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Biomedical subjects

T Tobe

Publications and source records attributed to T Tobe.

At least 415 records · Page 23Linked to original sources

Relationship of deranged energy metabolism in liver and kidney to arterial ketone body ratio following liver ischemia in rats.

Changes in energy metabolism in the liver and kidney in liver ischemia induced in rats were simultaneously studied, in terms of energy charge (EC) and mitochondrial oxidoreduction state. Mean arterial blood pressure, glucose and lactate, total ketone bodies (acetoacetate + beta-hydroxybutyrate) and the ketone body ratio in arterial blood (KBR) were also investigated. During and after liver ischemia, both organs showed similar patterns of reversibility, and KBR, which reflects the mitochondrial oxidoreduction state, correlated well with EC, in both organs. Referring to the mortality and changes in substrates above mentioned, KBR is a pertinent parameter for detection of viability following induced liver ischemia. It was also suggested that KBR may indicate a regulating role by the liver, in kidney energy metabolism.

Adenine Nucleotides↗

Bile secretion in regenerating liver--a comparison of hepatic resection and ligation of the portal vein branch in dogs.

To elucidate the mechanism of bile secretion in the regenerating liver, changes of bile secretion were investigated in dogs during 12 weeks or more after 70% hepatectomy and after ligation of the portal vein branch supplying 70% of the area of the liver. The remnant liver weight increased remarkably and reached a normal level at 2 weeks after 70% hepatectomy. Liver weight increased in the nonligated lobes and decreased in the ligated lobes after ligation of the portal vein branch, but the whole liver weight was unchanged. Bile flow increased and continued for 12 weeks or more in the remnant liver except for a period of 2 weeks in the nonligated lobes. It decreased markedly in the ligated lobes. The taurocholic acid-independent bile flow was higher in the remnant liver than in nonligated lobes in both of which it was higher than normal liver. In the ligated lobes, taurocholic acid-independent bile flow was lower and taurocholic acid-dependent bile flow was higher than normal liver. When gallbladder bile was infused into the terminal ileum, bile flow increased in both the remnant liver and the nonligated lobes, except for 2 weeks in the remnant liver. Therefore it is suggested that in the regenerating liver enterohepatic circulation of bile acid and the new balance of the bile acid pool size participates in not only in bile flow but also in liver regeneration.

Animals↗

Adenylate energy charge and cytochrome a (+a3) in the cirrhotic rat liver.

In the cirrhotic rat liver induced by phenobarbitone and carbon tetrachloride, adenylate energy charge, mitochondrial oxidative phosphorylation, and respiratory enzyme concentrations were studied along with serum albumin concentrations. Cytochrome a (+a3) concentrations of the liver increased with the severity of cirrhosis and were negatively correlated with the ATP-synthesizing ability per unit of cytochrome a (+a3). These changes were associated with the decrease in hepatic energy charge. Such decreased energy charge may be responsible for the decreased serum albumin level in the cirrhotic rat. It is suggested that such falls in hepatic energy charge may be one of the most important factors contributing to the decreased functional reserve of cirrhotic patients.

Adenosine Diphosphate↗

Heat shock regulatory gene (htpR) of Escherichia coli is required for growth at high temperature but is dispensable at low temperature.

Nonsense mutations affecting the positive regulatory gene (htpR) of heat shock response have been obtained in a strain of Escherichia coli carrying no suppressor. The mutants can grow only at temperatures below 34 degrees C-35 degrees C. Heat, ethanol, and coumermycin induce major heat shock proteins in the wild-type but not in the htpR mutants. In contrast, the level of heat shock proteins synthesized at low temperature is unaffected. The htpR gene product is thus required for induction of heat shock proteins by heat or other stresses but not for their "basal-level" synthesis. Nucleotide sequence has been determined for the wild-type and the mutant alleles of htpR. The coding region appears to consist of 852 nucleotide pairs that correspond to 284 amino acids. Sequences commonly considered as signals for transcriptional initiation and termination were found flanking the coding region. Within this region, six amber, one opal, and two missense mutations were identified; the nonsense mutations are scattered along the gene, some being very close to the presumed amino terminus. These results indicate that the absence of htpR gene product is directly responsible for the failure to respond to heat shock or other stresses and for the inability to grow at high temperature. We propose that htpR represents a new class of genes that are essential for growth only at high temperatures (greater than 35 degrees C). Implications of the sequence homologies found among htpR, rpoD, and nusA proteins are discussed.

Aminocoumarins↗

Isolation and characterization of rabbit H of the alternative complement pathway.

Rabbit factor H, a control protein of the alternative complement pathway, was isolated from rabbit serum by polyethylene glycol precipitation, DEAE-Sephacel chromatography, and gel chromatography on Sephadex G200. The protein migrated as a single-chain polypeptide with a molecular weight of 160,000 on sodium dodecyl sulfate-gel electrophoresis with Laemmli's buffer system, but hardly migrated into the gel with Fairbanks' buffer system. Physical and chemical properties of rabbit H were similar to those of human H, except that fragments produced by limited tryptic digestion from rabbit H had different molecular sizes from those produced from human H. Significant species-specificity was observed in the functional activity of factor H; activation of the alternative complement pathway was inhibited more efficiently with homologous H than with heterologous H. In contrast, factor H inhibited the hemolysis of homologous erythrocytes less than that of heterologous erythrocytes.

Amino Acids↗

Biosynthesis of the internal thioester bond of the third component of complement.

C3-translational product, which was synthesized with rabbit liver mRNA in a reticulocyte lysate protein-synthesizing system, did not react with [14C]methylamine, indicating the lack of an internal thioester bond. Instead, the C3-translational product reacted with iodo[1-14C]acetamide, as determined by gel electrophoresis in the presence of sodium dodecyl sulfate after immunoprecipitation of the product, indicating the presence of a reactive thiol group. When the C3-translational product was treated with rabbit liver homogenate, the product acquired reactivity with [14C]methylamine and lost the reactivity with iodo[1-14C]acetamide. Thus, the liver homogenate seemed to contain a factor (or factors) required for the formation of an internal thioester bond. The factor was partially purified from the liver homogenate by ammonium sulfate precipitation and ion-exchange chromatography on DEAE-cellulose.

Animals↗

Significance of mitochondrial enhancement in hepatic energy metabolism in relation to alterations in hemodynamics in septic pigs with severe peritonitis.

Liver mitochondrial phosphorylative activity, hepatic adenine nucleotides, and hemodynamic parameters were studied in 23 pigs with peritonitis induced by cecal ligation and perforation. Between 2 and 7 days after treatment, the onset of an apparent hyperdynamic state, characterized by an increased cardiac index and decreased total peripheral resistance index, occurred. In this period, the energy charge level was barely maintained and the occurrence of liver mitochondrial enhancement was observed. However, 10-14 days after treatment, the onset of a hypodynamic state with its inverse patterns in hemodynamics took place. In this period, the energy charge level fell to 0.68, concomitant with a marked decrease in mitochondrial function. Further, a high positive correlation between the cardiac index and liver mitochondrial phosphorylative activity was noted (r = 0.85, p less than 0.01). These results suggest that liver mitochondria play a major role in the metabolic and hemodynamic adaptations occurring during sepsis.

Adenine Nucleotides↗

Changes in blood glucose levels in relation to blood ketone body ratio following hypertonic glucose infusion in 70% hepatectomized rabbits.

The effects of postoperative infusion of a hypertonic glucose solution on the blood glucose level, blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), and plasma alanine and proline levels were studied in 70% hepatectomized rabbits (group A) and in rabbits 70% hepatectomized and, in addition, subjected to bile duct obstruction at 12 h after hepatectomy (group B). Glucose infusion was started at the end of hepatectomy and continued for 20 h. The blood glucose level in group A remained at approximately 300 mg/dl throughout the study; however, it reached 789 mg/dl in group B at 20 h. The blood ketone body ratio, which reflects hepatic mitochondrial redox potential, decreased from 0.90 +/- 0.09 in untreated rabbits to 0.38 +/- 0.05 in group A, and to 0.19 +/- 0.03 in group B at 20 h. As the blood ketone body ratio decreased, plasma proline and alanine levels increased rapidly (proline, r = -0.601, p less than 0.02; alanine, r = -0.640, p less than 0.001). In addition, the blood ketone body ratio was positively correlated with the hepatic energy charge level [(ATP + 0.5 ADP)/(ATP + ADP + AMP)] (r = 0.57, p less than 0.001). It is suggested that the entry of glucose and amino acids into the Krebs cycle is inhibited as the blood ketone body ratio decreases, and under such conditions the infused glucose tends to accumulate, resulting in severe hyperglycemia.

Alanine↗

Cholangiocellular carcinoma associated with multiple liver cysts.

A 46-year-old woman visited our outpatient clinic complaining of dull right hypochondrial pain. Ultrasonography revealed four cysts in the right lobe of the liver. Arteriography and CT could not determine whether these cysts were benign or malignant. Because one of these cysts contained chocolate-colored fluid, amebic abscess was suspected, and the cyst was drained. No amebae were found in the cultured exudate, and fresh bleeding continued; therefore, laparotomy was performed. A tumor was present on the surface of the liver. Right lobectomy was performed. The resected specimen contained one nonepithelialized cyst which was invaded by surrounding cholangiocellular carcinoma and three epithelialized cysts. Preoperative diagnosis of this kind of cholangiocellular carcinoma seems to be very difficult. Recently cholangiocellular carcinoma associated with developmental cysts has been classified as a new entity different from cystadenocarcinoma. Cholangiocarcinoma, which belongs to this group, seems to deserve special attention.

Adenoma, Bile Duct↗

[A case of alpha-fetoprotein producing rectal cancer].

A case of AFP producing rectal cancer was represented in this paper. The patients, 68 years old man, was admitted because of anal bleeding and preoperative examinations revealed rectal cancer without liver metastasis and hepatocellular carcinoma. Serum AFP measured preoperatively was 2750-3500 ng/ml and CEA was 23-33 ng/ml. The patient underwent amputation of the rectum and there were no abnormal masses in the liver at surgery. After operation serum AFP and CEA levels were normalized. Histology of the rectal tumor showed a tubular adenocarcinoma of moderately differentiated type. In the specimen, AFP producing tumor cells were detected by immunoenzymatic labelling (PAP) methods.

Adenocarcinoma↗

[Range of operation for cancer of the pancreas].

In order to improve the dismal results of the patients with cancer of the pancreas, we have been encouraged to perform an extended type of total or subtotal pancreatectomy. In this procedure, the peripancreatic tissues which tend to accept direct or metastatic involvement by cancer are resected en bloc with the portal vein, and Billroth I type of anastomosis is made for purposes of absorption of fat and release of gut hormones in the upper jejunum. Twenty-eight patients, consisting of 18 cancers of the head of the pancreas, six cancers of the body of the pancreas and four others, underwent this extended pancreatectomy. Only one died postoperatively, and the six including two long survivors are now living.

Humans↗

Susceptibility of healed gastric ulcers to chemical carcinogenesis in rats and implications of cellular kinetic changes.

The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty-eight adenomatous hyperplasias and six-adenocarcinomas developed in the pyloric mucosae of rats, including five cases of adenomatous hyperplasia which developed in the periphery of the healed ulcer. In contrast, only one adenomatous lesion was found in the regenerated mucosa of the healed pyloric ulcer. No neoplasm was observed in the healed fundic ulcer area. The results demonstrated an increased incidence of neoplasms in the peripheral area of the healed pyloric ulcer and a decreased incidence of neoplasms in the regenerated mucosa within the healed pyloric ulcer scar, although these differences were not statistically significant in comparison with the intact pyloric mucosae of the MNNG-treated rats. Histoautoradiographs of the gastric mucosae demonstrated increased labeling indices in the healed ulcer periphery of the pyloric mucosa and decreased labeling indices in the regenerated mucosa within the healed pyloric ulcer scar of MNNG-treated rats, which might be related to the differential susceptibility of the two regions to gastric carcinogenesis. Intestinal metaplasia preferentially developed near the pyloroduodenal junction in MNNG-treated rats but was not localized in control rats. In the fundic ulcer scar area, an unusual squamous cell metaplasia was observed in one rat.

Animals↗

Minimal requirement of the remnant pancreas for protein and DNA synthesis of cultured hepatocytes prepared from pancreatectomized rats.

The incorporation of 3H-thymidine and 3H-leucine into the hepatocytes was studied, using cultured hepatocytes prepared from normal and pancreatectomized rats. (1) In the cultured hepatocytes prepared from 80% pancreatectomized rats, the incorporation of 3H-thymidine and 3H-leucine into hepatocytes remained unchanged compared with those of sham-operated controls. In contrast, in those from totally pancreatectomized rats, the incorporation of 3H-thymidine and 3H-leucine decreased to approximately 67% and 37% respectively of sham-operated controls. However, those returned to near normal in the cultured hepatocytes from totally pancreatectomized rats treated by 0.8 IU/kg of insulin. (2) The addition of insulin (10(-4) M) to the culture medium stimulated the incorporation of 3H-thymidine into cultured hepatocytes prepared from normal rats to 148% of controls. The insulin-stimulated incorporation was inhibited by the addition of glucagon to the culture medium. The combined addition of insulin and glucagon did not synergistically act on DNA synthesis. It is suggested that the portal blood insulin in the presence of more than 20% of the pancreas is imperative for maintaining spontaneous regeneration.

Animals↗