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 of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer]

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.     

The role of gallium 67 imaging in non-Hodgkin's lymphoma of the gastrointestinal tract

To evaluate the clinical usefulness of gallium 67 imaging in the detection of gastrointestinal (GI) non-Hodgkin's lymphoma (NHL) and in the assessment of the therapeutic effects, images were reviewed in 24 cases (25 lesions: stomach, 20; ileum, 2; and terminal ileum and/or cecum, 3) and were compared using barium studies and, in 16 cases, computerized tomography (CT). In all, 23 (92.0%) of the 25 lesions were detected by⁶⁷Ga citrate imaging, the barium studies detected all 25, and CT detected 15 of 16 lesions (93.8%). The two lesions not identified by imaging and the one not found by CT were the smallest of all. In 2 (8.7%) of the 23 lesions positively identified by⁶⁷Ga-citrate imaging, both CT and imaging revealed the extent of the tumor more accurately than did the barium studies. In all but one of the patients, a close correlation existed between the imaging results and the therapeutic effects. These data suggest that⁶⁷Ga imaging is useful in conjunction with CT and barium studies for the detection of GI NHL and for the assessment of both the spatial extent of disease and the therapeutic effects, although a lack of⁶⁷Ga uptake after therapy does not always indicate a good therapeutic effect.     

Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic,renal, cerebral,and coronary circulation of dogs anesthetized with enflurane

Summary In beagle dogs anesthetized with enfluranenitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1–10 g/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3–10 g/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs.     

Loss of mammalian Sprouty2 leads to enteric neuronal hyperplasia and esophageal achalasia

We report here that loss of the Sprouty2 gene (also known as Spry2) in mice resulted in enteric nerve hyperplasia, which led to esophageal achalasia and intestinal pseudo-obstruction. Glial cell line-derived neurotrophic factor (GDNF) induced hyperactivation of ERK and Akt in enteric nerve cells. Anti-GDNF antibody administration corrected nerve hyperplasia in Sprouty2-deficient mice. We show Sprouty2 to be a negative regulator of GDNF for the neonatal development or survival of enteric nerve cells.     

Relation between benign prostatic hyperplasia and obesity and estrogen

PURPOSE: There have been few reports on correlations between resection volume of benign prostatic hyperplasia, body mass index (BMI) and estrogen. This study was undertaken to evaluate the correlations. METHOD: In this study, we considered 50 patients who had benign prostatic hyperplasia (BPH) and underwent suprapubic prostatectomy (SPP). Men with prostate cancer or prior prostate surgery were excluded. The relationship between prostate resection volume and BMI was examined. Additionally, patients were divided into two groups according to BMI: less than 25, and more than 25. The two groups were evaluated according to stained estrogen receptors. RESULTS: BMI was correlated positively with prostate volume (p < 0.01). However, positive rates of estrogen receptors showed no significant difference between the two groups. CONCLUSIONS: This was a study describing the relationship between BMI and prostate volume. Obesity has been hypothesized to be associated with BPH because of the endocrine changes in men that occur with age, including increased estrogen and decreased testosterone. Our findings suggest that estrogen may play a pathophysiologic role in benign prostatic hyperplasia. Further studies of large populations are needed to validate this assumption.     

Kampo medicines Rikkunshito and Hangeshashinto prevent cisplatin-induced intestinal mucosal injury in rats

Background/PurposeWe examined the effects and mechanisms of rikkunshito (RKT) and hangeshashinto (HST) on cisplatin-induced mucosal injuries in the rat small bowel.MethodsJuvenile rats were divided into 6 groups: sham control, cisplatin injection without kampo medicines, and cisplatin injection with oral administration of low and high doses of RKT (1000 mg/kg and 2000 mg/kg) and HST (500 mg/kg and 1000 mg/kg). Fecal condition, intestinal morphological changes, enterocyte proliferation, and enterocyte apoptosis were assessed.ResultsDiarrhea and atrophy of ileal villi observed in the cisplatin group were significantly improved in all kampo groups. Injury scores of the jejunum were significantly lower with RKT (2000 mg/kg) and HST (500 and 1000 mg/kg) than with cisplatin, and those of the ileum were significantly lower with HST (500 and 1000 mg/kg) than with cisplatin. Enterocyte proliferation of the jejunum was significantly increased with RKT (2000 mg/kg) and HST (500 mg/kg) compared with cisplatin, and those of the ileum were significantly increased in all kampo groups compared with the cisplatin group. Jejunal and ileal apoptosis following cisplatin administration was significantly inhibited by HST.ConclusionsRKT and HST prevented cisplatin-induced intestinal mucosal injury with increasing proliferation of intestinal epithelial cells. HST also attenuated cisplatin-induced crypt cell apoptosis.     

Molecular-pathological Analysis of a Patient with Three Synchronous Squamous Cell Carcinomas in the Aerodigestive Tract

A case of synchronous squamous cell carcinomas in the soft palate,larynx and esophagus is reported, along with findings of molecular-pathologicalanalysis. A biopsy sample from the aryngeal carcinoma revealedwell differentiated squamous cell carcinoma harboring two pointmutations at codons 144 and 148 of the p53 gene but not at codon299, and more than 50% of the cancer cells showed accumulationof p53 protein immunohistochemically. The esophageal tumor,which was moderately differentiated squamous cell carcinoma,showed immunoreactivity for p53 within the nuclei of 25–50%of cancer cells with a missense mutation at codon 299 but notat codon 144 or 148. This cancer also showed immunoreactivityfor transforming growth factor alpha. On the other hand, thepoorly differentiated squamous cell carcinoma in the soft palateshowed negative immunoreactivity for p53 and no point mutationin exons 5 to 8 of the gene. These results suggest that thethree synchronous squamous cell carcinomas arose as independentevents.     

Modulating the endoplasmic reticulum stress response with trans-4,5-dihydroxy-1,2-dithiane prevents chemically induced renal injury in vivo.

Agents that disrupt functions of the endoplasmic reticulum (ER) induce expression of ER stress-response genes including ER chaperones. Increased expression of the major ER chaperone, Grp78, protects cells, including renal epithelial cells, from chemically induced injury and death in vitro. In this study, we determined if pharmacological manipulation of the ER stress-response gene is an effective strategy to protect the kidney from chemical stress in vivo. Treatment with trans-4,5-dihydroxy-1,2-dithiane (DTTox), a novel inducer of ER stress proteins, stimulated a time-and dose-dependent increase in Grp78 expression in the kidney, but it did not cause detectable injury. Furthermore, prior treatment with DTTox protected the proximal tubular epithelium against a subsequent challenge with the nephrotoxicant S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine (TFEC). In contrast, activating a heat shock response did not have a protective effect. Prior treatment with DTTox did not reduce covalent binding of radiolabeled reactive metabolites of (35)S-TFEC to renal proteins, indicating that protection was not due to an effect on the metabolic activation of TFEC to the reactive metabolite(s) responsible for renal injury. Antisense grp78 expression in the renal epithelial cell line LLC-PK1 blocked the DTTox-induced Grp78 increase and ablated the protective effect against TFEC damage, indicating that the induction of grp78 expression and the ER stress response were critical for the protective effect of DTTox. These findings suggest that increased expression of Grp78 plays a major role in the protection of renal epithelial cells from reactive intermediate-induced chemical injury in vivo and that pharmacological manipulation is an effective strategy to prevent damage by some classes of nephrotoxicants.     

Small follicular lymphoma arising near the ampulla of vater

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.