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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 235 records · Page 13Linked to original sources

Quantitation of flavonoid constituents in citrus fruits.

Twenty-four flavonoids have been determined in 66 Citrus species and near-citrus relatives, grown in the same field and year, by means of reversed phase high-performance liquid chromatography analysis. Statistical methods have been applied to find relations among the species. The F ratios of 21 flavonoids obtained by applying ANOVA analysis are significant, indicating that a classification of the species using these variables is reasonable to pursue. Principal component analysis revealed that the distributions of Citrus species belonging to different classes were largely in accordance with Tanaka's classification system.

Analysis of Variance↗

Isolation of furocoumarins from bergamot fruits as HL-60 differentiation-inducing compounds.

The HL-60 differentiation-inducing compounds in bergamot fruits were isolated with column chromatography and identified as bergamottin, bergapten, and citropten by (1)H and (13)C NMR. Their HL-60 differentiation-inducing activity was measured by examining nitro blue tetrazolium (NBT) reducing, nonspecific acid esterase (NSE), specific esterase (SE), and phagocytic activities, and bergamottin showed the strongest activity among the coumarins isolated from bergamot fruits. The structure-activity relationship obtained from HL-60 differentiation assay suggests that hydrophobicity of furocoumarins is correlated with their activity.

Antineoplastic Agents↗

The antiproliferative effect of acridone alkaloids on several cancer cell lines.

Fifteen acridone alkaloids were examined for their antiproliferative activity toward monolayers and suspension of several types of cancer and normal human cell lines. As a result, atalaphyllidine (9), 5-hydroxy-N-methylseverifoline (11), atalaphyllinine (12), and des-N-methylnoracronycine (13) showed potent antiproliferative activity against tumor cell lines, whereas they have weak cytotoxicity on normal human cell lines. The structure-activity relationship established from the results revealed that a secondary amine, hydroxyl groups at C-1 and C-5, and a prenyl group at C-2 played an important role for antiproliferative activities of the tetracyclic acridones.

Acridines↗

Argatroban increases nitric oxide levels in patients with peripheral arterial obstructive disease: placebo-controlled study.

Intravenous argatroban infusion therapy is widely used for the restoration of peripheral microcirculation in patients with peripheral arterial obstructive disease (PAOD). We investigated the effect of argatroban infusion therapy on plasma levels of nitric oxide (NO) and nitrosylhemoglobin (HbNO) in patients with PAOD compared with a placebo-treated PAOD group. The chemiluminescence method was used to determine plasma NO and HbNO. Argatroban was administered as a continuous intravenous infusion for 60 minutes and repeated daily over a period of 2 weeks in 10 patients with PAOD. Treatment significantly improved the clinical signs and symptoms. Serial thermograms showed a 1-2 degrees C rise in the temperature of the affected legs in all patients immediately after intravenous argatroban infusion therapy. Enhancement of the peripheral circulation was maintained after the end of argatroban infusion for up to 90 minutes despite elimination of argatroban from the circulation. Furthermore, there was a progressive and significant increase in the mean concentration of plasma NO in PAOD patients after commencement of argatroban infusion (baseline, 58.0 +/- 13. 7;90 minutes after infusion, 65.7 +/- 13.4 microM; P < 0.01). HbNO significantly increased from a baseline value of 1063 +/- 126 to 1460 +/- 250 nM at 30 minutes after infusion (P < 0.01). However, the level of HbNo decreased thereafter, although it remained significantly elevated, even at 90 minutes after the end of argatroban infusion. Our results suggest that argatroban may lead to increased HbNO and plasma NO, and this may contribute to the improved microcirculation in PAOD patients.

Aged↗

Assessment of hepatic functional reserve in cirrhotic patients by computed tomography of the caudate lobe.

In order to investigate whether the size of the caudate lobe of the cirrhotic liver is related to the hepatic functional reserve, the morphometric analysis of the caudate lobe was preformed retrospectively using computed tomography in 106 consecutive patients of whom 67 had compensated (group 1), and 39 uncompensated (group 2) liver cirrhosis. In 51 patients, hepatic measurements were repeated in follow-up. Age- and gender-matched controls were studied. The size of the caudate lobe and the ratio of the caudate to right lobe were correlated with liver function. The caudate lobe was larger in the study patients than in the controls, and larger in group 1 than in group 2 (P<0.01). The caudate to right lobe ratios were also greater in the study patients especially in group 1 (P<0.01). In follow-up, the regression coefficient for the caudate to right lobe ratio was positive in group 1 and negative in group 2 (P<0.05). Even though the caudate lobe of patients with uncompensated liver cirrhosis was larger than that of the controls, patients with compensated liver cirrhosis had a larger caudate lobe and higher caudate to right lobe ratio compared to the patients with uncompensated liver cirrhosis. The caudate lobe may have played an important role in maintaining proper liver function in these patients.

Chronic Disease↗

Facilitated engraftment by intramedullary administered enriched allogeneic CD34+ cells?

An 11-year-old girl with Ph+ CML received a marrow-ablative cytoreductive regimen, but both blood and marrow grafts obtained from her two-loci-mismatched father were rejected. At the third attempt, she was directly injected with purified CD34+ blood cells from the same donor into the bone marrow cavity with regular disposable bone marrow biopsy needles. The peripheral hemogram recovered rapidly thereafter, and she maintained stable complete donor type hematopoiesis until 8 months later, when she developed renal failure due to thrombotic microangiopathy, which was the primary cause of her death. This experience suggests that we revisit an old maneuver in the light of new developments.

Antigens, CD34↗

The Pib gene for rice blast resistance belongs to the nucleotide binding and leucine-rich repeat class of plant disease resistance genes.

Rice blast, caused by the fungal pathogen Magnaporthe grisea, is one of the most serious diseases of rice. Here we describe the isolation and characterization of Pib, one of the rice blast resistance genes. The Pib gene was isolated by a map-based cloning strategy. The deduced amino acid sequence of the Pib gene product contains a nucleotide binding site (NBS) and leucine-rich repeats (LRRs); thus, Pib is a member of the NBS-LRR class of plant disease resistance genes. Interestingly, a duplication of the kinase 1a, 2 and 3a motifs of the NBS region was found in the N-terminal half of the Pib protein. In addition, eight cysteine residues are clustered in the middle of the LRRs, a feature which has not been reported for other R genes. Pib gene expression was induced upon altered environmental conditions, such as altered temperatures and darkness.

Amino Acid Sequence↗

Characterization of the novel mitochondrial protein import component, Tom34, in mammalian cells.

Tom34 is a newly-found component of the mitochondrial protein import machinery in mammalian cells with no apparent counterpart in fungi. RNA blot and immunoblot analyses showed that the expression of Tom34 varies among tissues and differs from that of the core translocase component Tom20. In contrast to a previous report [Nuttal, S.D. et al. (1997) DNA Cell Biol. 16, 1067-1074], the present study using a newly-prepared anti-Tom34 antibody with a high titer showed that Tom34 is present largely in the cytosolic fraction and partly in the mitochondrial and membrane fractions after fractionation of tissues and cells, and that the membrane-associated form is largely extractable with 0.1 M sodium carbonate. The in vitro import of preproteins into isolated rat mitochondria was strongly inhibited by DeltahTom34 which lacks the NH2-terminal hydrophobic region of human Tom34 (hTom34). Import was also strongly inhibited by anti-hTom34. In pulse-chase experiments using COS-7 cells, pre-ornithine transcarbamylase (pOTC) was rapidly processed to the mature form. Coexpression of hTom34 resulted in a stimulation of pOTC processing, whereas the coexpression of hTom34 antisense RNA caused inhibition. The results confirm that Tom34 plays a role in mitochondrial protein import in mammals, and suggest it to be an ancillary component of the translocation machinery in mammalian cells.

Animals↗

Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease?

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose (DSC) column is commonly performed for extracorporeal removal of LDL in hypercholesterolemic patients with peripheral arterial obstructive disease. We investigated whether the use of heparin or nafamostat mesilate as anticoagulants in a single LDL apheresis produced different clinical effects, or brought about the production of bradykinin and endogenous nitric oxide (NO) in these patients. LDL apheresis was performed in ten patients with peripheral arterial obstructive disease. We measured plasma levels of bradykinin, NO and nitrosylhemoglobin as well as skin temperature. Plasma levels of bradykinin increased 12-fold during LDL apheresis with heparin, but did not increase during LDL apheresis with nafamostat mesilate. LDL adsorption resulted in an immediate rise in skin temperatures (1-2 degrees C) of the lower ischemic legs irrespective of the type of anticoagulant used, and this persisted after the end of LDL apheresis for up to 60 min. There was a progressive and significant increase in plasma NO after the commencement of single LDL apheresis in both groups (heparin group: 64.0 +/- 17.3 micromol/l at baseline, 73.3 +/- 15.2 micromol/l 60 min after apheresis, P<0.005; nafamostat mesilate group: 65.0 +/- 18.8 micromol/l at baseline, 75.5 +/- 17.5 micromol/l 60 min after apheresis, P<0.001). On the other hand, levels of nitrosylhemoglobin increased significantly after 1000 ml of plasma treatment but the level decreased thereafter, although it was significantly higher than baseline 60 min after LDL apheresis. Our results suggest that a single LDL apheresis enhanced peripheral microcirculation, probably as a result of increased production of NO, irrespective of changes in bradykinin release.

Aged↗

Chemoprevention by the oxygenated carotenoid beta-cryptoxanthin of N-methylnitrosourea-induced colon carcinogenesis in F344 rats.

Beta-cryptoxanthin (betaCx), one of 4 major carotenoids in the blood, was investigated for anticarcinogenic activity in F344 rats. Four groups of 25 rats each received an intrarectal dose of 2 mg of N-methylnitrosourea 3 times a week for 5 weeks, and were fed the diet supplemented with 0 ppm (control), 25 ppm, 5 ppm or 1 ppm betaCx throughout the experiment. The colon cancer incidence at week 30 was significantly lower in the betaCx (25 ppm) diet group, but not in the betaCx (5 ppm) and betaCx (1 ppm) diet groups, than in the control diet group: 68%, 84%, 80% vs. 96%. The results suggested that dietary betaCx may affect colon carcinogenesis after accumulation in the colonic mucosa, perhaps due to absorption from the colon as well as the small intestine.

Animals↗

Autoimmune cholangitis and primary biliary cirrhosis--an autoimmune enigma.

AIMS/BACKGROUND: Autoimmune cholangitis/cholangiopathy (AIC) is an enigmatic disease marked by chronic cholangitis, antinuclear antibodies (ANA) and sero-negativity for conventionally detected antimitochondrial antibodies (AMA). We examined whether AIC is a distinct entity, an AMA-negative variant of primary biliary cirrhosis (PBC), or a cholangiopathic variant of autoimmune hepatitis (AIH) by comparing the clinical, laboratory and autoantibody profiles of 21 cases of AIC, 37 cases PBC and 16 cases of AIH from selected Japanese patients. METHODS: The specificities of AMA and ANA were determined by immunofluorescence, immunoblotting and enzyme inhibition assays using various mitochondrial and nuclear autoantigens, and the frequencies for these groups were compared. RESULTS: By clinical, biochemical and histological data, AIC and PBC were similar and both were clearly distinct from AIH. Serologically, by immunofluorescence of AMA and ANA, there was polarisation. By immunoblotting, and notwithstanding the negative test for AMA, a proportion of the AIC sera reacted with the E2 subunits of the 2-oxo-acid dehydrogenase enzyme complexes, but more particularly with the lower molecular weight E2 subunits. The antinuclear reactivity in AIC was with centromere, Sp100 and nuclear pore complex proteins as in PBC, but preferentially with the nuclear pore complex. CONCLUSION: Our results demonstrate that AIC and PBC are similar diseases. However this duo is of interest because, usually, among sets of autoimmune syndromes, differences in serological targetting are matched by differences in clinical presentation: AIC and PBC are an exception to this.

Adult↗

Randomized controlled trial of lymphoblastoid interferon alpha for chronic hepatitis C (comparison of 9-MU and 6-MU doses). IFN Treatment Group of Affiliated Hospitals of the Third Department of Internal Medicine at Nagoya University School of Medicine.

OBJECTIVE: We conducted a randomized controlled trial to compare the efficacy of two different dosages of lymphoblastoid interferon alpha (IFN) for the treatment of chronic hepatitis C. METHODS: Eighty-four patients with chronic hepatitis C were enrolled and randomly assigned into the two groups; group A was treated with 6 million units (MU) and group B with 9 MU daily for the first 2 wk, and then thrice weekly for an additional 14 or 22 wk. RESULTS: Eighty patients were evaluated (39 patients in group A and 41 in group B); 14 patients in group A (35.9%) and 15 in group B (36.6%) obtained sustained response. The percentages of patients who became negative for HCV RNA at the end of the second wk differed slightly between the groups, without statistical significance (56.4% and 68.3%). When assessed in detail, patients with genotype 1 and < 1 Meq/ml of viral load became negative for HCV RNA significantly more frequently in group B (eight of eight) than in group A (three of seven) (p < 0.05) at the end of the second week, whereas the sustained response rate was similar between the groups (five of eight and four of seven). Predictors of sustained response by multivariate analysis were low viral load (< 1.0 Meq/ml) and negativity of HCV RNA at the end of the second wk of IFN. CONCLUSIONS: The results indicated that there was no difference in sustained response rate between the 6-MU and 9-MU doses. The earlier disappearance of HCV RNA, at the end of the second wk or at least by the end of the fourth week, is an essential condition for sustained response.

Antiviral Agents↗

TT virus infection in hemodialysis patients.

OBJECTIVE: Recently, TT virus (TTV), associated with posttransfusion hepatitis, was discovered. Prevalence of TTV infection in maintenance hemodialysis (HD) units and its pathogenicity to liver was investigated. METHODS: A total of 115 patients on HD were assessed for presence of serum TTV. DNA was purified from sera, and nested polymerase chain reaction was done for the detection of TTV DNA. RESULTS: TTV was detected in 59 patients on HD (51.3%), as compared with healthy blood donors (15 of 91 [16.5%], p < 0.0001). Serum HCV RNA and HBs antigen were positive in 16 and three patients, respectively. The prevalence rate of TTV was already 58.3% in the patients on HD for only 1 yr, and did not change according to the duration of HD until 15 yr on HD. TTV was positive in 51.2% (43 of 84) of the patients with history of blood transfusion, and in 51.6% (16 of 31) of those without it. In HCV-negative patients, alanine aminotransferase (ALT) levels of TTV-positive patients were similar to those of TTV-negative patients. Contrarily, in HCV-positive patients, ALT levels were more frequently > or =15 IU/L in TTV-positive patients (14 of 18) than in TTV-negative patients (five of 15) (p < 0.05). CONCLUSIONS: TTV infection is remarkably prevalent in patients on HD and in healthy blood donors. It is suggested that TTV generally does not cause liver disease by itself, but there remains the possibility that TTV may aggravate liver disease caused by HCV.

Aged↗

Serum hepatocyte growth factor in patients with peripheral arterial occlusive disease.

Hepatocyte growth factor (HGF) is a multifunctional protein implicated in tissue regeneration, wound healing, and angiogenesis. We measured serum HGF concentrations in 37 patients with peripheral arterial occlusive disease (PAOD). Among them, 36 patients underwent arteriography. Serum HGF concentrations were also measured in 40 control subjects who remained free of vascular, liver, kidney, or lung disease. Patients with PAOD showed elevated serum HGF concentrations compared with control subjects (0.40+/-0.02 vs. 0.19+/-0.01 ng/mL; P<0.001). Serum HGF concentrations were significantly higher in smokers compared with nonsmokers (0.45+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.003). The serum HGF concentrations in patients with collaterals tended to be higher than those in patients without collaterals (0.43+/-0.03 vs. 0.35+/-0.02 ng/mL; P = 0.06). Moreover, in patients who underwent bypass surgery or angioplasty, serum HGF concentrations decreased from 0.41+/-0.03 to 0.21+/-0.04 ng/mL after treatment (P<0.001). Serum HGF may be an useful marker for the diagnosis of PAOD. HGF may play an important role in angiogenesis and collateral vessel growth in PAOD.

Adult↗

cDNA sequence and expression of a cold-responsive gene in Citrus unshiu.

A cDNA clone encoding a protein (CuCOR19), the sequence of which is similar to Poncirus COR19, of the dehydrin family was isolated from the epicarp of Citrus unshiu. The molecular mass of the predicted protein was 18,980 daltons. CuCOR19 was highly hydrophilic and contained three repeating elements including Lys-rich motifs. The gene expression in leaves increased by cold stress.

Amino Acid Sequence↗

Antiproliferative activity of flavonoids on several cancer cell lines.

Twenty-seven Citrus flavonoids were examined for their antiproliferative activities against several tumor and normal human cell lines. As a result, 7 flavonoids were judged to be active against the tumor cell lines, while they had weak antiproliferative activity against the normal human cell lines. The rank order of potency was luteolin, natsudaidain, quercetin, tangeretin, eriodictyol, nobiletin, and 3,3',4',5,6,7,8-heptamethoxyflavone. The structure-activity relationship established from comparison among these flavones and flavanones showed that the ortho-catechol moiety in ring B and a C2-C3 double bond were important for the antiproliferative activity. As to polymethoxylated flavones, C-3 hydroxyl and C-8 methoxyl groups were essential for high activity.

Antineoplastic Agents, Phytogenic↗

Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer.

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

Aged↗

Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.

OBJECTIVE: In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. RESEARCH DESIGN AND METHODS: Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). RESULTS: Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA.

Age Factors↗