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Biomedical subjects

Y Niwa

Publications and source records attributed to Y Niwa.

At least 37 records · Page 2Linked to original sources

Genomic organization and organ-specific expression of a nuclear gene encoding phage-type RNA polymerase in Nicotiana sylvestris.

We have isolated and sequenced a nuclear gene and cDNA encoding bacteriophage T7-type single subunit RNA polymerase, NsRpoT-A, from Nicotiana sylvestris. NsRpoT-A consists of 19 exons and 18 introns; the first intron is 17 kb, the longest yet identified in a plant gene. Genomic Southern analysis indicated that N. sylvestris contains a small family of NsRpoT genes. Quantitative RT-PCR revealed that steady-state mRNA levels are highest in the leaves and lowest in the cotyledons. Phylogenetic analysis of NsRpoT-A and the RpoT proteins of other plant species suggested that NsRpoT-A is a mitochondrial protein. The TargetP program predicted localization of the NsRpoT-A gene product to the mitochondria. Using a transient expression assay and protoplasts from N. sylvestris mesophyll cells, we clearly demonstrated that the N-terminal sequence of NsRpoT-A targets the protein to the mitochondria. We therefore named this protein NsRpoTm.

Amino Acid Sequence↗

Endothelium-dependent relaxation by cilostazol, a phosphodiesteras III inhibitor, on rat thoracic aorta.

The relaxation effect of cilostazol, a phosphodiesterase III inhibitor, on the thoracic aorta was investigated. Cilostazol induced the relaxation of the thoracic aorta precontracted by phenylephrine in a concentration-dependent manner. The concentration-dependent relaxation was shifted to the right in the endothelium denuded aorta compared with that of intact endothelium, suggesting that this relaxation was partly dependent on endothelium. Cilostazol-induced relaxation of thoracic aorta tone was reversed by treatment with N(G)-nitro L-arginine (L-NNA), a competitive inhibitor of nitric oxide (NO) synthase. Cilostazol also significantly increased the NO level in the porcine thoracic aorta. In rats treated with cilostazol, the urinary excretion of nitrites, a stable metabolite of NO, and basal production of NO of the aortic ring were significantly greater than in those without treatment. These findings indicate that cilostazol-induced vasodilation of the rat thoracic aorta was dependent on the endothelium, which released NO from aortic endothelial cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Modification of Arg-13 of mu-conotoxin GIIIA with piperidinyl-Arg analogs and their relation to the inhibition of sodium channels.

mu-Conotoxin GIIIA, a peptide toxin isolated from the marine snail Conus geographus, preferentially blocks skeletal muscle sodium channels in vertebrates. In this study, analogs of mu-conotoxin GIIIA in which essential Arg-13 was replaced with arginine analogs consisting of a piperidyl framework to regulate length and direction of the side chain were synthesized. Synthesized analogs exhibited similar CD and NMR spectra to that of GIIIA, suggesting a three-dimensional structure identical to that of the native toxin. The biological activities of piperidyl analogs were decreased or lost despite the small change in the side chain of Arg-13. The investigated structure-activity relationships in inhibiting electrically stimulated muscle contraction suggest that the guanidinium group at amino acid position 13 interacts best when spaced with three to four carbons and placed in a vertical direction from the peptide loop. Thus, the position of the guanidinium group at Arg-13 of GIIIA must be located in a certain range for its strong interaction with the channel protein.

Amino Acid Sequence↗

Effect of palmitic acid on neutrophil functions in vitro.

BACKGROUND: It has been shown that in acne comedones the proportion of linoleic acid is markedly decreased, while palmitic acid is significantly increased. We previously reported that the decreased proportion of linoleic acid, which markedly suppresses neutrophil reactive oxygen species (ROS) generation and phagocytosis, contribute to the worsening of acne inflammation. The aim of this study was to examine the effect of palmitic acid on neutrophil functions in vitro. METHODS: We investigated the effect of palmitic acid on inflammatory parameters such as neutrophil chemotaxis, phagocytosis, and ROS generation. Reactive oxygen species generation in a cell-free, xanthine-xanthine oxidase system was also assessed. The species examined were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). RESULTS: Palmitic acid significantly decreased H2O2 generation both by neutrophils and in the xanthine-xanthine oxidase system, while neutrophil chemotaxis and phagocytosis as well as O2- and OH. generation by both systems were not markedly affected in the presence of palmitic acid. CONCLUSIONS: The present study suggests that palmitic acid may be involved in the pathogenesis of acne inflammation from a standpoint of oxidative tissue injury.

Chemotaxis, Leukocyte↗

Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats.

1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.

Age Factors↗

Clinical results and development of variable-stiffness video colonoscopes.

BACKGROUND AND STUDY AIMS: This study was designed to assess the usefulness of variable-stiffness video colonoscopes, compared with conventional videoscopes. PATIENTS AND METHODS: The first prototype XCF-QAY1 and the latter prototype XCF-Q240A1 used in this study can be varied to 4 levels of stiffness of tube insertion during examination. In 352 consecutive colonoscopic examinations performed using these and two conventional scopes, the following data were recorded: time for intubation to the cecum, frequency of changes in the patients' posture, frequency of abdominal pressure attempts, and pain score. The degree of stiffness of the insertion tube and the examiners' impressions score were recorded only in procedures where the variable-stiffness scopes were used. RESULTS: There was no significant difference between colonoscopes in the pain score. Total colonoscopy rate was 97.4%. The frequency of usage of the varying stiffness control in the colon according to site was as follows: descending colon, 57.3%; transverse colon, 32.8%, sigmoid colon, 7.6%; and ascending colon, 2.3%. A significant difference in the mean time for intubation to the cecum between the XCF-Q240A1 and conventional scopes was observed. Moreover, there were significant differences in the frequency of abdominal pressure attempts and changes in the patient's posture between conventional scopes and the new scopes. CONCLUSIONS: These results suggest that only one scope, the XCF-Q240A1, is needed for any colonic examination by any examiner.

Aged↗

Efficacy of a distal attachment in endoscopic resection of colorectal polyps situated behind semilunar folds.

BACKGROUND AND STUDY AIMS: It is difficult, dangerous, and time consuming to resect colorectal polyps situated behind the semilunar folds. The aim of this study was to examine the efficacy of a distal attachment in the endoscopic resection of these polyps. PATIENTS AND METHODS: The study group consisted of 11 patients, each with a colorectal polyp situated behind a semilunar fold, and of which the base was invisible without the use of a distal attachment. With the attachment fitted to the distal end of the endoscope, we pressed the semilunar fold situated at the anal side of the polyp so that the polyp, including its base, could be brought within the visual field. Maintaing the optimal position, we snared, ligated, and resected all polyps by electrocautery. RESULTS: The polyps were of sessile type in eight patients and pendunculated type in three, with a diameter ranging from 7 to 18 mm (mean 11 mm). Although the base of the polyp was invisible under conventional observation, pressing the fold brought good visualization. The optimal position for snaring the polyp was secured by fine endoscopic adjustment, and the polyps were easily resected in all patients. CONCLUSION: We conclude that the distal attachment is a simple but very valuable tool in the endoscopic resection of colorectal polyps situated behind the semilunar folds, and recommend its routine use in both diagnostic and therapeutic colonoscopy.

Adenoma↗

Piecemeal endoscopic aspiration mucosectomy for large superficial intramucosal tumors of the stomach.

BACKGROUND AND STUDY AIMS: As endoscopic techniques continue to develop, endoscopic mucosal resection is increasingly being used in the treatment of intramucosal gastric tumors. The aim of this study was to explore the feasibility of piecemeal endoscopic aspiration mucosectomy for large superficial intramucosal tumors of the stomach. PATIENTS AND METHODS: The study group consisted of five consecutive patients with large superficial intramucosal tumors of the stomach, 4 cm or more in diameter. Piecemeal endoscopic aspiration mucosectomy using a cap-fitted panendoscope was carried out. The initial resection was undertaken at the oral side of the lesion. Subsequent resections were carried out along the anal margin of the previous resection site, until the marks around the boundary of the tumor completely disappeared. RESULTS: The shape of the tumors was slightly elevated in four cases and slightly depressed in one. The mean diameter of the tumors was 4.8 cm. The diameters of the resected specimens ranged from approximately 1.0 cm to 2.3 cm. The numbers of piecemeal resection procedures needed per lesion ranged from five to 18 (mean 11). The visual field was well ensured by the cap, and the tumors were macroscopically completely resected without any complications in all patients. The final histological diagnoses in the specimens were adenoma in one case and mucosal carcinoma in adenoma in four. One patient had residual or recurrent tumor, and received full treatment with additional endoscopic procedures. CONCLUSIONS: Piecemeal endoscopic aspiration mucosectomy is a simple and very useful technique for treating large superficial intramucosal tumors of the stomach.

Adenoma↗

Involvement of Ca2+ -activated K+ channels in ginsenosides-induced aortic relaxation in rats.

Ginsenosides (GS), an extract of Panax ginseng, have been reported to be effective in inducing vascular relaxation mediated by nitric oxide (NO) release. The present experiments were designed to determine whether this GS-induced vasorelaxation also involves Ca2+ -activated K+ (KCa) channels in vascular smooth muscle cells (VSMC) in addition to endothelium-derived NO. GS induced vasorelaxation in rat aortic rings, which had been precontracted with phenylephrine, in a concentration-dependent manner. This GS-induced relaxation was partially reversed by tetraethylammonium (TEA), an inhibitor of KCa channels; methylene blue (MB), an inhibitor of soluble guanylate cyclase; as well as Nomega-nitro-L-arginine (L-NNA), but not by glybenclamide. In cultured VSMC and endothelial cells, KCa channels were activated by GS. This action was abolished by TEA, but was not blocked by glybenclamide. In addition, the GS-induced activity of KCa channels was partially inhibited by MB or H-8. These results indicate that the activation of KCa channels involved, at least in part, the GS-induced vasorelaxation of rat aorta.

Analgesics↗

Asymptomatic inflammatory bowel disease with special reference to ulcerative colitis in apparently healthy persons.

OBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In all, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary.

Adult↗

Involvement of adenosine in vascular contractile preconditioning.

Measurements of isometric tensions of rat aortic rings revealed the fact that when aortic rings with intact endothelium were precontracted (preconditioned) for 20 min by the alpha1-adrenergic agonist phenylephrine (10 microM), the tonic level of subsequent contraction by the same agonist was depressed and/or declined regardless of the presence or absence of endothelium during the second contraction. The removal of endothelium before preconditioning showed no such phenomenon. With the use of specific blockers, involvements of adenosine or of ATP-sensitive K+ (K(ATP)) channels during preconditioning or second contraction, respectively, were evaluated. Actions of nitric oxide synthase, cyclooxygenase, P(2) ATP purinoceptors, or K(ATP) channels during preconditioning appear not to be involved. Exogenous adenosine (up to 100 microM) without endothelium could mimic the preconditioning; however, contractile preconditioning by phenylephrine, mechanical stretching, or activation of protein kinase C needed to be done. The release of adenosine and adenine nucleotides from aortic rings was augmented by phenylephrine or by mechanical stretching of the rings with intact endothelium. Our results suggest that during vasocontraction, endothelium-derived adenosine acquires an ability to protect vascular tone against subsequent repeated contractions by mediating a delayed, possibly indirect, opening of K(ATP) channels.

Adenine Nucleotides↗

Geranylgeranyl diphosphate synthase from Scoparia dulcis and Croton sublyratus. Plastid localization and conversion to a farnesyl diphosphate synthase by mutagenesis.

cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene-producing plants, Scoparia dulcis and Croton sublyratus, have been isolated using the homology-based polymerase chain reaction (PCR) method. Both clones contained highly conserved aspartate-rich motifs (DDXX(XX)D) and their N-terminal residues exhibited the characteristics of chloroplast targeting sequence. When expressed in Escherichia coli, both the full-length and truncated proteins in which the putative targeting sequence was deleted catalyzed the condensation of farnesyl diphosphate and isopentenyl diphosphate to produce geranylgeranyl diphosphate (GGPP). The structural factors determining the product length in plant GGPPSs were investigated by constructing S. dulcis GGPPS mutants on the basis of sequence comparison with the first aspartate-rich motif (FARM) of plant farnesyl diphosphate synthase. The result indicated that in plant GGPPSs small amino acids, Met and Ser, at the fourth and fifth positions before FARM and Pro and Cys insertion in FARM play essential roles in determination of product length. Further, when a chimeric gene comprised of the putative transit peptide of the S. dulcis GGPPS gene and a green fluorescent protein was introduced into Arabidopsis leaves by particle gun bombardment, the chimeric protein was localized in chloroplasts, indicating that the cloned S. dulcis GGPPS is a chloroplast protein.

Alkyl and Aryl Transferases↗

Growth of occult arteriovenous malformation after cerebral hemorrhage demonstrated by serial magnetic resonance imaging--case report.

A 19-year-old male presented with sudden onset of right hemiparesis caused by left cerebral hemorrhage. Cerebral angiography demonstrated no vascular abnormality, and the hematoma was removed surgically. At operation, no abnormal vascular lesion was found in the brain adjoining the hematoma. Two years later, magnetic resonance (MR) imaging demonstrated a few foci of flow voids adjacent to the hematoma cavity. Four years after the hemorrhage, MR imaging showed more extensive flow-void abnormalities that indicated growth of an occult arteriovenous malformation (AVM). Cerebral angiography indicated a definite AVM supplied mainly by branches of the middle cerebral artery. Total resection of this lesion was performed. The histological diagnosis was typical AVM. Immunohistochemistry with vascular endothelial growth factor showed staining in the walls of the abnormal vessels. Serial MR imaging is very useful for the diagnosis and management of occult AVMs.

Adult↗

The nutritional status of elderly bed-ridden patients receiving tube feeding.

Long-term enteral feeding by tube has become a frequently used procedure in elderly patients. However, only a few studies dealing with the nutritional assessment of such patients are currently available. This study was designed to clarify this issue. Anthropometric and biochemical variables, energy expenditure and dietary intake were investigated in 44 hospitalized bed-ridden patients with and without tube feeding over 65 years of age and 41 age-matched free-eating elders in a nursing home. All patients with tube feeding received enteral nutrition by nasogastric tube. The body weight, body mass index, mid-upper-arm circumference, arm muscle circumference and serum level of albumin were significantly lower in the patients with and without tube feeding, compared with free-eating elders of both genders (p<0.05). Energy intakes of the patients with tube feeding were 1,171+/-286 kcal/d (about 26 kcal/kg/d), which is comparable to the predicted total energy expenditure (1.2 x basal energy expenditure). Protein intake was 44.9+/-13.1 g/d (about 1.0 g/kg/d) and the percentage of protein per total energy was 15%. These intakes are generally considered to be optimal for bed-ridden patients receiving tube feeding. However, the incidence of protein-malnutrition, as evidenced by decreased arm muscle circumference (<80% of normal) and hypoalbuminemia (<35 g/L), in the patients with tube feeding was significantly higher than that in the healthy elders. In addition, the orally fed bed-ridden patients were also malnourished, suggesting that the bed-ridden patients easily became malnourished even if they were fed energy and protein which approximated calculated predicted values. These findings raise a problem concerning nutritional management of bed-ridden patients.

Aged↗

Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer.

The beta-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I. A marked increase in plasma RANTES level (> 10,000 pg/ml) was found in 27% of patients with progressive malignancy but in none of those in clinical remission. The platelet RANTES content was correspondingly decreased in those patients with increased plasma RANTES levels. Beta-TG showed a pattern similar to RANTES both in plasma and platelets, but with much less dramatic differences between patients with different stages of disease. Other allergic parameters, IgE, eosinophils and plasma IFN-gamma, IL-2, -5, and -10, were not elevated in the cancer patients. The RANTES content was markedly elevated in the primary tumor and metastatic lesions (lymph node or skin) from all of the patients with breast or cervical cancer, irrespective of the plasma RANTES level. In addition, in patients with progressive breast or cervical cancer, but not in patients thought to be cured of these tumors, the RANTES content was markedly increased in clinically normal tissue taken from near the operative site several months postoperatively, as well as in intact skin or mucosa taken perioperatively near the excised tumor. This study suggests an as-yet-undefined but important role played by RANTES in carcinogenesis, as well as the possibility that a RANTES assay in tissue surrounding a tumor or postoperative tumor site may help predict prognosis in these patients.

Adult↗

Induction of inducible nitric oxide synthase by ginsenosides in cultured porcine endothelial cells.

Mechanism of Nitric oxide (NO) production by ginsenosides was investigated in cultured porcine endothelial cells. Beta-nicotinamide adenine dinucleotide phosphate (beta-NADPH) staining showed that the NO production was significantly enhanced by the presence of 40 microg/ml ginsenosides with 10 microM L-arginine after 12 h incubation. NO production was suppressed by addition of 0.5 microM Nomega-Nitro-L-arginine (L-NNA), an inhibitor of NO synthases (NOSs), to the incubation medium. In addition, the immunoreactive signals of inducible NOS (iNOS) were appeared in endothelial cells after 12-h incubation of ginsenosides, whereas the signals were not observed in non-treated cells. Our findings suggest that ginsenosides can enhance NO production by induction of iNOS in addition to its direct effect on endothelial cells by increasing intracellular Ca2+ concentration.

Animals↗