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Biomedical subjects

T Higashiguchi

Publications and source records attributed to T Higashiguchi.

At least 37 records · Page 2Linked to original sources

Nitric oxide may upregulate in vivo hepatic protein synthesis during endotoxemia.

Nitric oxide (NO) has been implicated as a mediator of hemodynamic and metabolic changes associated with endotoxemia and inflammation. In vitro studies suggest that NO inhibits hepatocyte protein synthesis but the role of NO in the regulation of hepatic protein synthesis in vivo is not known. In this study, rats were given endotoxin or saline after pretreatment with the NO synthase inhibitor NG-nitro-L-arginine or solvent, and plasma levels of nitrite (NO2), nitrate (NO3), and aspartate aminotransferase and hepatic protein synthesis rate in vivo were measured after 4 and 10 hours. The NG-nitro-L-arginine effectively blocked the increase in serum NO2/NO3 seen in endotoxemia and also inhibited the increase in hepatic protein synthesis in endotoxemic rats. The aspartate aminotransferase levels were elevated in endotoxemic rats pretreated with NG-nitro-L-arginine. Results support previous reports of a protective effect of NO on the liver in endotoxemia and suggest that NO may upregulate hepatic protein synthesis in vivo. Further study is needed to clarify the reason for the apparent difference between the effect of NO on hepatic protein synthesis in vivo and in vitro.

Amino Acid Oxidoreductases↗

Effect of tumor necrosis factor or interleukin-1 on muscle amino acid uptake and the role of glucocorticoids.

Muscle amino acid uptake is inhibited during sepsis and endotoxemia. Cytokines, in particular tumor necrosis factor (TNF) and interleukin-1 (IL-1), have been implicated as mediators of metabolic alterations in sepsis and other critical illness. In this study, we examined the effect of TNF and IL-1 on muscle amino acid uptake and tested the hypothesis that cytokine-induced changes in muscle amino acid uptake are mediated by glucocorticoids. Intraperitoneal injection in rats of 100 micrograms per kilogram body weight of human recombinant TNF alpha (rTNF alpha) or rIL-1 alpha resulted, two hours later, in 36 and 24 percent reduction, respectively, of amino acid transport in incubated soleus muscles, determined as intracellular uptake of alpha-aminoisobutyric acid. When rats were treated with the glucocorticoid receptor antagonist RU 38486 (5 milligrams per kilogram of body weight) two hours before cytokine injection, the inhibitory effect on muscle amino acid transport of TNF was blocked, whereas that of IL-1 was unaffected. The present results suggest that TNF and IL-1 may regulate amino acid transport in skeletal muscle and that the effect of TNF, but not that of IL-1, is at least partly mediated by glucocorticoids.

Amino Acids↗

Increased intestinal protein synthesis during sepsis and following the administration of tumour necrosis factor alpha or interleukin-1 alpha.

The influence of sepsis on intestinal protein synthesis was studied in rats. Sepsis was induced by caecal ligation and puncture (CLP); control rats were sham-operated. Protein synthesis was measured in vivo in the jejunum and ileum following a flooding dose of [14C]leucine. At 8 h after CLP the protein synthesis rate was increased by approx. 15% in jejunal mucosa, and at 16 h after CLP, the protein synthesis rate was increased by 50-60% in the mucosa and seromuscular layer of both jejunum and ileum. In a second series of experiments, rats were treated with recombinant tumour necrosis factor alpha (rTNF alpha) or recombinant interleukin-1 alpha (rIL-1 alpha) administered at a total dose of 300 micrograms/kg body weight over 16 h. Control rats received corresponding volumes of solvent. Treatment with rTNF alpha resulted in an approx. 25% increase in mucosal protein synthesis in jejunum. Following treatment with rIL-1 alpha, protein synthesis increased by 25% in jejunal mucosa and almost doubled in ileal mucosa. The results suggest that sepsis stimulates intestinal protein synthesis and that this response may, at least in part, be mediated by TNF and/or IL-1.

Animals↗

Evidence that tumor necrosis factor participates in the regulation of muscle proteolysis during sepsis.

The role of tumor necrosis factor (TNF) in the regulation of muscle protein turnover was studied in rats. Protein synthesis and total and myofibrillar protein breakdown rates were measured in incubated extensor digitorum longus muscles. Intraperitoneal administration of recombinant TNF-alpha (300 micrograms/kg of body weight) increased total and myofibrillar protein breakdown rates by 28% and threefold, respectively, with no effect on protein synthesis. In subsequent experiments, sepsis was induced by cecal ligation and puncture or a sham-operation was performed. Rats received TNF antiserum (1 mL/100 g of body weight) or control serum 2 hours before cecal ligation and puncture or sham-operation. Treatment with TNF antiserum reduced the mortality rate from 25% to 5% following cecal ligation and puncture. The treatment had no effect on protein synthesis but reduced total and myofibrillar protein breakdown rates by 26% and 39%, respectively, in septic animals. Results suggest TNF is involved in the regulation of sepsis-induced muscle proteolysis.

Animals↗

Effect of sepsis or cytokine administration on release of gut peptides.

The effect of sepsis on plasma levels of various gut peptides was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control animals underwent sham operation. Sixteen hours after CLP or sham operation, portal and systemic blood was drawn, and plasma levels of gastrin, vasoactive intestinal peptide (VIP), secretin, peptide YY (PYY), gastrin-releasing peptide (GRP), and substance P were determined by radioimmunoassay. Plasma levels of gastrin, VIP, PYY, and secretin were elevated in septic rats compared with nonseptic animals, with the highest levels noted in portal blood. There was no effect of sepsis on GRP or substance P levels. In other experiments, human recombinant interleukin 1 alpha (IL-1 alpha) or recombinant tumor necrosis factor alpha (TNF alpha) was injected intraperitoneally (300 micrograms/kg body weight in 3 divided doses over 16 hours). There was no change in plasma levels of gut peptides after IL-1 alpha injection. TNF alpha induced elevation of PYY levels in portal plasma with no change in other gut peptide levels. The results suggest that sepsis stimulates release of certain gut peptides and that TNF, but not IL-1, may be partly responsible for this response. The mechanism of the release of gut peptides and its significance in the pathophysiologic changes induced by sepsis remain to be determined.

Animals↗

Individual regulation of different hepatocellular functions during sepsis.

The purpose of this study was to test the hypothesis that different hepatocellular functions are regulated individually during sepsis. This was done by simultaneously measuring bile production, release of liver transaminases, and synthesis of secreted proteins in perfused livers from control and septic rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham-operated. After 16 hours, livers were perfused in situ, and bile flow, synthesis rates of albumin and alpha 1-acid glycoprotein (a major acute-phase protein in rats), and release of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) into perfusate were determined. Within the same livers, sepsis resulted in a 54% increase in the synthesis of alpha 1-acid glycoprotein and approximately 30% inhibition of albumin synthesis concomitant with 50% lower bile flow. The concentrations of GOT and GPT in the perfusate increased slightly during the experiments, both when control and septic livers were perfused. The maintained tissue levels of adenosine triphosphate (ATP) and the uptake of Evans blue dye by less than 1% of the hepatocytes, although a late test of viability, suggest that both control and septic livers remained viable during perfusion. The results are consistent with the concept that different hepatocellular functions are individually regulated during sepsis. Thus, impairment of certain hepatocellular functions does not necessarily imply generalized liver failure.

Adenosine Triphosphate↗

Chromosomal assignments of 17 structural genes and 11 related DNA fragments in rats (Rattus norvegicus) by Southern blot analysis of rat x mouse somatic cell hybrid clones.

DNA from 18 rat x mouse somatic cell hybrid clones, which segregated individual rat chromosomes, was analyzed by Southern blot for chromosomal gene assignments. Through the use of 17 DNA probes cloned from 7 rat genes, A2M, ATP1A1, ATP1A2, ATP1A3, B2M, GSTP, and SMST; 5 mouse genes, Ncam, Ngfg, Pim-1, Tcp-1, and Trp53; and 5 human genes, MBP, MYB, NEFM, SCN2A, and TCRGC1, 17 structural genes including 15 newly assigned genes and 11 related DNA fragments were assigned to particular rat chromosomes. Syntenic conservation of the genes among rats, mice, and humans is discussed.

Animals↗

Semidominant expression of absence-like seizure in tremor rats.

Tremor rats (tremor homozygous rats) exhibit spontaneous absence-like seizure, which is characterized by a sudden immobility with staring and the appearance of 5- to 7-Hz spike and wave complexes in cortical and hippocampal electroencephalogram (EEG). In this study, we examined the development of the seizure and the mode of inheritance. All tremor homozygous and heterozygous rats exhibited the seizure by 14 and 26 weeks of age, respectively. The frequency and total duration in tremor heterozygous rats were significantly lower in comparison with those in tremor homozygous rats. None of the seven tremor wild-type homozygous rats exhibited the seizure. In an EEG study of backcross progeny of (BN/fMaiKyo x tremor heterozygous rats)F1 (tm/+) x tremor heterozygous rats at 5 months of age, the ratio of rats with and without the seizure was 23:7 (chi 2 = 0.09 for 3:1 ratio). These results suggest that the absence-like seizure is semidominantly expressed, in contrast to other recessive mutant traits in tremor rats.

Animals↗

Influence of sepsis in rats on muscle protein turnover in vivo and in tissue incubated under different in vitro conditions.

We studied the influence of sepsis on muscle protein synthesis and degradation in vivo and in muscles, incubated flaccid or at resting length. Sepsis was induced in rats by cecal ligation and puncture (CLP). Control rats were sham-operated. A flooding dose of 14C-phenylalanine was used to determine muscle protein synthesis rate in vivo, and protein breakdown was calculated from the difference between protein synthesis and growth rates. Protein synthesis rate in vitro was assessed by determining incorporation of 14C-phenylalanine into protein in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles. Total and myofibrillar protein breakdown rates were determined from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Muscle protein synthesis rate in vivo was reduced by 35%, similar to the reduction observed in muscles incubated flaccid or at resting length. The calculated protein breakdown rate in vivo was increased by 31% in septic rats. In incubated muscles, the increase in total protein breakdown (ie, tyrosine release) during sepsis was almost identical in muscles incubated flaccid or at resting length, ie, 83% to 88% in EDL and 47% to 49% in SOL. Myofibrillar protein degradation in vitro (ie, 3-MH release) was increased approximately 10-fold in EDL muscles incubated flaccid or at resting length, but was not significantly affected by sepsis in SOL. Results suggest that sepsis-induced changes in protein synthesis observed in muscles incubated either flaccid or at resting length reflect changes in vivo. Changes in protein breakdown were qualitatively similar in vivo and in vitro, but results in incubated muscles may overestimate the increase in muscle proteolysis caused by sepsis.

Adenosine Triphosphate↗

[Effect of neurotropin on experimental osteoarthritis].

The effect of Neurotropin on osteoarthritis was investigated in comparison with those of prednisolone and indomethacin. 1) There were remarkable decreases in the staining intensity to safranin-O and in the contents of uronic acid, total hexosamine and hexose in the articular cartilage of rabbits in which experimental osteoarthritis was induced by the injection of papain into the knee joint. In the Neurotropin-treated group, the decrease in the staining intensity to safranin-O and the contents of uronic acid, total hexosamine and hexose were evidently recovered. On the other hand, in the prednisolone- or indomethacin-treated group, the degeneration of the cartilage was even more pronounced than in the control group treated with papain alone. 2) Neurotropin had no effect on the autolytic degradation of cartilage, but promoted the incorporation of 14C-acetate into the proteoglycan in the articular cartilage of rabbits. 3) Both prednisolone and indomethacin inhibited the autolytic degradation and the incorporation of 14C-acetate into the proteoglycan. These results suggested that the therapeutic effect of Neurotropin on osteoarthritis may be due to the improvement of decreased proteoglycan content in the matrix of articular cartilage; and in this respect, it is different from anti-inflammatory drugs such as prednisolone and indomethacin.

Acetates↗

[Importance of nutritional management for the treatment of carcinoma of the pancreas].

Because the majority of patients with carcinoma of the pancreas are already in a state of malnutrition on admission, various complications can easily occur after surgery and adjuvant therapy such as radiation and chemotherapy. Therefore, the importance of nutritional management in the treatment of pancreatic carcinoma was examined in our department and the following results were obtained: 1) Preoperative nutritional assessment The nutritional state was evaluated using the Prognostic Nutritional Index for Surgery: PNI-S = -0.147 X (ratio of weight loss) + 0.046 X (weight for height) + 0.010 X (% triceps skin fold thickness) + 0.051 X (hepaplastin test), which was calculated from our results. In patients with the PNI-S of over 8, total pancreatectomy was performed safely, and when the PNI-S was more than 6, pancreaticoduodenectomy was done successfully. When the PNI-S was more than 5, it was possible to perform distal pancreatectomy or bypass operation. Depending on the nutritional assessment before surgery, the appropriate operative method could be selected, and the operative results could be improved by preoperative nutritional support. 2) Postoperative nutritional management Administration of a high-calorie by both parenteral and enteral nutrition during the early postoperative period produces good operative results, accompanied by a reduction of postoperative complications, such as fatty liver and so on. This approach also reduces the adverse effects of adjuvant therapy, such as radiation and chemotherapy, with an improvement of prognosis. Thus, it was revealed that nutritional assessment and management was very important for improving the therapeutic results in cases of carcinoma of the pancreas.

Enteral Nutrition↗

[Studies on adequate components and amounts of transfusion solution after hepatectomy from the viewpoint of the development of lung edema].

The purpose of this study was to evaluate the mechanism of development of lung edema and to determine adequate components and amounts of transfusion solution after major hepatic resection in normal and Dimethylnitrosamine (DMNA)-induced cirrhotic dogs. The dogs were administered maintenance dose (1-2 ml/kg/h) or large volumes (10-20 ml/kg/h) of lactated Ringer's solution (RL), 10% Dextrose or Dextran 40 (D40) after surgery. 1) In the groups transfused with maintenance dose or large volumes of RL, or large volumes of D40 after 80% and 70% hepatectomy in normal dogs and 40% hepatectomy in DMNA-induced cirrhotic dogs, the extravascular lung water (EVLW) increased with a high incidence of the development of lung edema. On the other hand, in the groups transfused with maintenance dose or large volumes of 10% Dextrose, or maintenance dose of D40, EVLW did not increase, thus preventing the development of lung edema. 2) The lower the functional reserve of the remaining liver and reticuloendothelial function, the more the volume of EVLW increased. The increments in plasma endotoxin titers through the spill over phenomenon, due to the decline of reticuloendothelial function after hepatectomy, caused an increase in the permeability of lung capillaries. Moreover, the decrease of colloid hydrostatic pressure gradient (CHPG) also caused an increase in EVLW. It is clear that both the permeability of lung capillaries and CHPG contribute to the development of lung edema after hepatectomy.

Animals↗

Changes of total acetylcholine content and the activity of related enzymes in SART (repeated cold)-stressed rat brain and duodenum.

In SART-stressed rats regarded as pathologically diseased model animals with vagotonic-type autonomic imbalance, a decrease of total acetylcholine (T-ACh) content and enhancements of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were recognized in the basal ganglia and hypothalamus. In contrast, in the duodenum, an increase in T-ACh content and a decrease in AChE activity were found, while CAT activity showed no change. These findings suggest that in both brain areas of basal ganglia and hypothalamus in SART-stressed rats, ACh neurons may be activated.

Acetylcholine↗

Total acetylcholine content, and activities of choline acetyltransferase and acetylcholinesterase in brain and duodenum of SART-stressed (repeated cold-stressed) rat.

The cholinergic activities in SART (specific alternation of rhythm in temperature)-stressed (repeated cold-stressed) rats, which are diseased rats with vagotonic-type dysautonomia, were examined with the following results. A decreased content of total acetylcholine (T-ACh) and increased activities of choline acetyltransferase (CAT) and acetylcholinesterase (ACh) in the basal ganglia and an increase in the T-ACh content and decrease in the AChE activity in the duodenum of SART-stressed rats reached the respective plateaus on day 5 of stress, which were maintained thereafter. CAT activity, however, in the hypothalamus was activated most on day 2. These changes in SART-stressed rats were different from those in simple cold-stressed rats. Subdiaphragmatic vagotomy inhibited the appearance of the changes in the duodenum, but not those in the hypothalamus of SART-stressed rats. The sedative analgesic Neurotropin prevented all the changes in SART-stressed rats described above. These results suggest that cholinergic neurons may be activated in both the hypothalamus and basal ganglia of the brain of SART-stressed rats, and the characteristic peripheral changes of the cholinergic system in the duodenum of SART-stressed rats may be under the control of the parasympathetic center.

Acetylcholine↗

[Scintigraphic imaging of autotransplanted splenic grafts by 99mTc-labeled heat-damaged erythrocytes].

Splenectomy is known to increase the risk of bacterial infection. Recently splenic autotransplantation has been suggested as a method of preserving splenic function. In order to demonstrate the viability of transplanted tissue, spleen scintigraphy using 99mTc labeled heat damaged erythrocytes were carried out. So far 21 studies have done in 12 patients. Spleen scans were positive 1 month after surgery, though images showed poor contrast against considerable background of bone marrow and blood pool. The quality of the images much improved five to twelve months after surgery. Functioning splenic autografts could be also shown by scintigraphy using 99mTc sulfur colloid, but the image quality was poorer, particularly within the early stage after operation. Labeling yields were 79.8% on the average, ranging from 45.6-92.3%, that affected little the quality of images. Important techniques in the splenic autotransplantation imaging include a thorough elimination of free 99mTcO4- before injection and to use comparatively small volume of damaged erythrocytes.

Adolescent↗

[Case of simultaneous multiple primary lung cancer].

The incidence of multiple primary bronchogenic carcinomas has increased in Japan as the incidence of bronchogenic malignancy has increased. The patient was a 71-year-old man with simultaneous multiple bronchogenic carcinomas. He had large cell carcinoma in the left upper lobe and adenocarcinoma in the left lower lobe. We reviewed 66 reported Japanese cases with multiple lung cancers with special reference to sex distribution, age, simultaneous or metachronous, location, histological types, treatment and prognosis.

Adenocarcinoma↗