Comparative Results of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus Assays for Detection of Tuberculosis Infection in Clinical Samples.

The QuantiFERON-TB Gold plus (QFT-Plus) assay, an interferon gamma (IFN-γ) release assay (IGRA), was recently introduced as the next version of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay for diagnosing latent tuberculosis (TB). Whereas the QFT-GIT assay uses only one TB tube that induces a cell-mediated immune (CMI) response of CD4+ T cells, the QFT-Plus has an additional TB antigen 2 tube (TB2) for the CMI response of CD8+ T and CD4+ T cells, in addition to a TB antigen 1 (TB1) tube for the CMI response of CD4+ T cells only. We compared the results of the QFT-Plus and QFT-GIT assays as routine clinical tests for diagnosing TB. Samples from 220 patients referred for routine IGRA in various clinical departments were used. Correlations between IFN-γ levels in the QFT-GIT and QFT-Plus assays were strong and showed good agreement (kappa value = 0.69). Seven cases with positive QFT-GIT assay results and negative QFT-Plus assay results showed IFN-γ values near the cutoff value. However, 10 cases with active TB, recent TB, or immune problems showed discordance with the positive results only in the TB2 tube in QFT-Plus, unlike the negative results in TB1 and TB tubes. In these cases, IFN-γ levels in the TB2 tube were significantly higher than those in other tubes. This is the first study to compare these assays as routine IGRAs in the clinical setting. The QFT-Plus assay showed good agreement with the QFT-GIT assay and is presumably advantageous for patients with active TB, recent TB, and specific immune conditions involving CD8+ T-cell responses.

Sesame cake extract attenuates dextran sulfate sodium-induced colitis through inhibition of oxidative stress in mice.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease occurring in the gut causing chronic diarrhea and abdominal pain with severe complications. Sesame cake is a by-product of sesame oil production, possessing various beneficial properties; however, little is known about the effect of sesame cake extract (SCE) against IBD. The aim of this study was to investigate the protective effect of SCE against dextran sulfate sodium (DSS)-induced colitis in mice. Administration of SCE was first performed at 7 days before treating mice with 2.5% DSS to induce colitis for 7 days. SCE pretreatment improved symptoms of DSS-induced colitis. In addition, SCE ameliorated histopathological damages of the mucus layer in colon tissues and decreased pro-inflammatory cytokines in colitis-induced mice. SCE also suppressed apoptosis and oxidative stress in colitis-induced colon tissues. Together, these findings suggest that SCE could be potential nutraceuticals for treating colitis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01367-1.

Selective addition of CXCR3(+) CCR4(-) CD4(+) Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro.

Increasing importance is being given to the stimulation of Th1 response in cancer immunotherapy because its presence can shift the direction of adaptive immune responses toward protective immunity. Based on chemokine receptor expression, CXCR3(+) CCR4(-) CD4(+) T cells as Th1-type cells were investigated its capacity in monocyte-derived dendritic cell (DC) maturation and polarization, and induction of antigen specific cytotoxic T lymphocytes (CTL) in vitro. The levels of IL-4, IL-5 and IL-10 were decreased to the basal level compared with high production of IFN-gamma, TNF-alpha, and IL-2 in CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4(+) or CXCR3(+) CCR4-CD4(+) T cells with DC (CD4(+/) DC or CXCR3(+) CD4(+/) DC, respectively) particularly up-regulated IL-12 and CD80 expression compared with DC matured with TNF-a and LPS (mDC). Although there was no significant difference between the effects of the CXCR3(+) CCR4(-) CD4(+) and CD4(+) T cells on DC phenotype expression, CXCR3(+) CD4(+/) DC in CTL culture were able to expand number of CD8(+) T cells and increased frequencies of IFN-gamma secreting cells and overall cytolytic activity against tumor antigen WT-1. These results demonstrated that the selective addition of CXCR3(+) CCR4(-) CD4(+) T cells to CTL cultures could enhance the induction of CTLs by DC in vitro, and implicated on a novel strategy for adoptive T cell therapy.

A membrane-bound form of IL-4 enhances proliferation and antigen presentation of CD40-activated human B cells.

CD40-activated B (CD40-B) cells might be an attractive source of autologous antigen-presenting cells (APCs) for immunotherapy due to the ability to obtain them from peripheral blood and expand them in vitro. However, soluble IL-4 (sIL-4) in B-cell culture may not represent the "immunological synapse" between B and CD4+ T cells. In this study, the K562 cell line, which expresses CD40L and membrane-bound IL-4 (mbIL-4), could induce higher B-cell proliferation and antigen-presenting surface molecules, including adhesion, costimulatory and HLA molecules, compared with sIL-4. The differentiation to plasmablasts was decreased in CD40-B cells treated with mbIL-4 (CD40-B/mbIL-4) based on flow cytometry analysis. Furthermore, CD40-B/mbIL-4 cells were as potent as mature dendritic cells in the allogeneic lymphocyte reaction and the ability to generate cytotoxic T lymphocytes specific for cytomegalovirus pp65 antigen in vitro. Our results suggest that mbIL-4 could be used to generate CD40-B cells as potent APCs for cellular vaccines and adoptive immunotherapy.

A nursing home telehealth system: keeping residents connected.

Live video and detailed images of nursing home residents can be transmitted in real time via the Internet. This telehealth system allows residents and long-term care health professionals to connect with experts not available on-site. Electronic stethoscope, otoscope, dermascope, dentalscope, and electrocardiogram are available for use via the Internet. Impediments to implementing telehealth systems in long-term care include costs and the lack of reimbursement for telehealth services. Reimbursement for telemedicine in nursing homes is limited by originating site, current procedural terminology codes, and facility location.

Differential parental transmission of markers in BCL3 among Korean cleft case-parent trios.

OBJECTIVES: Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of approximately 1 in 700 live births. The B-Cell Leukemia/lymphoma 3 (BCL3) gene has been suggested as a candidate gene for CL/P based on association and linkage studies in some populations. This study tests for an association between markers in BCL3 and isolated, non-syndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. METHODS: Forty case-parent trios were genotyped for two single nucleotide polymorphisms (SNPs) in the BCL3 gene. We performed a transmission disequilibrium test (TDT) on individual SNPs, and the FAMHAP package was used to estimate haplotype frequencies and to test for excess transmission of multi-SNP haplotypes. RESULTS: The odds ratio for transmission of the minor allele, OR (transmission), was significant for SNP rs8100239 (OR=3.50, p=0.004) and rs2965169 (OR=2.08, p=0.027) when parent-of-origin was not considered. Parent-specific TDT revealed that SNP rs8100239 showed excess maternal transmission. Analysis of haplotypes of rs2965169 and rs8100239 also suggested excess maternal transmission. CONCLUSIONS: BCL3 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission.

White blood cell count and risk for all-cause, cardiovascular, and cancer mortality in a cohort of Koreans.

The authors conducted a 10-year prospective cohort study of mortality in relation to white blood cell counts of 437,454 Koreans, aged 40-95 years, who received health insurance from the National Health Insurance Corporation and were medically evaluated in 1993 or 1995, with white blood cell measurement. The main outcome measures were mortality from all causes, all cancers, and all atherosclerotic cardiovascular diseases (ASCVD). Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards models with adjustment for age and potential confounders. During follow-up, 48,757 deaths occurred, with 15,507 deaths from cancer and 11,676 from ASCVD. For men and women, white blood cell count was associated with all-cause mortality and ASCVD mortality but not with cancer mortality. In healthy nonsmokers, a graded association between a higher white blood cell count and a higher risk of ASCVD was observed in men (highest vs. lowest quintile: hazard ratio = 2.10, 95% confidence interval: 1.50, 2.94) and in women (hazard ratio = 1.35, 95% confidence interval: 1.17, 1.56). In healthy smokers, a graded association between a higher white blood cell count and a higher risk of ASCVD was also observed in men (highest vs. lowest quintile: hazard ratio = 1.46, 95% confidence interval: 1.25, 1.72). These findings indicate that the white blood cell count is an independent risk factor for all-cause mortality and for ASCVD mortality.

Major gene evidence after MTHFR-segregation analysis of serum homocysteine in families of patients undergoing coronary arteriography.

Elevated levels of homocysteine is a risk factor for coronary artery disease. Polymorphic alleles in the MTHFR genes that cause recessively inherited increased homocysteine level can explain only a small proportion of the observed variation in homocysteine level. To investigate additional genetic influences, we examined environmental, familial, and genetic influences on serum homocysteine levels in 661 family members of 112 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine if an unobserved Mendelian major gene could explain the familial homocysteine distribution. Adjustments for age, lifestyle (smoking and alcohol consumption), serum folate and vitamin B12, and the measured genotype effect of the MTHFR C677T mutation was carried out separately for males and females using multiple regression models for homocysteine, before and after log-transformation prior to this segregation analysis. After excluding the effects of mutations in the MTHFR genes, we found evidence of a major gene acting in a co-dominant manner. Estimated mean homocysteine levels for the three putative genotypes (LL, LH, and HH) were 8.0, 10.1, and 15.9 micro mol/l, respectively, with relative frequencies of 56.8%, 37.2%, and 6%, respectively. Our analysis suggested the presence of a co-dominantly expressed major gene, in addition to the effects of the MTHFR C677T mutation. The results of this study also indicated that multifactorial inheritance was supported more strongly than Mendelian inheritance alone. Our findings may have implications for attempts to identify new homocysteine susceptible genes.