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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 397 records · Page 22Linked to original sources

Radical surgery for advanced gallbladder carcinoma.

Forty-four patients with advanced gallbladder carcinoma (18 with stage pT3 and 26 with stage pT4 of the Union Internacional Contra la Cancrum classification) were aggressively managed by extended heptatic resection in 33 patients, bile duct resection in 28, pancreaticoduodenectomy in seven, gastrointestinal resection in eleven and portal vein resection and reconstruction in seven. Adjacent organ involvement was classified as follows: type I, hepatic involvement with or without gastrointestinal invasion (Ia, Ib); type II, bile duct involvement with or without gastrointestinal invasion (IIa, IIb); type III, hepatic and bile duct involvement with or without gastrointestinal invasion (IIIa, IIIb); type IV, gastrointestinal involvement without hepatic or bile duct invasion. Fourteen of 15 patients with type I tumours had a curative resection compared with seven of 26 with type III lesions (P < 0.0001). The surgical mortality rate was two of 15 patients with type I tumours, seven of 26 with type III tumours and nine of 44 for the whole group. The long-term survival rate after curative resection was four and two of 23 at 3 and 5 years respectively, significantly better than two and none of 21 at 1 and 2 years after non-curative resection (P < 0.01). The survival rate after curative resection for patients with type I tumours was four and two of 14 at 3 and 5 years respectively, significantly better than for other types (P < 0.05). This classification of advanced gallbladder carcinoma according to involvement of adjacent organs might be helpful in planning surgery for this condition; in particular, type I tumours should be treated by a radical surgical procedure to achieve a favourable outcome.

Adenocarcinoma↗

Reduced hepatic acute-phase response after simultaneous resection for gastrointestinal cancer with synchronous liver metastases.

Serum cytokines and hepatic acute-phase responses were studied in seven patients undergoing simultaneous resection of primary gastrointestinal cancer and synchronous metastatic liver tumours and in 12 undergoing partial hepatectomy alone for metachronous hepatic metastases. The incidence of postoperative infectious complications was significantly higher after simultaneous resection than after partial hepatectomy alone (P < 0.05). Although the peak interleukin 6 level was significantly higher after simultaneous resection (P < 0.05), plasma levels of acute-phase proteins were significantly lower (P < 0.05). The results suggest that simultaneous resections further reduce the hepatic acute-phase response and render patients liable to infection compared with partial hepatectomy alone, and result in a higher incidence of postoperative infective complications.

Acute-Phase Proteins↗

High-resolution T2-weighted MR imaging of the inner ear using a long echo-train-length 3D fast spin-echo sequence.

The purpose of this study was to assess the value of a long echo-train-length 3D fast spin-echo (3D-FSE) sequence in visualizing the inner ear structures. Ten normal ears and 50 patient ears were imaged on a 1.5T MR unit using a head coil. Axial high-resolution T2-weighted images of the inner ear and the internal auditory canal (IAC) were obtained in 15 min. In normal ears the reliability of the visualization for the inner ear structures was evaluated on original images and the targeted maximum intensity projection (MIP) images of the labyrinth. In ten normal ears, 3D surface display (3D) images were also created and compared with MIP images. On the original images the cochlear aqueduct, the vessels in the vicinity of the IAC, and more than three branches of the cranial nerves were visualized in the IAC in all the ears. The visibility of the endolympathic duct was 80%. On the MIP images the visibility of the three semicircular canals, anterior and posterior ampulla, and of more than two turns of the cochlea was 100%. The MIP images and 3D images were almost comparable. The visibility of the endolymphatic duct was 80% in normal ears and 0% in the affected ears of the patients with Meniere's disease (p < 0.01). In one patient ear a small intracanalicular tumor was depicted clearly. In conclusion, the long echo train length T2-weighted 3D-FSE sequence enables the detailed visualization of the tiny structures of the inner ear and the IAC within a clinically acceptable scan time. Furthermore, obtaining a high contrast between the soft/bony tissue and the cerebrospinal/endolymph/ perilymph fluid would be of significant value in the diagnosis of the pathologic conditions around the labyrinth and the IAC.

Adult↗

Establishment and characterization of a human colon cancer cell line, OUMS-23, from a patient with familial adenomatous polyposis.

A human colon carcinoma cell line designated OUMS-23 has been established from metastatic pericardial fluid of a male familial adenomatous polyposis patient with colon cancer. Since 1984, the epithelial cells have been maintained in culture. Ultrastructural studies revealed the presence of numerous microvilli on the cell surface and desmosomes between the adjacent cells. The cells secreted carcinoembryonic antigen into the culture medium (15 ng/10(6) cells-1 24 h-1). The cells expressed heat-stable placental-type-like alkaline phosphatase, whereas the normal counterparts expressed tissue-unspecific alkaline phosphatase. Karyotypic analysis showed that the cell line was of human origin and that the chromosome number was broadly distributed between 53 and 118. Southern blot analysis of the APC gene revealed no abnormalities in OUMS-24 cells, while Northern blot analysis demonstrated that the expression of the gene was about one-half that of the normal human fibroblasts. No mutations at the "hot spots" of codons 12 and 61 of H-, K- and N-ras proto-oncogenes were detected in the cells. The cells could grow in soft agar at a cloning efficiency of 6.5%, and upon transplantation into nude mice the cells formed tumors, which were diagnosed as differentiated adenocarcinoma.

Adenomatous Polyposis Coli↗

Reduction of hepatic acute phase response after partial hepatectomy in elderly patients.

The hepatic capacity for acute phase protein synthesis after partial hepatectomy in the elderly patients was prospectively studied. Forty-one patients who consecutively underwent a partial hepatectomy were grouped according to age of greater or less than 70 years; 12 were in the older group and 29 in the younger. The changes in the levels of serum interleukin-6, alpha 1-antitrypsin, alpha 1-acid glycoprotein, haptoglobin, and plasma fibrinogen were measured after surgery. The postoperative changes in standard liver function tests were also measured. The incidence of postoperative infected complications was 25% in the older group and 7% in the younger (P = 0.28). Although postoperative levels of serum interleukin-6 were similar between the two groups, those of serum alpha 1-antitrypsin, alpha 1-acid glycoprotein, and haptoglobin were significantly lower in the elderly (P < 0.05). Postoperative levels of serum alpha 1-antitrypsin and plasma fibrinogen showed an increase of about 30% compared with the preoperative values (P < 0.05) in the younger group, but no significant increase in the older. Postoperative deterioration of serum albumin levels and hepaplastin test values was also significantly more severe in the older group (P < 0.05). We conclude that in the older patients, a reduction of acute phase protein synthesis occurs after partial hepatectomy as a result of a global deterioration of liver function, and may render patients liable to infection.

Acute-Phase Proteins↗

Purification and characterization of angiotensin II-generating chymase from hamster cheek pouch.

Hamster cheek pouch vascular tissues contain an angiotensin II-forming enzyme which is inhibited by chymostatin but not by any angiotensin-converting enzyme inhibitors. The enzyme was purified to apparent homogeneity by gel filtration and heparin-Sepharose affinity chromatography. The molecular mass estimated by sodium dodecyl sulphate polyacrylamide gel electrophoresis was 28 kDa and the optimum pH was between 7.5 and 9.0. The angiotensin II-forming activity was inhibited by chymostatin, soybean trypsin inhibitor and phenylmethylsulfonyl fluoride, but not by aprotinin. The N-terminal sequence showed high homology with chymases from various species. Thus, the angiotensin II-generating enzyme obtained from hamster cheek pouch vessels is a chymase.

Amino Acid Sequence↗

Antinociceptive effects of angiotensin-converting enzyme inhibitors and an angiotensin II receptor antagonist in mice.

Potential involvement of brain endogenous angiotensin II in the nociception was investigated in mice by using ACE inhibitors and an angiotensin II antagonist. The mice were allocated to the groups which were orally treated with spirapril (5 mg/kg), trandolapril (5 mg/kg), enalapril (30 mg/kg), losartan (10 mg/kg), or vehicle for 1 day (single dose groups) and 7 days (repeated doses groups). Significantly longer jump latencies were obtained for the groups repeatedly treated with spirapril, trandolapril and losartan, while the group with enalapril gained no effect. In contrast, the single dosing of all agents failed to show antinociceptive effect. The brain ACE activity was determined ex vivo immediately after the hot-plate test, and showed to be suppressed for the groups repeatedly treated with spirapril or trandolapril. In the group repeatedly treated with losartan, ex vivo autoradiography depicted the marked decrease in angiotensin II-binding capacity to the sites containing exclusively AT1 receptors within the blood-brain barrier. The antinociceptive effects of repeated doses of spirapril and losartan were reversed by naloxone. These results suggest that brain endogenous angiotensin II is likely to be involved in central nociceptive mechanisms by its antagonistic interaction with endogenous opioid system.

Administration, Oral↗

Glycylsarcosyl-L-histidylglycine, A peptide with a "breakpoint" in complex formation: hydrolysis of the complex [CuH-1L].

Coordination of CU(II) with glycylsarcosyl-L-histidylglycine to form the series of [CuL] and [CuH-1L] was studied potentiometrically and spectroscopically. [CuL] includes the Cu(N2O)O chromophore, in which Cu(II) coordinates with nitrogens from the terminal amino and imidazole groups and a carbonyl oxygen of the Gly-Sar bond, and shows a d-d transition band at 696 nm in the absorption spectrum and at 648 nm in the CD spectrum. The predominant species around pH 8 was [CuH-1L] with Cu(N3O) chromophore, in which Cu(II) coordinates with three nitrogens from a terminal amino, a deprotonated Sar-His peptide bond, and an imidazole of a histidyl residue, and shows the d-d transition band at 652 and 580 nm in the absorption and CD spectra, respectively. This species was hydrolyzed at the Gly-Sar peptide bond, yielding the Cu(II) complex of sarcosyl-L-histidylglycine.

Amino Acid Sequence↗

Possible release of nitric oxide from cholinergic axons in the thalamus by stimulation of the rat laterodorsal tegmental nucleus as measured with voltammetry.

By means of the differential direct current voltammetry technique with carbon fiber electrodes in urethane-anesthetized rats, we monitored nitric oxide (NO) concentrations in the thalamus in the basal condition and following electrical stimulation of the laterodorsal tegmental nucleus (LDT), whose neurons have the strongest activity of NADPH-diaphorase, or NO synthase, together with acetylcholine. NO levels, measured as the height of the peak at +970-1000 mV in the voltammetry (NO was soon oxidized in vivo to be detected at the voltage of this peak, so that NO levels in this report are, in the strict sense, levels of the oxidized metabolites reflecting very possibly those of NO in physiological conditions; see Section 2, Methods), increased just after repetitive stimulation of the LDT. Stimulation of the surrounding areas or the cerebellum produced virtually no change in NO levels. An intravenous injection of L-nitroarginine methyl ester reduced the basal level of NO, but stimulation of the LDT still increased NO levels, which may be due to very strong activity of NO synthase in the LDT neurons. These results are consistent with the notion that NO can be released from axons of the LDT neurons by their excitation.

Animals↗

Effect of light exposure on fracture toughness and flexural strength of light-cured composites.

OBJECTIVES: This study was conducted to investigate the curing characteristics of light-cured composites and their related mechanical properties. METHODS: Single-edge notch specimens [25 mm x 2.5 mm x 5 mm with a 5 mm notch (a/W = 0.5)] were prepared for fracture toughness measurements. For flexural strength testing, a stainless steel mold (25 mm x 2 mm x 2 mm) was used. Light-cured composites were condensed into the mold, and the middle third of the specimen was first activated for 30 s with 400 mW/cm2, for 60 s with 200 mW/cm2, or for 120 s with 100 mW/cm2. Then the remaining thirds were activated at the same intensity and curing time as the middle third. After 24 h storage in 37 degrees C water, three-point bending tests were performed with a span length of 20 mm at a crosshead speed of 0.5 mm/min. A one-way ANOVA, followed by a Newman-Keuls test (p < 0.05), were used to compare the data obtained from each group to test the effect of the curing conditions. RESULTS: Fracture toughness, flexural strength, and flexural modulus varied with resin composites. Among the three curing conditions for each material, there were no significant differences in fracture toughness, flexural strength, or flexural modulus. SIGNIFICANCE: The fracture toughness and the flexural strength were the same when irradiations with the same amount of energy (light intensity multiplied by curing time) were used. It was found that, at lower light intensity, longer curing was required to provide comparable mechanical properties. An accumulated irradiation energy obtained through a product of the light intensity and curing time may serve as a guideline to produce samples exhibiting equivalent fracture toughness as well as flexural strengths.

Analysis of Variance↗

Pyridinoline collagen cross-links in patients with chronic viral hepatitis and cirrhosis.

BACKGROUND/AIMS: The mature form of collagen cross-linking increases the resistance of collagen to degradative enzymes, and thus renders the protein in the fibrotic lesions extremely stable and the fibrosis virtually irreversible. It is crucial to elucidate the extent of cross-linking in fibrotic and cirrhotic livers if we are to control the subsequent removal of the excessive deposited collagen, whether by natural enzymes or induced by therapy. We aimed to quantitate pyridinoline, a mature form of the cross-linking, in normal control livers, viral fibrotic livers with various degrees of fibrosis and viral cirrhotic livers. METHODS: Needle liver biopsy samples from 75 patients with chronic viral hepatitis and 13 patients with viral liver cirrhosis, and six normal control livers were analyzed. Collagen and pyridinoline contents were determined by high-performance liquid chromatography. RESULTS: Significantly higher levels of pyridinoline cross-links per collagen molecule were found in the viral cirrhotic livers (0.60 [0.46, 0.65] pmol/pmol of collagen; median [25%, 75%]) compared with those in normal livers (0.39 [0.24, 0.43] pmol/pmol of collagen, p = 0.03491). But no differences were found in levels between cirrhosis and chronic hepatitis with various degrees of fibrosis. These data suggest that liver collagen may be susceptible to degradation to a similar degree in viral cirrhosis and in chronic viral hepatitis. CONCLUSION: The extent of the pyridinoline cross-linking of hepatic collagen does not seem to be responsible for the irreversibility of viral liver fibrosis.

Adult↗

Effect of pituitary adenylate cyclase-activating polypeptide on exocrine and endocrine secretion in the ovine pancreas.

The role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of exocrine and endocrine pancreas was investigated in conscious sheep. Intravenous infusions of PACAP-27 and PACAP-38 (1, 3, and 10 pmol/kg/min) for 10 min during phase II of the duodenal migrating myoelectric complex accelerated pancreatic protein and amylase outputs dose-dependently. The responses in enzyme secretion to both PACAPs at the highest doses were inhibited significantly by atropine infusion (14.4 nmol/kg/min). Vasoactive intestinal polypeptide (VIP) at 3 pmol/kg/min significantly accelerated protein but not amylase outputs, although the response to the highest dose was not significantly influenced by atropine. PACAP-27 and VIP increased pancreatic juice flow and bicarbonate output dose-dependently; however, the responses to the highest dose were not altered significantly by atropine. On the other hand, intravenous injection of PACAP-38 (100 pmol/kg) did not influence basal plasma concentration of insulin, glucagon, and glucose. Moreover, PACAP-38 (1-100 pmol/kg) altered neither pancreatic endocrine response to intravenous infusion of glucose (20 mumol/kg/min) not that to n-butyric acid (33 mumol/kg/min). These results suggest that PACAP contributes to the regulation of exocrine secretion of the ovine pancreas but not to endocrine secretion. PACAP appears to accelerate pancreatic enzyme secretion mostly via the cholinergic nerves.

Animals↗

Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.

We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.

Amino Acid Sequence↗

An orally active antitumor cyclohexanediamine-Pt(IV) complex: trans,cis,cis-bis(n-valerato)(oxalato)(1R,2R-cyclohexane diamine)Pt(IV).

In order to develop orally active antitumor platinum complexes, several cyclohexanediamine-Pt(IV) complexes of a general formula trans,cis,cis-[Pt(IV) (OCOCnHn+1)2 (oxalato)(1R,2R-cyclohexanediamine)] were synthesized by derivatizing oxaliplatin [Pt(II)(oxalato)(1R,2R-cyclohexanediamine), I-OHP], which is a potent antitumor cyclohexanediamine-Pt(II) complex we have prepared and now undergoing clinical trials. The I-OHP derivatives were found to be stable, lipophilic and reduced to yield I-OHP, an active species, quantitatively by ascorbate in vitro. All the derivatives were antitumor active against mouse lymphocytic leukemia L1210 when given i.p. In particular, trans-bis-valerato-oxalato-1R,2R-dach-Pt(IV), C5-OHP, showed markedly high activity. C5-OHP also exhibited significant antitumor activity against L1210 when orally administered. C5-OHP was considered to be a suitable candidate for the oral cancer chemotherapy agent to be developed.

Animals↗

Effect of aging on arteriolar dilatation induced by prostaglandin E(1) incorporated in lipid microspheres.

To investigate the effect of aging on vasodilation of arterioles induced by prostaglandin E1 incorporated in lipid microspheres (lipo-PGE(1)), we measured the diameter of the anterior ciliary artery in patients aged <65 years (young group) and in patients aged >65 years (elderly group). An eyelid retractor was affixed to the right eyelid while patients were under general anesthesia, and changes in the diameter of the arteriole were continuously monitored by surgical stereomicroscopy for 10 min after the intravenous (i.v.) injection of lipo-PGE(1) (0.2 mu g/kg). We also measured mean arterial pressure (MAP) and heart rate (HR) during the study. The diameter of the arteriole in the young group began to increase significantly 1 min after the injection (p < 0.01), reaching the maximal increase (42.3 +/- 7.4% above the preinjection level) at 3 min after continuous dilatation at the end of the study. In the elderly group, the diameter began to increase 2 min after the injection (p <0.01), reached the maximal value (33.2 +/- 12.7% above the preinjection level) at 5 min, and then gradually decreased to the baseline value. MAP decreased continuously after the injection in both groups; there was no significant difference between the groups. HR in the young group began to increase after the injection and then returned to the baseline level, but in the elderly group it showed continuous increase throughout the study. These results suggest that aging impaired the vasodilatory response to lipo-PGE(1) in the anterior ciliary artery.

Adult↗

Leukophagocytosis in human parvovirus B19-induced transient bicytopenia in a healthy child.

A previously health 11 year old boy had transient leukopenia and thrombocytopenia associated with human parvovirus B19 (B19) infection. This case suggested that low-grade hemophagocytosis can be involved in developing B19-related cytopenia even in an otherwise healthy child. Bone marrow aspiration at an early stage could reveal the underlying mechanism of B19-related cytopenia.

Biopsy, Needle↗

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy.

It has been proposed that a major hepatectomy impairs the liver-related host defense mechanism. The changes in the levels of serum inflammatory cytokines and plasma acute-phase proteins synthesized in the liver were measured after partial hepatectomy. Peak levels of serum interleukin-6 were significantly higher after extended lobectomy than after lobectomy or segmentectomy (p < 0.01). Serum interleukin-1 beta and tumor necrosis factor alpha levels showed no significant changes. Plasma levels of acute-phase proteins were significantly lower after lobectomy or extended lobectomy (p < 0.05). A reduced hepatic acute-phase response probably renders patients liable to infection after major hepatectomy.

Acute-Phase Proteins↗

Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity.

To evaluate liver dysfunction in patients with obstructive jaundice (OJ), morphological and functional hepatic mass was analyzed in comparison with cirrhosis (LC). Total hepatic parenchymal ratio (THPR) was estimated by morphometric analysis and hepatic functional mass by galactose tolerance test (GaTT) in 30 patients who underwent hepatectomy. The value of GaTT in patients with LC was remarkably depressed compared to those with normal liver function (p < 0.001). It was also depressed in OJ (p < 0.05 vs. normal liver), but less than in LC (p < 0.05). However, THPR decreased only in LC (p < 0.05 vs. either normal liver or OJ). A significant correlation between the value of GaTT and THPR was revealed in patients with LC, but not in OJ. These results suggested that liver dysfunction in OJ was independent of the decreased number of hepatocytes, differing from LC.

Adult↗