Microsatellite scan identifies new candidate genes for susceptibility to alcoholic chronic pancreatitis in Japanese patients.

Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.

Safety and driving ability following low-dose propofol sedation.

Background And Aim: Automobile driving is prohibited after midazolam sedation because of the slow recovery of psychomotor function. This study prospectively assessed the safety of low-dose propofol sedation (study 1) and compared driving ability following propofol and midazolam sedation (study 2).

Methods: Study 1: We prospectively investigated bolus injection of a low-dose of propofol (40-80 mg for <70 years and 30 mg for >or=70 years) for diagnostic esophagogastroduodenoscopy (EGD).

Investigation of the association between Toll-like receptor 2 gene polymorphisms and Behçet's disease in Japanese patients.

Behçet's disease (BD) is a chronic systemic inflammatory disorder characterized by recurrent ocular symptoms, oral and genital ulcers, and skin lesions. The etiology of BD is still uncertain, but genetic and environmental factors likely both play an important role in BD development. In the present study, we investigated whether polymorphisms of Toll-like receptor 2 (TLR2), previously reported to recognize BD candidate antigens, are associated with BD.

Two hypoxia sensor genes and their association with symptoms of acute mountain sickness in Sherpas.

Introduction: Hypoxia-inducible factor (HIF) and von Hippel-Lindau tumor suppressor protein (VHL) are hypoxia sensors that control cellular responses to hypoxia. Although many Sherpas live at high altitudes for their entire lives, some of them manifest symptoms of acute mountain sickness (AMS) during mountaineering at extremely high altitudes. We hypothesize that the two hypoxia sensor genes might associate with the occurrence of AMS symptoms in Sherpas at extremely high altitude.

Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

A nine-yr-old girl developed AdV-associated HC after bone marrow transplantation. Intravenous GCV markedly reduced urinary AdV DNA loads and improved clinical findings. This appeared to result partly from a high concentration of GCV in urine.

Co-operative thermal inactivation of herpes simplex virus and influenza virus by arginine and NaCl.

Elevated temperatures have been used to inactivate viruses for plasma-derived biopharmaceuticals. This paper describes the effects of arginine and NaCl in conjunction with elevated temperature for inactivation of two enveloped viruses, i.e.

Propofol sedation for endoscopic procedures in patients 90 years of age and older.

Background And Aim: There are only a few studies on propofol sedation for very elderly patients. The present study was undertaken to evaluate the safety of propofol sedation in patients 90 years of age and older undergoing endoscopic procedures.

Methods: We prospectively assessed endoscopic procedures for patients 90 years of age and older using propofol sedation.

Production of curcuminoids by Escherichia coli carrying an artificial biosynthesis pathway.

Curcuminoids, which are produced specifically by plants of the order Zingiberales, have long been used as food additives because of their aromatic, stimulant and colouring properties and as traditional Asian medicines because of their anti-tumour, antioxidant and hepatoprotective activities. Curcuminoids are therefore attractive targets for metabolic engineering. An artificial curcuminoid biosynthetic pathway, including reactions of phenylalanine ammonia-lyase (PAL) from the yeast Rhodotorula rubra, 4-coumarate : CoA ligase (4CL) from Lithospermum erythrorhizon and curcuminoid synthase (CUS) from rice (Oryza sativa), a type III polyketide synthase, was constructed in Escherichia coli for the production of curcuminoids.

Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma.

Aims: The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan.

The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese.

Objective: The transforming growth factor beta-1 gene (TGFB1) is one of the most promising candidate genes for chronic obstructive pulmonary disease (COPD). Several case-control studies have been performed and generated inconsistent results. The possible reasons for these discrepancies include the diversity of ethnic populations and the heterogeneity of COPD, including emphysema and airway disease.

Butyroyl-arginine as a potent virus inactivation agent.

Virus inactivation is a critical step in the manufacturing of recombinant therapeutic proteins, in particular antibodies, using mammalian expression systems. We have shown in the previous paper that arginine is effective in inactivation of herpes simplex virus type 1 (HSV-1) and influenza virus at low temperature under mildly acidic pH, i.e.

Anterograde labeling of the corticospinal tract in jimpy mutant mice by Di I injection into the motor cortex.

Carbocyanine fluorescent dye, DiI, is an excellent anterograde/retrograde neural tracer, but its efficacy for the anterograde labeling of neural circuits in the adult brain tends to decrease with ages. The present study shows that an injection of DiI into the motor cortex of the young adult jimpy mutant mice (Plp1(jp)/+) resulted in successful anterograde labeling of corticospinal tract fibers. Furthermore, an injection of Fast Blue into the lumbar spinal cord of the mutant mice resulted in retrograde labeling of layer 5 corticospinal tract neurons within the motor cortex.

Association of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with type 1 autoimmune hepatitis in Japanese.

Aim: Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA DR4 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed by T-cells that acts largely as a negative regulator of T-cell responses, and polymorphisms of CTLA4 have been reported to be associated with susceptibility to various autoimmune diseases.

Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients.

Objectives: Autoimmune pancreatitis (AIP) is characterized by high serum IgG4 concentrations, lymphoplasmacytic inflammation, and a favorable response to corticosteroid treatment. Although the HLA DRB1*0405-DQB1*0401 haplotype and Fc receptor-like 3 polymorphisms have been associated with AIP, the role of other genetic factors is largely unknown. As cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms have recently been linked with several autoimmune diseases, we sought to determine if CTLA4 polymorphisms and serum sCTLA4 levels were associated with AIP as well.

Adaptation to high altitude in Sherpas: association with the insertion/deletion polymorphism in the Angiotensin-converting enzyme gene.

Objective: Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear.

Effect of caffeine on the multiplication of DNA and RNA viruses.

The present study examined the effect of caffeine on RNA and DNA viruses, revealing that it inhibits the multiplication of both. In the presence of caffeine, the progeny virus yield of both herpes simplex virus type 1 (HSV-1) and poliovirus decreased with increasing concentrations of the reagent, although HSV-1 was much more sensitive than poliovirus. The influenza virus was not affected by caffeine at the same concentrations.

In vitro synthesis of curcuminoids by type III polyketide synthase from Oryza sativa.

Curcuminoids, major components of the spice turmeric, are used as a traditional Asian medicine and a food additive. Curcumin, a representative curcuminoid, has received a great deal of attention because of its anti-inflammatory, anticarcinogenic, and antitumor activities. Here we report a novel type III polyketide synthase named curcuminoid synthase from Oryza sativa, which synthesizes bisdemethoxycurcumin via a unique mechanism from two 4-coumaroyl-CoAs and one malonyl-CoA.

Lack of association of Toll-like receptor 9 gene polymorphism with Behçet's disease in Japanese patients.

Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Genetic polymorphisms within the TLR9 gene have been reported to be associated with a variety of inflammatory and infectious diseases. Behçet's disease (BD) is a chronic inflammatory disease, and the etiology of BD has yet to be fully elucidated.

Precursor-directed biosynthesis of stilbene methyl ethers in Escherichia coli.

Stilbenes are bioactive compounds that show beneficial effects for humans, such as anti-tumor activity and survival improvement. Resveratrol, a representative of stilbenes and showing various health-improving activities, is rapidly metabolized in humans, and modified resveratrols are therefore desired as anti-cancer drugs and dietary polyphenols. An Escherichia coli system, in which an artificial stilbene biosynthetic pathway, including steps of phenylalanine ammonia-lyase, 4-coumarate:CoA ligase, and stilbene synthase, was reconstructed, produced stilbenes in high yields: resveratrol from tyrosine and pinosylvin from phenylalanine.

MDR1 polymorphisms effect cyclosporine AUC0-4 values in Behçet's disease patients.

Cyclosporine (CYA) is used to preventing ocular attacks in Behçet's disease patients. Yet there are inter-individual variations in efficacy. In order to analyze the relationship between CYA fluctuation with treatment effectiveness and genetic factors, an association of area under the plasma concentration time at 0-4 hours (AUC0-4) values and polymorphism for multidrug resistance 1 (MDR1) and cytochrome3A5 (CYP3A5) genes was investigated.

A single nucleotide polymorphism analysis of the LAMA1 gene in Japanese patients with high myopia.

Although a myopia susceptibility gene has not yet been elucidated, ten candidate regions (MYP1-MYP10) have been associated with myopia by linkage analysis employing large pedigrees. We report herein on the results of our analysis pertaining to polymorphisms of LAMA1 (alpha subunit of laminin), a promising candidate gene for high myopia present in the MYP2 region of Japanese subjects with high myopia. Three hundred and thirty Japanese subjects with high myopia at a level of greater than -9.

Expression of zebrafish ROR alpha gene in cerebellar-like structures.

Mouse genetic studies have identified several genes involved in cerebellar development. The mouse mutants staggerer and lurcher are functionally deficient for the retinoid-related orphan receptor alpha (ROR alpha) and glutamate receptor delta2 (Grid2) genes, respectively, and they show similar functional and developmental abnormalities in the cerebellum. Here, we report the cloning and expression pattern of zebrafish ROR alpha orthologues rora1 and rora2, and compare their expression pattern with that of grid2.

Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli.

Flavonoids and stilbenes have attracted much attention as potential targets for nutraceuticals, cosmetics, and pharmaceuticals. We have developed a system for producing "unnatural" flavonoids and stilbenes in Escherichia coli. The artificial biosynthetic pathway included three steps.

Expression of hypoxia-inducible factor 1alpha, hypoxia-inducible factor 2alpha, and von Hippel-Lindau protein in epithelial ovarian neoplasms and allelic loss of von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1alpha is an independent prognostic factor in ovarian carcinoma.

The hypoxia-inducible factor (HIF) is a transcriptional factor with important roles in tumor biology. To clarify the possible involvement of the HIF-alpha subunit and von Hippel-Lindau (VHL) protein in the development and progression of ovarian carcinoma, we analyzed the immunohistochemical expressions of HIF-1alpha, HIF-2alpha, and VHL in 107 cases of epithelial ovarian tumors. In addition, we examined loss of heterozygosity (LOH) at VHL gene loci.