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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 55 records · Page 3Linked to original sources

Nicotianamine synthase gene expression differs in barley and rice under Fe-deficient conditions.

Nicotianamine (NA) is an intermediate in the biosynthetic pathway of the mugineic acid family phytosiderophores (MAs), which are crucial components of the iron acquisition apparatus of graminaceous plants. In non-graminaceous plants, NA is thought to be an essential chelator for metal cation homeostasis. Thus NA plays a key role in Fe metabolism and homeostasis in all higher plants. Nicotianamine synthase (NAS, EC 2.5.1.43) catalyzes the trimerization of S-adenosylmethionine to form one molecule of NA. Barley, a plant that is resistant to Fe deficiency, secretes large amounts of MAs, whereas rice, a plant that is susceptible to Fe deficiency, secretes only small amounts. In this study we isolated a genomic fragment containing HvNAS1 from barley and three rice cDNA clones, osnas1, osnas2 and osnas3, from Fe-deficient rice roots. We also isolated a genomic fragment containing both OsNAS1 and OsNAS2. In contrast to barley, in which Fe deficiency induces the expression of NAS genes only in roots, Fe deficiency in rice induced NAS gene expression in both roots and chlorotic leaves. The amounts of endogenous NA in both the roots and leaves were higher than in barley. We introduced barley genomic DNA fragments containing HvNAS1 with either 9 or 2 kb of the 5'-flanking region into rice, using Agrobacterium-mediated transformation. Fe deficiency induced HvNAS1 expression in both roots and leaves of the transgenic rice, as occurs with rice NAS genes. Barley and rice NAS genes are compared in a discussion of alteration of the NAS genes during adaptation to Fe deficiency.

Alkyl and Aryl Transferases↗

Role of UGT1A1 mutation in fasting hyperbilirubinemia.

BACKGROUND AND AIM: Low-grade fasting hyperbilirubinemia is a common observation in healthy subjects (HS), whereas high-grade fasting hyperbilirubinemia is believed to be a characteristic finding of Gilbert's syndrome. This study was undertaken to assess the role of mutation in bilirubin UDP- glycosyltransferase gene (UGT1A1) on fasting hyperbilirubinemia. METHODS: Analysis of UGT1A1 and a caloric restriction test (400 kcal for 24 h) were performed in 56 healthy subjects (25 males, 31 females), and 28 patients with Gilbert's syndrome (18 males, 10 females). There were 29 healthy subjects with no mutation in UGT1A1, and 27 healthy subjects and 26 Gilbert's syndrome patients with mutations in the coding and/or promoter (TATA box) regions of UGT1A1. RESULTS: The mean increment of serum bilirubin (DeltaSB) was 7.6 micromol/L [corrected] (males) and 4.1 micromol/L (females) in subjects with no UGT1A1 mutation. Subjects with mutation in UGT1A1 showed higher levels of DeltaSB than individuals without mutation. Among healthy subjects, gender difference in DeltaSB values was observed only in individuals with the wild type of UGT1A1, but not in those with mutations in this gene. CONCLUSION: The results of the present study suggest that UGT1A1 mutation has a role in the development of high-grade fasting hyperbilirubinemia after caloric restriction.

Adult↗

Myocardium extending from the left atrium onto the pulmonary veins: a comparison between subjects with and without atrial fibrillation.

Rapid discharges from the myocardium extendingfrom the left atrium onto the pulmonary vein (PV) have been shown to initiate AF, and AF may be eradicated by the catheter ablation within the PV. However, if there is any difference in the distribution patterns of the myocardial sleeve onto the PV between the subjects with and without AF is to be determined. Twenty-one autopsied hearts were examined. Eleven patients previously had AF before death and another 10 patients had normal sinus rhythm as confirmed from the medical records including ECGs before death. After exposing the heart, the distance to the peripheral end of the myocardium was measured from the PV-atrial junction in each PV. Then, the PVs were sectioned and stained and the distal end of myocardium and the distribution pattern were studied. The anteroposterior diameter of the left atrium was also measured. In 74 of 84 PVs, the myocardium extended beyond the PV-atrial junction. The myocardium was localized surrounding the vascular smooth muscle layerforming a myocardial sleeve. The peripheral end of the myocardial sleeve was irregular and the maximal and minimal distances were measured in each PV. The myocardium extended most distally in the superior PVs compared to the inferior ones and the maximal distance to the peripheral end was similar between the AF and non-AF subjects (8.4 +/- 2.8 vs 8.7 +/- 4.4 mm for the left superior and 6.5 +/- 3.5 vs 5.1 +/- 3.9 mm for the right superior PV, respectively). A significant difference was found in the maximal distance in the inferior PVs: 7.3 +/- 4.6 vs 3.3 +/- 2.8 mm for the left (P < 0.05) and 5.7 +/- 2.4 vs 1.7 +/- 1.9 mm for the right inferior PV (P < 0.001) in the subjects with and without AF, respectively. The diameter of left atrium was slightly dilated in AF patients but insignificantly (4.1 +/- 0.1 vs 3.6 +/- 0.1 cm, P > 0.07). The myocytes on the PV were less uniform and surrounded by more fibrosis in patients with AF compared to those without AF. In conclusion, the myocardium extended beyond the atrium-vein junction onto the PVs. The distribution patterns of the myocardium was almost similar between subjects with and without AF, but the histology suggested variable myocytes in size and fibrosis in patients with AF.

Aged↗

CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3alpha might be involved in the amplification of local necroinflammatory response in the liver.

It is not fully understood how antigen-specific or-nonspecific T cells migrate into the liver in various liver diseases. Macrophage inflammatory protein (MIP)-3alpha is a chemokine that is expressed mostly in the liver, and the receptor CCR6 is reported to be expressed on memory T cells. In the present study, we focused on the expression of CCR6 on T cells from peripheral blood (PB) and inflamed liver, and analyzed the involvement of MIP-3alpha and CCR6 in the immunopathogenesis of liver diseases. Intrahepatic T cells showed significantly (P <.0001) higher percentages of CCR6(+)CD4(+) T cells compared with PB, which is significantly (P =.037) correlated with the necroinflammatory response in the liver. Most of intrahepatic CCR6(+)CD4(+) cells were also positive for CCR5, which is known to express on T-helper 1 cells. MIP-3alpha was stained in the cells located near piecemeal necrosis, where dendritic cells (DCs) are often observed, and coculture of activated DCs with apoptotic cells induced MIP-3alpha production from the DCs. These data suggest that MIP-3alpha is produced by periportal DCs and/or macrophages after necroinflammatory response, leading to the recruitment of activated T cells into the liver. This process could be important to augment the local immune response in the livers of various liver diseases. The finding might be important not only for the understanding of immunopathogenesis of liver diseases but also for the therapeutic strategy to control the local immune response in the liver.

Antigens, CD↗

Overexpression of co-stimulatory molecules in peripheral mononuclear cells of Helicobacter pylori-positive peptic ulcer patients: possible difference in host responsiveness compared with non-ulcer patients.

BACKGROUND/AIM: Helicobacter pylori is the principal cause of gastritis and peptic ulcer disease. However, H. pylori-positive patients do not always have peptic ulcer. This study was carried out in order to determine the difference in host immune reaction to H. pylori between patients with peptic ulcer and those without. METHODS: Ten H. pylori-positive patients with peptic ulcer, 10 H. pylori-positive non-ulcer patients, and 10 healthy volunteers were examined for expression of surface molecules in peripheral blood mononuclear cells. The surface molecules were stained with immunofluorescence-labelled specific antibodies and analysed by flow cytometry. RESULTS: More mononuclear cells expressed molecules ICAM-1, VLA-4, Leu-M3 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were also more cells expressing CD28, SLe(x), CD4, HLA-DR, and NU-B2 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. There were fewer cells expressing CD8 in H. pylori-positive ulcer patients than in non-ulcer patients and healthy volunteers. CONCLUSION: H. pylori infection may cause immunological reactions which are reflected in peripheral mononuclear cells. However, the activity and characteristics of peripheral mononuclear cells, in terms of expression of adhesion molecules, may differ between ulcer and non-ulcer patients who are infected with H. pylori.

Adult↗

Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1beta.

BACKGROUND: In a previous study we showed that interleukin 1beta (IL-1beta) caused recurrence of gastric ulcers in rats, and that adhesion molecules (intercellular adhesion molecule 1 and leucocytic beta2 integrins) play a role in this recurrence. Although gastric acid plays an important role in many types of gastric injuries, including peptic ulcer recurrence, the mechanism(s) remains unclear. AIMS: To examine the involvement of gastric acid in induction of ulcer recurrence by IL-1beta, and to investigate the role of gastric acid in inflammatory responses during ulcer recurrence. METHODS: Rats with healed ulcers were used. Rats were given 1 microg/kg IL-1beta intraperitoneally. Another group of rats was given 20 mg/kg omeprazole for three days to inhibit acid secretion, and received IL-1beta 20 hours after the first administration of omeprazole. They were then given 0.15 N HCl or vehicle at 0, 12, 24, and 36 hours after IL-1beta treatment. Some rats were given acid alone at the same time points. Expression of adhesion molecules was examined immunohistochemically and concentrations of IL-1beta and tumour necrosis factor alpha (TNF-alpha) were measured by ELISA in scar tissue 24 hours after IL-1beta treatment. RESULTS: IL-1beta increased expression of adhesion molecules and concentrations of IL-1beta and TNF-alpha in scar tissue by 24 hours after IL-1beta treatment, and nine of 11 healed ulcers had recurred by 48 hours. Omeprazole inhibited the effects of IL-1beta. HCl acid abolished the inhibitory effects of omeprazole. Acid alone affected neither expression of adhesion molecules nor cytokine concentrations, and did not cause recurrence. CONCLUSIONS: Gastric acid is required for recurrence of gastric ulcers caused by IL-1beta, and gastric acid stimulates the inflammatory process in scarred mucosa during ulcer recurrence.

Analysis of Variance↗

Extrahepatic expression of apolipoprotein A-II in mouse tissues: possible contribution to mouse senile amyloidosis.

Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2C) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1-Apoa2C mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition.

Aging↗

Novel neuronal nitric oxide synthase (nNOS) selective inhibitor, aplysinopsin-type indole alkaloid, from marine sponge Hyrtios erecta.

Two novel aplysinopsin-type indole alkaloids, 1 and 2, and three known indole alkaloids were isolated from the marine sponge Hyrtios erecta. These compounds exhibited selective inhibitory activity against the neuronal isozyme of nitric oxide synthase (nNOS). Furthermore, new quinolone 7 was also isolated from the same marine sponge. The chemical structures of these new compounds were elucidated on the basis of spectroscopic analysis.

Animals↗

[Improvement of method to estimate guidance by pharmacists and trial to obtain standard pharmaceutical management and guidance services program].

The level of understanding of taking medicine was examined at the start and the end of medicine-taking guidance, based on the estimation by pharmacists and inpatients. Six items for the estimation, such as "the way of taking medicines" were evaluated using a five-grade system. The significant improvement was observed in all items, suggesting that inpatients' understanding is improved by the guidance. A markedly positive correlation was found between the estimation by inpatients and that by pharmacists (p < 0.001). This confirms the appropriateness of estimation by pharmacists. Inpatients whose estimation was significantly different from that by pharmacists (difference of two grades or more) were examined to identify clear and potential problems with taking medicine. The problems were classified into such seven categories as "types of medicine". For each item with differences in estimation (two grades or more), problems were biased in some specific categories. On the basis of such a bias, a flow chart was prepared to clarify problems. In addition, a standard pharmaceutical management and guidance services program was drafted, in which measures in observation, treatment and education against problems by pharmacists were described according to the frequency of occurrence. Information about the program available on the Internet enables its use by other hospitals.

Aged↗

The expression of a barley HvNAS1 nicotianamine synthase gene promoter-gus fusion gene in transgenic tobacco is induced by Fe-deficiency in roots.

Nicotianamine (NA) is a precursor for mugineic acid-family phytosiderophores, which are a critical component of the Fe aquisition process in graminaceous plants. In addition, nicotianamine synthase (NAS) is strongly induced in these plants by Fe deficiency. NA is essential for Fe metabolism also in dicots, but NAS is not induced by Fe deficiency. We introduced a barley HvNAS1 promoter-gus fusion gene into tobacco. GUS activity was induced in the roots of these plants by Fe deficiency, and was constitutively expressed at a low level in their leaves.

Alkyl and Aryl Transferases↗

Chromosome 13 locus, Pbd2, regulates bone density in mice.

Bone density is inherited as a complex polygenic trait. Previously, we identified two quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected by bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains: SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. In this study, we report the effects of the Chr 13 QTL on peak bone density (Pbd2). First, we constructed a congenic strain P6.P2-Pbd2b, which carried a single genomic interval from the Chr 13 of SAMP2 on an SAMP6-derived osteoporotic background, to dissect this polygenic trait into single gene factors. This congenic strain had a higher bone density than the background strain using three measurement methods with different principles for bone density. Next, we measured the peak relative bone mass of the AKR/J strain and the 13 senescence-accelerated mouse (SAM) strains, which are considered to be a series of recombinant-like inbred (RI) strains derived from the AKR/J strain and other unspecified strains. We then determined the microsatellite marker haplotypes of these strains around the Pbd2 locus, in which three strains with a high relative bone mass shared the same haplotype over the 26-centimorgan (cM) region. In the Pbd2 locus, a high relative bone mass was associated with alleles of the unknown strain, whereas a low relative bone mass was associated with the alleles from the AKR/J strain. These results confirmed the existence of a Pbd2 locus regulating bone density in the SAM strains.

Alleles↗

Migration of a lumboperitoneal shunt catheter into the spinal canal--case report.

A 50-year-old female suffered upward migration of a lumboperitoneal (LP) shunt catheter into the spinal canal, manifesting as disturbance of short-term memory. Revision of the shunt confirmed that the tube had migrated into the spinal canal. The tube was pulled back into the peritoneal cavity and attached firmly to the fascia with a new anchoring device. LP shunts have the advantages of technical simplicity and extracranial procedure, but firm fixation is recommended since movements of the spine may cause proximal tube migration.

Female↗

[Morphological investigation of H. pylori and its culture method].

H. pylori plays important roles in the pathogenesis of active gastritis, peptic ulcer, and gastric cancer. Culture of H. pylori from suspicious materials is one of gold standard methods for the diagnosis of its infection. H. pylori has two types of morphological manifestation, spiral (mobile) and coccoid (immobile) forms. Morphological conversion from spiral to coccoid form and its reversion may be important role in its pathophysiology including bacterial properties, pathogenicity, and etiology. However, the mechanism and significance of such transformation of H. pylori have remained unknown. In this chapter, we introduce the conventional and new culture methods of H. pylori and review the current knowledge regarding both two types of morphological manifestation and pathophysiological significance of such transformation.

Bacteriological Techniques↗