous report of two FCRC kindreds and have important implications for renal surveillance in FCRC. The molecular basis of CCRCC susceptibility was investigated in nine FCRC kindreds and seven isolated cases with features of possible genetic susceptibility to CCRCC (four bilateral CCRCC aged <50 years and three with unilateral CCRCC aged <30 years). No germline mutations were detected in the VHL or MET genes, suggesting that FCRC is not allelic with VHL disease or HPRC. As binding of the VHL gene product to the CUL2 protein is important for pVHL function, we then searched for germline CUL2 mutations. Although CUL2 polymorphisms were identified, no pathogenic mutations were detected. These findings further define the clinical features of FCRC and exclude a major role for mutations in VHL, MET, or CUL2 in this disorder.


Keywords: familial clear cell renal carcinoma; VHL; MET; CUL2     

18F-FLT PET does not discriminate between reactive and metastatic lymph nodes in primary head and neck cancer patients.

Repopulation of clonogenic tumor cells is inversely correlated with radiation treatment outcome in head and neck squamous cell carcinomas. A functional imaging tool to assess the proliferative activity of tumors could improve patient selection for treatment modifications and could be used for evaluation of early treatment response. The PET tracer 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) can image tumor cell proliferation before and during radiotherapy, and it may provide biologic tumor information useful in radiotherapy planning. In the present study, the value of (18)F-FLT PET in determining the lymph node status in squamous cell carcinoma of the head and neck was assessed, with pathology as the gold standard. METHODS: Ten patients with newly diagnosed stage II-IV squamous cell carcinoma of the head and neck underwent (18)F-FLT PET before surgical tumor resection with lymph node dissection. Emission (18)F-FLT PET and CT images of the head and neck were recorded and fused, and standardized uptake values (SUVs) were calculated. From all 18 (18)F-FLT PET-positive lymph node levels and from 8 (18)F-FLT PET-negative controls, paraffin-embedded lymph node sections were stained and analyzed for the endogenous proliferation marker Ki-67 and for the preoperatively administered proliferation marker iododeoxyuridine. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for (18)F-FLT PET. RESULTS: Primary tumor sites were oral cavity (n=7), larynx (n=2), and maxillary sinus (n=1). Nine of the 10 patients examined had (18)F-FLT PET-positive lymph nodes (SUV(mean): median, 1.2; range, 0.8-2.9), but only 3 of these patients had histologically proven metastases. All metastatic lymph nodes showed Ki-67 and iododeoxyuridine staining in tumor cells. In the remaining 7 patients, there was abundant Ki-67 and iododeoxyuridine staining of B-lymphocytes in germinal centers in PET-positive lymph nodes, explaining the high rate of false-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value of (18)F-FLT PET were 100%, 16.7%, 37.5%, and 100%, respectively. CONCLUSION: In head and neck cancer patients, (18)F-FLT PET showed uptake in metastatic as well as in nonmetastatic reactive lymph nodes, the latter due to reactive B-lymphocyte proliferation. Because of the low specificity, (18)F-FLT PET is not suitable for assessment of pretreatment lymph node status. This observation may also negatively influence the utility of (18)F-FLT PET for early treatment response evaluation of small metastatic nodes.     

Genetic and epigenetic analysis of von Hippel-Lindau (VHL) gene alterations and relationship with clinical variables in sporadic renal cancer

Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumor suppressor gene are common in sporadic conventional renal cell carcinoma (cRCC). Further insight into the clinical significance of these changes may lead to increased biological understanding and identification of subgroups of patients differing prognostically or who may benefit from specific targeted treatments. We have comprehensively examined the VHL status in tissue samples from 115 patients undergoing nephrectomy, including 96 with sporadic cRCC. In patients with cRCC, loss of heterozygosity was found in 78.4%, mutation in 71%, and promoter methylation in 20.4% of samples. Multiplex ligation-dependent probe amplification identified intragenic copy number changes in several samples including two which were otherwise thought to be VHL-noninvolved. Overall, evidence of biallelic inactivation was found in 74.2% of patients with cRCC. Many of the mutations were novel and approximately two-thirds were potentially truncating. Examination of these and other published findings confirmed mutation hotspots affecting codons 117 and 164, and revealed a common region of mutation in codons 60 to 78. Gender-specific differences in methylation and mutation were seen, although not quite achieving statistical significance (P = 0.068 and 0.11), and a possible association between methylation and polymorphism was identified. No significant differences were seen between VHL subgroups with regard to clinicopathologic features including stage, grade, tumor size, cancer-free and overall survival, with the exception of a significant association between loss of heterozygosity and grade, although a possible trend for survival differences based on mutation location was apparent.     

Allergic reactivity of bambara groundnut (Vigna subterranea) proteins

All food proteins have a potential to be allergic for some people. Nuts and legumes are some of the main food allergens, which are consumed by large numbers of people. Several researches had been reported about the allergenicity of peanut, soybean, tree nuts, but not of the bambara groundnut (Vigna subterranea), one of the legumes consumed largely by the population in Indonesia. The reported study aimed to isolate bambara groundnut protein and to analyze its allergic reactivity. The protein isolate reactivity was tested by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting, involving six peanut and soybean allergic human sera. ELISA analysis showed that the bambara groundnut protein had allergenic proteins. Furthermore, immunoblotting analysis revealed that serum IgE from the donors could bind to individual allergens to various degrees, demonstrating the specificity of IgE reactivity. In conclusion, bambara groundnut contained allergenic proteins, and the research demonstrated a cross-reactivity to peanut and soybean.