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Biomedical subjects

H Naito

Publications and source records attributed to H Naito.

At least 19 recordsLinked to original sources

Effects of zatebradine and propranolol on canine ischemia and reperfusion-induced arrhythmias.

1,3,4,5-Tetrahydro-7,8-dimethoxy-3[3-[[2-(3, 4-dimethoxyphenyl)-ethyl]methylamino]propyl]-2H-3-benzazepin-2-one -hy drochloride (Zatebradine) is a specific bradycardiac agent, blocking the hyperpolarization-activated pacemaker current (I(f)), and thus has no negative inotropic effect. The purpose of this study was to examine whether zatebradine is effective against ischemia and reperfusion-induced arrhythmias in dogs compared to propranolol. Arrhythmia was induced by ligation of the left anterior descending coronary artery followed by reperfusion. Ischemia-induced biphasic arrhythmias were suppressed in both zatebradine and propranolol groups. During ischemia, fatal ventricular fibrillation occurred in four dogs in the control group, 0 in the zatebradine group, and two dogs in the propranolol group. Of the 31 dogs subjected to reperfusion, mortality rates in the zatebradine, propranolol, and control groups were 56%, 75%, and 86%, respectively, and there were no significant differences. In the heart beating 10 beats/min faster than the predrug heart rate by atrial pacing, both zatebradine and propranolol attenuated ischemia-induced arrhythmias but did not affect reperfusion arrhythmias. Our results suggest that I(f) and/or beta-adrenoceptors rather than the bradycardiac action might be related to the antiarrhythmic effects during ischemia, but that they do not play a role in the generation of the reperfusion-induced ventricular arrhythmias.

Adrenergic beta-Antagonists

Preparation, solubility, and cytocompatibility of zinc-releasing calcium phosphate ceramics.

Zinc is an essential trace element with stimulatory effects on bone formation. Therefore, zinc was doped into beta-tricalcium phosphate to develop zinc-releasing biomaterials to promote bone formation. The zinc-doped beta-tricalcium phosphate, beta-tricalcium phosphate, and hydroxyapatite powders were mixed at a (Ca+Zn)/P molar ratio of 1.60, followed by sintering into a dense body at 1100 degrees C for 1 h. The sintered body was a composite ceramic consisting of zinc-doped beta-tricalcium phosphate and hydroxyapatite phases. The composite ceramic contained zinc oxide when the zinc content was higher than 1.20 wt %. The composite ceramic released zinc under pseudophysiological conditions. However, the release of calcium and phosphate decreased with an increase in zinc content in a range higher than 0.12 wt % owing to a decrease in solubility of the zinc-doped beta-tricalcium phosphate phase. Proliferation of osteoblastic MC3T3-E1 cells was significantly increased on the composite ceramic with a zinc content from 0.6 to 1.20 wt %, compared with those without zinc. When the zinc content was higher than 1.20 wt %, release of zinc from the zinc oxide caused cytotoxicity. Therefore, the zinc content of the composite ceramic must be <1.20 wt %.

Animals

The role of lipid peroxidation on gastric mucosal lesions induced by water-immersion-restraint stress in rats.

This study was designed to determine the effect of water-immersion-restraint stress (WIRS) and pretreatment by reduced glutathione on both the production of gastric mucosal lesions and the content of gastric mucosal phosphatidylcholine hydroperoxide (PCOOH). Sprague-Dawley rats were divided into control and treatment groups (treated with reduced glutathione before stress). After graded durations of WIRS, the macroscopic ulcer index (UI) was measured and the PCOOH content was examined by a chemiluminescence-high performance liquid chromatography assay. The UI in the control group increased significantly in a time-dependent fashion. Elevation of the PCOOH level was observed in combination with the UI for up to 2h of WIRS, but then showed a declining tendency. Pretreatment with reduced glutathione significantly lowered both the UI and the PCOOH level. Lipid peroxidation is probably involved in the pathogenesis of gastric injury induced by WIRS at least in the early phases. However, in the late phases, other mechanisms causing gastric mucosal lesions may also be involved. We therefore believe this study to be the first to accurately and quantitatively assess the degree of lipid peroxidation in the gastric mucosa as a result of stress.

Animals

Short-term exercise training improves diaphragm antioxidant capacity and endurance.

These experiments tested the hypothesis that short-term endurance exercise training would rapidly improve (within 5 days) the diaphragm oxidative/antioxidant capacity and protect the diaphragm against contraction-induced oxidative stress. To test this postulate, male Sprague-Dawley rats (6 weeks old) ran on a motorized treadmill for 5 consecutive days (40-60 min x day(-1)) at approximately 65% maximal oxygen uptake. Costal diaphragm strips were excised from both sedentary control (CON, n=14) and trained (TR, n=13) animals 24 h after the last exercise session, for measurement of in vitro contraction properties and selected biochemical parameters of oxidative/antioxidant capacity. Training did not alter diaphragm force-frequency characteristics over a full range of submaximal and maximal stimulation frequencies (P > 0.05). In contrast, training improved diaphragm resistance to fatigue as contraction forces were better-maintained by the diaphragms of the TR animals during a submaximal 60-min fatigue protocol (P < 0.05). Following the fatigue protocol, diaphragm strips from the TR animals contained 30% lower concentrations of lipid hydroperoxides compared to CON (P < 0.05). Biochemical analysis revealed that exercise training increased diaphragm oxidative and antioxidant capacity (citrate synthase activity +18%, catalase activity +24%, total superoxide dismutase activity +20%, glutathione concentration +10%) (P < 0.05). These data indicate that short-term exercise training can rapidly elevate oxidative capacity as well as enzymatic and non-enzymatic antioxidant defenses in the diaphragm. Furthermore, this up-regulation in antioxidant defenses would be accompanied by a reduction in contraction-induced lipid peroxidation and an increased fatigue resistance.

Animals

The entire nucleotide sequence of two hepatitis G virus isolates belonging to a novel genotype: isolation in Myanmar and Vietnam.

A novel genotype of hepatitis G virus (HGV) was recently identified in sera of subjects from countries in South-East Asia. These isolates were recovered from serum of Myanmarese (designated HGV-MY14) and Vietnamese (designated HGV-VT48) subjects, respectively. To characterize the viral genome in more detail, the full-length nucleotide sequence of the two different HGV isolates belonging to the novel genotype was cloned. Both HGV isolates were composed of 9228 nt and had a single open reading frame spanning 8529 nt and encoding 2843 aa residues. The isolates differed from previously reported HGV/GBV-C isolates types 1 to 3 by 13-15% (nucleotide sequence) and 4-6% (amino acid sequence). The putative core region of both isolates was not clearly identifiable as it consisted of only 16 aa residues. Based on phylogenetic analysis of full-length genome sequences and 5'-UTR sequences, HGV-MY14 and HGV-VT48 isolates can be classified as a novel genotype, designated type 4.

Adolescent

Heat stress attenuates skeletal muscle atrophy in hindlimb-unweighted rats.

This study tested the hypothesis that elevation of heat stress proteins by whole body hyperthermia is associated with a decrease in skeletal muscle atrophy induced by reduced contractile activity (i.e. , hindlimb unweighting). Female adult rats (6 mo old) were assigned to one of four experimental groups (n = 10/group): 1) sedentary control (Con), 2) heat stress (Heat), 3) hindlimb unweighting (HLU), or 4) heat stress before hindlimb unweighting (Heat+HLU). Animals in the Heat and Heat+HLU groups were exposed to 60 min of hyperthermia (colonic temperature approximately 41.6 degrees C). Six hours after heat stress, both the HLU and Heat+HLU groups were subjected to hindlimb unweighting for 8 days. After hindlimb unweighting, the animals were anesthetized, and the soleus muscles were removed, weighed, and analyzed for protein content and the relative levels of heat shock protein 72 (HSP72). Compared with control and HLU animals, the relative content of HSP72 in the soleus muscle was significantly elevated (P < 0.05) in both the Heat and Heat+HLU animals. Although hindlimb unweighting resulted in muscle atrophy in both the HLU and Heat+HLU animals, the loss of muscle weight and protein content was significantly less (P < 0.05) in the Heat+HLU animals. These data demonstrate that heat stress before hindlimb unweighting can reduce the rate of disuse muscle atrophy. We postulate that HSP70 and/or other stress proteins play a role in the control of muscle atrophy induced by reduced contractile activity.

Animals

Metabolic properties of normal and mutant mannan-binding proteins in mouse plasma.

Human mannan-binding protein (MBP) is a serum lectin involved in innate immunity. MBP activates the complement pathway through its interaction with mannose-rich carbohydrates on various microorganisms and a common opsonic defect has been shown to be associated with a low serum concentration of MBP. This low serum concentration is closely associated with a single base mutation in codon 52, 54 or 57 of the human MBP gene, which results in a change of Arg52 to Cys, Gly54 to Asp, or Gly57 to Gln, respectively, in the collagen-like region of the molecule and prevents the formation of higher oligomers. However, the mechanism underlying the low serum concentration in such patients is completely unknown. The levels of protein synthesis and secretion of the normal and mutant MBPs seem to be similar according to our previous in vitro results. In this study, we examined the plasma clearance of the normal and mutant human (Gly54Asp) MBPs in mice, and found that the half-life of the mutant MBP is about half that of the normal MBP, explaining in part the difference in the plasma levels between the two types of MBP.

Amino Acid Substitution

Plasma glicentin in diabetic and gastrectomized patients.

Recent successful synthesis of human glicentin prompted us to establish an immunoassay method for determination of human glicentin in plasma. Human glicentin in plasma was measured using a newly developed sandwich ELISA. The mean fasting levels of human glicentin were 18.6+/-2.4 and 19.7+/-2.1 pM in normal subjects and diabetic patients, respectively. In diabetic patients with renal failure, plasma glicentin was elevated, exceeding 100 pM. In normal subjects, plasma glicentin increased to a peak level of about 130 pM at 60 min after an oral glucose load, and then decreased. In patients who underwent gastrectomy, plasma glicentin rapidly increased to a peak of about 300 pM at 30 min after oral glucose load. In a patient with short bowel syndrome plasma glicentin did not change following an oral glucose load. These results correspond with previous findings for gut glucagon-like immunoreactive materials (GLI) or enteroglucagon. We conclude that glicentin is secreted from the small intestine in response to intraluminal glucose stimulation in humans.

Blood Glucose

Monitoring and antibacterial treatment for postoperative bacterial overgrowth in Crohn's disease.

PURPOSE: Bacterial overgrowth sometimes complicates the clinical course of Crohn's disease and may lead to inappropriate treatment. To clarify the effect of antibiotic therapy, we monitored the hydrogen concentration in expiratory breath after fasting. METHODS: We evaluated 18 patients (15 males; median age, 32.7; range, 22.3-60 years) for postoperative bacterial overgrowth symptoms and for intestinal dilation by plain abdominal x-ray. Five patients had ileitis and 13 patients had ileocolitis. Various intestinal resections were performed in all, and strictureplasties were done at the same time in 13 patients. The median postoperative period was 10.2 (range, 1.2-102) months. Nine patients, who had symptoms such as bloating, nausea, vomiting, or pain, were classified as the symptomatic group, whereas nine other patients, who had no symptoms, were classified as the symptom-free group. Sixteen patients who had undergone intestinal resections for noninflammatory bowel disease served as the control group. After overnight fasting, hydrogen concentration in end-expiration, breath was measured with gas chromatography. At the same time clinical examinations of white blood cell count, hemoglobin, total protein, serum albumin, iron, sialic acid, and C-reactive protein in the peripheral blood were performed. To assess the effect of antibacterial treatment, changes in symptoms were assessed in eight patients who received antibacterial treatment. Hydrogen concentration was measured repeatedly before and after treatment in six patients. RESULTS: The symptomatic group had an expiratory hydrogen concentration level significantly higher (median, 40; range, 20-139 ppm) than the control group (median, 3; range, 1-6 ppm) and the symptom-free group (median, 4; range, 1-10 ppm). After the antibiotic treatment the symptoms were improved in all of the patients, and the hydrogen concentration level was significantly reduced (median, 4.5; range, 2-13 ppm). CONCLUSIONS: Antibacterial treatment was useful in the postoperative patients whose assessments were complicated by bacterial overgrowth. Using a hydrogen breath test, bacterial overgrowth was effectively monitored and managed, effecting a change in clinical symptoms.

Adult

Management of urinary complications in Crohn's disease.

Among the 127 patients who underwent surgical treatment for Crohn's disease at Tohoku University Hospital, urinary complications were noted in 13 patients (10.2%), including urolithiasis in 6 patients (4.7%), a ureteral obstruction in 4 (3.1%), and urinary fistula in 3 (2.4%). In patients with urolithiasis, conservative therapy was effective. An ureteral obstruction was detected on the right side in all 4 of these cases because of the inflamed terminal ileum. In 2 of the 4 cases, the symptoms improved by either preoperative total parenteral nutrition or elemental diet therapy. A resection of the inflamed intestine was necessary in all cases. In patients with urinary fistulas, a resection of the inflamed intestine combined with a reconstruction of the urinary tract was carried out after total parenteral nutrition. In conclusion, conservative therapy with preoperative total parenteral nutrition or elemental diet therapy proved to be effective for a ureteral obstruction since it improved the intestinal inflammation. As a definitive treatment, surgery is still necessary for the management of urinary fistulas and ureteral obstruction. Based on our findings, patients with urolithiasis in Crohn's disease should thus be treated conservatively in the same way as patients without Crohn's disease.

Adolescent

Turcot syndrome with colonic obstruction and small intestinal invagination: report of a case.

We report herein the case of a 16-year-old boy diagnosed as having Turcot syndrome, otherwise known as glioma-polyposis syndrome. The patient was transferred from the Department of Neurosurgery where he was undergoing investigation of a brain tumor, to the Department of Medicine for investigation of gastrointestinal symptoms. The patient was diagnosed as having Turcot syndrome, and was then transferred to the Department of Surgery for treatment of an obstruction in the sigmoid colon and small intestinal invagination. A subtotal colectomy with side-to-end ileoproctostomy and release of the invaginations was carried out. Multiple polyps were found in the colon, two of which, including a large polyp that obstructed the colonic lumen, were confirmed histologically to be adenocarcinoma. The remaining polyps were adenomas. A biopsy of the brain tumor confirmed a diagnosis of astrocytoma (WHO grade II). This case report describes the characteristic features of Turcot syndrome presented by this patient.

Adenocarcinoma

Familial hyperparathyroidism: report of a case.

We report herein a case of familial primary hyperparathyroidism diagnosed in a 23-year-old woman who presented with hypercalcemia and urolithiasis. The parathyroid gland was removed, and pathological examination revealed chief cell adenoma. The proband's younger sister had undergone surgery for parathyroid adenoma at the age of 19, and her aunt had a history of urolithiasis with a high level of serum parathyroid hormone. We have not yet found evidence of any other endocrine disorders suggesting multiple endocrine neoplasia (MEN) type 1 in this pedigree.

Adenoma

Exercise training protects against contraction-induced lipid peroxidation in the diaphragm.

Endurance exercise training promotes a small but significant increase in antioxidant enzyme activity in the costal diaphragm (DIA) of rodents. It is unclear if these training-induced improvements in muscle antioxidant capacity are large enough to reduce oxidative stress during prolonged contractile activity. To test the hypothesis that training-related increases in DIA antioxidant capacity reduces contraction-induced lipid peroxidation, we exercise trained adult female Sprague-Dawley (n = 7) rats on a motor-driven treadmill for 12 weeks at approximately 75% maximal O2 consumption (90 min/day). Control animals (n = 8) remained sedentary during the same 12-week period. After training, DIA strips from animals in both experimental groups were excised and subjected to an in vitro fatigue contractile protocol in which the muscle was stimulated for 60 min at a frequency of 30 Hz, every 2 s, with a train duration of 330 m. Compared to the controls, endurance training resulted in an increase (P < 0.05) in diaphragmatic non-protein thiols and in the activity of the antioxidant enzyme superoxide dismutase. Following the contractile protocol, lipid peroxidation was significantly lower (P < 0.05) in the trained DIA compared to the controls. These data support the hypothesis that endurance exercise training-induced increases in DIA antioxidant capacity protect the muscle against contractile-related oxidative stress.

Animals

Colonization of microflora in mice: mucosal defense against luminal bacteria.

To investigate the pathogenesis of inflammatory bowel disease, it is critical to develop a system that uses simple and reproducible models for analyzing the "normal" mucosal defense mechanism. In the present study, germ-free mice were conventionalized by the oral administration of microorganisms prepared from the feces of genetically identical mice. Histological assessment and mucin characterization of small intestine and colon were then carried out. Histological findings in the gut were site-dependent and clearly time-dependent. Acute inflammation was most evident in the cecum. The cecal mucosa exhibited hyperplastic changes in epithelial cells, infiltration of polymorphonuclear cells, crypt abscesses, and epithelial projections on the epithelial surface 7 days after conventionalization. Some of the changes were similar to those seen in human ulcerative colitis. The histological findings in the conventionalized mice were comparable to those in specific pathogen-free mice after 28 days. Mucin histochemistry revealed that bacterial colonization altered the number of rectal goblet cells and the mucin composition in a time-dependent fashion. Although this model shares only some characteristics of human inflammatory bowel disease, it is unique in demonstrating the acquisition of mucosal defense. Understanding of this process is critical for the elucidation of inflammatory bowel disease pathogenesis.

Animals

Isolation of bacteria from cervical lymph nodes in patients with oral cancer.

Thirty patients with oral mucosal cancer were studied in relation to oral mucosal damage and bacterial translocation to the regional lymph nodes in the neck. All 30 patients (gingiva 11, tongue 13, cheek mucosa four, oral floor two) underwent extensive, clean-contaminated, head-and-neck surgery (including neck dissection) with free flap reconstruction. A total of 153 lymph nodes was harvested for microbial and histological examination. Viable bacteria were isolated from 70 lymph nodes (45.8%) from 25 patients (83.3%). Bacterial cells in the nodes were detected by scanning electron microscopy. Bacterial translocation was found more often in metastatic nodes (75.0%) than in uninvolved nodes (40.3%) (p = 0.015; chi2 test). Gingival carcinoma yielded 56.4% of bacterial growth in the regional lymph nodes compared to tongue (40.3%), oral floor (40.0%) and cheek mucosa (37.5%). As the gingival carcinoma group includes more T4 cases (11/11; 100%) than the other three groups (7/19; 36.8%), bacterial translocation in uninvolved nodes could be caused by the size and invasion of the primary oral tumor. Oral streptococci (Streptococcus intermedius, Strep. constellatus, Strep. oralis, Strep. mitis, Strep. sanguis, Strep. salivarius) were the most common isolates. Aerobic enteric bacteria (Enterococcus, Escherichia, Klebsiella etc.) were also found in the lymph nodes. Among the anaerobic bacteria, Peptostreptococcus spp. were isolated from 12 patients. Damaged oral mucosa in patients with oral cancer might allow the new bacterial colonization on the surface and subsequently drain the bacteria into the regional lymph nodes as well as the general circulation.

Bacteria

Prevalence of GBV-C/hepatitis G virus viraemia among blood donors, health care personnel, chronic non-B non-C hepatitis, chronic hepatitis C and hemodialysis patients in Egypt.

A new RNA virus, designated GBV-C/hepatitis G virus (HGV) has been identified recently. To evaluate the prevalence of GBV-C/HGV infection among Egyptians, five groups were enrolled in this study: group I, healthy blood donors (82); group II, health care personnel (30); group III, chronic non-B non-C hepatitis patients (63); group IV, chronic hepatitis C patients (100); group V, renal dialysis patients (79). GBV-C/HGV-RNA was detected by nested reverse transcription-polymerase chain reaction (RT-PCR) using primers derived from 5'-non coding region of GBV-C/HGV. GBV-C/HGV-RNA was detected in 57 of 354 tested sera with an overall prevalence of 16.1%. Meanwhile, isolated GBV-C/HGV infection was detected in 16/57 (28.1%), GBV-C/HGV coinfection with hepatitis C virus (HCV) in 37/57 (64.9%) and with hepatitis B virus (HBV) in 4/57 (7.6%) of cases. The highest prevalence was encountered among dialysis patients reaching 30% followed by chronic hepatitis C (14%), blood donors (12.2%), chronic non-B non-C hepatitis (11.1%), whereas the lowest prevalence rate of 6.6% was detected among health care personnel. Nucleotide sequence analysis in three Egyptians confirmed that these PCR products were derived from GBV-C/HGV genome and all isolates classified into US/European type (type 2) of GBV-C/HGV genotypes. The risk factors of all cases were non-transfusion parenteral exposure, e.g. reusing syringes, dental treatment, surgery, invasive medical maneuvers, with an exception of renal dialysis patients who have had repeated blood transfusion. It is concluded that there is a relatively high prevalence of GBV-C/HGV-RNA among different Egyptian groups compared to international figures. The main risk factors were direct percutaneous exposure rather than blood transfusion. The Egyptian GBV-C/HGV isolates are very similar to the American isolate PNF 2161.

Base Sequence

Neurological prognosis correlated with variations over time in the number of subependymal nodules in tuberous sclerosis.

In tuberous sclerosis (TS), brain CT reveals subependymal nodules, cortical tubers and white matter lesions. This study is a retrospective analysis of the relationship between the variations over time in the number of subependymal nodules and the clinical course in cases of tuberous sclerosis. Twenty-four children with tuberous sclerosis, who attended the National Children's Hospital as outpatients, were followed by means of brain CT examinations for 7 years and 1 month on average. Cranial MRI was also performed in 22 cases. Brain CT disclosed subependymal nodules already in early infancy. In almost all cases, the number of subependymal nodules gradually increased with age, especially around the frontal horn of the lateral ventricle. The increase stopped at around age 10. The cases with five or more subependymal nodules at the initial or subsequent CT examination ( 17 patients; Group A) exhibited a significantly greater number of cortical tubers than those with less than five (five patients; Group B) and had white matter lesions unlike Group B. In addition, the number of cases with either infantile spasms or mental retardation was significantly higher in Group A than Group B (P < 0.005). In conclusion, the number of ventricular subependymal nodules may allow prediction of the severity of the cerebral dysfunction in TS. Our results suggest that its variation may reflect the degree of the embryologic disorder when neuronal cells grow in the early gestational period.

Adolescent