Irreversibility line and the hierarchy of weak links in Bi2Sr2CaCu2O8+ Delta.
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Journal Article↗
Biomedical subjects
Y Yamaguchi
Publications and source records attributed to Y Yamaguchi.
Retrovirally transmitted gene therapy for gastric carcinoma using herpes simplex virus thymidine kinase gene.
BACKGROUND: Herpes simplex thymidine kinase (HTK) is known to phosphorylate ganciclovir (GCV). Phosphorylated GCV is incorporated into genomic DNA, which leads to inhibition of cell growth and cell death in the replicating cells. Recently, much attention has been drawn to the use of retrovirally mediated gene therapy using HTK as a new therapeutic approach for brain tumors. However, little is known about this phenomenon in gastrointestinal carcinomas. METHODS: The authors transfected the HTK gene packaged in retroviral vector into TMK-1 gastric carcinoma cells (TMK-HTK cells). Sensitivity of TMK-HTK cells to GCV was examined in vitro. Moreover, TMK-HTK cells were transduced into nude mice subcutaneously, and the effects of GCV therapy was examined at the concentration of 20 mg/kg daily for 14 days. RESULTS: TMK-HTK cells were sensitive to GCV at the concentration of 0.1 to 100 micrograms/ml in a dose- and time-dependent manner in vitro. Moreover, 12 of 13 TMK-HTK tumors, which were transduced into nude mice subcutaneously, shrunk from the average diameter of 6.5 mm. CONCLUSION: The results indicate that retrovirally transmitted gene therapy with GCV may provide a new therapeutic approach for treatment of gastric carcinomas.
Animals↗
[Differences in clinical findings between drug-induced and viral liver diseases].
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Chemical and Drug Induced Liver Injury↗
Determination of urinary valproylcarnitine by gas chromatography-mass spectrometry with selected-ion monitoring.
A modified method for the determination of valproylcarnitine in urine samples of patients receiving sodium valproate by gas chromatography-mass spectrometry with selected-ion monitoring is described. The chemically analogous internal standard 2-ethylpentanoylcarnitine was added to the urine samples. Valproic acid and its metabolites were removed by extraction with chloroform at pH 5.0. The samples were then applied onto a C18 Sep-Pak column. Inorganic and water soluble compounds were washed out with water. Valproylcarnitine and internal standard were eluted with methanol and were derivatized to the corresponding acyl-containing lactones by heating at 100 degrees C for 60 min in dimethylformamide. Urinary valproylcarnitine levels of epileptic patients receiving valproate were determined according to the present method. The data obtained might be useful for diagnosis of carnitine deficiency.
Calibration↗
Hepatocyte growth factor is involved in formation of osteoclast-like cells mediated by clonal stromal cells (MC3T3-G2/PA6).
Osteoclast formation from hemopoietic precursors has been shown to require the support of stromal cells in bone tissue. In this study, we demonstrated that hepatocyte growth factor (HGF) is one of the stromal cell-derived molecules responsible for osteoclast-like cell formation. For our experiments, we used a coculture system for osteoclastic cell formation and activation in which hemopoietic blast cells are cocultured with calvaria-derived stromal MC3T3-G2/PA6 (PA6) cells on dentine slices in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Addition of anti-HGF neutralizing IgG to the cocultures inhibited the formation of osteoclastic cells and their dentine-resorbing activity. We detected a single 6.0-kb transcript for HGF in PA6 cells, and also recognized immunoreactive M(r) 81,000 and 88,000 forms of HGF in conditioned medium (CM) from PA6 cell cultures, the level of which reached 6 ng/ml. Both the CM and HGF stimulated the proliferation of blast cells synergistically with granulocyte-macrophage colony-stimulating factor, resulting in an increased number of osteoclast precursors that respond to 1,25(OH)2D3 that are tartrate-resistant acid phosphatase-positive multinucleate cells in stromal cell-free blast cell cultures in plastic wells. The effect of the CM was diminished by the addition of anti-HGF IgG. However, neither the CM nor HGF stimulated the formation of osteoclastic cells and pits on dentine slices in the absence of PA6 cells. These results suggest that although HGF cannot completely replace stromal cells, it is one of the paracrine mediators produced by stromal cells that act on proliferation of osteoclastic cell precursors.
Acid Phosphatase↗
Autoantibodies to glutamic acid decarboxylase in patients with autoimmune thyroid disease: relation to competitive insulin autoantibodies.
We evaluated the presence of autoantibodies to glutamic acid decarboxylase (GAD), competitive insulin autoantibodies (IAA) and islet cell antibodies (ICA) in sera from 288 non-diabetic patients with autoimmune thyroid disease (AITD), including 212 patients with Graves' disease and 76 with Hashimoto's thyroiditis, and in 235 age- and sex-matched healthy control subjects. GAD antibodies and IAA were assayed using radioimmunoassay with 125I-labelled purified pig brain GAD and human insulin, respectively. Titers of greater than 4.7 units for GAD antibodies and 50 nU/ml for IAA, respectively, the mean + 3SD of 235 age- and sex-matched healthy individuals, were defined as positive. The mean titers of GAD antibodies in patients with Graves' disease and in patients with Hashimoto's thyroiditis were 3.6 +/- 4.6 (mean +/- SD, range 0.6-52.0) units and 3.2 +/- 1.4 (range 0.6-10.0) units, respectively. Titer of GAD antibodies in patients with AITD was significantly higher than in healthy controls (P < 0.0005). Thirteen of 212 (6.1%) patients with Graves' disease and 6 of 76 (7.9%) patients with Hashimoto's thyroiditis had positive GAD antibody titers, whereas titers in healthy control sera were < 4.7 units in all but two individuals (P < 0.005). In competition analysis with purified unlabelled GAD, binding tracer was inhibited in all of 13 GAD antibody-positive Graves' sera and 5 of 6 GAD antibody-positive sera from patients with Hashimoto's thyroiditis. Eight of 212 (3.8%) patients with Graves' disease and 3 of 76 (3.9%) patients with Hashimoto's thyroiditis, but none of healthy controls had IAA levels exceeding the range for normal controls (P < 0.005). Positive IAA levels ranged between 50 and 2383 nU/ml. Strikingly, all of 19 GAD antibody-positive sera were negative for IAA. ICA were not detected in any of the patients or healthy controls. These data demonstrate that GAD antibodies in sera of AITD patients are of low titer but significantly elevated compared to healthy controls, and are independent of the appearance of IAA. They also indicate that, in patients with AITD, an autoimmune response to GAD may occur with no relationship to production of IAA.
Adult↗
Characterization of hepatic allograft infiltrates in rats pretreated with donor-specific blood transfusion (DST).
A single intravenous injection of 1 ml freshly heparinized donor blood given 7 days prior to transplantation prolonged significantly the survival of subsequent hepatic allografts in fully allogeneic ACI(RT1a)-to-LEW(RT1(1)) rats. The cellular identity of allograft infiltrates was investigated at various times after transplantation using OX8 (CD8) and W3/25 (CD4) monoclonal antibodies. The number of CD8+ cells increased rapidly and reached a peak on Day 3 after transplantation of the untreated allografts. Similarly, the number of CD8+ cells in the allografts from DST-treated rats was maximum on Day 3 and decreased gradually thereafter. The maximum number of CD4+ cells was found on Day 3 in untreated allografts. In contrast, no significant infiltration of CD4+ cells occurred during the first 7 days after transplantation in DST-treated allografts. Thereafter, the number of CD4+ cells increased rapidly and reached a peak on Day 14. CD4+ cells remained persistently elevated in hepatic allografts of rats pretreated with DST, but did not become functionally competent or initiate rejection. These findings suggest that persistent infiltration by CD4+ cells is a characteristic feature of long-surviving hepatic allografts in rats pretreated with DST.
Animals↗
Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs.
This study was designed to determine the effects of thromboxane A2 (TxA2) on the distribution of vascular resistance, lung weight, and microvascular permeability in isolated dog lungs perfused at a constant pressure with autologous blood. The stable TxA2 analogue (STA2; 30 micrograms, n = 5) caused an increase in pulmonary capillary pressure (Pc) assessed as double-occlusion pressure to 14.0 +/- 0.4 mmHg from the baseline of 7.9 +/- 0.3 mmHg with progressive lung weight gain. Pulmonary vascular resistance increased threefold exclusively due to pulmonary venoconstriction. Pulmonary venoconstriction was confirmed in lungs perfused in a reverse direction from the pulmonary vein to the artery (n = 5), as evidenced by marked precapillary vasoconstriction and a sustained lung weight loss. Furthermore, in lungs perfused at a constant blood flow (n = 5), STA2 also caused selective pulmonary venoconstriction. Vascular permeability measured by the capillary filtration coefficient and the isogravimetric Pc at 30 and 60 min after STA2 infusion did not change significantly from baseline in any lungs studied. Moreover, elevation of Pc by raising the venous reservoir of the intact lobes (n = 5) to the same level as the STA2 lungs caused a greater or similar weight gain compared with the STA2 lungs. Thus, we conclude that TxA2 constricts selectively the pulmonary vein resulting in an increase in Pc and lung weight gain without significant changes in vascular permeability in isolated blood-perfused dog lungs.
Animals↗
Acute renal failure associated with Candida albicans infection.
A 16-year-old male with a long history of steroid-responsive nephrotic syndrome developed fever, abdominal pain, thrombocytopenia and acute renal failure. The clinical course and renal histology were similar to, but not typical of, haemolytic uremic syndrome. Positive cultures (throat, oesophagus, stool), an elevation in serum levels of specific antibody and fungal polysaccharide (1,3) beta-D-glucan and response to the antifungal therapy indicated an association between this syndrome and infection with Candida albicans.
Acute Kidney Injury↗
Microcephaly and early-onset nephrotic syndrome--confusion in Galloway-Mowat syndrome.
We report a 2-year-old girl with nephrotic syndrome, microcephaly, seizures and psychomotor retardation. Histological studies of a renal biopsy revealed focal glomerular sclerosis with mesangiolysis and capillary microaneurysms. Dysmorphic features were remarkable: abnormal-shaped skull, coarse hair, narrow forehead, large low-set ears, almond-shaped eyes, low nasal bridge, pinched nose, thin lips and micrognathia. Cases with this rare combination of microcephaly and early onset of nephrotic syndrome with various neurological abnormalities have been reported. However, clinical manifestations and histological findings showed a wide variation, and there is a lot of confusion in this syndrome. We therefore reviewed the previous reports and propose a new classification of this syndrome.
Child, Preschool↗
Recipient Kupffer cell influx into xenografted liver.
Previously we reported that the combination of total lymphoid irradiation (TLI), cyclosporine A (CsA), and splenectomy have an immunosuppressive effect sufficient to significantly prolong liver xenograft survival in the LVG hamster to the LEW rat model. Using this model, we have investigated recipient Kupffer cell influx into the xenografted liver. In the rat liver, the Kupffer cells are heavily stained with Ki-M2R, a rat anti-macrophage monoclonal antibody, whereas sinus endothelial cells and liver parenchymal cells are invariably negative. Kupffer cells of the hamster liver are not stained with Ki-M2R. In the xenografted animals, we found cells in the sinusoidal wall of the xenograft stained, with progressively increased activity, in animals 45-60 days after transplant. The morphological pattern of these Ki-M2R-positive cells in the hepatic xenograft resembled the Kupffer cells of the normal rat liver. These findings indicate recipient macrophage influx into the xenografted liver.
Animals↗
Neutrophil elastase inhibitor (ONO-5046) prevents lung hemorrhage induced by lipopolysaccharide in rat model of cerulein pancreatitis.
The protective effects of a neutrophil elastase inhibitor (ONO-5046) on cerulein-induced pancreatitis followed by a septic challenge with intraperitoneal lipopolysaccharide (LPS) were studied in a rat model. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-hr intervals). ONO-5046 was administered by continuous intravenous infusion via the right jugular vein (50 mg/kg/hr, 30 min prior to the first cerulein injection to 20 hr following the last cerulein injection). Significant differences in serum amylase and pancreatic wet weight ratio were not observed between the animals with pancreatitis treated with or without ONO-5046. There was no significant difference in the in vitro tumor necrosis factor-alpha (TNF-alpha) production by peritoneal macrophages from rats with pancreatitis treated with or without ONO-5046. In a second experiment, LPS (10 mg/kg) was administered intraperitoneally as the septic challenge 6 hr following the first cerulein injection. Lung hemorrhage was seen in the animals with pancreatitis untreated with ONO-5046 24 hr following the first cerulein injection. No significant lung hemorrhage was observed in the animals with pancreatitis treated with ONO-5046 administering 30 min prior to the first cerulein injection. These results suggest that lung hemorrhage in cerulein-induced pancreatitis that follows a septic challenge with LPS can be prevented by the intravenous administration of ONO-5046. Thus there is a significant role for neutrophil elastase in pancreatitis-associated lung injury.
Animals↗
Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese--class II antigen and autoimmune thyroid disease.
HLA-DQA1 and DPB1 alleles were examined in relation to autoimmune thyroid disease (AITD) in the Japanese type 1 diabetic patients. The subjects consisted of 14 type 1 diabetic patients with Graves' disease, 12 patients with Hashimoto's thyroiditis and 32 type 1 diabetic patients without AITD. Comparisons were made with 35 normal controls. Among the type 1 diabetic patients with Graves' disease, the age at onset of diabetes was 31.8 +/- 14.6 years old, which was later than that of those without AITD (P < 0.01). DR9 was increased (57.1% vs. 25.9%, P < 0.05, RR: 3.85, chi 2:4.36) in the patients with Graves' disease. DQA1*0301 was increased and DQA1*0103 was decreased in the patients with Graves' disease and those without AITD. HLA-DPB1*0501 was increased (92.9% vs. 54.3%, P < 0.05, RR: 11.0, chi 2:6.57) in the patients with Graves' disease. These findings suggest the existence of a Graves' complicated subgroup characterized by the increasing association of DPB1*0501 and late onset of diabetes in Japanese type 1 diabetic patients. There exists a heterogeneity in Japanese type 1 diabetes.
Adult↗
Adjuvant immunotherapy with interleukin 2 and lymphokine-activated killer cells after noncurative resection of primary lung cancer.
A randomized controlled study of immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells was conducted in 105 patients after noncurative resection of primary lung cancer. Half the patients received only the standard postoperative radiation therapy or chemotherapy (control group). The other half received immunotherapy with IL-2 and LAK cells in addition to the standard therapy (immunotherapy group). The primary endpoint was survival. The 7-year survival rate was greater in the immunotherapy group than in the control group (39.1% vs. 12.7%, P < 0.01). Among patients with squamous cell carcinoma, there was no statistical difference in outcome. In contrast, the 7-year survival rate among patients with adenocarcinoma in the control group was only 5.2% but for those in the immunotherapy group it was 38.9% (P < 0.05). If resection was noncurative because of pulmonary metastasis, residual cancer or incomplete resection of lymph nodes, then immunotherapy was effective. If resection was noncurative because of residual cancer in the chest wall or diaphragm, or because of carcinomatous pleuritis or pleural dissemination, then there was no statistical difference in survival between the control group and the immunotherapy group.
Adenocarcinoma↗
Effects of ginsenosides on impaired performance induced in the rat by scopolamine in a radial-arm maze.
The effects of ginsenosides Rg1, Rd and Rb1 on impaired performance induced in the rat by scopolamine were examined in a radial-arm maze. Scopolamine caused a reduction in the number of initial correct responses in the maze. A single IP injection of Rg1, but not Rd or Rb1, prevented the reduction. The inhibition of the reduction in initial correct responses was associated with a bell-shaped dose-response curve for Rg1. A lesion in the medial septum caused spatial learning deficits. Rg1 did not overcome these deficits. It is suggested that cholinergic neurons in the medial septum are involved in the ameliorative effect of Rg1 on impaired performance induced by scopolamine.
Animals↗
Pancreaticoduodenal artery aneurysm: a case report and review of the literature.
A case of true pancreaticoduodenal artery (PDA) aneurysm is reported. A calcified lesion was initially detected by plain x-ray films, and an essential diagnosis was made before operation by intravenous digital subtraction angiography (IVDSA). Surgical resection of the aneurysm was performed successfully. Additionally, we reviewed a total of 82 cases with PDA aneurysm out of the 88 cases that had been reported in the English-language literature up to 1993. Fifty-three cases were accompanied by aneurysmal rupture (rupture group), and 29, including our case, were without rupture (nonrupture group). Because of the high mortality rate (49.1%) in the rupture group, a precise diagnosis and adequate treatment of PDA aneurysm before rupture is important. In the nonrupture group, a calcification on radiography appeared in 61.6% of the cases in which aneurysms were not found incidentally; this seems to be a significant indication for angiography. Moreover, intravenous digital subtraction angiography is quite useful for the screening of PDA aneurysm because it is an easy and noninvasive examination.
Aged↗
Macrophages in childhood IgA nephropathy.
The role of glomerular macrophages in IgA nephropathy in children was investigated using a new monoclonal antibody (KP1) as a probe. The average number of glomerular macrophages per patient (ANM/P) was closely correlated with the degree of hematuria (P < 0.01) as well as with the degree of leukocyturia (P < 0.01) in the absence of any correlation with proteinuria, serum IgA levels or the interval between the detection of urine abnormalities and renal biopsy. ANM/P was significantly higher in patients diagnosed pathologically as having focal and diffuse proliferative glomerulonephritis than in patients with minor glomerular abnormalities or advanced sclerosis (P < 0.05). Among various types of glomerular morphology in individual patients, macrophages predominantly infiltrated glomeruli with cell-proliferative lesions despite an absence of any increase in glomeruli with minor abnormalities or with sclerosis. Macrophages were mainly localized within the capillary lumen in association with endocapillary proliferative lesions (tuft necrosis), they accumulated in areas of mesangial proliferation, and they were attached to Bowman's capsule in segmental lesions. Macrophages were less evident in sclerosis. Furthermore, ultrastructural analysis revealed macrophages in the paramesangial areas in close proximity to lytic changes in the glomerular basement membrane and effacement of epithelial foot processes. In addition, some cases in repeat biopsy shows prolonged or increased values of ANM/P after several years of interval in association with progression of proliferative lesions. These results suggest that macrophages infiltrate glomeruli during acute glomerular inflammation, and that they are involved in mesangial proliferation or the development of extracapillary lesions in the absence of apparent clinical symptoms. Furthermore, recurrence or prolonged infiltration may promote progression of IgA nephropathy.
Antibodies, Monoclonal↗
Decreased expression of the GLUT4 glucose transporter protein in adipose tissue during pregnancy.
Insulin resistance involves impaired activities of the glucose transport system in insulin target tissues. We therefore investigated the GLUT4 glucose transporter protein in adipose tissues from the pregnant women with normal glucose tolerance and from women with gestational diabetes mellitus, and compared these to nonpregnant women. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 6), pregnant women with normal glucose tolerance (N = 6, gestational week 38.0 +/- 0.3), and pregnant women with gestational diabetes mellitus (N = 3, gestational week 38.6 +/- 0.3). The abdominal subcutaneous adipose tissues obtained from each group were subjected to analysis of the GLUT4 glucose transporter protein. The presence of the GLUT4 glucose transporter protein in the three groups was quantitatively determined by Western blot analysis of detergent-soluble adipose tissue extracts using anti-GLUT4 antibody. GLUT4 glucose transporter protein concentration in the adipose tissue of pregnant women were significantly lower than that in nonpregnant women, and this difference was more profound in women with gestational diabetes mellitus. We demonstrated that the content of GLUT4 protein was decreased in adipose tissue from normal pregnancy compared to nonpregnant women.
Adipose Tissue↗