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Biomedical subjects

T Hirata

Publications and source records attributed to T Hirata.

At least 109 records · Page 6Linked to original sources
PubMed1999

Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFalpha gene and HLA genes.

OBJECTIVE: To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor alpha (TNFalpha) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). METHODS: One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFalpha, HLA-A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. RESULTS: The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFalpha gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFalpha -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). CONCLUSION: The -1,031C/-863A allele and the -857T allele of the TNFalpha gene, both of which are related to high production of tumor necrosis factor alpha, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

Arthritis, Juvenile↗
PubMed1999

Inducible types of cyclooxygenase and nitric oxide synthase in adaptive cytoprotection in rat stomachs.

Roles of cyclooxygenases (COX-1 and COX-2) and nitric oxide (NO) synthases (nNOS and iNOS) in adaptive cytoprotection induced by 20 mM taurocholate dissolved in 50 mM HCl (TC) were investigated in rat stomachs. Intragastric administration of 0.6 N HCl caused haemorrhagic damage in the stomach. These lesions were prevented by pretreatment of the animals with TC p.o. 0.5 h before 0.6 N HCl, and a significant protection persisted for more than 5 h. The protection afforded by TC given 0.5 h before HCl was almost totally reversed by indomethacin and slightly mitigated by N(G)-nitro-L-arginine methyl ester (L-NAME) but not affected by NS-398 or aminoguanidine. By contrast, the mucosal protective action of TC given 5 h before HCl was significantly reversed by NS-398, L-NAME and aminoguanidine as well as indomethacin. Mucosal prostaglandin E2 (PGE2) contents were significantly increased for over 5 h after TC, while luminal NOx output tended to elevate at 0.5 h and be significantly increased at 5 h after TC. The increased PGE2 generation observed 0.5 h after TC was attenuated only by indomethacin, while that observed 5 h after TC was inhibited by NS-398 as well as indomethacin. On the other hand, the NOx output determined at 5 h after TC was significantly reduced by both L-NAME and aminoguanidine. The expression of mRNA for both COX-2 and iNOS was apparently detected in the stomach from 3 h after TC treatment. These results suggest that TC induced adaptive cytoprotection in the rat stomach against 0.6 N HCl, the effect lasting for over 5 h, and the underlying mechanism differs depending on the period after the irritation. The early phase is mediated mainly by COX-1/PGs, while the later phase is mediated by iNOS/NO, in addition to prostaglandins (PGs) produced by both COX-1 and COX-2.

Animals↗
PubMed1999

Effects of S-0509, a novel CCKB/gastrin receptor antagonist, on acid secretion and experimental duodenal ulcers in rats.

BACKGROUND: S-0509, 2-[(tert-butoxycarbonylmethyl) [(m-(carboxy-phenyl)-ureidomethyl-carbonyl]] aminobenzo phenone, was developed as a potent and selective CCKB/gastrin receptor antagonist that does not affect the central nervous system. METHODS: We evaluated the effects of S-0509 on gastric acid secretion and duodenal ulcerogenic and healing responses in rats comparing it with L-365,260, another CCKB/gastrin receptor antagonist. RESULTS: S-0509 (0.1 approximately 10 mg/kg, i.d.) was able to dose-dependently decrease basal acid secretion and inhibit the acid secretory responses induced by both pentagastrin (60 microg/kg/h, i.v.) and peptone (10%, i.g.) but not histamine (4 mg/kg/hr, i.v.) or carbachol (60 microg/kg/h, i.v.). L-365,260 (10 and 30 mg/kg, i.d.) caused only partial a suppression of the acid secretory response to pentagastrin but not to other stimuli, including peptone treatment. On the other hand, a duodenal ulcerogen, mepirizole (200 mg/kg, s.c. ) caused an increase in acid secretion and resulted in penetrating ulcers in the proximal duodenum, and these ulcers gradually healed over 3 weeks. S-0509 significantly inhibited both the acid secretory (> 1.0 mg/kg, i.d.) and ulcerogenic (> 3 mg/kg, p.o.) responses induced by mepirizole when it was given as a pre-treatment. It also promoted significantly the healing of these ulcers (> 3 x 2 mg/kg, p. o.) when it was given twice daily for 14 days. In contrast, L-365, 260 (30 mg/kg) tended to reduce the severity of mepirizole-induced duodenal ulcers, with a slight inhibition of acid secretion, but it caused no influence on the healing response of these ulcers. CONCLUSION: These results confirmed that S-0509 is a selective CCKB/gastrin receptor antagonist with potent antisecretory action in vivo conditions, and further demonstrated that this agent not only prevents the development of duodenal ulcers but also shows healing promoting action on duodenal ulcers, probably through the blockade of CCKB/gastrin receptors.

Animals↗
PubMed1999

Study on the effectiveness of toborinone (OPC-18790) in the treatment of heart failure in patients following cardiac surgery.

Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-qui nolinone, CAS 128667-95-8, OPC-18790), a novel cardiotonic agent with an inhibitory action on phosphodiesterase, is known to have a potent positive inotropic action with no positive chronotropic effect. The effectiveness of this drug in the treatment of heart failure occurring immediately after extracorporeal circulation (ECC) in cardiac surgery was investigated. The study was conducted in 12 patients with valvular heart disease showing a cardiac index (CI) of below 2.8 l/min/m2 and/or pulmonary capillary wedge pressure (PCWP) or pulmonary arterial diastolic pressure (PAD) of above 8 mmHg immediately after extracorporeal circulation. In group A (n = 6), toborinone was infused at a rate of 40 micrograms/kg/min for the first 5 min and then at 10 micrograms/kg/min for 85 min. In group B (n = 6), the drug was infused at a rate of 10 micrograms/kg/min for the entire 90 min. CI, mean systemic arterial pressure (mSAP), mean pulmonary artery pressure (mPAP), CVP, PCWP, and heart rate were measured at 5, 15, 30, 60, and 90 min after the start of infusion. The infusion volume required to maintain a constant PCWP was also estimated. In group A, CI increased rapidly and significantly from the baseline of 2.48 +/- 0.23 l/min/m2 to 3.57 +/- 1.07 l/min/m2 at 5 min after the start of infusion, and at that time mSAP was slightly decreased. In group B, CI increased gradually from the baseline of 2.53 +/- 0.18 l/min/m2 to 3.08 +/- 0.34 l/min/m2 at 15 min after the start of infusion, but almost no change was seen in mSAP. During the first 30 min, group A required a significantly larger infusion volume (983 +/- 395 ml) than group B (475 +/- 184 ml). From 30 to 90 min after the start of infusion, CI remained increased to similar levels in both groups and mSAP levels were also similar. There were no significant differences between the two groups in any other parameter. Continuous infusion of toborinone appears to be effective for treating heart failure occurring immediately after ECC in cardiac surgery. Initial loading at a rate of 40 micrograms/kg/min rapidly increased CI but was accompanied by mild hypotension. Constant infusion at 10 micrograms/kg/min brought about a more gradual effect that was similar to that of loading at 40 micrograms/kg/min, but without inducing hypotension. Thus, infusion at 10 micrograms/kg/min is considered preferable in order to avoid a larger-than-necessary infusion volume.

Aged↗
PubMed1999

Clinical application of biodegradable rib connecting pins in thoracotomy.

BACKGROUND: To assess the usefulness in rib reconstruction of biodegradable connecting pins made of polylactide (PLA), PLA rib pins were compared with conventional non-absorbent aluminous ceramic rib pins (alumina rib pins) in terms of their ability for fixing and healing of cut ribs in thoracic surgery. METHODS: There were 13 cases of rib fixation after thoracotomy using PLA rib pins and 11 cases using alumina rib pins, all of which were inserted into the medulla of the stump of the ribs that had been cut at thoracotomy to secure a larger surgical field. The observation period was 6 months after the operation. RESULTS: The degree of vertical shift of the ribs connected with PLA rib pins was significantly reduced compared with the degree using alumina rib pins. In chest radiographs clear zones around the pins, indicating a delay in bone neogenesis, were observed frequently around the alumina rib pins but were absent around the PLA rib pins. Osteosynthesis using PLA rib pins was significantly more favorable than with alumina rib pins. CONCLUSIONS: These results demonstrated that the PLA rib pin was superior to the alumina rib pin for fixing and healing of the cut rib.

Adult↗
PubMed1999

Electrophysiological properties of the left atrium evaluated by coronary sinus pacing in patients with atrial fibrillation.

Repetitive atrial firing (RAF), marked fragmentation of atrial activity (FAA), and interatrial conduction delay (CD) have been shown to be electrophysiological features of the atrium in patients with atrial fibrillation (AF). Moreover, it has been observed that atrial extrastimuli are more likely to induce AF when delivered from the right atrial appendage (RAA) than from the distal coronary sinus (CSd). We examined the electrophysiological properties of the atrial muscle by CS and RAA stimulation in patients with paroxysmal AF. Patients were divided into two groups: group I, consisting of 18 patients with clinical paroxysmal AF; and group II, consisting of 22 patients with various cardiac arrhythmias in which the substrate does not exist in the atrium. In group I, the following values of electrophysiological parameters of the atrium indicated that AF was more likely to be induced during RAA pacing than CSd pacing: atrial effective refractory period (RAA vs CSd: 201 +/- 28 ms vs 240 +/- 35 ms, P < 0.001), RAF zone (16 +/- 25 ms vs 0 +/- 0 ms, P < 0.03), FAA zone (38 +/- 37 ms vs 5 +/- 19 ms, P < 0.01), maximum interatrial conduction time (144 +/- 19 ms vs 93 +/- 19 ms, P < 0.0001) and CD zone (53 +/- 21 ms vs 9 +/- 18 ms, P < 0.0001). The values of the electrophysiological parameters of the atrium evaluated by CSd pacing in group I patients were not significantly different from those in group II patients. In conclusion, when coronary sinus stimulation is performed, electrophysiological properties of the atrium in patients with AF show a significant decrease in atrial vulnerability compared to stimulation from RAA and also show similar values to those in patients without AF. It might be suggested that the left posterior or posterolateral atrium is electrophysiologically stable even in patients with paroxysmal AF.

Adult↗
PubMed1999

Preserved hypocapnic pial arteriolar constriction during hyperammonemia by glutamine synthetase inhibition.

Ammonia intoxication, which results in astrocytic edema and glutamine accumulation, blocks cerebral vasodilation during hypercapnia but not during hypoxia. Ammonia's effect on blood flow during hypocapnia is unclear, with some brain regions showing a paradoxical increase in flow. Here, we studied the responses to hypocapnia of pial arterioles not surrounded by astrocytic end feet to avoid mechanical compression by local edema. Blood flow was measured by microspheres in pentobarbital sodium-anesthetized rats equipped with closed cranial windows that permitted intravital microscopy. The normal pial arterial constriction in hypocapnia (12 +/- 1%; mean +/- SE) was blocked (2 +/- 1%) during a 6-h intravenous infusion of ammonium acetate, with some regions (cerebrum, midbrain) showing increased flow during hypocapnia. After pretreatment with methionine sulfoximine (MSO), which inhibits glutamine synthesis, the normal hypocapnic constrictor response was retained in pial arterioles (11 +/- 2%) during hyperammonemia. The increase in the calculated cerebrovascular resistance also was retained. An analog of MSO that does not block glutamine synthesis (buthionine sulfoximine) was ineffective in maintaining hypocapnic reactivity. In a sodium acetate-treated control group, MSO did not alter the pial arteriolar response. Normal vasoconstrictive ability was shown during ammonium infusion in response to U-46619, a thromboxane analog. We conclude that the inhibition of hypocapnic responsivity induced by ammonium is not due to paralysis of the pial arteriolar smooth muscle or to vascular compression by swollen astrocytes but is in some way due to glutamine metabolically produced from the ammonium.

Acetates↗
PubMed1999

Mitochondrial injuries in rat lungs preserved for 17 h: An ultrastructural study.

Mitochondria of the small vasculature endothelial cells were examined in preserved rat lungs before and after reperfusion, and the ultrastructural changes were correlated with pulmonary function after reperfusion. Rat lungs were flushed with perfusate and prostaglandin E1 and divided into five groups (n = 5 in each group): group A, normal control group; group B, University of Wisconsin solution; group C, Euro-Collins solution; group D, ET-Kyoto solution, and group E, new ET-Kyoto solution. After preservation at 4 degrees C for 17 h, the left lungs were reperfused at 37 degrees C for 60 min. Tissue was sampled and mitochondria of the small vasculature endothelial cells were ultrastructurally analyzed by transmission electron microscopy before and after reperfusion. The ultrastructure of the mitochondria was well maintained in groups A, B and E before and after reperfusion. In group C, the number of severely degenerated mitochondria in the sectional area of 100 microm2 before reperfusion was 18.0 +/- 3.9, which was significantly larger than in the other groups (p < 0.01), and the total number of mitochondria significantly decreased with reperfusion (from 24.8 +/- 3.5 to 8.2 +/- 2.4, p < 0.05). In group C, the shunt fraction, mean pulmonary arterial pressure and the wet-dry ratio of the lung tissue after reperfusion C were significantly higher than in the other groups (p < 0.05; 76.3 +/- 1.5%, 54.8 +/- 4.2 mm Hg, and 20.6 +/- 2.5, respectively). A positive correlation was found between the percentage of the mitochondrial degeneration before reperfusion and the physiological parameters after reperfusion. Mitochondrial damage associated with cold ischemia is probably involved in lung injury caused by cold preservation and reperfusion.

Animals↗
PubMed1999

Influence of deflated and anaerobic conditions during cold storage on rat lungs.

Energy depletion closely correlates with ischemia-reperfusion (I-R) injury in solid organs, but there has been no conclusion about the lungs that contain air. We investigated the alveolar state during cold storage and its relation to energy metabolism and I-R injury in an ex vivo rat lung model. The lung was deflated (DEF group) or inflated with either room air (RA group) or nitrogen (N(2) group) for 6 h at 4 degrees C, and reperfusion samples of buffer and bronchoalveolar lavage fluid (BALF) was collected (n = 6, each). Furthermore, the static lung compliance, the intrapulmonary high-energy phosphates, lactate, and pyruvate were measured. The pulmonary functions of the DEF and N(2) groups were significantly worse than those of the RA group. In the N(2) group, the intrapulmonary levels of energy charge and pyruvate/lactate ratio were significantly lower than those in the DEF and RA groups, whereas there were no significant differences between the DEF and RA groups. In the DEF group, total protein and lactate dehydrogenase (LDH) in the BALF were significantly higher whereas the static lung compliance was significantly lower compared with the N(2) and RA groups. We concluded that aerobic metabolism would be essential for attenuating I-R injury of the lung, and inflation of the alveoli would be necessary for avoiding mechanical damage during reexpansion.

Air↗
PubMed1999

A 20-kDa protein with the GTP-binding and trypsin inhibitory activities from Glycine max.

A 20-kDa protein (p20) with a GTP binding activity was purified from the cultured cells of Glycine max (soybean). The amino acid sequence of p20 showed 65% identity in a 23 amino acid overlap against the Kunitz-type trypsin inhibitor of soybean reported. Furthermore, it was found that a Kunitz-type soybean trypsin inhibitor of commercial origin also binds GTP.

Amino Acid Sequence↗
PubMed1999

High molecular weight corticotropin measured with immunoradiometric assay in a patient with asymptomatic pituitary corticotropinoma.

A 57-yr-old female with corticotropinoma showing no Cushingoid stigmata is reported. Basal plasma levels of ACTH measured with immunoradiometric assay and beta-endorphin were high, 12.6-15.9 pmol/l and 3.5 pmol/l, respectively. Plasma cortisol level and urinary free cortisol excretion were normal, 303-359 nmol/l and 171-226 nmol/day, respectively. Plasma ACTH markedly increased to 70.5 pmol/l with intravenous administration of 100 microg CRH. Diurnal rhythm of plasma ACTH was seen, but its level in the night was still high. Plasma ACTH suppression with dexamethasone was insufficient. CRH stimulation after dexamethasone suppression increased plasma ACTH level from 4.4 to 13.7 pmol/l. Intravenous administration of 4 microg desmopressin increased plasma ACTH from 15.6 to 19.6 pmol/l. Oral administration of 16 mg lepramide insufficiently decreased plasma ACTH from 7.3 to 5.3 pmol/l. However, plasma cortisol responses in these conditions were normal. Postoperative pathological study revealed subtype 1 corticotropinoma immunohistochemically and electron-microscopically. Postoperative basal plasma ACTH decreased to 3.9 pmol/l, although plasma cortisol did not change. Diurnal rhythm and dexamethasone suppressibility of plasma ACTH became normal. Plasma sample was chromatographed on a Sephadex G-75 column. The elution profile showed two peaks of ACTH, one of which was compatible with 1-39 ACTH and another with higher molecular weight ACTH which was probably secreted from corticotropinoma. Anomaly in processing of proopiomelanocortin was suspected.

Adenoma↗
PubMed1999

Aspergillus osteomyelitis in a child who has p67-phox-deficient chronic granulomatous disease.

Here we describe Aspergillus osteomyelitis of the tibia in a 9-year-old boy who has an autosomal recessive form of chronic granulomatous disease (CGD). The patient showed a p67-phagocyte oxidase (phox) deficiency, which is rare type of CGD in Japan. The initial treatment which consisted of surgical debridement and antibiotic therapy with amphotericin B (AMPH), did not control the infection. Aspergillus fumigatus (A. fumigatus) pure isolated from drainage fluid and necrotic bone tissue demonstrated less susceptible to antifungal agents, including AMPH, fluconazole and flucytosine. Recombinant interferon gamma was then administrated, and it was effective in controlling the course of severe invasive aspergillosis. This report indicates the use of interferon gamma might be helpful in control for Aspergillus osteomyelitis of the tibia in a child with CGD demonstrated p67-phox deficiency refractory to conventional therapy with AMPH.

Amphotericin B↗
PubMed1999

Environmental control of collateral branching and target invasion of mitral cell axons during development.

During development, mitral cell axons, the major efferents of the olfactory bulb, exhibit a protracted waiting period in the lateral olfactory tract (LOT) before giving off collateral branches and innervating the target olfactory cortex. To investigate the target invasion mechanism, a series of heterochronic and heterotopic cocultures of olfactory bulbs with various olfactory cortical strips were conducted. These experiments indicated that development of collateral branches is triggered by environmental cues but not by intrinsic mechanisms in mitral cells. The collateral-inducing cues are apparently different from the cues directing outgrowth of primary mitral cell axons. Coculture experiments also indicated that the target olfactory cortex undergoes a developmental change to become accessible to mitral cell fibers. Primary mitral cell axons, however, still preferred the LOT position over such accessible piriform cortex when encountered both the locations. These results suggest that mitral cell projection comprises multiple steps which are controlled by various environmental cues.

Animals↗
PubMed1999

[Surgical management of pulmonary disease due to nontuberculous mycobacteria].

Between 1983 and 1998, 9 patients with nontuberculous mycobacteriosis (NTM) underwent pulmonary resection. 8 patients were men and 1 was woman. Mean length of preoperative period was 20.3 months (range 6 months to 51 months). Most operative indication was localized NTM resistant to multidrug therapy. Lobectomy was performed in 7 patients, segmentectomy in one, partial resection in one. We have no operative mortality but air leaks occurred in one and he needed thoracoplasty. Mean postoperative follow up period was 67.7 months. Only one patients relapsed 34 months after the first operation. For localized NTM, early surgical management results good outcome.

Adult↗
PubMed1998

Membrane topology of the staphylococcal tetracycline efflux protein Tet(K) determined by antibacterial resistance gene fusion.

To determine the membrane topology of Tet(K), conventional antibiotic resistance genes were used as reporter molecules. A series of fusion genes comprising a resistance gene-beta-lactamase (amp) or chloramphenicol acetyl transferase (cat)-and one loop of the 14 putative transmembrane segments of Tet(K) was constructed. Escherichia coli TG1 with the tet(K)-amp fusion gene at the site of the putative periplasmic loop showed resistance to ampicillin, but the bacterium with the tet(K)-cat fusion gene at the site of the putative cytoplasmic loop showed resistance to chloramphenicol. These findings supported a topology of 14 membrane-spanning segments for Tet(K). Three exceptional cases were observed, which were apparently due to the presence of an acidic residue, Glu, in the preceding transmembrane segment. Mutants in which these acidic residues was substituted for alanine were also constructed, and the effect of glutamic acid in the transmembrane segment on the topology of the fusion proteins was examined.

Amino Acid Sequence↗