Search PubMed⌕ Search

Biomedical subjects

M Itakura

Publications and source records attributed to M Itakura.

At least 181 records · Page 10Linked to original sources
PubMed1986

Increase of amidophosphoribosyltransferase activity and phosphoribosylpyrophosphate concentration as the basis for increased de novo purine biosynthesis in the regenerating rat liver.

The labeling of hepatic purines with [14C]glycine increased in the regenerating rat liver 12 hours after a 70% hepatectomy and it reached the 2.4 folds higher peak 12 hours after the surgical operation in comparison to sham-operated control. These observations suggest that the rate of de novo biosynthesis increases in the regenerating rat liver to supply purine ribonucleotides to the cells. In the regenerating rat liver the activity of amidophosphoribosyltransferase (ATase) significantly increased and reached the 1.8 folds higher peak than control 18 hours after surgery. Hepatic 5-phosphoribosyl 1-pyrophosphate (PRPP) concentration significantly increased and reached the 3.0 folds higher peak 12 hours after surgery. Although the mean hepatic concentration of ATP and GTP showed a 13 and 15% decrease respectively in the regenerating rat liver 12 hours after surgery, they were counterbalanced by the increased concentrations of AMP and GMP by 13 and 44% respectively. These results suggest that the increased rate of de novo purine biosynthesis in the regenerating rat liver is mediated by the increased enzymatic activity of ATase and by the increased concentration of PRPP.

Amidophosphoribosyltransferase↗
PubMed1986

The mechanism of insulin-induced increase of the rate of de novo purine biosynthesis in primary cultured rat hepatocytes.

The effect of insulin on the rate of de novo purine biosynthesis was studied in freshly isolated hepatocytes from adult male rats. Insulin started to increase the rate of de novo purine biosynthesis at 1.5 X 10(-10) M and plateaued at 1.5 X 10(-8) M with the magnitude of increase of about 280%. Insulin at 1.5 X 10(-9) M or the higher concentration increased the 5-phosphoribosyl 1-pyrophosphate (PRPP) availability for purine ribonucleotide synthesis to about 230%. Insulin increased ATP concentration to 127% and decreased AMP, ADP, GMP and GDP concentration to 73, 69, 73 and 69% in association with the increased adenylate energy charge of 0.90 in comparison to the control level of 0.83. But the total adenine and guanine nucleotide concentration in the cell was not significantly changed. In addition insulin increased the specific activity of amidophosphoribosyltransferase (ATase) with the increased Vmax and the unchanged Km for PRPP.

Amidophosphoribosyltransferase↗
PubMed1986

In vivo inhibition of the rate of de novo purine synthesis in rat liver by glucagon.

The rates of de novo purine and protein synthesis were assessed in vivo in rat liver after bolus administration of glucagon. The specific activity of hepatic purines and the specific activity ratio of hepatic purine/protein were used as an index of the rate of de novo purine synthesis and the rate relative to protein. Glucagon at doses of 0.01 mg to 0.1 mg/200 g body weight (BW), administered as an intravenous bolus, inhibited dose-dependently the rate of de novo purine synthesis and the rate relative to protein although it increased dose-dependently the hepatic concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP). The inhibition of the rate of de novo purine synthesis recovered to control levels during the period between 60 and 90 minutes after glucagon administration. Dibutyryl cyclic AMP (Bt2 cAMP) partially mimicked this effect of glucagon in that it did not increase the rate of de novo purine synthesis in spite of increased concentrations of PRPP. These results suggest that an intravenous bolus of glucagon inhibits the rate of de novo purine synthesis through increasing cAMP concentration. The data are consistent with inhibition of amidophosphoribosyltransferase (ATase) in spite of increased PRPP concentrations.

Animals↗
PubMed1986

Increased rate of purine biosynthesis in rat liver after bilateral adrenalectomy.

In bilaterally adrenalectomized rat liver the increased rate of de novo purine synthesis was shown by the increased [14C]glycine incorporation into hepatic acid-soluble purines with unchanged rapidly miscible glycine pool size and its turnover rate and by the increased rate of chasing of radiolabeled purines. At 24 h after adrenalectomy, the rate of de novo purine synthesis increased by 70%, 5-phosphoribosyl-1-pyrophosphate (PRPP) content increased by 200%, the specific activity of amidophosphoribosyltransferase (EC 2.4.2. 14; ATase) did not change, ATP and GTP showed a 33 and 24% decrease, and AMP and ADP showed a 245 and 38% increase. Combined, the metabolic pool size data reflected an unchanged total inhibitory potential on ATase. Replacement with corticosterone acetate for 24 h partially restored some of these abnormalities. These results suggest that the increase in the rate of de novo purine synthesis in adrenalectomized rat liver is secondary to increased catabolism of purine ribonucleotides and mediated by increased PRPP concentrations.

Adenosine Diphosphate↗
PubMed1986

Increased rate of de novo purine synthesis and its mechanism in regenerating rat liver.

In regenerating rat liver at 12 h after a 70% hepatectomy, [14C]glycine incorporation to hepatic acid-soluble purines increased by 2.4-fold with a 26% increase of the mean rapidly miscible glycine pool size and its comparable turnover rate. Amidophosphoribosyltransferase (EC 2.4.2.14, ATase) activity increased 1.8-fold at 18 h and 5-phosphoribosyl-1-pyrophosphate (PRPP) concentration increased 3.0-fold at 12 h after surgery. Decreases in ATP and GTP concentrations of 13 and 15%, respectively, in regenerating rat liver at 12 h after surgery were counterbalanced by increased AMP and GMP concentrations of 13 and 44%, respectively, with comparable inhibitory potentials on ATase. These results suggest than an increased rate of de novo purine synthesis in regenerating rat liver is mediated by the increased ATase activity and PRPP concentrations.

Adenosine Monophosphate↗
PubMed1986

Responsiveness of hypophyseal-adrenocortical axis to repetitive administration of synthetic ovine corticotropin-releasing hormone in patients with isolated adrenocorticotropin deficiency.

The primary lesion site in isolated ACTH deficiency was studied in three patients by examining the responses of immunoreactive ACTH to insulin-induced hypoglycemia, lysine vasopressin, and synthetic ovine corticotropin-releasing hormone (CRH). In all patients, no significant changes in immunoreactive ACTH followed insulin-induced hypoglycemia or lysine vasopressin. Fifty micrograms (greater than or equal to 1 microgram/kg BW) of CRH administered as an iv bolus dose daily for 6 consecutive days elicited no significant increase in plasma immunoreactive ACTH, beta-lipotropin, or cortisol levels in all patients. Eight iv bolus injections of 0.63 microgram/kg BW CRH at 4-h intervals also failed to induce a significant response of immunoreactive ACTH to an iv bolus dose of 1 microgram/kg CRH at 36 h in one patient. In contrast, a single bolus dose of 50 micrograms CRH induced a response of plasma immunoreactive ACTH in a patient with Cushing's disease and a patient with Addison's disease. The present results suggest that the primary lesion of isolated ACTH deficiency is not the hypothalamus, but, rather, is located in pituitary ACTH-secreting cells.

Addison Disease↗
PubMed1986

Limited synthesis of labile hemoglobin A1 in vivo and in vitro by the preexisting hemoglobin A1 in diabetic subjects.

The synthesis of labile hemoglobin A1 in vivo was studied in subjects with non-insulin dependent diabetes mellitus, impaired and normal glucose tolerance. The labile hemoglobin A1 index defined as delta labile hemoglobin A1 divided by delta plasma glucose at 30 min after oral glucose load, representing the rate of labile hemoglobin A1 synthesis in vivo, was low in diabetic subjects and high in normal subjects, showing an inverse correlation with the amount of preexisting hemoglobin A1. The study on the synthesis of labile hemoglobin A1 in vitro showed a lower initial rate of synthesis and a smaller increase in labile hemoglobin A1 at saturation in red blood cells from diabetic subjects with a relatively large amount of preexisting hemoglobin A1, as opposed to red blood cells from normal subjects. Although the further study is necessary in which delta plasma glucose levels are kept relatively constant in each of 3 groups by glucose-clamp methods, our data suggest that the synthesis of labile hemoglobin A1 is limited in vivo and in vitro in diabetic subjects by the preexisting hemoglobin A1 due to the saturability of its synthesis.

Adult↗
PubMed1986

Malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) increases liver de novo purine synthesis and amidophosphoribosyltransferase activity.

The effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on de novo purine synthesis was studied in rat liver in vivo and in primary cultured rat hepatocytes in vitro. In the in vivo system, malotilate increased [14C]glycine incorporation by 1.4- to 1.7-fold into acid soluble hepatic purines 4 to 18 hr and the rapidly miscible glycine pool size at least by 2.0-fold 12 hr after administration. Malotilate did not change 5-phosphoribosyl-1-pyrophosphate concentration but increased significantly amidophosphoribosyltransferase (E.C. 2.1.2.14) activity per unit of DNA or per unit of liver protein. Malotilate also increased significantly the hepatic cyclic AMP concentration 2 to 12 hr after administration. In the in vitro system, malotilate increased [14C] formate incorporation into acid soluble purines with accompanying increases in 5-phosphoribosyl-1-pyrophosphate availability and the specific activity of amidophosphoribosyltransferase. These results suggest that malotilate increases the rate of de novo purine synthesis in the liver by its direct action on hepatocytes, the mechanism of this increase is due to the combined increase of amidophosphoribosyltransferase activity and 5-phosphoribosyl-1-pyrophosphate supply and cyclic AMP may play a role for this response.

Adenosine Triphosphatases↗
PubMed1984

A possible role for oxygen inactivation in the regulation of amidophosphoribosyltransferase activity in mammalian cells.

Human and other mammalian forms of ATase, including the Chinese hamster enzyme, are oxygen-sensitive enzymes and human ATase, like the enzyme from B. subtilis, is an iron-sulfur protein. When protein synthesis is inhibited in cultured Chinese hamster cells, ATase activity is lost in an oxygen-dependent reaction. The hypothesis is developed that the sensitivity of ATase to oxygen inactivation controls the rate of degradation of this enzyme in mammalian cells, similar to the mechanism which has been demonstrated for regulation of ATase degradation in B. subtilis.

Amidophosphoribosyltransferase↗
PubMed1984

A case of glycogen storage disease type I associated with an incomplete type of Fanconi syndrome; the protective role of lysosomal alpha 1,4-glucosidase and insulin deficiency against hypoglycemia.

A 59-year-old Japanese farmer with asymptomatic fasting hypoglycemia and with exaggerated hypoglycemic episodes induced by insulin and oral hypoglycemic agent administered for his postprandial hyperglycemia was diagnosed as glycogen storage disease type I. This diagnosis was suggested by unresponsiveness of blood glucose level to glucagon and confirmed by 13% normal level of glucose 6-phosphatase activity in liver biopsy specimen and by the presence of PAS positive amylase digestable glycogen in liver specimen. This case was associated with an incomplete type of Fanconi syndrome characterized by hyperphosphaturic hypophosphatemia, partial aminoaciduria, mild proteinuria and hyperuricosuric normouricemia in spite of the lactic acidemia due to glycogen storage disease type I. The etiology for the absence of hypoglycemia and other typical manifestations of glycogen storage disease type I was studied. The glucose production from glycogen by lysosomal alpha 1,4-glucosidase especially at prolonged fasting and the presence of postprandial hyperglycemia by insulin deficiency are regarded as responsible for keeping this patient free from typical manifestations of glycogen storage disease type I.

Biopsy↗
PubMed1984

Neuraminidase activity in human peripheral lymphocytes: its increase in chronic active liver disease.

The activity of neuraminidase (sialidase) in peripheral white blood cells was measured by a fluorometric method using 4-MU NANA as a substrate. The activity in mononuclear cells, which was predominantly lymphocytes, was 2.5 times higher than that in polymorphonuclear cells (neutrophils). The former's activity was directly proportional to the number of the cells, but that of the latter was found to be suppressed by an increasing number of cells. Thus, the increased number of PMN contaminated in MNC fraction somewhat obscured neuraminidase activity affecting suppressively . The enzyme activity in MNC of 25 control subjects (15 males and 10 females) was 254 +/- 73 pmoles per hour per 10(6) cells and there was no difference between the values in males and females (233 +/- 59 vs. 284 +/- 81). The activity in 20 patients with chronic active liver disease was significantly higher than that in controls (551 +/- 135, p less than 0.01). The amount of sialic acid in MNC, which was 1.4 times more than that in PMN, revealed a tendency for a positive correlation between neuraminidase activity. A new finding of the increase of lymphocyte neuraminidase activity was introduced and its pathological significance particularly in liver disease was discussed.

Chronic Disease↗
PubMed1984

[Shift of placental alkaline phosphatase isoenzymes in the course of pregnancy].

It is generally accepted that every placental protein shows its characteristics vicissitude pattern during pregnancy and that alkaline phosphatases (ALP) are subdivided into three kinds of isoenzymes, i.e.: tissue-unspecific, intestinal and termplacental ALPs. In this study, the changes in ALP isoenzyme profile throughout the course of pregnancy was studied by biochemistry, enzyme- and immuno-histochemistry, and the following results were obtained. In early pregnancy, ALP activity was composed mostly of tissue-unspecific ALP isoenzyme, and its activity revealed a peak value around 10 weeks of pregnancy as in the case of the hCG serum concentration. At the end of the second trimester of pregnancy, instead of tissue-unspecific isoenzyme, ALP activity was mainly composed of term placental ALP isoenzyme, but a very small amount of the isoenzyme was proved to exist in the villi at the 6th week of gestation. The above results were confirmed by morphological studies such as enzyme-cytochemistry and immuno-cytochemistry. It was therefore concluded that at least two genes of ALP isoenzymes existed in the villi and that the regulation of gene activity changed during the course of pregnancy. Furthermore, since tissue-unspecific ALP isoenzyme showed a pattern of change similar to that of serum hCG, the existence of a developmental phase-specific gene set was postulated.

Alkaline Phosphatase↗
PubMed1983

Association of isolated adrenocorticotropin deficiency with a variety of neuro-somatic abnormalities in congenital facial diplegia (Moebius) syndrome.

A male patient with recurring episodes of hypoglycemic attacks was diagnosed as having isolated ACTH deficiency as well as renal glycosuria and ichthyosis vulgaris. In addition, he had facial diplegia and abducens palsy consistent with Moebius syndrome, muscle atrophy with proximal dominancy, high arched palate, hammer toes, and mental retardation. There was electrophysiological evidence of peripheral neuropathy. Muscle biopsy of the deltoid showed mild myofiber atrophy with occasional cylindrical laminated bodies. The association of these disorders has never been reported and it could be coincidental. However, considering the high rate of association of isolated hypogonadotropic hypogonadism and Moebius syndrome with peripheral neuropathy, the present case may indicate a causal relationship between isolated ACTH deficiency and Moebius syndrome, reflecting the disorders in the organ systems derived from a common ectoderm.

Adrenocorticotropic Hormone↗
PubMed1983

A case of porphyria cutanea tarda with hemangioma of the liver.

The clinical incidence of porphyria cutanea tarda is apparently less in Japan than in European countries and the U.S.A.. In the last 7 years, porphyria cutanea tarda was encountered in the dermatologic clinic of Tokai University Hospital at the rate of one in twelve thousand patients with various kinds of skin diseases. This case is the first case in our medical clinic at Tokai University Hospital in the past 7 years, among 2,456 cases of liver diseases in which laparoscopy with needle biopsy of the liver was performed. The physiopathological aspects remain obscure. Unexpectedly, a hemangioma was disclosed under laparoscopic observation but it was clear that the hemangioma had no significant relation to the thrombopenia-hemangioma syndrome in this case.

Adult↗