Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Measures of Explained Variation for a Regression Model Used in Survival Analysis

This paper describes a measure of explained variation (MEV) of survival times for a given regression model used in survival analysis. It quantifies the predictive power of a set of prognostic factors in the model, and therefore provides useful information for more precise prediction of patient prognosis, and for designing randomized clinical trials with the capability of determining treatment effects. The MEV defined in this article is asymptotically derived from the squared product-moment correlation; it can be interpreted as an adaptation of the multiple correlation coefficient for the normal linear model to the survival time regression model. Monte-Carlo simulations are performed to investigate the statistical behavior of the proposed MEV. The MEV is applied to estimate the predictive power of several sets of prognostic factors for gastric cancer in Japan using data from a large clinical trial.     

The significance of CA-50, SLX and ST-439 in lung cancer]

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).     

Two cases of acute disseminated encephalomyelitis with lesions in the thalamus or basal ganglia on MRI]

Lesions in the thalamus or basal ganglia have rarely been reported in acute disseminated encephalomyelitis (ADEM). We experienced 2 cases of ADEM, in which MRI showed lesions in the thalamus or basal ganglia. Case 1, a 4-year-old boy, had gait disturbance, hyperesthesia and hyperreflexia. MRI (T2 weighted image) showed multiple high intensity areas in the right frontal lobe, bilateral parietal lobes and bilateral thalami. Case 2, a 4-year-old girl, complained of gait disturbance following a febrile episode, and displayed hyperreflexia. Several days later, she had visual disturbance of the left eye. MRI (T2 weighted image) revealed multiple high intensity areas in the dentate nucleus of left cerebellum, left occipital lobe, bilateral caudate nuclei, and the anterior part of bilateral lenticular nuclei. In both cases, CT could not demonstrate these lesions. Both of them were treated with corticosteroid and recovered rapidly. They had no recurrence. MRI is useful in diagnosis and follow-up of ADEM and may reveal lesions other than cerebral or cerebellar white matters.     

Phenytoin desensitization monitored by antigen specific T cell response using carboxyfluorescein succinimidyl ester dilution assay

We evaluated drug-specific T cell responses in a patient with refractory partial seizures and paroxysmal kinesigenic choreoathetosis successfully treated with clinical desensitization to phenytoin. Drug-induced lymphocyte transformation test before desensitization was negative with a stimulation index of 130%. The frequencies and cytokine-producing phenotypes of phenytoin-specific T cells were examined simultaneously by using a carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Before desensitization, the proportion of CFSElow CD4+ cells in whole CD4+ was 3.09%; 13.6% of CFSElow CD4+ cells were stained with anti-interferon gamma antibody. After desensitization, phenytoin-specific CFSElow CD4+ cells decreased to background level. These results indicate that CFSE dilution assay will be useful for the diagnosis and monitoring of drug hypersensitivity.     

Proto-oncogene expression and nuclear factor specifically bound to c-myc gene in peripheral blood mononuclear cells from progressive systemic sclerosis patients as the indicator of clinical activity

In the present study, we examined the expression of various protooncogenes and the specific binding of nuclear factor to c-myc gene in peripheral blood mononuclear cells (PBMC) from progressive systemic sclerosis (PSS) patients. We demonstrated first amplified expression of c-myc and c-myb gene and the existence of a nuclear protein specifically bound to 5'-non-coding fragment of c-myc gene. We then found a positive correlation between the degree of expression and/or affinity for the c-myc gene fragment of the nuclear protein and clinical disease activity. The amount of the factor was significantly reduced along with or prior to the amelioration of clinical symptoms and laboratory abnormalities with treatment. The significance of c-myc and c-myb proto-oncogene expression and nuclear factor specifically bound to c-myc gene is discussed.     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.