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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 361 records · Page 20Linked to original sources
PubMed1997

[A case of concurrent bilateral adrenocortical adenoma causing Cushing's syndrome].

A 43-year-old woman presented with obesity and lumbago. Endocrinological examinations revealed normal plasma cortisol levels and a suppressed serum adrenocorticotropic hormone (ACTH) level. On venous sampling, markedly elevated plasma cortisol levels were observed for bilateral adrenal veins (243 and 62.3 micrograms/dl on the right and left sides, respectively). Although the computed tomogram revealed bilaterally enlarged adrenal glands, 131I-adosterol scintigram showed a strong uptake only on the right side. Right adrenalectomy successfully relieved Cushing's syndrome. Pathological diagnosis was adrenocortical adenoma, 3.5 cm in diameter. Cushing's syndrome recurred in 9 years. At that time, she underwent left subtotal adrenalectomy including a 3-cm adrenocortical adenoma. Postoperative convalescence has been uneventful with oral steroid supplementation. All 14 previously reported cases of bilateral adrenocortical adenoma (BAA) causing Cushing's syndrome as well as the present case were concurrent and dominant in females of reproductive age. This suggests that some cofactors other than ACTH, such as estrogen, contribute to the pathogenesis of BAA.

Adenoma↗
PubMed1997

Serial quantitation of serum core protein and viral RNA of hepatitis C virus after interferon therapy: increase in viral loads in biochemical responders.

OBJECTIVES: Interferon (IFN) therapy is often ineffective in eradicating hepatitis C virus (HCV). Some patients show normal serum ALT levels for a long time after IFN therapy despite the presence of HCV. These patients are considered not virological responders but biochemical responders. We investigated the changes in the amount of HCV after IFN therapy in biochemical responders. METHODS: Nine biochemical responders and 11 nonresponders were studied. Serum HCV amount was measured by fluorescence enzyme immunoassay for HCV core (pg/ml) and Amplicor HCV Monitor test for HCV RNA (logarithms of copy numbers per milliliter). RESULTS: In biochemical responders, core protein and HCV RNA were increased significantly at 1 month after IFN therapy (291 +/- 191 pg/ml and 5.4 +/- 0.9, respectively; p < 0.05 for both) and at 1 yr (324 +/- 189 pg/ml and 5.6 +/- 0.7, respectively; p < 0.01 for both) compared with pretreatment values (122 +/- 114 pg/ml and 4.8 +/- 0.9, respectively). The change ratios of core protein at 1 month and 6 months after therapy to the pretreatment values were significantly higher in biochemical responders (3.2 +/- 2.4 and 2.9 +/- 2.3, respectively) than in nonresponders (0.9 +/- 0.7 and 1.1 +/- 0.8, respectively) (p < 0.05 for both). Similarly, the change ratios of HCV RNA at 1 month and 1 yr after IFN therapy were significantly higher in biochemical responders (9.9 +/- 14.6 and 12.8 +/- 15.1) than in nonresponders (0.6 +/- 0.5 and 1.2 +/- 1.2) (p < 0.05 for both). CONCLUSIONS: HCV amount increased significantly after IFN therapy in biochemical responders, whereas it did not change notably in nonresponders.

Alanine Transaminase↗
PubMed1997

Genetic and molecular dissection of quantitative traits in rice.

Recent progress in the generation of a molecular genetic map and markers for rice has made possible a new phase of mapping individual genes associated with complex traits. This type of analysis is often referred to as quantitative trait locus (QTL) analysis. Increasing numbers of QTL analyses are providing enormous amounts of information about QTLs, such as the numbers of loci involved, their chromosomal locations and gene effects. Clarification of genetic bases of complex traits has a big impact not only on fundamental research on rice plant development, but it also has practical benefits for rice breeding. In this review, we summarize recent progress of QTL analysis of several complex traits in rice. A strategy for positional cloning of genes at QTLs is also discussed.

Chromosome Mapping↗
PubMed1997

Preharvest nitroprusside flush improves posttransplantation lung function.

BACKGROUND: Morbidity as a result of early allograft dysfunction remains a significant problem in clinical lung transplantation. We previously demonstrated that nitroprusside (NP), a potent nitric oxide donor, administered before storage and again during reperfusion, reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage effects, reperfusion effects, or both. MATERIALS AND METHODS: Fifteen dogs underwent left lung allotransplant. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (FIO2 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase (MPO) activity and wet to dry weight (W/D) ratio were assessed. Animals were divided into three groups for timing of NP administration. Group I (n = 5) animals received no NP. In group II (n = 5), donor lungs received NP (10 mg/L) in the flush solution only. In group III (n = 5), recipient animals received NP (0.2 mg/kg) just before reperfusion, as well as a continuous infusion (0.1 mg/kg/hr) during the assessment period. RESULTS: Significant improvement in gas exchange was apparent in groups II and III compared with group I, but there was no significant difference between groups II and III. After 6-hour reperfusion, mean PaO2 values were 85.46 +/- 13.32 mm Hg in group I, 298.74 +/- 61.25 mm Hg in group II (p < 0.05), and 311.12 +/- 43.39 mm Hg in group III (p < 0.05). Systemic vascular resistance was significantly lower in group III than in group I (p < 0.05). MPO activities decreased in groups II (p < 0.05) and III (p < 0.05), indicating reduced neutrophil sequestration. W/D ratio was significantly lower in groups II and III. CONCLUSION: Both methods of NP administration are effective, but NP administration in the recipient is accompanied by a decrease in systemic vascular resistance. From a clinical point of view, NP administration in the flush solution is a sufficiently effective and practical method to reduce lung allograft reperfusion injury.

Analysis of Variance↗
PubMed1997

Is there evidence for intrauterine HBV infection in newborns of hepatitis B carrier mothers?

It has been proposed that some neonates infected with hepatitis B virus (HBV), acquire their infections in utero as demonstrated by HBV seromarkers in venous blood samples at birth. In this study, paired blood samples from 13 HBsAg-positive, 19 HBsAg- and HBeAg-positive, 2 HBsAg-negative mothers and 34 of their neonates, were drawn 24-72 hours after birth and tested for HBV-DNA in their peripheral blood mononuclear cells (PBMC). The presence of HBV-DNA in PBMC was detected in 69.2% (9/13) of HBsAg-positive mothers, 94.7% (18/19) of HBsAg- and HBeAg-positive mothers, and in none of their neonates. The conclusion from these results is that the evidence for hepatitis B infections occurring in neonates of hepatitis B carrier mothers in utero is uncommon.

DNA, Viral↗
PubMed1997

The advantage of gastrectomized patients in management of their chronic hepatitis C.

Because the majority of patients with chronic hepatitis C do not respond to interferon, alternative treatments need to be established. Several lines of evidence suggest that iron depletion is beneficial for such patients. Thus, gastrectomized patients with a reduced capacity for iron absorption might have an advantage in treatment of their liver damage over patients with intact gastrointestinal tracts. Four male gastrectomized patients had post-transfusion chronic hepatitis C. The iron load in three patients was adjusted below 10 ng/ml of serum ferritin level by phlebotomy. Subsequent interferon treatment for the four patients without iron load cleared circulating hepatitis C virus RNA in one patient only. However, serum ferritin concentrations were stabilized at low levels without maintenance phlebotomy, and sustained normalization of serum liver enzyme activities was obtained in all four patients. Similar treatments were done for 10 male patients with intact gastrointestinal tracts. The amount of removed iron from these patients was more than that from gastrectomized patients. Interferon also failed to clear circulating hepatitis C virus RNA except in one case. Low ferritin levels and sustained normalization of liver enzymes were seen in three patients. A transient elevation of ferritin levels with low enzyme activities was seen in two patients. Relapsing hepatitis was seen in five of the seven patients who needed maintenance phlebotomy due to a rebound in serum ferritin levels, probably because of active iron absorption from the intestine. Our data suggest that depletion of cytotoxic iron is a key to managing patients with chronic hepatitis C.

Adult↗
PubMed1996

Influence of aortic impedance on the development of pressure-overload left ventricular hypertrophy in rats.

BACKGROUND: Aortic input impedance, which represents LV afterload, is considered to be a major determinant for the development of pressure-overload left ventricular (LV) hypertrophy. METHODS AND RESULTS: To test whether the sustained change in aortic input impedance might affect the mode of development of LV hypertrophy, coarctation of either the ascending aorta (G1, n = 13) or suprarenal abdominal aorta (G2, n = 12) was performed over 4 weeks in 6-weeks-old Wistar rats. Although peak LV pressure and total systemic resistance were increased similarly in G1 and G2, time to peak LV pressure was decreased by 24% (P < .01) in G1 compared with G2. The aortic input impedance spectra revealed that the early systolic loading in G1 was characterized by an increase in characteristic impedance, whereas the late systolic loading in G2 was by an augmented arterial wave reflection. G1 showed a smaller increase (P < .01) in either the ratio of LV weight (mg) to body weight (g) or LV wall thickness than G2 after aortic banding. Myocyte diameter was also smaller (P < .05) in G1 (14.3 +/- 0.7 mm) than in G2 (16.1 +/- 1.2 mm). The ex vivo passive pressure-volume relation had a rightward shift in G1 compared with G2, suggesting less concentric LV hypertrophy in G1. CONCLUSIONS: The sustained early systolic loading due to the increase in characteristic impedance was accompanied by less concentric, reduced hypertrophy, whereas the sustained late systolic loading due to the augmented arterial wave reflection was accompanied by concentric, adequate hypertrophy.

Aldosterone↗
PubMed1996

Anti-interleukin-6 receptor antibody prevents muscle atrophy in colon-26 adenocarcinoma-bearing mice with modulation of lysosomal and ATP-ubiquitin-dependent proteolytic pathways.

Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Interleukin-6 (IL-6) has been reported to be responsible for the loss of lean body mass during cancer cachexia in colon-26 adenocarcinoma (C-26)-bearing mice. This study was carried out to elucidate the intracellular proteolytic pathways operating in skeletal muscle in C-26-bearing mice, and to examine the effect of anti IL-6 receptor antibody on muscle atrophy. On day 17 after tumor inoculation, the gastrocnemius muscle weight of C-26-bearing mice had significantly decreased to 69% of that of the pair-fed control mice. This weight loss occurred in association with increases in the mRNA levels of cathepsins B and L, poly-ubiquitin (Ub) and the subunits of proteasomes in the muscles. Furthermore, enzymatic activity of cathepsin B+L in the muscles also increased to 119% of the control. The administration of anti-murine IL-6 receptor antibody to C-26-bearing mice reduced the weight loss of the gastrocnemius muscles to 84% of that of the control mice, whose enzymatic activity of cathepsin B+L and mRNA levels of cathepsin L and poly-Ub were significantly suppressed compared with those of the C-26-bearing mice. Our data indicate that both the lysosomal cathepsin pathway and the ATP-dependent proteolytic pathway might be involved in the muscle atrophy of C-26-bearing mice. The results also suggest that anti IL-6 receptor antibody could be a potential therapeutic agent against muscle atrophy in cancer cachexia by inhibiting these proteolytic systems.

Adenocarcinoma↗
PubMed1996

Temperature-dependent enhancement of proteolysis in C2C12 myotubes in association with the activation of 26S proteasome.

The effect of temperature on protein metabolism of C2C12 myotubes was investigated in order to estimate the potential effect of fever on muscle catabolism. The half-life of long-lived proteins in C2C12 myotubes was significantly (13%) shorter when incubated at 40 degrees C than at 37 degrees. The activities of cathepsins B and L were not significantly different at 37 and 40 degrees C, nor were the levels of the protein and mRNA of the two cathepsins. In contrast, the chymotrypsin-like activity of 26S proteasome was elevated by 53% at 40 degrees C, compared to that at 37 degrees C, although it was not associated with an increase in the levels of the protein and mRNA of proteasome subunits. mRNA levels of calpain and ubiquitin were not affected by temperature. It is concluded that temperature-dependent enhancement of proteolysis in C2C12 myotubes is associated with an increase in 26S proteasome activity.

Animals↗
PubMed1996

Characterization and mapping of cDNA encoding aspartate aminotransferase in rice, Oryza sativa L.

Fifteen cDNA clones, putatively identified as encoding aspartate aminotransferase (AST, EC 2.6.1.1.), were isolated and partially sequenced. Together with six previously isolated clones putatively identified to encode ASTs (Sasaki, et al. 1994, Plant Journal 6, 615-624), their sequences were characterized and classified into 4 cDNA species. Two of the isolated clones, C60213 and C2079, were full-length cDNAs, and their complete nucleotide sequences were determined. C60213 was 1612 bp long and its deduced amino acid sequence showed 88% homology with that of Panicum miliaceum L. mitochondrial AST. The C60213-encoded protein had an N-terminal amino acid sequence that was characteristic of a mitochondrial transit peptide. On the other hand, C2079 was 1546 bp long and had 91% amino acid sequence homology with P. miliaceum L. cytosolic AST but lacked in the transit peptide sequence. The homologies of nucleotide sequences and deduced amino acid sequences of C2079 and C60213 were 54% and 52%, respectively. C2079 and C60213 were mapped on chromosomes 1 and 6, respectively, by restriction fragment length polymorphism linkage analysis. Northern blot analysis using C2079 as a probe revealed much higher transcript levels in callus and root than in green and etiolated shoots, suggesting tissue-specific variations of AST gene expression.

Amino Acid Sequence↗
PubMed1996

Characterization and genetic mapping of simple sequence repeats in the rice genome.

We searched partial sequences of over 22,706 rice cDNA and 1220 genomic DNA clones to find and characterize simple sequence repeats (SSRs) in the rice genome. The most frequently found repeated SSR motif in both cDNA and genomic DNA sequences was d(CCG/CGG)n. The second most frequently found SSR was d(AG/CT)n. In contrast with mammalian genomes, in which d(AC/GT)n sequences are the most abundant, d(AG/GT)n sequences were not frequently observed in rice. Sequences containing d(CCG/CGG)n, d(AG/CT)n repeats, and other SSRs were chosen for polymorphism detection. It was predicted that 17 of 20 SSRs in cDNA sequences were located in 5'-untranslated regions near initiation codons. Twenty-two loci can be mapped on our RFLP linkage map by these SSRs. Six markers were tested with 16 japonica rice varieties as templates for PCR. Two markers exhibited amplified fragment length polymorphism among these rice varieties, implying that SSRs are polymorphic among rice varieties which have similar genetic backgrounds. Even these polymorphic SSRs are located within or around genes which code ubiquitous proteins.

Base Sequence↗
PubMed1996

Synthesis and structure-activity relationships of 2-substituted D-tryptophan-containing peptidic endothelin receptor antagonists: importance of the C-2 substituent of the D-tryptophan residue for endothelin A and B receptor subtype selectivity.

Continuing studies on modifications of potent cyclic pentapeptide endothelin (ET) receptor antagonists, represented by BQ-123, and potent linear tripeptide derivative ET receptor antagonists, represented by BQ-788, are described herein. The introduction of D-tryptophan analogues with C-2 substituents in these peptidic ET antagonists resulted in potent ET receptor antagonists with various ETA/ETB subtype selectivity. Combined ETA/ETB receptor antagonists were found in both cyclic pentapeptide and linear tripeptide series with 2-halo- and 2-methyl-D-tryptophans. In contrast, compounds with 2-cyano-D-tryptophan were ETB receptor-selective antagonists. The C-2 substituent of the D-tryptophanyl residue appeared to be very important for the discrimination of ETA/ETB subtype selectivity of the antagonists. The potent ET receptor antagonists with various ETA/ETB subtype selectivity synthesized in this study may be useful tools for elucidating the physiological and pathophysiological roles of ET and ET receptors.

Animals↗
PubMed1996

T-cell membrane-associated serine protease, tryptase TL2, binds human immunodeficiency virus type 1 gp120 and cleaves the third-variable-domain loop of gp120. Neutralizing antibodies of human immunodeficiency virus type 1 inhibit cleavage of gp120.

It has been suggested that the third variable domain (V3) loop of human immunodeficiency virus type 1 (HIV-1) gp120 has to interact with a cell-surface-associated protease(s) that acts as a cofactor after binding of gp120 to the CD4 receptor during entry of HIV-1 into susceptible cells. We isolated the membrane-associated serine protease, tryptase TL2, from human CD4-positive lymphocytes. This enzyme specifically binds gp120 through interaction with its V3 domain. To investigate the role of tryptase TL2 in HIV infection, we examined the affinity of the interaction and the proteolytic susceptibility of various recombinant gp120 expressed in mammalian cells to the enzyme, and we determined the cleavage sites. Tryptase TL2 bound gp120 with an apparent dissociation constant of 38 nM. The affinity was lower than that of gp120 for CD4 which suggests that gp120 initially binds to CD4, followed by interaction with tryptase TL2 which is localized close to CD4 on the cell surface. After binding, tryptase TL2 cleaved recombinant gp120 expressed in mammalian cells into two protein species of 70 kDa and 50 kDa but did not cleave gp120 expressed in insect cells, which indicates that the structure of the oligosaccharides linked to the polypeptide backbone of gp120 affects the proteolytic susceptibility. Cleavage was specifically inhibited by a neutralizing antibody against the V3 loop. Cleavage-site determination revealed that tryptase TL2 cleaved gp120 at various sites in the V3 in a strain-dependent manner. The amino acid variability at the cleavage site(s) in almost all HIV-1 isolates was restricted to amino acids which are susceptible to the chymotryptic and/or tryptic activities of tryptase TL2.

Amino Acid Sequence↗
PubMed1996

Rat hepatocytes transport water mainly via a non-channel-mediated pathway.

During bile formation by the liver, large volumes of water are transported across two epithelial barriers consisting of hepatocytes and cholangiocytes (i.e. intrahepatic bile duct epithelial cells). We recently reported that a water channel, aquaporin-channel-forming integral protein of 28 kDa, is present in cholangiocytes and suggested that it plays a major role in water transport by these cells. Since the mechanisms of water transport across hepatocytes remain obscure, we performed physiological, molecular, and biochemical studies on hepatocytes to determine if they also contain water channels. Water permeability was studied by exposing isolated rat hepatocytes to buffers of different osmolarity and measuring cell volume by quantitative phase contrast, fluorescence and laser scanning confocal microscopy. Using this method, hepatocytes exposed to hypotonic buffers at 23 degrees C increased their cell volume in a time and osmolarity-dependent manner with an osmotic water permeability coefficient of 66.4 x 10(-4) cm/s. In studies done at 10 degrees C, the osmotic water permeability coefficient decreased by 55% (p < 0.001, at 23 degrees C; t test). The derived activation energy from these studies was 12.8 kcal/mol. After incubation of hepatocytes with amphotericin B at 10 degrees C, the osmotic water permeability coefficient increased by 198% (p < 0.001) and the activation energy value decreased to 3.6 kcal/mol, consistent with the insertion of artificial water channels into the hepatocyte plasma membrane. Reverse transcriptase polymerase chain reaction with hepatocyte RNA as template did not produce cDNAs for three of the known water channels. Both the cholesterol content and the cholesterol/phospholipid ratio of hepatocyte plasma membranes were significantly (p < 0.005) less than those of cholangiocytes; membrane fluidity of hepatocytes estimated by measuring steady-state anisotropy was higher than that of cholangiocytes. Our data suggests that the osmotic flow of water across hepatocyte membranes occurs mainly by diffusion via the lipid bilayer (not by permeation through water channels as in cholangiocytes).

Animals↗
PubMed1996

Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.

The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.

Animals↗
PubMed1996

The long-term pathological evolution of chronic hepatitis C.

Most patients infected with hepatitis C virus (HCV) develop chronic hepatitis. Unfortunately, the pathological evolution of this disease over time is not completely understood. We studied 70 HCV-positive patients, from whom 2 to 10 liver biopsy specimens (mean, 3.9) had been obtained during an interval of 1 to 26 years (mean, 8.8 years). Each biopsy specimen was evaluated independently by four pathologists who each provided a numerical score for the grade of portal/periportal necroinflammation (0-4), grade of lobular necroinflammation (0-4), their sum (final grade), and the stage of fibrosis (1-4). The scores were correlated with progression of disease, if any, and transition to cirrhosis. During follow-up, 35 patients (50%) developed cirrhosis. Cirrhosis developed in all patients with a high final grade (> or = 5) of necroinflammation on initial biopsy who were followed for 10 years and in 96% of patients with an intermediate final grade (3.5-4.9) who were followed for 17 years. Only 30.4% of patients with low final grade (< or = 3.4) on initial biopsy developed cirrhosis after 13 years. All patients with evidence of septal fibrosis with incomplete nodularity (stage 3.0-3.4) in the initial biopsy progressed to unequivocal cirrhosis by 10 years. The rate of progression to cirrhosis was accelerated in patients whose initial biopsies showed high-grade and -stage lesions. This study demonstrates the importance of grading and staging liver biopsy lesions in chronic hepatitis C, particularly for patients with high-grade necroinflammation, septal fibrosis, and regions of modularity on initial biopsy who are at high risk of developing advanced cirrhosis in the ensuing decade.

Biopsy↗
PubMed1996

Clinical evaluation of non-insulin-dependent diabetes mellitus patients with autoantibodies to glutamic acid decarboxylase.

We evaluated the frequency of antibodies to glutamic acid decarboxylase (GAD-Ab) in Japanese patients diagnosed initially as having non-insulin-dependent diabetes mellitus (NIDDM) and investigated a possible link between the presence of GAD-Ab and development of the insulin-dependent (ID) state. The population sample consisted of 583 Japanese NIDDM patients (age at onset > 30 years) who were initially non-ketotic and did not require insulin treatment during at least 6 months of observation. GAD-Ab were measured using radioimmunoassay. The clinical characteristics of GAD-Ab+ patients were carefully examined at four-year intervals from the onset of diabetes. We also examined the ID state by measuring the level of postprandial serum C-peptide and i.v. glucagon-stimulated serum C-peptide. The overall prevalence of GAD-Ab in Japanese NIDDM patients was 3.8%. The frequency of GAD-Ab+ did not significantly decrease with a long history of diabetes. GAD-Ab+ patients had a lower body mass index, compared with GAD-Ab- (20.8 +/- 2.9 vs 23.0 +/- 3.7, P < 0.005), lower postprandial C-peptide levels (0.7 +/- 0.6 vs 1.4 +/- 1.2, P < 0.01), and an early commencement of insulin therapy (3.6 +/- 4.7 vs 8.3 +/- 6.6, P < 0.01). GAD-Ab+ patients who had already developed the ID state had characteristically higher titers of GAD-Ab (421.4 +/- 359.1) and a higher frequency of islet cell antibodies (ICAs) (77.8%), compared with GAD-Ab+ NID patients (titer: 60.2 +/- 86.9, P < 0.005, 23.1%, P < 0.05, respectively). GAD-Ab+ ICAs+ patients showed higher frequencies of ID state at any diabetic duration compared with GAD- ICAs-, while GAD-Ab+ ICAs- patients did not differ in the frequency of the ID state from GAD- ICAs-. Our results suggest that the presence of both GAD-Ab and ICAs represents a high risk for IDDM in GAD-Ab+ NIDDM patients.

Adult↗