Search PubMed⌕ Search

Biomedical subjects

Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 523 records · Page 29Linked to original sources

Prolonged survival of rat hepatic allografts pretreated with a single donor-specific blood transfusion: the distribution of donor cells expressing class I major histocompatibility complex antigens in the recipient.

We previously reported that a pretransplant transfusion of either ACI strain rat donor blood or PVG.r1 strain blood, which shares only the RT1.A class I major histocompatibility complex (MHC) region with an ACI donor, significantly prolonged the survival of ACI-to-LEW rat hepatic allografts, suggesting that the class I MHC antigens can be immunosuppressive in rat hepatic allografts. The distribution of the donor cells expressing RT1.Aa class I MHC antigens in the recipients was investigated using a MN4-91-6 mouse anti-rat class I (RT1.Aa) MHC monoclonal antibody. The donor class I MHC-positive cells accumulated mainly in the splenic white pulp and lymph nodes at 12 and 24 hr after blood transfusion, while very few cells were seen in the thymus, liver, lungs, and kidneys. The number of cells began to decrease in the splenic white pulp and lymph nodes at 24 hr after transfusion. This may indicate the destruction of donor cells by the recipient cells. Within 48 hr after transfusion, most cells disappeared from the recipient tissue. In an attempt to study the role of the spleen in inducing immunological unresponsiveness, a splenectomy was performed at the time of transplantation and this abrogated the prolongation of hepatic allograft survival in the recipients which received the donor blood. These findings suggest that the presence of class I MHC-positive cells in the splenic white pulp, a T-dependent area, may play an important role in inducing immunological unresponsiveness.

Animals↗

Dietary cholesterol enhances impaired endothelium-dependent relaxations in aortas of salt-induced hypertensive Dahl rats.

We investigated the effect of hypercholesterolemia on the vascular reactivity of thoracic aortas isolated from hypertensive Dahl salt-sensitive (DS) rats. DS rats were fed on a low-sodium diet (control group), a low-sodium plus high-cholesterol diet (CHOL group), a high-sodium diet (NaCl group) or a high-sodium plus high-cholesterol diet (NaCl + CHOL group) for 8 weeks. Hypercholesterolemia developed in the CHOL and NaCl + CHOL groups, while hypertension developed in the NaCl and NaCl + CHOL groups, with these changes being greatest in the NaCl + CHOL group. Aortic cholesteryl ester accumulation was attenuated in the aortic rings from the NaCl and NaCl + CHOL groups, compared to the control group. The degree of attenuation in the NaCl + CHOL group was significantly greater than that in the NaCl group. Endothelium-dependent relaxations induced by the calcium ionophore A23187 were attenuated only in the NaCl + CHOL group. Endothelium-independent relaxations in response to sodium nitroprusside were slightly but significantly attenuated in the NaCl + CHOL group. The relaxations in the CHOL group were comparable to those in the control group. These findings indicate that cholesterol feeding strikingly enhances the impaired endothelium-dependent relaxations and the slightly impaired endothelium-independent relaxations in the aorta of DS rats with salt-induced hypertension, parallel to the development of hypertension, hypercholesterolemia and cholesterol deposition.

Acetylcholine↗

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↗

Suppression of hepatic allograft rejection in the rat by mitomycin C-treated donor splenocytes: in situ splenic distribution of donor class I major histocompatibility complex antigen-positive cells in the recipient.

A single intravenous injection of 3 x 10(6) donor splenocytes treated with mitomycin C (MMC) 7 days before hepatic transplantation prolongs survival of hepatic allografts in the ACI(RT1a) to LEW(RT1(1)) rat combination. This effect is donor specific. The in situ distribution in the recipient of the donor cells administered preoperatively was investigated using intracellularly fluorescence-labeled donor splenocytes. The donor cells were accumulated mainly in the splenic white pulp and lymph nodes at 12 and 24 hr after injection. Contrarily, very few cells were seen in the thymus, liver, kidney, and lung. The number of cells with dull and weak fluorescence began to increase in the splenic white pulp and lymph nodes at 24 hr after injection. This may indicate the breakdown of donor cells by recipient cells. In contrast, a number of donor cells could be detected even after 48 hr and a few cells at 7 days after splenocyte injection in the LEW-to-LEW isogeneic combination. As we previously revealed the role of class I major histocompatibility complex (MHC) antigens in prolonging hepatic allograft survival in the rat, the splenic distribution of donor class I MHC-positive cells in the recipient after intravenous administration of MMC-treated donor splenocytes was studied using immunostaining with a MN4-91-6 mouse anti-rat RT1.Aa class I MHC monoclonal antibody. The donor class I-positive cells accumulated mainly in the splenic white pulp at 12 and 24 hr after injection. This is similar to that observed in the fluorescence study. Within 48 hr after injection, most cells had disappeared from the recipient tissue. These findings suggest that the splenic white pulp, a T-dependent area, may play an important role in inducing immunological unresponsiveness.

Animals↗

Thymus-related liposarcoma: report of a case and review of the literature.

We report herein the case of a 77-year-old woman who was admitted to our hospital for further evaluation of an abnormal shadow in the right upper mediastinum that had been revealed by a routine chest X-ray. Computed tomography (CT) and magnetic resonance imaging (MRI) scans confirmed the presence of a thymic tumor, but did not show any evidence of invasion into the central vessels or adjacent structures. Thus, an extended thymectomy with resection of the tumor was performed. Microscopically, normal thymic tissue was found among the tumor cells, and a pathological diagnosis of well-differentiated liposarcoma was established. From the operative and microscopic findings, it is apparent that the tumor was related to the thymus. Postoperative irradiation of 60 Gy was delivered to the operative site and the patient has remained free of disease for 29 months since the operation.

Aged↗

Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver.

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.

Amino Acid Chloromethyl Ketones↗

Technique for orthotopic reduced-size hepatic transplantation combined with ex vivo liver cut down in the rat.

A technique is described for orthotopic reduced-size hepatic transplantation combined with ex vivo liver cut down in the rat. Following perfusion of the donor liver with cold heparinized saline, the portal veins, bile ducts, and hepatic arteries to the median and left lobes together were dissected in situ, encircled, and divided. After harvesting the donor liver, a hepatectomy was performed by ex vivo liver cut down of the median and left lobes. The remnant amounted to 32% of the whole liver. As a result, the suprahepatic vena cava could be well visualized with adequate exposure for vascular anastomosis. Orthotopic reduced-size hepatic transplantation was performed using the right and caudate lobes of the liver. The suprahepatic vena cava was anastomosed with a 7-0 silk running suture. A simplified cuff without processes was made with an obliquely cut polyethylene tube and used for the portal and infrahepatic caval anastomoses. A Teflon tube stent was used for the biliary anastomosis. The newly devised angled clamp and flexible arm were used for the cuff attachment and operative procedure. Transplant survival following ex vivo liver cut down was as good as that with whole liver transplantation. Reestablishment of the hepatic artery restores liver function following transplantation. The maximum hepatocyte labeling index (LI) occurs 24 hr after a 68% hepatectomy, and at 36 hr following a reduced-size hepatic transplantation with or without hepatic arterialization. Possible explanations for the slight delay in achieving the maximal LI may include damage that is induced by the operation itself, pregraft preservation, and reperfusion injuries. In conclusion, the anatomical features of the hepatic lobes in rats are well suited to successful completion of ex vivo liver cut down.

Animals↗

Effects of growth temperature on the fatty acid composition of the free-living nematode Caenorhabditis elegans.

The effects of growth temperature on the fatty acid compositions of the phosphatidylcholine (PC), phosphatidylethanolamine (PE), and total lipid (TL) fractions of the free-living nematode Caenorhabditis elegans were investigated. A reduction in growth temperature from 25 to 15 degrees C caused the proportions of eicosapentaenoic acid (20:5n-3) to increase from 23.6 to 32.5% in the PC, from 7.4 to 10.8% in the PE, and from 12.9 to 19.9% in the TL fractions. Conversely, the levels of dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in these phospholipid fractions and the TL fraction both decreased with decreasing growth temperature. Analysis of the positional distribution of fatty acids in the PC fraction revealed that the change in the composition of C20 polyunsaturated fatty acid was obvious in position sn-2. Lowering the growth temperature induced an increase in the level of the diacyl subclass of PE from 58% at 25 degrees C to 71% at 15 degrees C, with a concomitant decrease in the levels of the alkylacyl and alkenylacyl subclass of PE of C. elegans. These changes observed in the phospholipids of C. elegans might be one mechanism for adaptation to low temperature.

Adaptation, Physiological↗

Efficient production of IgG human monoclonal antibodies by lymphocytes stimulated by lipopolysaccharide, pokeweed mitogen, and interleukin 4.

Extensive screening of the mitogens lipopolysaccharide (LPS), pokeweed mitogen (PWM), and Staphylococcus aureus Cowan I (SAC I), alone and in combination and with and without interleukin (IL) was performed for in vitro activation of regional lymph node lymphocytes from lung cancer patients for the production of human IgG, IgM, and IgA. As assessed by electrofusion of the lymphocytes following their exposure to these agents with mouse myeloma cells and incubation of the fused hybridoma, a remarkable stimulatory effect was shown by LPS and particularly by LPS plus IL-4, which was substantially greater than that of either SAC I or PWM with or without various IL. Optimization studies indicated that the addition of PWM to LPS and IL-4 in the culture medium further stimulated the human antibody (Ab) production, and that the optimal formulation for stimulation of human IgG production was a culture medium containing 20 micrograms/ml of LPS, 1/500 of PWM, and 100 u/ml of IL-4.

Antibodies, Monoclonal↗

TNF-alpha stimulates glucose uptake in L6 myoblasts.

The mechanism of TNF-alpha to regulate glucose metabolism remains unclear. To further delineate the TNF-alpha signal transduction pathway mediating glucose metabolism, we utilized L6 rat myoblasts which contain the receptors for the insulin-like growth factor-I (IGF-I) and TNF-alpha, and the ability of both ligands to stimulate glucose uptake was compared. IGF-I (6.5 nM) maximally stimulated glucose uptake 7-fold after 24 h incubation, while 23 nM TNF-alpha maximally stimulated glucose uptake 3-fold only after 48 h incubation. IGF-I receptor beta-subunit, insulin receptor substrate-1 (IRS-1), and mitogen-activated protein (MAP) kinase were all phosphorylated in response to 6.5 nM IGF-I after 10 min incubation. In contrast, the treatment with 23 nM TNF-alpha failed to phosphorylate either IGF-I receptor beta-subunit or IRS-1 but did phosphorylate MAP kinase as much as IGF-I did. Despite a similar extent to which TNF-alpha induced MAP kinase phosphorylation as IGF-I did, TNF-alpha stimulated glucose uptake less compared to IGF-I. The results indicate that MAP kinase phosphorylation is not sufficient for glucose uptake in L6 myoblasts. TNF-alpha-elicited signal transduction to glucose uptake may utilize a different pathway from that seen with IGF-I.

Animals↗

Adjuvant chemo-immunotherapy after curative resection of Stage II and IIIA primary lung cancer.

Out of 642 primary lung cancer patients who underwent surgery between 1986 and 1992, 82 cases who underwent curative resection were enrolled for a randomized prospective controlled study of postsurgical adjuvant immunotherapy using Interleukin 2 (IL-2) and lymphokine activated killer (LAK) cells. From 1986 to 1989 (the initial period), Stage IIIA patients were divided into three groups: group A (chemo-immunotherapy) received IL-2, LAK cell adoptive immunotherapy after two courses of anticancer (CDDP, VDS, MMC) chemotherapy, group B (control) received no adjuvant therapy, and group C (chemotherapy) received the same anticancer chemotherapy as group A. In the latter (1990-1992) period, group C was discontinued because of poor results and Stage II and IIIA cases were randomly assigned to group A or B. The 5- and 7-year survival rates of group A (33 cases) and B (36 cases) were 58.2% and 31.5%, respectively in Stage II and IIIA cases. The prognosis of group A was significantly better than that of group B (P = 0.0038 by the Cox-Mantel (C-M) test and 0.0033 by the generalized Wilcoxon (G-W) test). The 5- and 8-year survival rates of each group for Stage IIIA cases were 53.4% (group A, 25 cases), 33.4% (group B, 26 cases), and 30.8%, 15.3% (group C, 13 cases). The prognosis of group A was significantly better than that of group B (P = 0.045 by the C-M and 0.036 by the G-W test). The difference between group A and B was also significant in N0, N1 (P < 0.01), in T1, T2 (P < 0.01), and T3 (P < 0.05) cases. These results indicate that adjuvant immunotherapy using IL-2 and LAK cells in combination with chemotherapy is significantly effective in improving the postsurgical prognosis of lung cancer patients.

Adenocarcinoma↗

Cigarette smoke-modified low density lipoprotein impairs endothelium-dependent relaxation in isolated rabbit arteries.

1. We investigated the effects of cigarette smoke-modified low-density lipoprotein (CS-LDL) on endothelium-dependent relaxations in various isolated rabbit arteries, and compared them with those of oxidized LDL (Ox-LDL). 2. In aorta rings, acetylcholine-induced endothelium-dependent relaxations were attenuated by preincubation with CS-LDL and Ox-LDL. Endothelium-independent relaxations induced by sodium nitroprusside were not modified. Similar changes were observed in rings of coronary and basilar arteries. 3. These findings indicate that CS-LDL, as well as Ox-LDL, may decrease the release or activity of endothelium-derived relaxing factor in vascular endothelial cells.

Acetylcholine↗

Enhancing effects of alpha-,beta-monoglycosylceramides on natural killer cell activity.

We examined the in vitro and in vivo natural killer (NK) cell activity enhancing effects of alpha-, beta-galactosylceramide (GalCer) and alpha-, beta-glucosylceramide (GluCer) which have the same ceramide moiety, and of other alpha-, beta-GalCer having a different ceramide portion, and found that alpha-types show stronger enhancing effects than beta-types and the alpha-GalCer possesses the most potent activity among GalCers and GluCers having the same ceramide moiety. When the comparison of tumor growth inhibitory effects of alpha, beta-GalCer on mice subcutaneously inoculated with B16 cells was performed, the alpha-GalCer showed stronger suppressive activity than its beta-type, paralleling their enhancing effects on NK cell activity. These results suggest that the manner of combination between sugar and ceramide plays an important role in antitumor activity as well as enhancing effect on NK cell activity of GalCers.

Animals↗

Generation of human monoclonal antibodies recognising membranous antigens of the lung adenocarcinoma cell line A549 using an AMeX immunohistostaining method.

Four monoclonal antibodies (MAbs) from hybridoma obtained by in vitro stimulation of regional lymph node lymphocytes from lung cancer patients and electrofusion of the stimulated cells with murine or human-mouse myeloma cells were reactive to lung cancer cells in enzyme-linked immunoabsorbent assay, and to lung cancer tissue in immunohistochemical analysis using acetone-methyl benzoate-xylene (AMeX) fixed tissue and in immunofluorescence analysis. Three of the MAbs (designated ZLG40, 27D57 and 28K29) recognised cell-surface antigens of the lung adenocarcinoma cell line A549 and the remaining one (designated 29D38) recognised nuclear membrane antigens of the same cell line. The three surface-binding MAbs showed a significant complement-dependent cytotoxicity (CDC) to the A549 cells, but the membrane-binding 29D38 showed no CDC to the A549 cells. Western blotting of the extracts of the A549 or PC6 (small-cell lung cancer) cell lines by the four MAbs showed a 28K29 antigen band at M(r) of approximately 600,000 (+/- 2-ME), a ZLG40 antigen band at M(r) 50,000 (+/- 2-ME), and one 29D38 antigen band at M(r) of more than 1,000,000 (-2-ME) and M(r) between 20,000 and 80,000 (+2-ME), but no detectable band for 27D57 antigen.

Adenocarcinoma↗

Kupffer cell production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion injury in rats.

We investigated the role of hepatic macrophages in the inflammatory response following reperfusion injury by blocking Kupffer cell phagocytosis with gadolinium chloride (GdCl3). Liver ischemia was induced in rats by occluding the portal vein for 30 minutes. A bolus of GdCl3 (7 mg/kg) was injected intravenously 1 and 2 days before surgery. The serum levels of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, peaked after 6 hours, and then gradually decreased. GdCl3 or heparin alone significantly decreased the serum levels of CINC (P < .05). In addition, pretreatment with GdCl3/heparin further inhibited the rise in the serum levels of CINC following reperfusion compared with those in untreated animals (P < .01). The in vitro production of CINC by Kupffer cells, obtained from animals pretreated with heparin or GdCl3, was significantly lower than that of cells isolated from untreated animals. Pretreatment with GdCl3/heparin further decreased CINC production by Kupffer cells compared with that of cells from animals that were pretreated with heparin or GdCl3 alone. The expression of CINC transcripts in Kupffer cells or in liver tissue peaked 3 hours after reperfusion in untreated animals. Pretreatment with heparin, GdCl3, or both significantly decreased the levels of CINC messenger RNA (mRNA) transcripts. Pretreatment with heparin, GdCl3, or GdCl3/heparin significantly decreased the number of neutrophils that accumulated in the liver 24 hours following reperfusion, compared with those in untreated animals. These results suggest that Kupffer cells release CINC and may play an important role in early neutrophil infiltration into the liver following ischemia/reperfusion.

Animals↗

Characterization of the purified cytosolic thymidine kinase from murine ehrlich ascites tumor: interconversion of two different relative molecular weight forms.

Cytosolic thymidine kinase was purified 18,000-fold of the homogenate from murine Ehrlich ascites tumor, using the [p-aminophenyl 3' -dTMP]-CH-Sepharose affinity column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single protein band of molecular weight 26,000. Two different forms, relative molecular weight 50,000 and 70,000, were found by gel filtration, depending on the existence of dithiothreitol, ATP and other nucleotides. These agents also stabilize and stimulate the enzyme activity. The existence of two forms was also manifested by DEAE-Sephacel column chromatography, where the 50,000 form was eluted by 50 mM NaCl and the 70,000 form by 400 mM NaCl.

Adenosine Triphosphate↗

The effects of sevoflurane, enflurane, and isoflurane on baroreceptor-sympathetic reflex in rabbits.

This study was designed to determine the effects of sevoflurane, enflurane, and isoflurane ranging from 0.5 to 1.25 minimum alveolar anesthetic concentration (MAC) on spontaneous efferent renal sympathetic nerve activity (RNA) and the barorecptor-sympathetic reflex in rabbits. Enflurane produced significant decreases in spontaneous RNA by 22.5% +/- 6.6% at 1.0 MAC, while sevoflurane and isoflurane, at the equivalent MAC, did not. All of the anesthetics attenuated the baroreflex gain similarly when mean blood pressure (MBP) was changed by sodium nitroprusside or phenylephrine intravenously. However, the sensitivity of baroreceptors at the aortic wall was not changed by any anesthetic, because no changes in the relationship between aortic nerve activity and MBP were obtained in anesthetic concentration even at 1.25 MAC. Furthermore, these anesthetics suppressed the sympathoinhibitory response to aortic nerve stimulation above 1.0 MAC. In conclusion, enflurane inhibits RNA to a greater degree than sevoflurane or isoflurane. However, all three anesthetics depress the reflex regulation of RNA to the same degree. The suppression on the baroreceptor-sympathetic reflex does not appear to be related to a change in the receptor sensitivity on the aorta, but is mediated by suppression of the central or peripheral sympathetic integrating system.

Anesthetics, Inhalation↗

Detection of K-ras point mutations at codon 12 in pure pancreatic juice for the diagnosis of pancreatic cancer by PCR-RFLP analysis.

The present study was undertaken to detect K-ras point mutations at codon 12 in pure pancreatic juice (PPJ) for the diagnosis of pancreatic cancer (PC) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PPJ was collected through a cannula under a duodenal fiberscope from 26 patients with PC and 32 patients with chronic pancreatitis (CP). DNA was extracted from PPJ and was used as the template for PCR. Analysis of PPJ by PCR-RFLP with BstNI revealed that the incidence of K-ras point mutations at codon 12 was 81% (21/26) in patients with PC and 6% (2/32) in those with CP. With reference to the location of PC, the incidence of K-ras mutations was 79% (11/14) in the head, 86% (6/7) in the body, and 80% (4/5) in the tail of the pancreas. The incidence of K-ras mutants was 50% (1/2) in tumor size 1 (TS1; < or = 2.0 cm in size), 71% (5/7) in TS2 (2.1 to < or = 4.0 cm), 89% (8/9) in TS3 (4.1 to < or = 6.0 cm), and 88% (7/8) in TS4 (> 6.1 cm). These results suggested that analysis of K-ras point mutations at codon 12 in PPJ using the PCR-RFLP method is a promising new genetic test for the diagnosis of PC.

Adult↗