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Biomedical subjects

Y Nishida

Publications and source records attributed to Y Nishida.

At least 91 records · Page 5Linked to original sources

[Prediction of restenosis after percutaneous transluminal coronary angioplasty using coronary flow reserve. Kansai Doppler Guide Wire Study Group].

This multi-center prospective study attempted to predict restenosis after percutaneous transluminal coronary angioplasty(PTCA) using coronary flow reserve. Intracoronary blood flow velocity was measured in 47 patients(37 males, 10 females, mean age 66 +/- 9 years) with a Doppler guide wire, following successful PTCA. Twenty-four patients had prior myocardial infarction. After successful PTCA, a Doppler guide wire was placed at the distal portion of the target lesion, and coronary blood flow velocity was measured before and during intravenous administration of adenosine triphosphate. Follow-up coronary angiography was performed 154 +/- 69 days after PTCA, and the diameter stenosis of the target lesion was measured using quantitative coronary angiography. Follow-up angiography showed restenosis in 13 patients(28%). Sensitivity and specificity for predicting restenosis were low(50%, 45%, respectively) with a post-PTCA% diameter stenosis cut-off point of 27%. Sensitivity and specificity were 67% and 61% with a minimal lumen diameter cut-off of 1.8 mm. The reference coronary artery diameter(cut-off point 2.5 mm) was better for predicting restenosis(sensitivity 78% and specificity 76%). Sensitivity and specificity were 62% and 67%, respectively, using coronary flow reserve(cut-off point 2.0). The restenosis rate of patients with a reference diameter of more than 2.5 mm was 10%, but 54% for those with less than 2.5 mm(p < 0.05). In patients with a reference diameter of less than 2.5 mm, coronary flow reserve was useful for predicting restenosis(cut-off point 1.9, sensitivity 71% and specificity 83%). Coronary flow reserve is useful for predicting restenosis after PTCA, when combined with reference coronary artery diameter.

Aged↗

Two cases of hypothyroidism complicated by renal dysfunction.

We report two patients in whom hypothyroidism was considered to cause renal dysfunction. Case 1 was a 65-year-old woman who stopped taking levothyroxine sodium for hypothyroidism. After 6 months, she developed proteinuria, edema, weight gain, and renal dysfunction. Renal biopsy revealed focal segmental proliferative glomerulonephritis. After re-administration of levothyroxine sodium, thyroid function and renal function both recovered. Case 2 was a 51-year-old man who presented with edema, difficulty in swallowing, muscular weakness, and fatigue. We diagnosed hypothyroidism, and focal segmental proliferative glomerulonephritis was revealed by renal biopsy. After administration of levothyroxine sodium, his symptoms resolved and his thyroid function and renal function both improved. Our experience suggests that hypothyroidism should be taken into consideration as one of the causes of renal dysfunction.

Aged↗

[Small cell carcinoma of the urinary bladder: a case report].

We report a case of small cell carcinoma of the urinary bladder. The patient was a 58-year-old man complaining of gross hematuria. Clinical examination revealed a non-papillary, broad-based tumor on the right bladder wall with a clinical stage of T3a, N0, M0. Neoadjuvant intraarterial infusion chemotherapy with methotrexate, adriamycin and cisplatin was performed, but it was ineffective. Three weeks later we performed a radical cystectomy. The operative specimen of the tumor revealed small cell carcinoma. It was staged pT3aN0M0R0L2V1. Postoperatively, 1 course of adjuvant chemotherapy using cisplatin and etoposide was performed. The patient is alive without any evidence of tumor recurrence at 6 months after operation.

Antineoplastic Combined Chemotherapy Protocols↗

[Increased incidence of coronary artery disease and cardiac death in elderly diabetic nephropathy patients undergoing chronic hemodialysis therapy].

OBJECTIVES: The incidence of coronary artery disease and cardiac death was investigated in elderly diabetic patients undergoing chronic hemodialysis therapy. METHODS: Three hundred thirty-five patients who began hemodialysis therapy since 1992 were followed up by echocardiography and treadmill exercise testing. Coronary angiography was also performed in patients with angina pectoris. Angina pectoris was defined as clinical symptoms > Canadian Cardiovascular Society classification II, and asynergy findings by echocardiography or ST depression > 0.1 mV during the treadmill exercise test. Coronary artery stenosis was defined as narrowing > or = 75%. Patients were divided into 4 groups: diabetic nephropathy (DN) > or = 65 years old (Group O/DN, n = 56), DN < 65 years old (Group Y/DN, n = 84), non-DN > or = 65 years old (Group O/non-DN, n = 76) and non-DN < 65 years old (Group Y/non-DN, n = 119). RESULTS: Between 1992 and 1998, there were 137 patients with angina pectoris (40.9%), 79 with coronary artery stenosis (23.6%) and 37 with cardiac death (11.0%). Cumulative incidences of angina pectoris, coronary artery stenosis and cardiac death were significantly higher in the following order of groups; O/DN > Y/DN > O/non-DN > Y/non-DN. Five-year cumulative incidences of angina pectoris, coronary artery stenosis and cardiac death in Groups O/DN vs Y/non-DN were 72.2% vs 38.6%, 53.7% vs 12.2% and 50.6% vs 3.5%, respectively. Relative risks of aging and diabetic nephropathy for angina pectoris, coronary artery stenosis and cardiac death were 3.8, 7.9 and 22.4, respectively (p < 0.0001). CONCLUSIONS: Aging and the presence of diabetes are strong risk factors for coronary artery disease and cardiac death in hemodialysis patients. Therefore, diagnosis and treatment of coronary artery disease should be achieved at the early stage of hemodialysis therapy.

Aged↗

[A preliminary study on dihydropyrimidine dehydrogenase activity in breast cancer].

We studied dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS), key enzymes in regulating the pharmacokinetics and chemosensitivity to 5-FU, in 36 breast cancer patients as a control group and 18 patients as a 5-FU group, in which 5-FU was given orally for 2 weeks before surgery at a dose of 200 mg/day. Cancer tissues with adjacent normal tissue were sampled and stored until the assay. The DPD activity and TS amount were determined according to the radio-enzymatic assay and radiobinding assay, respectively. The DPD activity was significantly higher in breast cancer than in the adjacent breast tissue. This finding was observed in T1 and T2, node negative and ER positive breast cancers in the control group as well as in the 5-FU group. The DPD activity in T3 was significantly lower than in T1, and that of the adjacent breast tissue in T3 was significantly higher than in T1; therefore, the tumoral/non-tumoral ratio of DPD activity was significantly lower in T3 than T1. TS was significantly elevated in both groups, without significant differences. The clinical implication of elevated DPD activity in T1, T2, node negative or ER positive breast cancer compared to the respective normal breast tissue activity remains to be studied, because it is still unclear whether or not the tumoral DPD activity regulates the local concentration of 5-FU within the tumor. The amount of TS and DPD activity was not influenced by the oral administration of 5-FU for 2 weeks at the dose of 200 mg/day.

Antimetabolites, Antineoplastic↗

A case of adenoma of the ampulla of Vater.

A case of adenoma of the ampulla of Vater is presented in a 48-year-old man who was admitted with epigastric pain. Gastroendoscopy revealed a sessile tumor about 3 cm in diameter at the ampulla of Vater, and the pathological diagnosis of a biopsy specimen was adenoma with moderate atypia. Because of the possibility of a malignant component, pylorus-preserving pancreatoduodenectomy was performed to avoid local recurrence. The final pathological diagnosis was adenoma with severe atypia.

Adenoma↗

Lipid-lowering therapy and coagulation/fibrinolysis parameters in patients on peritoneal dialysis.

Patients on continuous ambulatory peritoneal dialysis (CAPD) often have abnormalities of lipid metabolism or coagulation and fibrinolysis, these patients may thus be more susceptible to atherosclerosis than those on hemodialysis. It has been reported that hypercoagulability and hyperfibrinolysis are correlated with abnormalities of lipid metabolism. Therefore, we investigated the effect of a decrease in lipids on the coagulation and fibrinolysis system in CAPD patients with hyperlipidemia who received lipid-lowering therapy. The patients included 5 men and 13 women, with a mean age of 52.5 years. Pravastatin sodium (10 mg/day) and ethyl icosapentate (1800 mg/day) were administered concomitantly for 8 weeks. Lipid levels and coagulation/fibrinolysis parameters were measured before and after therapy. The patients were divided into two groups depending on their response to therapy: responders showed a decrease in total cholesterol or triglycerides by at least 20% and non-responders showed less improvement. In the responders, the levels of protein C, tissue plasminogen activator/plasminogen activator inhibitor-I complex, factor XIII, alpha2-plasmin inhibitor, and D-dimer were significantly lower after therapy than before therapy. Protein C, factor XIII, and alpha2-plasmin inhibitor were also significantly decreased after therapy in non-responders, but the extent of the decrease was smaller. The plasminogen level was significantly increased after therapy in non-responders. These findings suggest that a decrease in lipid levels and/or some other action by lipid-lowering agents may correct abnormalities of coagulation and fibrinolysis in CAPD patients.

Adult↗

Involvement of mitochondrial aldehyde dehydrogenase ALD5 in maintenance of the mitochondrial electron transport chain in Saccharomyces cerevisiae.

The physiological role of mitochondrial aldehyde dehydrogenase (ALD5) was investigated by analysis of the ald5 mutant (AKD321) in Saccharomyces cerevisiae. K(+)-activated ALDH activity of the ald5 mutant was about 80% of the wild-type in the mitochondrial fraction, while the respiratory activity of the ald5 mutant was greatly reduced. Cytochrome content was also reduced in the ald5 mutant. Enzymatic analysis revealed that the alcohol dehydrogenase activity of the ald5 mutant was higher than that of the wild-type, while glycerol 3-phosphate dehydrogenase activity was the same in the two strains. Ethanol as a carbon source or addition of 1 M NaCl with glucose as the carbon source in the growth medium increased beta-galactosidase activity from an ALD5-lacZ fusion. Overexpression of another mitochondrial ALDH gene (ALD7) had no effect on increasing respiratory function of the ald5 mutant, but showed improved growth on ethanol. These observations show that mitochondrial ALD5 plays a role in regulation or biosynthesis of electron transport chain components.

Aldehyde Dehydrogenase↗

Identification and characterization of Drosophila homolog of Rho-kinase.

The Rho family of small GTPases and their associated regulators and targets are essential mediators of diverse morphogenetic events in development. Mammalian Rho-kinase/ROK alpha, one of the targets of Rho, has been shown to bind to Rho in GTP-bound form and to phosphorylate the myosin light chain (MLC) and the myosin-binding subunit (MBS) of myosin phosphatase, resulting in the activation of myosin. Thus, Rho-kinase/ROK alpha has been suggested to play essential roles in the formation of stress fibers and focal adhesions. We have identified the Drosophila homolog of Rho-kinase/ROK alpha, DRho-kinase, which has conserved the basic structural feature of Rho-kinase/ROK alpha consisting of the N-terminal kinase, central coiled-coil and C-terminal pleckstrin homology (PH) domains. A two-hybrid analysis demonstrated that DRho-kinase interacts with the GTP-bound form of the Drosophila Rho. Drho1, at the conserved Rho-binding site. DRho-kinase can phosphorylate MLC and MBS, preferable substrates for bovine Rho-kinase, in vitro. DRho-kinase is ubiquitously expressed throughout development, in a pattern essentially identical to that of Drho1. These results suggest that DRho-kinase is an effector of Drho1.

Amino Acid Sequence↗

Antisense inhibition of hyaluronan synthase-2 in human articular chondrocytes inhibits proteoglycan retention and matrix assembly.

In order to define the role of cell-associated hyaluronan in cartilage matrix retention, human articular chondrocytes as well as cartilage slices were treated with phosphorothioate oligonucleotides comprised of sequence antisense to the mRNA of human HA synthase-2 (HAS-2). As a prerequisite for these studies, it was necessary to determine which HA synthase (HAS), of three separate human genes capable of synthesizing HA, designated HAS-1, HAS-2, or HAS-3, is primarily responsible for HA synthesis in human articular chondrocytes. The copy number of each HAS mRNA expressed in cultured human articular chondrocytes was determined using quantitative (competitive) reverse transcription-polymerase chain reaction (RT-PCR). Only HAS-2 and HAS-3 mRNA expression was detected. The level of HAS-2 mRNA expression was 40-fold higher than that of HAS-3. Cultures of human articular chondrocytes and cartilage tissue slices were then transfected with HAS-2-specific antisense oligonucleotides. This treatment resulted in time-dependent inhibition of HAS-2 mRNA expression, as measured by quantitative RT-PCR, and a significant loss of cell-associated HA staining. Sense and reverse HAS-2 oligonucleotides showed no effect. The consequences of reduced HA levels (due to HAS-2 antisense inhibition) were a decrease in the diameter of the cell-associated matrix and a decreased capacity to retain newly synthesized proteoglycan. These results suggest that HA synthesized by HAS-2 plays a crucial role in matrix assembly and retention by human articular chondrocytes.

Base Sequence↗

Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing.

Distinct and evolutionarily conserved signal-transduction cascades mediate the survival or death of cells during development. The c-Jun amino-terminal kinases (JNKs) of the mitogen-activated protein kinase superfamily are involved in apoptotic signalling in various cultured cells. However, the role of the JNK pathway in development is less well understood. In Drosophila, Decapentaplegic (Dpp; a homologue of transforming growth factor-beta) and Wingless (Wg; a Wnt homologue) proteins are secretory morphogens that act cooperatively to induce formation of the proximodistal axis of appendages. Here we show that either decreased Dpp signalling in the distal wing cells or increased Dpp signalling in the proximal wing cells causes apoptosis. Inappropriate levels of Dpp signalling lead to aberrant morphogenesis in the respective wing zones, and these apoptotic zones are also determined by the strength of the Wg signal. Our results indicate that distortion of the positional information determined by Dpp and Wg signalling gradients leads to activation of the JNK apoptotic pathway, and the consequent induction of cell death thereby maintains normal morphogenesis.

Acridine Orange↗

Cloning and expression of interleukin-18 binding protein.

Interleukin-18 binding protein is a novel glycoprotein that we successfully cloned and expressed. First, murine interleukin-18 binding protein was purified from the sera of mice with endotoxin shock using ligand affinity chromatography. The murine interleukin-18 binding protein cDNA was cloned after RT-PCR using mixed primer pair sequences based on partial murine interleukin-18 binding protein amino acid sequence analysis. Subsequently, human interleukin-18 binding protein cDNA was cloned from cDNA libraries of normal human liver using murine interleukin-18 binding protein cDNA as a probe. Next, we transiently expressed recombinant human and murine interleukin-18 binding proteins in COS-1 cells and purified them from culture supernatants. Both recombinant interleukin-18 binding proteins did not exhibit species specificity and prevented interleukin-18 binding to its receptor. In addition, they inhibited interleukine-18 dependent IFN-gamma production from KG-1 cells effectively. These results suggest that the interleukin-18 binding protein may possess interleukine-18 antagonist activity.

Amino Acid Sequence↗

Effects of 7-nitroindazole on renal sympathetic nerve activity during acute cardiac tamponade in conscious rabbits.

To investigate whether nitric oxide (NO) in the central nervous system is involved in the decrease in renal sympathetic nerve activity (RSNA) during acute cardiac tamponade in conscious rabbits, we examined the effect of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase in vivo, on RSNA during acute cardiac tamponade in chronically installed conscious rabbits. Cardiac tamponade was produced by intrapericardial infusion of physiological saline at 2 ml/30 s. Mean arterial pressure (MAP) remained constant initially but RSNA increased to 218+/-24% when we started injection of physiological saline into the pericardial space. Concomitantly after MAP fell to 51+/-1 mm Hg by subsequent injection of the saline into the pericardial space, RSNA decreased to 45+/-6%. If 7-NI (50 mg/kg) was administered intraperitoneally 35 min before the beginning of cardiac tamponade, the decline in RSNA caused by cardiac tamponade was markedly counteracted. Brain nitric oxide synthase (NOS) activity in the cerebral cortex and medulla oblongata, assessed by the conversion of labelled arginine to citrulline, was inhibited by 48% and 44% after the intraperitoneal administration of 7-NI. These results indicate that acute cardiac tamponade elicits a biphasic effect on RSNA, which rises during non-hypotensive period and then falls during hypotension in conscious rabbits. The decrease in RSNA was abolished by treatment with 7-NI, suggesting that the abrupt decrease in RSNA during hypotension induced by acute cardiac tamponade is mediated by NO in the central nervous system.

Acute Disease↗

Intravascular ultrasound-guided balloon angioplasty for treatment of in-stent restenosis.

We investigated the usefulness of intravascular ultrasound (IVUS)-guided balloon angioplasty for in-stent restenosis in 37 lesions of 34 consecutive patients. We divided these patients into two groups: a group in which the balloon size was determined by quantitative coronary angiography (QCA group; 17 patients, 19 lesions) and a group in which the balloon size was determined by IVUS (IVUS group; 17 patients, 18 lesions). We compared short-term and 6-month outcomes for these groups. In the IVUS group, we used a balloon of a size equal to 95% of the media-to-media diameter at the distal to the stent, as determined by IVUS. No significant differences were observed in patient or lesion characteristics between the two groups. The clinical success rate was 100% in both groups, and no clinical events were observed in either of the groups. The balloon/artery ratio was larger in the IVUS group than in the QCA group (1.33 +/- 0.35 vs. 1.16 +/- 0.13, P < 0.05), and the recurrent restenosis rate was lower (17% vs. 53%, P < 0.05). These results suggest that repeat balloon angioplasty using a balloon size determined by IVUS is useful for in-stent restenosis. Cathet. Cardiovasc. Intervent. 47:298-303, 1999.

Angioplasty, Balloon, Coronary↗

Functional and structural characterization of multiple galectins from the skin mucus of conger eel, Conger myriaster.

The complete amino acid sequence of an isogalectin, named congerin II, isolated from the skin mucus of conger eel, was determined by sequencing of the protein and its peptides generated by enzymatic and chemical cleavages. Congerin II consisted of 135 amino acids residues containing an acetylated N-terminus. Congerin II was found to be only 46% homologous in sequence to congerin I which was previously determined (Muramoto K., Kamiya H., Biochem. Biophys. Acta, 1992;1116:129-136), suggesting that the galectins with diverse molecular properties are present in the skin mucus of conger eel. However, it was confirmed by analysis of the secondary structures using circular dichroism that both congerins I and II shared similar folds characterized by beta structures. Congerins I and II showed different molecular properties such as thermostability, pH dependency for hemagglutinating activity and for binding specificity against the pyridylamino derivative of lactose. Congerin I showed more strict recognition specificity for lactose than did congerin II. Furthermore, the effects of chemical modification on congerins I and II were investigated in order to identify the type of amino acids involved in their different lectin activities. Modification of tyrosine and lysine residues did not affect the carbohydrate-binding activities of congerins. However, modification of tryptophan, arginine, histidine, glutamic acid and aspartic acid residues led to considerable loss of their activities, and a different mode of binding activity was observed between modified congerins I and II. These results suggest that multiple galectins from conger eel with the same scaffold have different biological functions and properties.

Amino Acid Sequence↗

Synthesis of an artificial glycoconjugate polymer carrying Pk-antigenic trisaccharide and its potent neutralization activity against Shiga-like toxin.

Fluorescence-labeled glycoconjugate polymers carrying carbohydrate segments of a globotriaosyl ceramide (Gb3) were synthesized and subjected to biological assays using Escherichia coli O-157 strains and Shiga-like toxins (Stx-I and Stx-II). For the fluorescence labeling, a new polymerizable fluorescent monomer with a TBMB carbonyl chromophore (Ex. 325 nm, Em. 410 nm) was designed. A glycosyl monomer of the trisaccharide segment of Gb3 was prepared from p-nitrophenyl beta-lactoside and copolymerized with acrylamide and the fluorescent monomer to prepare a fluorescence-labeled glycoconjugate copolymer carrying [alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl]-(1-->4)-beta- D-glucopyranoside. The polymer showed potent neutralization activity against Stx-I and also binding activity onto E. coli O-157 strains.

Antigens↗

A novel anti-diabetic drug, miglitol, markedly reduces myocardial infarct size in rabbits.

1. We examined whether N-hydroxyethyl-1-deoxynojirimycin (miglitol), a new human anti-diabetic drug with effects to inhibit alpha-1, 6-glucosidase glycogen debranching enzyme and reduce the glycogenolytic rate as well as to inhibit alpha-1,4-glucosidase, could reduce infarct size in the rabbit heart. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. 2. The infarct size as a percentage of area at risk was not reduced by pre-ischaemic treatment with 1 mg kg(-1) miglitol (42.7+/-4.0%, n=10) compared with the saline control group (41.7+/-2.3%, n=10). However, it was significantly and dose-dependently reduced by pre-ischaemic treatment with 5 or 10 mg kg(-1) of miglitol (25.7+/-4. 5%, n=10, and 14.6+/-2.4%, n=10, respectively) without altering the blood pressure, heart rate or blood glucose level. However, there was no evidence of an infarct-size reducing effect after pre-reperfusion treatment with 10 mg kg(-1) of miglitol (35.0+/-3.0%, n=10). 3. Another 40 rabbits given 1, 5 and 10 mg kg(-1) of miglitol or saline before ischaemia (n=10 in each) were sacrificed at 30 min of ischaemia for biochemical analysis. Miglitol preserved significantly the glycogen content, and attenuated significantly the lactate accumulation in a dose dependent manner in the ischaemic region at 30 min of ischaemia. 4. Pre-ischaemic treatment, but not pre-reperfusion treatment, with miglitol markedly reduced the myocardial infarct size, independently of blood pressure and heart rate. A dose-dependent effect of miglitol on infarct size, glycogenolysis and lactate formation suggests that the mechanism may be related to the inhibition of glycogenolysis. Thus, miglitol may be beneficial for coronary heart disease as well as diabetes mellitus.

1-Deoxynojirimycin↗