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.     

A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing.

Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.     

Prostate Risk Index (PRIX) as a New Method of Risk Classification for Clinically Localized Prostate Cancer

PURPOSE: The aim of this study is (1) to develop a new method of risk classification for clinically localized prostate cancer; (2) to examine it in terms of compatibility with existing data such as nomograms; and (3) to compare it with existing risk-grouping methods. MATERIAL AND METHODS: The new grading system introduced here consists of three factors. The first is a prostate-specific antigen (PSA) of 4.1-10.0 ng/ml (score 0), 10.1-20.0 ng/ml (score 1), and >20.0 ng/ml (score 2). The second is a Gleason score (GS) of 6 (score 0), 7 (score 1), and 8-10 (score 2). The third is T classifications (UICC 2002) of T1c-T2a (score 0), T2b-T2c (score 1), and T3a (score 2). The sum of the three scores was named Prostate Risk Index (PRIX). Then, the compatibility of PRIX with the Partin Table, Kattan Nomogram, and Roach's formula was examined. At the same time, PRIX was compared with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. RESULTS: PRIX 0 corresponded to 1-2% of pathologic lymph node involvement (pLN+) according to the Partin Table; PRIX 1 to 3-4%; PRIX 2 to 7-10%; PRIX 3 to 14-18%; PRIX 4 to 24-29%; PRIX 5 to 32-37%; and PRIX 6 to 42%. PRIX well separated the risks with relatively narrow ranges of probability, while D'Amico, NCCN, and Seattle classifications generally gave wide ranges especially for high-risk groups, both in the Partin Table and Kattan Nomogram. Roach's formula sometimes overestimated the risk compared to the Partin Table. CONCLUSION: PRIX fully corresponded to the Partin Table in terms of pLN+, and corresponded to the other nomograms better than any existing risk-grouping method. PRIX may thus function as a prognostic factor or contribute to patient selection in clinically localized prostate cancer.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)