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Biomedical subjects

Y Maruyama

Publications and source records attributed to Y Maruyama.

At least 19 recordsLinked to original sources
PubMed2006

Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells.

Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.

Animals↗
PubMed2006

High frequency of several PIG-A mutations in patients with aplastic anemia and myelodysplastic syndrome.

To clarify some characteristics of phosphatidylinositol glycan-class A gene (PIG-A) mutations in aplastic anemia (AA) and myelodysplastic syndrome (MDS) patients compared with those in paroxysmal nocturnal hemoglobinuria (PNH) patients, we investigated PIG-A mutations in CD59- granulocytes and CD48- monocytes from seven AA, eight MDS, and 11 PNH Japanese patients. The most frequent base or type abnormalities of the PIG-A gene in AA and MDS patients were base substitutions or missense mutations, respectively, and deletions or frameshift mutations, respectively, in PNH patients. Several PIG-A mutations, most of which were statistically minor, were found in glycosylphosphatidylinositol-negative cells from all AA and MDS patients but not from all PNH patients. However, the common PIG-A mutations during the clinical course between CD59- granulocytes and/or CD48- monocytes from each AA or MDS patient, except for Case 5, were not found. PIG-A mutations were different between the granulocytes and monocytes from five AA and five MDS patients. Our results indicate that there were some characteristics of PIG-A mutations in AA and MDS patients compared with PNH patients and that several minor PNH clones in these patients occurred at random during the clinical course. This partly explains the transformation of AA or MDS to PNH at intervals.

Adult↗
PubMed2006

Fatal hepatitis B virus reactivation in a chronic myeloid leukemia patient during imatinib mesylate treatment.

Reactivation of chronic hepatitis B virus (HBV) infection in patients undergoing chemotherapy is well-documented, but reactivation during imatinib mesylate treatment has not been reported. This study reports a 54-year-old man, without prior liver dysfunction but with chronic HBV infection, in whom fatal HBV reactivation occurred during treatment of chronic myeloid leukemia (CML) with imatinib mesylate. He developed fulminant hepatitis followed by marked elevation of HBV DNA polymerase, probably from the lymphocytopenic and immunosuppressive status induced by imatinib mesylate. Imatinib mesylate is widely used to treat CML patients. Although therapy with imatinib mesylate is generally well tolerated, the case presented here suggests that viral reactivation should be considered, even when using imatinib mesylate to treat CML.

Antineoplastic Agents↗
PubMed2006

Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.

BACKGROUND: Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level. METHODS: We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography. Malnutrition was assessed by subjective global assessment (SGA). RESULTS: At basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes mellitus, respectively. At baseline, the mean plasma pentosidine levels were similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19 pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly lower in the patients with carotid plaques than in the patients without carotid plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p < 0.01, respectively). The prevalence of hyperhomocysteinemia (tHcy level > 13.7 micromol/l) was 95%. In univariate analysis, the change in cIM area during the first year of dialysis was significantly correlated with basal plasma pentosidine level (p = 0.31, p = 0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy levels were correlated with cIM area at basal or at 12 months. In a stepwise multiple regression model, age and plasma pentosidine content, but not the tHcy level, associated with changes in the cIM area. CONCLUSION: Progression of atherosclerosis, as indicated by changes in carotid intima-media area during the course of dialysis treatment, was associated with pentosidine, but not with tHcy, levels at baseline in these CKD patients. This suggests that the accumulation of AGEs in CKD patients may have a role in the pathogenesis of CVD in these patients. Since almost all CKD patients have hyperhomocysteinemia, this finding, however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD patients.

Adult↗
PubMed2005

Poststreptococcal acute glomerulonephritis superimposed on bilateral renal hypoplasia.

An 8-year-old girl with preexisting chronic renal failure (CRF) due to bilateral renal hypoplasia presented with edema, gross hematuria and acute deterioration of renal function. The diagnosis of poststreptococcal acute glomerulonephritis (PSAGN) was made based on clinical presentation, red blood cell casts, low level of C3 and elevated antistreptolysin 0 titer. Her course was prolonged with serum creatinine increased from the baseline level of 1.1 mg/dl to 2.2 mg/dl, returning toward the baseline level (1.2 mg/dl) after one month. Serum creatinine then started to increase again. The slope of creatinine clearance over time became steeper after the episode of PSAGN. A severe course of PSAGN and subsequent deterioration of renal function have previously been reported in patients with diabetic nephropathy or focal glomerulosclerosis. The present case along with a literature review suggests that individuals with fewer nephrons are at higher risk of severe course and outcome of PSAGN. Conversely, patients with severe PSAGN may be born with fewer nephrons due to low birth weight, unrecognized renal hypoplasia or other unknown causes.

Acute Disease↗
PubMed2005

Using biosensors to detect the release of serotonin from taste buds during taste stimulation.

CHO cells transfected with high-affinity 5HT receptors were used to detect and identify the release of serotonin from taste buds. Taste cells release 5HT when depolarized or when stimulated with bitter, sweet, or sour tastants. Sour- and depolarization-evoked release of 5HT from taste buds is triggered by Ca2+ influx from the extracellular fluid. In contrast, bitter- and sweet-evoked release of 5HT is triggered by Ca2+ derived from intracellular stores.

Adenosine Triphosphate↗
PubMed2004

Ulnar recurrent adipofascial flap for reconstruction of massive defects around the elbow and forearm.

An ulnar recurrent adipofascial flap was raised and turned over to reconstruct massive defects around the elbow and forearm after wide resection of malignant tumours. Compared to the fasciocutaneous flap, the ulnar recurrent adipofascial flap has the following advantages: (1) a larger flap can be harvested without the problem of primary closure of the donor site, (2) the contour and scar of the donor site is reasonably acceptable since no tension is presented, (3) the flap can be turned over to cover a wider area, and (4) debulking of the flap can be performed during the operation if needed. The rotation arc of the ulnar recurrent adipofascial flap reaches a wide region, including the distal one-half of the upper arm, the elbow, and the proximal two-thirds of the forearm. Sensory deficit in the forearm was avoided in our patients because meticulous separation and preservation of the medial cutaneous nerve of the forearm was achieved without jeopardising the blood supply to the flap. The ulnar recurrent adipofascial flap is an easy and reliable option for one-stage reconstruction of massive defects around the elbow.

Elbow↗
PubMed2003

Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities and the response rate of carboplatin and 5-fluorouracil administered daily with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC) were enrolled. Carboplatin (20-40 mg m(-2) 2-h infusion, daily) and 5-fluorouracil (200 mg m(-2) 24-h continuous infusion, daily) were administered concurrently with radiotherapy on days 1-33. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions on days 1-40. In the phase I portion, the daily dose of carboplatin was escalated from 20 to 40 mg m(-2). Once the maximum tolerated dose (MTD) and recommended dose (RD) of carboplatin was determined, the study entered the phase II portion. In the phase I portion, the daily MTD and RD of carboplatin were 40 and 35 mg m(-2), respectively. The dose-limiting toxicity was neutropenia. In the following phase II study, 30 patients were entered and the objective response rate was 76.7% (95% CI, 62-92%) and the local control rate was 85.7%. The median survival time was 19.8 months, with a survival rate of 70% at 1 year, 36.7% at 2 years. The major toxicities of treatment were neutropenia (>or=grade 3, 87.9%) and thrombocytopenia (>or=grade 3, 23.3%). This combined therapy for locally advanced non-small-cell lung cancer is promising and shows acceptable toxicity.

Adult↗
PubMed2003

Alteration in haemodynamics and pathological changes in the cardiovascular system during the development of Type 2 diabetes mellitus in OLETF rats.

AIMS/HYPOTHESIS: The process of cardiovascular complications in Type 2 diabetes mellitus (DM) is unclear. We investigated pathophysiological changes of the heart and vessels in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat Type 2 DM model during a long time period. METHODS: Echocardiography was carried out at 22 and 62 weeks of age of OLETF ( n=10, each) and age-matched Long-Evans Tokushima Otsuka (LETO) rats ( n=10, each) as a reference. Haemodynamic measurements and histological examinations of the heart and the coronary and aortic vascular walls were done. RESULTS: The left ventricular (LV) maximal -dP/dt was reduced in OLETF rats at 62 weeks (-1085+/-35 mmHg/s) less than that at 22 weeks (-1892+/-396 mmHg/sec, p<0.05) and in LETO rats at 62 weeks (-1306+/-200 mmHg/sec, p<0.05). Wall thickening of intramyocardial coronary arteries, capillary tortuosity and thickening of basement membrane were evident in OLETF rats at 62 weeks. Intimal and medial wall thickening of the aorta were prominent in OLETF rats at 62 weeks (15+/-2.2 and 90+/-6.6 micro m, in LETO rats at 62 weeks, 2+/-0.4 and 65+/-5.2 micro m, p <0.05, and in OLETF rats at 22 weeks, 7+/-4.6 and 71+/-6.0 micro m, p<0.05, respectively). CONCLUSIONS/INTERPRETATION: In the Type 2 DM model, angiopathy, especially in coronary arteries including small vessels, as well as a LV relaxation abnormality, are induced in a late stage of DM. These are considered to be important complications in Type 2 DM.

Animals↗
PubMed2003

Effects of deicing salt on the vitality and health of two spruce species, Picea abies Karst., and Picea glehnii Masters planted along roadsides in northern Japan.

In northern Japan, the growth of Picea abies Karst., and Picea glehnii Masters, which have been planted along the highways, is often suppressed due to several environmental stresses. To examine the adverse effects of deicing salt, the primary source of stress,we measured needle life span, photosynthetic capacity, and water potential and transpiration rate of the two spruce species at a site with damaged trees, near the roadside and a site with healthy trees, located far from the highway. Results from the analysis showed large amounts of sodium and chlorine in the soil and snow at the damaged site. These elements had accumulated in the needles of the spruce. Moreover, physiological traits of the spruce, at the damaged site were also affected. Therefore, we concluded that poor physiological traits might be attributed to an accumulation of deicing salt in the needles, resulting in the suppression of tree growth.

Absorption↗
PubMed2003

Calcium signalling in and around the nuclear envelope.

We have compared calcium mobilization by Ins(1,4,5) P(3)(IP(3)), cADP-ribose (cADPR) and nicotinic acid-adenosine dinucleotide phosphate (NAADP) from the envelope of isolated nuclei with the calcium signalling in intact isolated pancreatic acinar cells. Ca(2+) uptake and release were studied with calcium-sensitive fluorescent probes. In the present study, we have shown that all calcium messengers induce Ca(2+) release from the nuclear envelope. Pre-treatment of nuclei with thapsigargin completely abolished the responses to the calcium messengers, indicating that Ca(2+) stores in isolated nuclei are thapsigargin-sensitive. Using different pharmacological tools, we show that Ca(2+) release from pancreatic nuclei is unlikely to occur from stores other than those with endoplasmic reticulum characteristics. We conclude that all three calcium messengers can release Ca(2+) from pancreatic acinar nuclear stores, as previously shown for IP(3) and cADPR. It would appear that NAADP releases Ca(2+) from the same IP(3)- and cADPR-sensitive stores with endoplasmic reticulum characteristics.

Animals↗
PubMed2002

Stepladder dorsal metacarpal flaps for dorsal finger and hand reconstruction.

The authors demonstrate successful cases of stepladder dorsal metacarpal V-Y advancement and rotation-advancement flaps for reconstructing defects on the dorsum of the finger and hand. One side of the flap is designed in a multilobed shape, and each lobed flap is designed on the dorsum of adjacent fingers. These flaps are supplied by dorsal metacarpal vessels. Consequently, this method has the elements of the stepped incision technique, in combination with the V-Y and rotation-advancement principle. All flaps survived completely. This technique may be a useful option for reconstruction of defects of the dorsum of the finger and hand.

Bowen's Disease↗
PubMed2002

Ultrasound changes of the carpal tunnel in patients receiving long-term hemodialysis: a cross-sectional and longitudinal study.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the major problems of long-term hemodialysis (HD), but sometimes difficult to distinguish from uremic or diabetic neuropathy by clinical symptoms. PATIENTS AND METHODS: To evaluate the diagnosis of CTS more precisely, we examined the ultrasonographic alterations of the carpal tunnel and tendons of 90 wrists from 45 patients undergoing HD for more than 5 years. We measured the thickness of the palmar radiocarpal ligament (PRL), corresponding to the posterior wall of the carpal tunnel (CT), and the width of the CT, and compared those values with sensory (SCV), motor conduction velocity (MCV) of the median nerve and clinical symptoms. In addition, we longitudinally measured CT and PRL in the same patients for 5 years, and compared ultrasonographic changes and clinical parameters. RESULTS: A linear positive relationship was found between HD duration and PRL thickness (r = 0.43, p < 0.01) or CT width (r = 0.53, p < 0.01). CT diameter was negatively correlated with MCV (r = -0.30, p < 0.01) and SCV (r = -0.33, p < 0.04). PRL thickness was also inversely correlated with MCV (r = -0.44, p < 0.01) and SCV (r = -0.46, p < 0.01) of the median nerve, respectively. The wrists with clinical CTS and/or previous CTS surgery had significantly greater CT and PRL values compared to patients without CTS (CT: 6.1 0.2vs. 8.0+/-0.3 mm,p<0.01;PRL: 1.9+/-0.1 vs. 3.6 +/- 0.2 mm, p < 0.01). There was a significant increase in CT width from 6.2 +/- 0.2 to 7.1 +/- 0.2 mm (p < 0.01) and PRL thickness from 2.4 +/- 0.2 to 2.8 +/- 0.2 mm (p <0.01) during the 5-year observation, respectively. PRL thickness was constantly increased at the rate of 0.4 mm during the study. However, no significant association was found between the 5-year increases in CT and PRL distance and age, gender, the prevalence of diabetes, or laboratory parameters such as blood beta2-microglobulin, pentosidine and Kt/V(urea). CONCLUSION: Our data suggest that echographic evaluation of the wrist tissue thickness was useful to assess the progression of CTS. Serial measurements of the wrist by echography may be helpful to clarify the advance of subclinical CTS in patients receiving long-term HD.

Adult↗
PubMed2002

Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody.

BACKGROUND: The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II. PATIENTS AND METHODS: Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters. RESULTS: Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01). CONCLUSION: The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.

Adult↗
PubMed2001

Hypothalamic cholinergic regulation of body temperature and water intake in rats.

Without disturbing the behavior of unanesthetized rats, the perfusion of neostigmine through microdialysis probe into the anterior hypothalamus (AH), paraventricular nucleus (PVN) and lateral ventricle (LV) decreased body temperature and increased water intake. On the other hand, the perfusion into the supraoptic nucleus (SON) increased the body temperature. The perfusion of neostigmine increased the extracellular concentration of acetylcholine in the perfusion sites except LV. Changes, both decrease and increase, in body temperature and increase in water intake were correlated with increases in c-fos-like immunoreactivity (Fos-IR) in the hypothalamus, pons and medulla. Distinct Fos-IR was found in the PVN, SON, median preoptic nucleus (MnPO), locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Co-administration of atropine with neostigmine completely suppressed the changes in the body temperature, water intake and Fos-IR, all of which were induced by the neostigmine perfusion into AH, PVN and SON. In the LV-perfused rats, on the other hand, co-administration of atropine and neostigmine only partially prevented body temperature reduction and still induced significant hypothermia. These results suggest that muscarinic receptor activation in specific regions of the hypothalamus and the activation of LC and NTS are implicated in the regulation of body temperature and water intake. Other receptor processes are involved in the LV-induced changes.

Animals↗