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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 1,081 records · Page 60Linked to original sources
PubMed1997

Synthesis of isomers of 18F-labelled amino acid radiopharmaceutical: position 2- and 3-L-18F-alpha-methyltyrosine using a separation and purification system.

To diagnose cancers with radiolabelled amino acid using positron emission tomography, we have constructed a separation and purification system for the production of L-18F-alpha-methyltyrosine (L-18FAmT). This system could provide radioprotection and consistent production of L-18FAmT. L-18FAmT was synthesized and purified and the efficiency of the system was examined. The radiochemical yield of L-18FAmT was 20.3 +/- 5.1% (n = 5) based on the radioactivity trapped in the reaction vessel. The radiochemical purity was greater than 99.4 +/- 0.3% (n = 5). The radiochemical stability in phosphate-buffered saline and human plasma was examined and little decomposition was observed by HPLC analysis. Our results indicate that the separation and purification system gave simple and quick synthesis of L-18FAmT with a large reduction in radiation exposure and consistent production of L-18FAmT.

Amino Acids↗
PubMed1997

Depressed contractile response to exercise in diabetic patients in the absence of cardiovascular disease: relationship to adrenergic cardiac dysinnervation.

We investigated the presence of subclinical left ventricular dysfunction by determining left ventricular diastolic filling at rest and the left ventricular ejection fraction (LVEF) response to exercise with radionuclide angiography. The subjects were 40 patients with non-insulin-dependent diabetes who showed no evidence of cardiovascular disease based on clinical findings, electrocardiography and 201T1 perfusion scintigraphy. We also used 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to investigate whether subclinical left ventricular abnormalities were related to adrenergic cardiac dysinnervation. The change on LVEF in response to exercise (delta LVEF) was < 5% in 1 of 20 normal controls and in 22 of 40 diabetic patients (P < 0.01). The peak filling rate was within normal limits in all controls but was abnormal (< 2.3 EDV s-1) in 5 of 40 patients (P = N.S.). Of the clinical and scintigraphic variables that correlated significantly with delta LVEF, the heart-to-mediastinum 123I-MIBG uptake ratio on the late planar images was the most important and independent predictor. Nearly half of the patients with non-insulin-dependent diabetes without apparent cardiovascular disease exhibited a depressed LVEF response to exercise. This subnormal response was significantly associated with diminished myocardial 123I-MIBG uptake, suggesting a causal relationship.

3-Iodobenzylguanidine↗
PubMed1997

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Amino Acid Sequence↗
PubMed1997

p16INK4 gene mutations are relatively frequent in ampullary carcinomas.

A high incidence of gene mutations or deletions of p16INK4, a cell cycle regulator which inhibits the activity of cyclin-dependent kinase 4/cyclin D complex and blocks the G1-to-S transition, has been reported in pancreato-biliary tract cancers. In order to investigate p16INK4 gene alterations in sporadic ampullary carcinomas, 17 sporadic ampullary carcinomas were examined. After histological diagnosis, DNA samples extracted separately from both cancerous and normal paraffin-embedded tissues were investigated. Loss of heterozygosity (LOH) was investigated utilizing 3 microsatellite markers on 9p21-22, and a mutational analysis was performed by cloning and sequencing. LOH was observed in 3 cases (17.6%) and somatic mutations with retention of heterozygosity were found in 7 cases (41.2%). Of note was that two mutations resulted in truncated incomplete proteins and one was a point mutation at the consensus site in the conserved ankyrin repeats, which would be crucial for function. Although two-hit inactivation was not evident in any of the mutation cases and further investigation would be needed to elucidate the role of altered p16INK4, these results suggest that the p16INK4 gene mutations are relatively frequent and its inactivation might be important in ampullary carcinogenesis.

Aged↗
PubMed1997

Transforming growth factor-beta and hepatocyte growth factor produced by gastric fibroblasts stimulate the invasiveness of scirrhous gastric cancer cells.

Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts. In the present study, we examined the effect of gastric fibroblasts on the invasiveness of a scirrhous gastric cancer cell line, OCUM-2D, using an invasion assay. Gastric fibroblast-derived conditioned medium (CM) significantly stimulated the invasiveness of OCUM-2D cells, as did transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF). The stimulating activity of gastric fibroblast-derived CM was inhibited significantly by anti-TGF-beta neutralizing antibody or anti-HGF neutralizing antibody. TGF-beta and HGF were detected in the gastric fibroblast-derived CM, and TGF-beta receptor and C-met (HGF receptor) were expressed on OCUM-2D cells. Thus, TGF-beta and HGF produced by gastric fibroblasts appear to affect the invasiveness of scirrhous gastric cancer cells. TGF-beta was also detected in the conditioned medium derived from OCUM-2D cells, though HGF was not. TGF-beta appears to affect the invasiveness of OCUM-2D cells in both paracrine and autocrine fashions.

Adenocarcinoma, Scirrhous↗
PubMed1997

Frequent somatic mutations of the APC and p53 genes in sporadic ampullary carcinomas.

Although a close relation of somatic mutations of the adenomatous polyposis coli gene with ampullary carcinomas in familial adenomatous polyposis patients has been reported, the possible association with sporadic ampullary neoplasms has not been fully examined. We have therefore investigated loss of heterozygosity at the adenomatous polyposis coli locus and the mutational status of a portion of the adenomatous polyposis coli gene, including the mutation cluster region, in 17 ampullary carcinomas of non-familial adenomatous polyposis patients. Alteration of the adenomatous polyposis coli gene was found in 8 of 17 (47.1%) cases, as missense or insertion mutations, with or without loss of heterozygosity. Additional investigation of p53 (exons 5-8) and K-ras (codons 12 and 13) gene mutations revealed a striking mutational pattern of the p53 gene. Nine of the 17 cases demonstrated a total of 12 mutations, 6 clustered at codon 189 and 3 at codon 166. Furthermore, 5 of the 12 mutations were nonsense mutations. Regarding the K-ras gene, 4 of the 17 (23.5%) cases had mutations in codon 12, 3 of the 4 cases being derived from the intraduodenal bile duct. The findings indicate that alterations of the adenomatous polyposis coli and the p53 genes are relatively frequent in sporadic ampullary carcinomas. In particular, the clustering at specific p53 codons might offer an etiological clue to clarify ampullary carcinogenesis. Mutations of the K-ras gene, on the other hand, might be characteristic of intraduodenal bile duct origin.

Adenomatous Polyposis Coli↗
PubMed1997

Delayed elevation of plasma endothelin-1 during unilateral alveolar hypoxia without systemic hypoxemia in humans.

BACKGROUND: The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. We investigated whether endothelin-1 (ET-1) could be detected in plasma during pulmonary alveolar hypoxia without systemic hypoxemia (one-lung hypoxia) and whether the levels could be related to hemodynamic status in humans. METHODS: Thirteen adult patients with primary lung carcinoma were studied prior to surgery. Anesthesia was induced with fentanyl, diazepam, and pancuronium iv. Differential lung ventilation was performed for 40 min. The right lung was ventilated with a mixture of 6% O2, 5% CO2, and 89% N2 and the left lung ventilated with 100% O2. Blood gas values, hemodynamic parameters, and plasma ET-1 levels were measured. RESULTS: Mean pulmonary artery pressure increased from 13.0 +/- 3.5 to 17.2 +/- 3.2 mm Hg (P < 0.01) after 20 min of one-lung hypoxia. The plasma ET-1 levels in arterial blood and wedged right pulmonary arterial blood increased from 1.69 +/- 0.61 to 2.13 +/- 0.48 pg/ml (P < 0.01) and from 1.75 +/- 0.47 to 2.26 +/- 0.40 pg/ml (P < 0.001), respectively, after 40 min of one-lung hypoxia. At baseline and after 40 min of one-lung hypoxia, there was a significant correlation between the mean pulmonary artery pressure and arterial plasma ET-1 levels (r = 0.650, P < 0.01) in the wedged pulmonary arterial plasma levels (r = 0.484, P < 0.05). The increase in plasma ET-1 levels in arterial blood and in the wedged pulmonary arterial blood of the hypoxic lung occurred slowly. CONCLUSION: We concluded that ET-1 may a supporting, but not a primary, role in human hypoxic pulmonary vasoconstriction.

Aged↗
PubMed1997

Analgesia after upper abdominal surgery using extradural administration of a fixed dose of buprenorphine in combination with lignocaine given at two infusion rates: a comparative study.

BACKGROUND: Extradural administration of combinations of local anaesthetics and opioids are frequently employed for postoperative pain relief. There is a scarcity of data on the analgesic effects of variations of the dose of local anaesthetic drug admixed to a fixed dose of opioid. METHODS: Twenty-four patients were investigated after elective upper abdominal surgery. During closure of the abdomen, 2% mepivacaine (8 ml) with buprenorphine 0.1 mg (0.5 ml) was given extradurally. After extubation, patients were randomly allocated to receive continuous extradural infusion of a fixed dose of buprenorphine (0.017 mg/h) in combination with 2% lignocaine at either 2.1 ml/h (low rate group, n = 14) or 6.3 ml/h (high rate group, n = 10). Postoperative pain at rest was assessed using visual analogue scale (VAS) scores and pain at movement by Prince Henry Pain Scale (PHPS) scores. Venous plasma lignocaine concentrations were measured. RESULTS: VAS scores at rest were similar in the two groups at 3 h postoperatively, whereas at 6-24 h postoperatively, VAS scores were higher in the low rate group than in the high rate group. PHPS scores were similar in the two groups at 3 h and at 18 h postoperatively, whereas at 6, 9, 12 and 24 h postoperatively, PHPS scores were higher in the low rate group than in the high rate group. Plasma lignocaine concentrations were higher at 23 h postoperatively in the high rate group than at 16 h in both groups, and at 23 h in the low rate group. At 3 h postoperatively, both the systolic and diastolic arterial pressures were higher in the low rate group than control values obtained on admission. Side effects were observed in one patient in the low rate group who complained of dizziness, and in one patient in the high rate group who complained of nausea. CONCLUSIONS: When added to a fixed dose of buprenorphine, continuous extradural infusion of 2% lignocaine at high rate provides better postoperative analgesia than when given at low rate without producing significant side effects.

Abdomen↗
PubMed1997

Laparoscopic adrenalectomy for bilateral pheochromocytoma: a case report.

We report a case of bilateral (2.4-cm left and 6.5-cm right) adrenal pheochromocytoma in a 27-year-old man that was treated by laparoscopic adrenalectomy. The patient had no evidence of multiple endocrine neoplasia, type II. The left adrenalectomy was performed first, with the patient in a semilateral position, and then the patient was turned before the procedure was begun on the right side. His postoperative convalescence was uneventful, and he continues corticosteroid replacement therapy. Transperitoneal laparoscopic adrenalectomy can be a safe procedure for bilateral pheochromocytoma, if the patients are carefully selected and the procedures are performed by experienced laparoscopists.

Adrenalectomy↗
PubMed1997

Single lead atrial synchronous ventricular pacing in Japanese patients with complete atrioventricular block.

The purpose of this study was to review our experience with atrial synchronous ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.) using single atrioventricular leads in Japanese patients with complete atrioventricular block and normal sinus function. Twenty patients with a mean age of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the amplitude of atrial signals in the supine position during normal breathing, which was measured directly using an external pacing system analyzer, ranged from 1.8 to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4 +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the patients. During a follow-up period, the percentage of atrial synchronization was >95% in 19 patients, and none of the patients had pacemaker related tachycardia or pacemaker related complications. These results were promising enough to warrant the extension of the clinical use of the VDD pacemaker.

Adult↗
PubMed1997

Nonpeptide mimic of bradykinin with long-acting properties at the bradykinin B2 receptor.

Kinins, members of a family of peptides released from kininogens by the action of kallikreins, exhibit a variety of biological activities including vasodilation, increased vascular permeability, contraction of smooth muscle cells, and activation of sensory neurons. However, investigation of the physiological actions of kinins has been greatly hampered because its effects are curtailed by rapid proteolysis in blood, lung, and liver. We describe the pharmacological characteristics of a novel nonpeptide bradykinin receptor agonist FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl ]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoli ne). FR190997 markedly stimulated phosphatidylinositol hydrolysis in Chinese hamster ovary cells permanently expressing the human bradykinin B2 receptor. The response of phosphatidylinositol hydrolysis was antagonized by the B2 receptor selective antagonist Hoe 140 (D-Arg-[hydroxyproline3,beta-thienylalanine4,D-Tic7,++ +Oic8]bradykinin). In competitive experiments using membranes prepared from Chinese hamster ovary cells expressing the human bradykinin receptor subtypes, FR190997 showed a high affinity binding to the B2 receptor with IC50 value of 5.3 nM and no binding affinity for the B1 receptor. In vivo, FR190997 mimics the biological action of bradykinin and induces hypotensive responses in rats with prolonged duration. Therefore, FR190997 is a highly potent and subtype-selective nonpeptide agonist which displays high intrinsic activity. This compound should represent a powerful tool for further investigation of the physiology and pathophysiology of bradykinin receptors.

Animals↗
PubMed1997

Developmental pattern of 3-oxo-delta 4 bile acids in neonatal bile acid metabolism.

AIMS: To investigate whether a fetal pathway of bile acid synthesis persists in neonates and infants. METHODS: 3-oxo-delta 4 bile acids were determined qualitatively and quantitatively in the urine, meconium, and faeces of healthy neonates and infants, using gas chromatography-mass spectrometry. RESULTS: The mean percentage of 3-oxo-delta 4 bile acids in total bile acids in urine at birth was significantly higher than that at 3 or 7 days, and at 1 or 3 months of age. The concentration of this component in meconium was significantly higher than that in faeces at 7 days and at 1 or 3 months of age. CONCLUSIONS: The presence of large amounts of urinary 3-oxo-delta 4 bile acids may indicate immaturity in the activity of hepatic 3-oxo-delta 4-steroid 5 beta-reductase in the first week of postnatal life. Large amounts of this component in meconium may be due to the ingestion of amniotic fluid by the fetus during pregnancy.

Bile Acids and Salts↗
PubMed1997

Modulation of jaw muscle spindle discharge during mastication in the rabbit.

Discharges of jaw muscle spindles were recorded during chewing carrot from mesencephalic trigeminal nucleus (Mes V) in the awake rabbit to evaluate contribution of the muscle spindles to the development of complete sequences of masticatory movements. The Mes V spindle units were divided into two types according to the maximum firing rates during mastication, with a dividing line at 200 Hz; high-frequency units and low-frequency units. Although both types of units fired maximally during the jaw-opening phase of chewing cycles, their firing rates and pattern varied according to three sequential stages of mastication (stages I, IIa, and IIb). The high-frequency units often increased firing before the start of mastication and built up firing in the first few chewing cycles. Their maximal firing rate was sometimes lower during stage IIa (chewing stage) than during stage I (ingestion stage) and stage IIb (preswallowing stage), although the jaw movements were greater in stage IIa than in other stages. The phase relationship of the firing to a jaw movement cycle in stage IIa was consistent in individual units. The low-frequency units did not build up activity before the onset of movements. They fired mostly during the jaw-opening phase, but the peak of firing did not necessarily coincide with the time of maximal opening. It was concluded that the difference in the firing pattern among masticatory stages may be ascribed to a stage-dependent modulation of both fusimotor activity and jaw movement pattern.

Animals↗
PubMed1997

Regulation of masticatory force during cortically induced rhythmic jaw movements in the anesthetized rabbit.

To examine the relationships between masticatory force, electromyogram (EMG) of masticatory muscles, and jaw movement pattern, we quantitatively evaluated the effects of changing hardness of a chewing substance on these three variables. Cortically induced rhythmic jaw movements of a crescent-shaped pattern were induced by electrical stimulation of the cerebral cortical masticatory area in the anesthetized rabbit. The axially directed masticatory force was recorded with a small force-displacement transducer mounted on the ground surface of the lower molars. EMGs were recorded from the masseter and digastric muscles simultaneously with jaw movements. Five test strips of polyurethane foam of different hardness were prepared and inserted between the upper molar and the transducer during the movements. The peak, impulse, and buildup speed of the masticatory force increased with strip hardness, whereas duration of the exerted force did not vary with strip hardness. The integrated activity and duration of the masseteric EMG bursts also increased with strip hardness. The integrated EMG activity of the digastric bursts was weakly related to strip hardness, whereas the duration was not. The minimum gape increased with strip hardness, but the maximum gape did not. The horizontal excursion of the jaw did not vary in a hardness-dependent manner, although it was greater in the cycles with strip application than in the cycles without strip application. Deprivation of periodontal sensation by cutting the nerves to the teeth reduced the buildup speed of the force, maximum gape, net gape, and horizontal jaw movements. The denervation also elongated the force duration and that of masseteric EMG bursts. However, the rate of the hardness-dependent changes in the above parameters did not alter after denervation. The latency of the masseteric EMG response to strip application was evaluated before and after denervation. In both conditions, it was > or = 6 ms in approximately 70% of the cycles and <6 ms in the remaining approximately 30%, which cannot be explained by a simple reflex mechanism. On the basis of the analysis of correlation coefficients, the masseteric integrated EMG seemed to be a good indicator of the peak and impulse of the masticatory force both before and after denervation. We conclude that periodontal afferents would be responsible for a quick buildup of masticatory force and that afferents other than those from periodontal tissue would contribute to the hardness-dependent change of masticatory force during cortically induced rhythmic jaw movements.

Animals↗
PubMed1997

Role of calcium conductances on spike afterpotentials in rat trigeminal motoneurons.

Intracellular recordings were obtained from rat trigeminal motoneurons in slice preparations to investigate the role of calcium conductances in the depolarizing and hyperpolarizing spike afterpotential (ADP and mAHP, respectively). The mAHP was suppressed by bath application of 1 microM apamin, 2 mM Mn2+, and 2 mM Co2+, and also by intracellular injection of ethylene glycol-bis(b-aminoethylenether)-N,N,N',N'-tetraacetic acid (EGTA), suggesting that the potassium conductance generating the mAHP is activated by Ca2+ influx. Mn2+ (2 mM) or Cd2+ (500 microM) reduced the ADP, whereas the ADP amplitude was increased by raising extracellular Ca2+ concentration from 2 to 8 mM by bath application of Ba2+ (0.5-5 mM) and by intracellular injection of EGTA. This would suggest that Ca2+ itself is likely to be the charge carrier generating the ADP. Focal application of omega-conotoxin GVIA (10-30 microM) suppressed the mAHP and enhanced the ADP, whereas focal application of omega-agatoxin IVA (10-100 microM) reduced the ADP amplitude without apparent effects on the mAHP. We conclude that Ca2+ influx through omega-agatoxin IVA-sensitive calcium channels is at least in part responsible for the generation of the ADP and that Ca2+ influx through omega-conotoxin GVIA-sensitive calcium channels contributes to the generation of the mAHP. Because of the selective suppression of the ADP and mAHP by omega-agatoxin IVA and omega-conotoxin GVIA, respectively, it is suggested that both calcium channels are separated geometrically in rat trigeminal motoneurons.

Animals↗
PubMed1997

History of vitamin D treatment of renal osteodystrophy.

Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.

Animals↗