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T Noguchi

Publications and source records attributed to T Noguchi.

At least 577 records · Page 32Linked to original sources
PubMed1992

Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in cultured rat hepatoma cells.

The mechanism of the accelerated syntheses of albumin and apolipoprotein B (apo B) in response to decreased oncotic pressure was investigated in cultured rat hepatoma H4-II-E cells. Addition of dextran (mol wt 6-9 x 10(4)) to the culture medium decreased the levels of albumin and apo B mRNAs in an oncotic pressure-dependent manner. The reductions of both mRNAs were attenuated with increase in the molecular weight of dextran, which resulted in a decrease in oncotic pressure. Addition of macromolecule increased the viscosity in medium; however, alteration of viscosity appeared not to correlate with albumin and apo B mRNA levels. Transcriptional run-on assays with isolated nuclei from dextran-treated vs. untreated hepatoma cells indicated that the changes in steady-state mRNA levels were mainly controlled at the transcriptional step. Treatment with cycloheximide increased albumin mRNA to the basal level, which was effectively suppressed by dextran, and resulted in superinduction of apo B mRNA. These changes occurred primarily at the transcriptional step. These results suggest that regulations of the expressions of the albumin and apo B genes for adaptive increases in the mRNAs may require the continued synthesis of a labile protein(s) or a limiting transcription factor(s). We conclude that oncotic pressure plays an important role in regulation of expression of the albumin and apo B genes at the transcriptional step.

Animals↗
PubMed1992

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Cloning and expression of the defective genes for delta-aminolevulinate dehydratase (ALAD) from a patient with inherited ALAD deficiency porphyria (ADP) were carried out. Cloning of cDNAs for the defective ALAD were performed from EBV-transformed lymphoblastoid cells of the proband, and nucleotide sequences were determined. Two separate point mutations resulting in a single amino acid change in each ALAD allele were identified. One, C718----T, termed 'G1', occurred in the allele within the substrate-binding site, producing an Arg240----Trp substitution; the other, G820----A, termed 'G2', occurred downstream of this site in the other allele, resulting in an Ala274----Thr substitution. Using the reverse transcription-polymerase chain reaction, the mother, the brother, and the sister were shown to have the G1 defect. Expression of the G1 cDNA in Chinese hamster ovary cells produced ALAD protein with little activity; the G2 cDNA produced the enzyme with approximately 50% normal activity. Pulse-labeling studies demonstrated that the G1 enzyme had a normal half life, while the G2 enzyme had a markedly decreased half life. These data thus define the separate point mutations in each ALAD allele, as well as the altered properties of the two enzymic proteins encoded by the mutant genes in a patient with ADP.

Alleles↗
PubMed1992

Increasing aromatase cytochrome P-450 level in human placenta during pregnancy: studied by immunohistochemistry and enzyme-linked immunosorbent assay.

We investigated the immunohistochemical localization of aromatase cytochrome P-450 (P-450arom) using a specific polyclonal antiserum (PAb R-8-2). We compared catalytic activity, as detected by the tritiated water assay, and tissue levels of P-450arom, as detected by the specific enzyme-linked immunosorbent assay, in placental samples from early pregnancy to term. Immunostaining and subsequent detection by light and electron microscopy demonstrated that P-450arom is localized in the microvilli and endoplasmic reticulum of the syncytiotrophoblasts of the chorionic villi, but is not present in the mitochondria, nuclei, or cytotrophoblasts at any time during gestation. The P-450arom concentration and aromatase activity were greater in the microsomal fraction than in the mitochondrial fraction or total homogenate at each gestational stage and increased linearly as pregnancy progressed. However, the specific activity of P-450arom was comparable among subcellular fractions in each gestational period. These results suggest that the nature and localization of P-450arom are unchangeable, and the P-450arom concentration increases during pregnancy. It appears that the aromatase detected in the mitochondrial fraction is a contamination of microsomal aromatase, and the increase in aromatase activity can be attributed to an increase in the number of P-450arom molecules rather than an increase in the catalytic ability of each molecule.

Aromatase↗
PubMed1992

Effects of dexamethasone on the production of insulin-like growth factor-I and insulin-like growth factor binding proteins in primary cultures of rat hepatocytes.

The effects of dexamethasone (Dex) on insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 production were investigated in primary cultures of rat hepatocytes. Dex enhanced the secretion of IGFBP-1 as measured by ligand blot analysis but did not show any prominent effect on immunoreactive IGF-I secretion. EC50 of Dex on IGFBP-1 secretion was calculated to be 3 x 10(-8) M. The content of IGFBP-1 mRNA in the cells increased greatly in the presence of Dex but the IGF-I mRNA content did not change significantly under the same conditions. Insulin showed the opposite effect of Dex by decreasing the production of IGFBP-1 and the cellular content of IGFBP-1 mRNA. This effect of insulin was observed also with Dex in the medium. These results show that the gene expression of IGF-I and IGFBP-1 is differently regulated by glucocorticoids and insulin in primary cultures of rat hepatocytes. The results most possibly explain the in vivo effects of glucocorticoids and insulin in regulation of IGF-I and IGFBP-1 production by liver.

Animals↗
PubMed1992

Renal microangiography and correlated histopathological observation of cows with nephropathy.

Seven Holstein-Friesian cows showing chronic nephropathy were studied by renal microangiography and its correlated histopathology. In cases of pyelonephritis associated with severe pathological lesions such as thickening of arterial walls, narrowing of the arterial and arteriolar lumen, and interstitial inflammation and abscess formation, patchy loss of the peritubular capillary plexus from the cortex to the medulla was clearly demonstrated by microangiography. Interlobular arteries were tortuous and attenuated or truncated. Opacification in the vasa rectae and interstitial capillaries was increased. Extensive non-perfused regions could be detected in the cortex. In cases of mild interstitial nephritis and moderate pyelonephritis, microangiography showed focal changes in the renal vasculature. Microangiography is thus shown to clearly demonstrate changes in the renal vasculature corresponding to the severity of the histopathological lesions.

Angiography↗
PubMed1992

Molecular mechanism of induction of key enzymes related to lipogenesis.

Key enzymes related to lipogenesis in the liver are induced by a high glucose diet or insulin and suppressed by starvation, diabetes, or glucagon. Most of these enzymes are also induced by dietary fructose, even in diabetic liver. This regulation occurs at the posttranscriptional level as well as at the transcriptional level. We studied extensively the molecular mechanism of induction of L-type pyruvate kinase (LPK). The transcription of the LPK gene in the liver was stimulated by insulin and inhibited by glucagon. This insulin action required ongoing protein synthesis and metabolism of glucose and was enhanced by glucocorticoid. On the other hand, the mechanism of induction of the LPK by dietary fructose depended on plasma insulin levels. Dietary fructose stimulated transcription of the LPK gene in normal rats, whereas it acted mainly at the posttranscriptional level in diabetic rats. These fructose effects were attributable to a common metabolite of fructose and glycerol. The induction of LPK mRNA by dietary glucose was impaired in the liver of Wistar fatty rats, a model of obese non-insulin-dependent diabetes mellitus, but fructose-induced accumulation of the mRNA was not. Studies on transgenic mice indicated that the 5'-flanking region up to -3 kb of the LPK gene contained all cis-acting elements necessary for tissue-specific expression of LPK and its stimulation by diets and insulin. Further analysis using a transient expression assay revealed the presence of three cis-acting elements necessary for expression of LPK in hepatocytes in the region up to -170 kb. However, these elements alone were not sufficient for dietary and hormonal regulation of this enzyme when analyzed in transgenic mice.

Animals↗
PubMed1992

Cloning and expression of the defective genes in delta-aminolevulinate dehydratase porphyria: compound heterozygosity in this hereditary liver disease.

Cloning and expression of the defective genes for ALAD from a patient with inherited ADP were carried out. Two separate point mutations, termed G1 and G2, resulting in a single amino acid change in each ALAD allele, were identified. The G1 mutation (C718-->T) occurred in the allele within the substrate-binding site, producing an Arg240-->Trp substitution; the G2 mutation (G820-->A) occurred downstream of this site in the other allele, resulting in an Ala274-->Thr substitution. Using RT-PCR, the mother, the brother, and the sister were shown to have the G1 defect. Expression of the G1 cDNA in CHO cells produced ALAD protein with little activity; the G2 cDNA produced the enzyme with approximately 50% normal activity. Pulse-labeling studies demonstrated that the G1 enzyme had a normal half-life, while the G2 enzyme had a markedly decreased half-life. These data thus define two separate point mutations, one in each ALAD allele, as well as the altered properties of the two enzymic proteins encoded by the mutant genes in this patient.

Adolescent↗
PubMed1992

Extensive portal tumor thrombi with portal hypertension in an autopsy case of intrahepatic cholangiocarcinoma.

Vascular invasion is not a prominent feature of cholangiocarcinoma (CCC), in contrast to hepatocellular carcinoma (HCC), which frequently shows extensive vascular tumor thrombi. We report an autopsy case of CCC with extensive portal tumor thrombi and portal hypertension. A 57-yr-old man presented with abdominal pain. Liver imaging revealed no tumors, but showed intrahepatic portal venous obstruction. HCC with portal tumor thrombi was suspected clinically. His clinical course was rapid; he died of hepatic failure 50 days after admission. At autopsy, the liver (2,700 g) was studded with diffuse whitish yellow granular areas with flecks of coalescent granules. Intrahepatic portal veins were diffusely occluded by tumor thrombi. Microscopically, the tumor was poorly differentiated adenocarcinoma with mucin; tumor cells were immunohistochemically positive for carcinoembryonic antigen, CA 19-9, DU-PAN-2, and biliary type cytokeratins, but negative for alpha-fetoprotein. Tumor cells were diffuse in the liver, and there were numerous tumor thrombi in the small portal veins. Hepatic veins and small arteries were occasionally occluded by tumor thrombi. There was ascites, splenomegaly and tumor thrombi in the gastric and esophageal veins, suggesting that portal hypertension had been present. This tumor seemed to have marked affinity to invade portal veins. It must be stressed that there are CCCs with extensive portal tumor thrombi and resultant portal hypertension.

Adenoma, Bile Duct↗
PubMed1992

A retrospective comparative study of reconstructive methods following pancreaticoduodenectomy--pancreaticojejunostomy vs. pancreaticogastrostomy.

Reconstructive methods following pancreaticoduodenectomy in our department are discussed and evaluated in this study. Between January 1980 and November 1990 fifty-two consecutive patients underwent pancreaticoduodenectomy because of pancreas head disease. Thirty-one patients underwent pancreaticojejunostomy and twenty-one had pancreaticogastrostomy as reconstructive procedures. Mortality rate was 6% in pancreaticojejunstomy versus zero in pancreaticogastrostomy. Six patients had leakage from the pancreaticojejunostomy, but only one patient had necrosis of the gastric stump and leakage from the pancreaticogastrostomy. This case had previous distal gastrectomy done for gastric ulcer. The residual stomach might not have been large enough, and the blood supply of the gastric stump might not have been adequate for pancreaticogastrostomy. Except for this case, none was observed with leakage from the pancreatic anastomosis in the pancreaticogastrostomy group. No statistical significance in operating time or blood loss was observed between the two methods. The pancreaticogastrostomy cases without complications had significantly less loss of body weight than those with pancreaticojejunostomy at the date of discharge (p < 0.05). It is concluded that pancreaticogastrostomy is the safer reconstructive method following pancreaticoduodenectomy, although it may not be indicated in patients with prior gastrectomy.

Adult↗
PubMed1992

[Pathophysiology and management of patients with diabetes mellitus in gastrointestinal surgery, with special reference to hepatectomy and pancreaticoduodenectomy].

In the 235 patients with hepatectomy, 111 with pancreaticoduodenectomy (PD) and 547 with gastrectomy for the past 15 years and 5 months, we compared the incidence of postoperative complications between patients with diabetes mellitus (DM) and those without DM, and studied glucose metabolism and management of diabetic patients. DM was most frequently found at 27.7% in hepatectomy, especially 38.7% in cirrhotic patients, followed by 24.3% in PD and only 5.9% in gastrectomy. The incidence of postoperative complications was not different between DM and non-DM after gastrectomy and PD. It was significantly higher in DM than in non-DM after hepatectomy (38.5% vs. 11.8%), although there was no statistically significant difference in the cirrhotic patients with hepatectomy (34.9% vs. 23.5%). The studies on insulin metabolism preoperatively determined by oral glucose tolerance test and postoperative control of DM revealed that diabetic patients with hepatectomy, especially hepatogenous DM, had a significantly reduced insulin uptake in the liver and exogenous insulin resistance to glucose. After PD for diabetic patients, a long-term care of impaired pancreatic exocrine and endocrine functions was considered to be required, especially paying attention to lipid and zinc metabolism.

Diabetes Complications↗
PubMed1992

[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].

A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.

Facial Nerve Diseases↗
PubMed1992

[Coagulation changes during liver resection].

Thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor (PAI) were measured during liver resection surgery in 8 patients. TAT and PAI activities of patients under liver resection were compared with those of 11 patients under resection of esophageal carcinoma. TAT activity increased during liver resection (P < 0.001) and reached 14 times (P < 0.001) of its control value in the recovery room. PAI activity was very stable during operation, but increased to twice (P < 0.01) of its control value in the recovery room. TAT activity of patients after liver surgery in the recovery room was (P < 0.05) more than twice of that of patients after esophageal surgery. We conclude that hypercoagulable state occurred during liver resection to a greater degree compared with that observed with esophageal surgery, and that its cause might be liver resection itself.

Antithrombin III↗
PubMed1992

[Hemodynamic management of LOS using prolonged VA bypass circulatory assist].

The authors managed five LOS patients using prolonged V-A bypass circulatory assist. Maximum CVP values were under 12 mmHg in three survivors, and 17 mmHg and 20 mmHg in two nonsurvivors. Maximum PCWP values were under 14 mmHg in survivors, and 19 mmHg and 20 mmHg in nonsurvivors. Dopamine was administrated in all cases and norepinephrine was administrated at a rate of less than 0.3 microgram.kg-1.min-1 in survivors, and in two nonsurvivors, norepinephrine was used at a rate of 0.36 and 1.2 micrograms.kg-1.min-1. Before and after disconnection of V-A bypass, the bypass flow of the three survivors were under 1.0 l.min-1 just before disconnection, and immediately after it, the preload did not increase, and the dose of administrated catecholamine increased. V-A bypass time intervals of the three survivors were 71, 42 and 87 hours, and those of the two nonsurvivors were 71 and 43 hours. Maximum bypass flow rate was above 40ml.kg-1.min-1 in four of five patients. The authors discussed the management of the patients' heart and of the V-A bypass machine during the prolonged V-A bypass circulatory assist.

Aged↗
PubMed1992

[Three M-components (IgG kappa, IgA kappa, IgM kappa) in a patient with non-Hodgkin's lymphoma].

Co-existence of three M-components in the serum or urine is rare. A case of non-Hodgkin's lymphoma was associated with three M-components. A 64-year-old woman was referred to our hospital because of M-proteinemia in June, 1989. On admission, serum electrophoresis on cellulose acetate membrane disclosed a triple M-peak. Immunoelectrophoresis showed M-bows for anti-IgG, anti-IgA, anti-IgM and anti-kappa simultaneously. In the urine, kappa type only Bence Jones protein was found. Scanning computed tomography revealed bulky masses in the lower abdomen, and the tumor masses were removed and diagnosed as non-Hodgkin's lymphoma. Immunohistochemical staining with antibodies to each immunoglobulins revealed the cells producing single M-component of each isotype of immunoglobulins. Although surgical removal of tumor caused a marked decrease in M-component especially IgA kappa, consistent presence of plasmacytoid lymphocyte was observed in peripheral blood. Combination therapy with melphalan and procarbazine resulted in disappearance of IgG kappa and IgA kappa from the serum. In January 1990, she achieved partial remission and was discharged. The patient has remained in remission for 16 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Quantitative evaluation of human placental aromatase during pregnancy by ELISA].

To examine the relationship between the modulation of estrogen synthesis and placental maturation during pregnancy, we measured enzyme quantities and catalytic activities of aromatase in 78 normal human placentas (7-41 weeks gestation). The quantity was determined by ELISA with monoclonal antibodies specific to aromatase cytochrome P-450 (P-450arom). The activity was assessed by radioassay with [1 beta-3H] androstenedione. Intracellularly, the P-450arom concentration was twice as great in the microsomal fraction of term placentas (0.18 +/- 0.07%) as in the homogenate and mitochondrial fractions. Aromatase activity was also twice as great in the microsomal fraction as in the other fractions. The P-450arom concentration in microsomes increased linearly as pregnancy progressed (r = 0.759, p less than 0.001). The total P-450arom quantity in the placenta increased quadratically as pregnancy progressed (r = 0.891). Similar results were observed for aromatase activity. These results indicated that the increase in P-450arom was responsible for the increase in aromatase activity in normal human placenta. Therefore, in addition to the increase in placental weight and substrate derived from fetal adrenal during pregnancy, a further increase in P-450arom contributes to the marked increase in maternal estrogen production.

Adrenal Glands↗
PubMed1992

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.

Adolescent↗
PubMed1991

Rat-liver-type phosphofructokinase mRNA. Structure, tissue distribution and regulation.

We have cloned a full-length cDNA for rat-liver-type phosphofructokinase. The similarities of the rat liver-type phosphofructokinase mRNA to the human and mouse counterparts were 94% and 99% in their amino acid sequences and 88% and 94% in the nucleotide sequences of their coding regions, respectively. Rat liver-type phosphofructokinase mRNA was expressed in all tissues examined, but its level was regulated tissue-specifically. The nutritional and hormonal regulations of the mRNA in the liver were examined in comparison with those of two other key glycolytic enzymes, glucokinase and L-type pyruvate kinase. The level of liver-type phosphofructokinase mRNA was essentially unchanged by starvation (72 h) or diabetes. The mRNA level also did not change significantly on refeeding starved rats on a high carbohydrate diet, or treating diabetic ones with insulin. These results suggested that rat liver-type phosphofructokinase mRNA in the liver was not under control of diet or insulin, in contrast to glucokinase and L-type pyruvate kinase.

Amino Acid Sequence↗