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Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 289 records · Page 16Linked to original sources

Enhanced hepatocyte growth factor expression associated with prolonged rat hepatic allograft survival in recipients pretreated with donor-specific blood.

BACKGROUND: Pretransplantation injection of freshly heparinized donor blood (donor-specific blood transfusion, or DST) significantly prolongs the survival of hepatic allografts from ACI(RT1a) to LEW(RT1l) rats. We investigated hepatocyte growth factor (HGF) expression in rat hepatic allografts of recipients pretreated with or without DST. METHODS: The levels of HGF mRNA and protein in hepatic allografts were determined after transplantation. The localization of HGF+ cells was identified with a rat anti-HGF monoclonal antibody. RESULTS: Plasma HGF concentrations in transplanted rats treated with DST were significantly and persistently increased compared to untreated rats with hepatic allografts. The number of HGF+ cells in hepatic allografts of recipients pretreated with DST on day 14 was significantly greater than that in allografts of untreated recipients on day 7. HGF+ cells were also found in the marginal zone and red pulp of recipient spleens. Northern blot analysis revealed the presence of three HGF+ cell phenotypes: HGF+ED1+, HGF+ED2+, and HGF+ED1-ED2-. Most HGF+ cells were ED1-ED2-. In situ hybridization demonstrated HGF mRNA in the mononuclear cells in the portal and sinusoidal areas as well as the marginal zone and red pulp in both DST-treated and untreated recipient spleens. CONCLUSIONS: Enhanced HGF expression in rat hepatic allografts is associated with immunologic unresponsiveness induced by DST.

Animals↗

Enzymatic assay for conjugated bilirubin (Bc) in serum using bilirubin oxidase (BOD).

We described an automated enzymatic assay for conjugated bilirubin (Bc) in serum using the Iatro D-Bil kit, with bilirubin oxidase (EC 1.3.3.5 BOD) from Myrothecium species. The specificity of the enzyme in the Iatro D-Bil kit was examined by analyzing unconjugated bilirubin (Bu), delta bilirubin (Bdelta), and Bc with high-performance liquid chromatography (HPLC), before and after the enzymatic reaction using BOD. The within-assay coefficients of variation (CV) of this method were 0.58 to 5.00% (n = 20) at 1.4 to 155.8 micromol/L. Day-to-day Cvs ranged from 1.61 to 7.14% at 1.2 to 182.1 micromol/L. The analytical recovery was 96 to 101%. The presence of ascorbic acid, reduced glutathione, L-cysteine, uric acid, urea, creatinine, glucose, lipemic material, anticoagulants, hemoglobin, or human serum albumin did not affect this assay system. The correlation coefficient between values obtained with the Iatro D-Bil kit (y) and HPLC method as reference for conjugated fractions (x) was; r = 0.983, y = 0.952x + 8.851 micromol/L, Sy/x = 11.97 (n = 56). We studied serum Bc levels, not including Bu and Bdelta, in patients with hepatic diseases or autoimmune hemolytic anemia. Levels of Bc obtained by the proposed method changed more rapidly than did those of direct bilirubin (D-Bil) obtained by diazo-dye method during the course of the diseases.

Anemia, Hemolytic↗

Expression of the c-kit proto-oncogene in rat hepatic allografts during acute rejection.

The role of the c-kit proto-oncogene in organ allograft rejection is not known. We investigated the level of c-kit expression following allogeneic transplantation of ACI rat liver grafts into LEW recipients. We studied c-kit mRNA and protein expression in groups of transplant recipients receiving hepatic isografts, hepatic allografts, or hepatic allografts after donor-specific blood transfusion (DST). Pretransplantation DST significantly prolonged survival of hepatic allografts. Infiltrates expressing c-kit were observed in allografts to untreated rats but not in groups receiving isografts or allografts following DST. Northern analysis also demonstrated abundant c-kit mRNA transcripts in the untreated allograft group in contrast to the isograft and the DST-treated groups. In addition, significantly more transcripts for interleukin-12 (IL-12), which is synergistic with c-kit, were present in untreated than in DST-treated allograft groups. In contrast, transforming growth factor beta (TGF-beta), which inhibits c-kit synthesis, was expressed abundantly in hepatic allografts to DST-treated rats but not in allografts to untreated animals. Transcripts for IL-10, which inhibits IL-12 production, were significantly more plentiful in hepatic allografts following DST than in those without DST. The results suggest that c-kit proto-oncogene expression in infiltrating cells is associated with rat hepatic allograft rejection.

Animals↗

Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver.

Hepatitis C virus (HCV) has been reported to potentially replicate in peripheral blood mononuclear cells (PBMCs), but direct information on the pathogenic implication of HCV infection in PBMCs is still limited. To investigate this issue, we compared the complexity of HCV quasispecies in serum, PBMCs, and livers of 13 patients with type C chronic liver disease. Hypervariable region 1 (HVR 1) was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were subcloned and sequenced. Considerable differences in the complexity of HVR 1 quasispecies were found in the serum, PBMCs, and liver in all patients, and the predominant sequences from each source were mutually different in 3 (23%) patients. An amino acid sequence unique to each source existed as well as a sequence common to serum and PBMCs, common to serum and livers, or common to PBMCs and liver. These results suggest infection of PBMCs by HCV, and that HCV in PBMCs may be differently exposed to host immunity from that in liver.

Adult↗

Peroxynitrite formation during rat hepatic allograft rejection.

The role of nitric oxide (NO) on tissue injury of hepatic allografts during rejection remains controversial. We investigated inducible nitric oxide synthase (iNOS) expression and formation of peroxynitrite in ACI rat liver grafts implanted in recipients. Animals were divided into four experimental groups: group I, isografts; group II, untreated hepatic allografts; group III, allografts treated with FK506; and group IV, allografts pretreated with donor-specific blood transfusion (DST). Serum nitrite/nitrate, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) concentrations increased significantly in group II rats after transplantation but were significantly lower in groups I, III, and IV. The numbers of macrophages that reacted with an antimacrophage iNOS monoclonal antibody as well as iNOS messenger RNA (mRNA) levels in liver specimens were also much lower in groups I, III, and IV as compared with group II. Immunostaining and Western blot analysis showed prominent tissue nitrotyrosine expression in untreated hepatic allografts, but not in allografts treated with FK506 or donor-specific blood. These results suggest that one of the mechanisms by which production of NO results in injury in rat hepatic allografts may be because of its reaction with superoxide to form peroxynitrite.

Animals↗

Autoantibodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screening.

It has been reported that there is a heterogeneity in the clinical course of Japanese patients with type 1 diabetes. To elucidate the associations of expression of autoantibodies to multiple islet antigens with age of onset and mode of diagnosis of diabetes in Japanese patients with type 1 diabetes, autoantibodies against the protein tyrosine phosphatase-like molecules ICA512 (IA-2) and phogrin (IA-2beta) (ICA512/phogrin-A), GAD (GADA), insulin (IAA), and islet cell cytoplasm (ICA) were determined in sera from 73 Japanese patients with type 1 diabetes obtained within 14 days of diagnosis. Patients were divided into groups based on the age of onset (</=10 years, n=24 and >10 years, n=49) or the mode of onset (abrupt onset, n=59 and urinary screening identified, n=14). Of 73 new-onset patients with type 1 diabetes, 43 (59%) and 32 (44%) had ICA512A and phogrin-A levels exceeding the 99th percentile of 184 normal control subjects, respectively. Forty-five patients (62%) were positive for either ICA512A or phogrin-A. The frequencies for other autoantibodies were 71% for GADA, 48% for IAA, and 62% for ICA. The frequency of ICA512/phogrin-A was significantly higher in patients with an age of onset less than 10 years (83%) than in patients aged >10 years (51%, P<0.01). The positivity of ICA512/phogrin-A was less in patients whose diabetes was diagnosed by the urine glucose screening test (21%, P<0.001) than in abrupt onset patients (71%). Combined analysis (>/=1 antibody) of GADA, IAA, and ICA512/phogrin-A detected 88% of abrupt onset and 93% of screening-positive patients vs. 70% and 29%, respectively, for ICA (P<0.0005). These results indicate that the expression of ICA512/phogrin-A and cytoplasmic ICA is less in patients identified by urinary glucose testing but indicate that with combined autoantibody testing 90% of patients can be identified independent of the mode of diagnosis.

Adolescent↗

The H(2)O(++) Ground State Potential Energy Surface.

At the correlation-consistent polarized-valence quadruple-zeta complete active space self-consistent field second-order configuration interaction level of ab initio theory (cc-pVQZ CASSCF-SOCI), we calculated 129 points on the ground electronic state potential energy surface of the water dication H(2)O(++); this calculation includes the energy of;X(3)Sigma(-) OH(+) at equilibrium and the energy of the triplet oxygen atom. We determined the parameters in an analytical function that represents this surface out to the (OH(+) + H(+)) and (O + 2H(+)) dissociation limits, for bending angles from 70 to 180 degrees. There is a metastable minimum in this surface, at an energy of 43 600 cm(-1) above the H(+) + OH(+) dissociation energy, and the geometry at this minimum is linear (D(infinityh)), with an OH bond length of 1.195 Å. On the path to dissociation to H(+) + OH(+), there is a saddle point at an energy of 530 cm(-1) above the minimum, and the geometry at the saddle point is linear (C(infinity Kv)) with OH bond lengths of 1.121 and 1.489 Å. Using the stabilization method, we calculated the lowest resonance on this surface. Relative to the metastable local minimum on the potential energy surface, the position of the lowest resonance for H(2)O(++), D(2)O(++), and T(2)O(++) is 1977(85), 1473(25), and 1249(10) cm(-1), respectively, where the width of each resonance (in cm(-1)) is given in parentheses. Copyright 1999 Academic Press.

Journal Article↗

Nucleotide sequences of the mouse globin beta gene cDNAs in a wild derived new haplotype Hbb(w1).

Haplotypes of the beta-globin gene complex (Hbb) in laboratory mice have been defined as d, p, and s. We previously found a new haplotype w1 in wild mice collected from northwestern China. This study analyzed the nucleotide sequences of b1 and b2-globin gene cDNAs of both the p and w1 haplotypes, in comparison with those of the d haplotype. In Hbb-b1 cDNA, six base substitutions were found between the d and w1 haplotypes and also between p and w1, but none existed between d and p. In Hbb-b2 cDNA, three base substitutions were found between the d and w1 haplotypes and also between d and p, but none between p and w1. This result indicated that the Hbb gene complex of the p haplotype carries b1(d) and b2(w1) genes and is probably a recombinant between d and w1 haplotypes. The hemoglobin containing the W1 phenotype showed oxygen-binding properties identical with those of the hemoglobins containing D and P phenotypes.

Animals↗

Self-organization of the heartbeat as coordination among ventricular myocardial cells through mechano-electrical feedback.

To elucidate the mechanism of the self-organizing control of heartbeats, models that include the electrical and mechanical processes of heartbeat are proposed. As the mutual interaction between the two processes, mechano-electrical feedback (MEF), mediated by stretch-activated ionic channels, is considered. Analyses of the models show that coordination of beats among myocardial cells is established by MEF even in the absence of electrical coupling. The coordination of heartbeats is found to show in-phase synchronization under normal conditions, while it is out of phase or irregular under mechanically abnormal conditions. It is concluded that coupling by MEF is important for the self-organization of heartbeats.

Animals↗

White coat hypertension in two adolescents.

We describe two adolescent boys with white coat hypertension. Both patients had significantly high blood pressure documented on more than three occasions at clinic. No cause for hypertension or target organ damage was demonstrated. Twenty-four-hour mean ambulatory blood pressure values were normal for height and sex, which led to the diagnosis.

Adolescent↗

Laparoscopic drainage of an intramural duodenal hematoma.

A 21-year-old man was admitted with vomiting and abdominal pain 3 days after sustaining blunt abdominal trauma by being tackled in a game of American football. A diagnosis of intramural hematoma of the duodenum was made using computed tomography and upper gastrointestinal tract contrast radiography. The hematoma caused obstructive jaundice by compressing the common bile duct. The contents of the hematoma were laparoscopically drained. A small perforation was then found in the duodenal wall. The patient underwent laparotomy and repair of the injury. Laparoscopic surgery can be used as definitive therapy in this type of abdominal trauma.

Abdominal Injuries↗

EUS and K-ras analysis of pure pancreatic juice collected via a duodenoscope after secretin stimulation for diagnosis of pancreatic mass lesion: a prospective study.

BACKGROUND: The early diagnosis of pancreatic cancer remains problematic. This prospective study assessed the utility of a combination of endoscopic ultrasound (EUS) and genetic analysis of pure pancreatic juice in the diagnosis of pancreatic mass lesions. METHODS: One hundred seventy-six patients with suspected pancreatic disease were enrolled and underwent ultrasonography (US), computed tomography (CT), endoscopic retrograde choleangiopancreatography (ERCP), and EUS. Pure pancreatic juice was collected endoscopically after secretin stimulation. K-ras point mutations at codon 12 in the juice were assayed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Thirty-six (20%) patients were found to have solid pancreatic masses including 19 with cancer (7 patients, </= 2 cm) and 17 patients with an inflammatory mass (13 patients, </= 2 cm). US and CT were both less sensitive, particularly in patients with small masses. In 13 patients, small masses (4 cancer and 9 inflammatory masses) were not delineated until EUS. The combination of EUS and K-ras analysis had a high sensitivity (100%; p < 0.05 vs. US) and its accuracy reached 94% (p < 0.01 vs. US). CONCLUSIONS: EUS and K-ras determination in pure pancreatic juice collected via a duodenoscope may be useful for the diagnosis of pancreatic mass lesions.

Adenocarcinoma↗

CTLA4 gene polymorphism correlates with the mode of onset and presence of ICA512 Ab in Japanese type 1 diabetes.

Recently, the association of CTLA4 gene polymorphism with type 1 diabetes and AITD has been reported in several populations. CTLA4 was originally reported to regulate T-cell activity and T-B cognate interaction. To investigate the role of CTLA4 in autoimmune diseases, we examined the correlation between CTLA4 gene polymorphism and the clinical characteristics of Japanese patients with type 1 diabetes, including the mode of onset of diabetes and presence of islet-specific autoantibodies (GAD, ICA 512 Ab) in the serum. We studied 111 patients with type 1 diabetes and 445 normal subjects. CTLA4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphism was defined, employing PCR-RFLP. Sixty-three (57%) patients had AITD. The allele frequencies of G and A in both 111 patients (G: 65%; A: 35%) and 63 patients (G: 62%; A: 38%) were not significantly different from the control subjects (G: 63%; A: 37%). Serum samples of 69 patients were obtained within a year after onset and used for pancreas specific autoantibodies analysis. These samples were also used for further analysis between CTLA4 gene polymorphism and clinical characteristics. The allele frequencies of G and A in patients who presented with diabetic ketoacidosis (DK+) (G: 75%; A: 25%) were significantly different from those in DK- patients (G: 50%, A: 50%, P = 0.003). Allele and genotype analyses showed significant differences between DK+ patients and control subjects (P = 0.014, P = 0.046, respectively). Allele frequencies of G and A were not significant between patients who were positive and negative for GAD Ab, but significant for ICA 512 Ab (G: 83%, A:17% versus G: 59%, A: 41%: positive patients versus negative patients, P = 0.004). Our results showed a significant correlation between CTLA4 gene polymorphism and ICA 512 Ab. Our results also indicated that CTLA4 gene polymorphism is associated with the onset mode of Japanese type 1 diabetes and the presence of ICA512 Ab. Further analysis of this polymorphism is necessary to fully understand the pathogenesis and progression of type 1 diabetes.

Abatacept↗

YoshixolTR inhibits B16 melanoma cell growth in vivo and induces apoptosis-like (quantum thermodynamic) cell death.

In this report, antitumor effects of YoshixolTR in vivo and in vitro were investigated in B16 melanoma cells. For in vivo experiments, the present study shows a dramatic inhibition of tumor growth of B16 melanoma transplanted on the leg or intraperitoneal cavity after treatment with YoshixolTR intraperitoneally. A proliferation of B16 cells in vitro was inhibited by YoshixolTR in a dose-and time-dependent manner. YoshixolTR induced apoptosis-like cell death in histological observations (phase-contrast, scanning and transmission electron microscopy), DNA fragmentation, and a smaller increase in lactate dehydrogenase (LDH) as a marker of cell leakage. Immunohistochemical investigation of cytoskeletal components, such as actin and tubulin, showed a cell wall disruption of B16 melanoma cells and a nuclear extrusion after the treatment with YoshixolTR. Treatment with YoshixolTR in vitro showed an arrest at the G0/G1 stage of the cell cycle, followed by a flow cytometric measurement. As a possible physiological mechanism of YoshixolTR on B16 melanoma cells, intracellular Ca++ was measured with Fura-2 technique. An adequate concentration of YoshixolTR, which induces apoptosis-like cell death, showed a decrease in intracellular free Ca++ concentration. In conclusion, YoshixolTR has an antitumor potency with a new biological mechanism of cell growth, proliferation, and differentiation, including cellular signalling pathways, and is a new candidate for an ideal chemotherapeutic agent against malignant tumors.

Animals↗

In vitro and in vivo antitumor activity of YoshixolTR against murine L1210 leukemic cells.

In this report, antiproliferative effects of YoshixolTR in vitro and in vivo were investigated in murine L1210 cells. A proliferation of L1210 cells in vitro was inhibited by YoshixolTR in a dose- and time-dependent manner. This inhibition showed an arrest at the G0/G1 stage of the cell cycle, followed by a flow cytometric measurement. YoshixolTR induced apoptosis-like cell death identified by histological observations (scanning electron and transmission electron microscopy), DNA fragmentation, and a smaller increase in lactate dehydrogenase (LDH). In the in vivo experiments, YoshixolTR (5 microl/kg of body weight, on days 1, 3, and 5) was injected intraperitoneally in mice inoculated with L1210 cells. No marked prolongation of survival occurred between the control group and treated group. However, a survival curve in the treated group showed a shift toward a possible longer survival time. Additionally, on the basis of apoptosis-like cell death due to YoshixolTR as indicated above, a possibility of immunotherapy as a tumor vaccine has been examined. A vaccination of rabbit anti-serum, which consisted of components from the L1210 cells killed by YoshixolTR, produced a dramatic improvement of viability in the leukemic mice. In conclusion, YoshixolTR has an anti-leukemic potency with a new biological mechanism and an inductive potency of super-antigens as immunotherapeutic agents against malignant tumors.

Animals↗

Cardiovascular effects of dihydrotestosterone in rats.

We conducted a study to evaluate the cardiovascular effects of 5 alpha-dihydrotestosterone (DHT), including the supplementary respiratory effects, using normal and obese groups of Wistar castrated male rats, and the association of the hormonal effect with sudden unexplained nocturnal death syndrome (SUNDS). The hormone-treated normal rats had a significantly greater weight of the right ventricular wall and atria and body weight ratio when compared with the controls. Cardiac function estimated from the parametric value multiplied heart rate by carotid maximum systolic pressure was significantly lowered in the hormone-treated rats, However, no difference in the right ventricular action between the hormone-treated and control rats was found. In respiratory parameters, expired CO(2) gas decreased significantly in the hormone-treated rats. On the other hand, the hormone-treated obese rats showed a significantly greater weight of the heart and body weight ratio. This was due to the significant gain of the ventricular septum weight, in addition to the weight gains of the right ventricular wall and atria. Cardiac function of the hormone-treated obese rats was significantly lower than that of the controls and lower than that of normal rats. Significant increase in respiratory rate and decrease in expired CO(2) gas were seen in the hormone-treated rats. Therefore, these results demonstrate that the hormone had hypertrophic effects mainly on the right ventricle or atria and suppressive effects on cardiovascular function or promotive effects on respiratory ventilation, with both of the latter effects enhanced comparatively in obese rats. These cardiac hypertrophic and ventilatory characteristics according to DHT do not seem to apply to the victims of SUNDS.

Journal Article↗

Phenolic antioxidants from the leaves of Corchorus olitorius L.

Six phenolic antioxidative compounds [5-caffeoylquinic acid (chlorogenic acid), 3,5-dicaffeoylquinic acid, quercetin 3-galactoside, quercetin 3-glucoside, quercetin 3-(6-malonylglucoside), and quercetin 3-(6-malonylgalactoside) (tentative)] were identified from the leaves of Corchorus olitorius L. (moroheiya) by NMR and FAB-MS. The contents of these phenolic compounds, ascorbic acid, and alpha-tocopherol in C. olitorius leaves were determined, and their antioxidative activities were measured using the radical generator-initiated peroxidation of linoleic acid. The results obtained showed that 5-caffeoylquinic acid was a predominant phenolic antioxidant in C. olitorius leaves.

Antioxidants↗