Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.     

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population

AIM: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. METHODS: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. RESULTS: Of the 2,500 persons investigated, 2,263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. CONCLUSIONS: Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.     

Cytokine response to human liver ischemia-reperfusion injury during hepatectomy: marker of injury or surgical stress?

BACKGROUND/AIMS: The aim of this study was to evaluate the inflammatory or antiinflammatory cytokine response to ischemia-reperfusion during hepatectomy and to find a useful marker of injury or surgical stress during hepatic ischemia-reperfusion. METHODOLOGY: In 9 patients with liver disease who underwent hepatectomy using the Pringle maneuver, serum cytokines, including alanine transaminase, aspartate transaminase, and hyaluronic acid, were measured just prior to vascular occlusion; 5, 10 and 15 min after initial clamping; and 3 min after initial declamping. RESULTS: The mean concentrations of aspartate transaminase and alanine transaminase did not significantly differ before and after ischemia-reperfusion during hepatectomy. However, mean concentrations of hyaluronic acid after ischemia-reperfusion were significantly (P < 0.03) higher than before clamping. Although there were no significant differences in the mean concentrations of IL-1 beta, IL-6, IL-8, IL-10 and TNF-alpha among, before and after ischemia-reperfusion, the mean concentrations of granulocyte colony-stimulating factor after ischemia-reperfusion and macrophage colony-stimulating factor after reperfusion were significantly (P < 0.05) higher than before clamping. CONCLUSIONS: Although hepatic parenchymal cell function was maintained after ischemia-reperfusion during hepatectomy, sinusoidal endothelial cell dysfunction was found. Release of granulocyte colony-stimulating factor and macrophage colony-stimulating factor after ischemia-reperfusion were also found. These cytokines and hyaluronic acid may be useful indicators in the early phase of human ischemia-reperfusion injury during hepatectomy.     

Hepatic resection for metastatic tumors from noncolorectal carcinoma

BACKGROUND/AIMS: The role of liver resection for hepatic metastases from noncolorectal carcinomas has yet to be clarified. The present study examines a single institutional experience of hepatic resection for noncolorectal metastases. METHODOLOGY: From January 1987 to March 1999, 14 patients underwent curative resection for liver metastases from noncolorectal carcinomas. Records of these patients were reviewed. RESULTS: Resections were performed for liver metastases from gastric cancers (n = 8), pancreatic cancers (n = 2), and cancers of bile duct, the papilla of Vater, kidney, and breast (n = 1, each). Six patients (5 with gastric cancers and 1 with pancreas cancer) presented with synchronous disease and 8 with metachronous disease. In the gastric cancer patients, there are 2 disease-free survivors (26 and 53 months) in the metachronous group, though all of the 5 patients with synchronous disease died within 29 months. All of the 4 patients with pancreatobiliary carcinomas died within 2 years. One case of breast cancer and another of renal cell cancer are alive without disease at 49 and 9 months, respectively. CONCLUSIONS: For metastases from gastric cancers, better survival after hepatic resection is expected in metachronous cases than in synchronous cases. Hepatic resection may afford little benefit for patients with liver metastases from pancretobiliary cancers.     

Gastrointestinal stromal tumor with a novel mutation of KIT proto-oncogene

The majority of human gastrointestinal mesenchymal tumors are gastrointestinal stromal tumors (GISTs). Recent reports have shown the existence of gain-of-function mutations in the juxta-membrane domain of receptor tyrosine kinase (KIT) in GISTs. We present a 77-year-old woman with GIST diagnosed by positive immunostaining of cluster designation (CD) 34 and KIT. This case had a novel mutation at codon 576 located in the juxta-membrane domain of KIT. Our results indicate the importance of mutations in this KIT region and suggest the possibility of the existence of other types of mutations in this region in GISTs.     

Unusual changes detected by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography in the process of acute myocardial infarction: a case report

Iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid myocardial single photon emission computed tomography(iodine-123 BMIPP myocardial SPECT) is useful for the diagnosis and evaluation of ischemic myocardial disease or cardiomyopathy. Changes in fatty acid metabolism in the post-myocardial ischemic state were evaluated using iodine-123 BMIPP myocardial SPECT. A 77-year-old woman was hospitalized for treatment of acute myocardial infarction. Emergency coronary angiography showed severe stenosis with delayed filling of contrast medium in the middle portion of the left anterior descending artery, so primary percutaneous transluminal coronary angioplasty was performed successfully. On the second day, iodine-123 BMIPP uptake was decreased slightly on the early imaging in the apico-anterior region, and increased slightly on the delayed imaging. On the seventh day, iodine-123 BMIPP uptake was decreased moderately or markedly in the apico-anterior region on the early imaging, and decreased markedly on the delayed imaging. Iodine-123 BMIPP myocardial SPECT subsequently became almost normalized. These unusual dynamic changes In iodine-123 BMIPP myocardial SPECT imaging may reflect metabolic changes of fatty acids in the ischemic state, the size of the triacylglycerol pool, and the degree of turnover in the triacylglycerol pool.     

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.     

Efficient gene transfer into macrophages and dendritic cells by in vivo gene delivery with mannosylated lipoplex via the intraperitoneal route

In this study, we developed an antigen-presenting cell (APC)-selective intraperitoneal (i.p.) gene delivery system with mannosylated cationic liposomes (Man-liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than cationic liposomes/plasmid DNA complex (lipoplex) or naked pCMV-Luc after i.p. administration, and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after i.p. administration was significantly higher than that after i.v. gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the i.p. route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80+ and CD11c+ cells in the spleen. These results show that gene delivery with Man-liposomes via the i.p. route could be an effective approach for APC-selective gene transfection.     

A case of normal tension glaucoma associated with Buerger's disease

Open angle glaucoma, a slowly progressive optic atrophy, is clinically characterized by visual field defects corresponding to excavation of the optic disc, called glaucomatous cupping. Open angle glaucoma is further divided into primary open angle glaucoma caused by elevated intraocular pressure (higher than the normal limit of 21 mmHg), and normal tension glaucoma, in which intraocular pressure is in the normal range. Here we report a case of normal tension glaucoma associated with Buerger's disease, also known as thromboangiitis obliterans, which causes systemic blood flow disturbance. A 66-year-old man suffering from Buerger's disease for 10 years was diagnosed as having branch retinal artery occlusion in his left eye. He was referred to our clinic due to progressive visual field disturbance in that eye. Ophthalmologic examinations revealed occlusion in the infero-temporal retinal artery in the left eye, and glaucomatous cupping, normal intraocular pressure, retinal vessel tortuosity and retinal arteriosclerosis in both eyes. Visual field examination revealed decreased retinal sensitivities in the areas within the visual field arches above and below fixation from the blind spot to the median raphe, corresponding to the arcuate retinal nerve fibers comprising the Bjerrum areas and the area corresponding to the retinal artery occlusion. Buerger's disease is characterized by the development of segmental thrombotic occlusions and vasospasm of the medium and small arteries. Our case suggests that the blood flow disturbance due to arteriosclerosis, thrombotic occlusions and vasospasm associated with Buerger's disease might affect the ophthalmic circulation system, thereby contributing to the etiology of normal tension glaucoma.