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Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 379 records · Page 21Linked to original sources
PubMed1988

ADP-ribosylation of bradykinin and effects on its biological activities.

We investigated the ADP-ribosylation of bradykinin by hen liver nuclear ADP-ribosyltransferase. Two Arg residues of the peptide were modified by this enzyme. Arg1 was preferentially modified as compared to Arg9; the Vmax/Km for Arg1 was 3 times higher than that for Arg9. These results were given support by data observed in experiments with des-Arg1 and des-Arg9 bradykinin; the Vmax/Km for des-Arg9 bradykinin was 3 times that for des-Arg1 bradykinin. ADP-ribosylation suppressed the biological activity of bradykinin, as related to both binding and contractile activities. The extent of ADP-ribosylation-induced suppression of both activities was higher in the case of the modification of Arg1 than that of Arg9. In view of the observation of ADP-ribosyltransferase activity in skeletal, cardiac, and smooth muscles (Soman, G. et al. (1984) Biochem. Biophys. Res. Commun. 120, 973-980; Shimoyama, M. et al. (1987) in The 8th International Symposium on ADP-Ribosylation, Texas, abstract p. 13), bradykinin functioning in the contraction of smooth muscle may be modified in this way in vivo.

ADP Ribose Transferases↗
PubMed1988

Increases in hepatic fructose-2,6-bisphosphate level and fructose-6-phosphate,2-kinase activity in rats with ventromedial lesions of the hypothalamus.

To investigate altered fructose-2,6-bisphosphate (fructose-2,6-P2) metabolism, we measured fructose-2,6-P2 levels and fructose-6-phosphate,2-kinase (fructose-6-P,2-kinase) activities in various tissues, including liver, kidney, heart, and skeletal muscle, of ventromedial hypothalamus (VMH)-lesioned rats during feeding and starvation. The plasma insulin level was 6 times or more higher in these rats than in the controls. The fructose-2,6-P2 level in liver was much greater in VMH-lesioned rats than in the controls: 15.1 +/- 2.2 nmol/g tissue versus 7.7 +/- 0.7 in the fed state, 5.3 +/- 1.1 versus 1.6 +/- 0.4 in the starved state. In kidney, heart, and skeletal muscle, fructose-2,6-P2 levels were not different between the two animal groups. The activity of hepatic fructose-6-P,2-kinase remained high after 20 h of starvation in VMH-lesioned rats, whereas it was decreased markedly in the controls. The hepatic concentration of fructose-6-phosphate was also high in VMH-lesioned rats. Both fructose-6-P,2-kinase activity and fructose-6-phosphate concentration in the liver of starved VMH-lesioned rats were comparable to those of control rats in fed conditions. These results indicate that the alteration of fructose-2,6-P2 metabolism is characteristic of liver in VMH-lesioned rats, and that the increase in hepatic fructose-2,6-P2 may activate hepatic glycolysis not only during feeding but also during starvation, leading to the enhanced lipogenesis in these obese rats.

Animals↗
PubMed1988

Presence of high concentration of 7B2 in pleural effusion.

7B2 (a novel pituitary protein) is a secretory protein in the neuroendocrine tissues and an increase in the plasma 7B2 concentration was noted in some patients with various endocrine tumors, including small cell carcinoma of the lung and acromegaly, suggesting that 7B2 is a possible marker for these tumors. Using a radioimmunoassay, the 7B2 concentration was measured in pleural fluid samples obtained from 36 patients with lung cancer and benign pulmonary disease to assess its concentration as a marker for small cell carcinoma of the lung (SCCL) or malignant effusion. 7B2-immunoreactivity (IR) was present in pleural fluid and its concentration was much higher than in plasma. However, there was no significant difference between pleural fluid 7B2 in patients with SCCL and in other histological types of lung carcinoma or in malignant and nonmalignant patients. In the chromatographic analysis of pleural fluid on gel permeation chromatography and reverse-phase high-performance liquid chromatography, there was no molecular heterogeneity between malignant and nonmalignant effusion. These results suggest that pleural fluid 7B2-IR is not a useful marker for SCCL or malignant effusion.

Chromatography, Liquid↗
PubMed1988

[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

Adult↗
PubMed1988

Distribution of hematoporphyrin derivative in normal and malignant tissue.

The distribution of [14C]hematoporphyrin derivative (HpD) has been studied in mice bearing human lung tumor and in guinea pig bearing Line 10 tumor. The amount of [14C]HpD in the transplanted tumor tissue of mice at various times following drug administration (20 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, spleen, lung and heart tissue. The distribution pattern of [14C]HpD in guinea pig at 2 days following injection was also similar to that in mice. Our data were different from those that suggested the selectivity of uptake and retention of HpD by malignant tissues, using fluorometric techniques.

Animals↗
PubMed1988

Erythrocyte glycolysis and its marked alterations by muscular exercise in type VII glycogenosis.

Levels of erythrocyte glycolytic intermediates after the phosphofructokinase (PFK) step, including 2,3-bisphosphoglycerate (2,3-DPG), were decreased at rest in patients from separate families with type VII glycogenosis. The concentration of 2,3-DPG was about half of the normal control value during a period of unrestricted daily activity but was further decreased to one third of normal after a one-day bed rest. Mild ergometric exercise rapidly increased the levels of fructose-1,6-bisphosphate, dihydroxyacetone phosphate plus glyceraldehyde-3-phosphate, and 2,3-DPG in patients' circulating erythrocytes but did not in those of normal subjects. This indicated that a crossover point at the PFK step in glycolysis disappeared after physical exercise and, consequently, the 2,3-DPG concentration, which had decreased because of blockage of the PFK step, was restored considerably. This apparently exercise-related alteration in intermediary metabolism at the beginning of glycolysis was reproduced in vitro by incubating normal erythrocytes in the presence of inosine or ammonia, both of which have increased levels in circulating blood during and after exercise in this disorder. We conclude that physical activity in addition to a genetic deficiency in erythrocyte PFK affects glycolysis in erythrocytes in type VII glycogenosis and that myogenic factors released from exercising muscles may be responsible for this change.

2,3-Diphosphoglycerate↗
PubMed1988

Inosine and adenosine formation in ischemic and non-ischemic contracting muscles of rats: difference between fast and slow muscles.

Inosine and adenosine formation was evaluated in different types of rat skeletal muscle during ischemic and non-ischemic contraction. Extensor digitorum longus (EDL, fast) and soleus (slow) muscles were stimulated electrically via the sciatic nerve (5 Hz, 10 min). Under non-ischemic condition, the concentrations of IMP, inosine, adenosine, and hypoxanthine increased in EDL muscles but not in soleus muscles during stimulation. Under ischemic condition, these metabolites increased in both EDL and soleus muscles, although the increases in IMP and inosine were greater in EDL muscles. The increase in inosine had a strong positive correlation with that in IMP in ischemic EDL and soleus muscles, but the ratio, delta inosine/delta IMP was smaller in EDL muscles. The increase in adenosine under ischemic condition was not significantly different between the two muscles. These findings suggest that ischemia enhances degradation of purine nucleotides in contracting fast and slow muscles, and that although the degradation of purine nucleotides to IMP is greater in fast muscles than in slow muscles, the relative degradation rate of IMP to inosine is rather smaller in fast muscles.

Adenosine↗
PubMed1988

[Separation and functional analysis of tumor-infiltrating lymphocytes in brain tumor tissues].

Separation of tumor-infiltrating lymphocytes (TIL) from surgical specimen of fourteen gliomas and 6 metastatic brain tumor tissues was achieved by discontinuous density gradients. Comparison of phenotypes between separated lymphocytes and TIL in situ was examined by immunohistochemical method using monoclonal antibodies. The cytotoxic activity of these separated lymphocytes was also examined in short-term 51Cr release assay against fresh autologous tumor cells. Immunohistochemical staining of separated lymphocytes revealed the preservation of cell surface antigens of the lymphocytes. Most of separated lymphocytes were T lymphocytes and both phenotypes cytotoxic/suppressor and helper/inducer T lymphocytes were found. The Leu-3a/2a ratio of separated lymphocytes were compared with TIL in situ in the same patients and these values were almost equal in both lymphocytes. Cell number of separated lymphocytes were 1.2 x 10(5)-2.1 x 10(5)/g in glioma and 1.1 x 10(5)-3.8 x 10(5)/g in metastatic patients. Cytotoxicity against autologous tumor cells was detected in 5 out of 12 glioma and 2 out of 6 metastatic patients. There was no correlation between the cytotoxicity and cell number of separated lymphocytes or HLA-DR antigen expression on tumor cells.

Adolescent↗
PubMed1987

ADP-ribosylation of Ca2+-dependent ATPase in vitro suppresses the enzyme activity.

We investigated the effect on the Ca2+-dependent ATPase activity of ADP-ribosylation of the enzyme from the rabbit skeletal muscle sarcoplasmic reticulum. A reconstituted ADP-ribosylation system of Ca2+-dependent ATPase in which the enzyme and ADP-ribosyltransferase, both were partially purified from the vesicles, and poly L-lysine were contained, was preincubated with 1 mM NAD, and the Ca2+-dependent ATPase activity was assayed. The NAD-dependent suppression of the enzyme activity depended on both the concentration of NAD and preincubation-time for the ADP-ribosylation, and was reversed by adding 20 mM arginine during the preincubation. These results taken together with the findings that Ca2+-dependent ATPase is a major acceptor protein for the modification in rabbit skeletal muscle sarcoplasmic reticulum [Hara et al. (1987) Biochem. Biophys. Res. Commun. 144; 856-862] suggest that Ca2+-transport in the sarcoplasmic reticulum may be regulated through changes in the rate of ADP-ribosylation of Ca2+-dependent ATPase.

Adenosine Diphosphate Ribose↗
PubMed1987

Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII.

To identify the mechanism of hyperuricemia in glycogen storage diseases (glycogenoses) that affect muscle, we studied the effects of exercise and prolonged rest on purine metabolism in two patients with glycogenosis type III (debrancher deficiency), one patient with type V (muscle phosphorylase deficiency), and one patient with type VII (muscle phosphofructokinase deficiency). All had hyperuricemia except for one patient with glycogenosis type III. Plasma concentrations of ammonia, inosine, and hypoxanthine increased markedly in all the patients after mild leg exercise on a bicycle ergometer. The plasma urate concentrations also increased, but with a delayed response. Urinary excretion of inosine, hypoxanthine, and urate increased greatly after exercise, consistently with the increases in plasma levels. Hypoxanthine and urate concentrations were extremely high in the plasma and urine of the patient with glycogenosis type VII. With bed rest, the plasma hypoxanthine level returned to normal within a few hours, and the plasma urate concentration decreased from 18.6 to 10.6 mg per deciliter (1106 to 630 mumol per liter) within 48 hours. Similarly, the urinary excretion of these purine metabolites was reduced by bed rest. These findings indicate that muscular exertion in patients with glycogenosis types III, V, and VII causes excessive increases in blood ammonia, inosine, and hypoxanthine due to accelerated degradation of muscle purine nucleotides. These purine metabolites subsequently serve as substrates for the synthesis of uric acid, leading to hyperuricemia.

Adult↗
PubMed1987

Mono(ADP-ribosyl)ation of Ca2+-dependent ATPase in rabbit skeletal muscle sarcoplasmic reticulum and the effect of poly L-lysine.

We investigated the endogenous mono(ADP-ribosyl)ation of the sarcoplasmic reticulum from rabbit skeletal muscle. The autoradiogram obtained after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the [adenylate-32P]NAD-treated sarcoplasmic reticulum vesicles revealed a major band corresponding to the MW 105 K Ca2+-dependent ATPase and other bands corresponding to proteins of MW 153, 60 and 38 K and those of 125 to 135 K range. The addition of poly L-lysine during the incubation led to an enhancement of the modification. Poly L-lysine is proving to be a pertinent tool for identifying acceptor proteins.

Adenosine Diphosphate Ribose↗
PubMed1987

Enhanced release of ammonia and hypoxanthine from exercising muscles in patients with idiopathic hypoparathyroidism.

Semiischemic forearm exercise tests were carried out in two patients with idiopathic hypoparathyroidism who had muscle cramps and high serum levels of creatine kinase. Although cubital venous lactate levels increased normally after forearm exercise, venous ammonia and hypoxanthine were greatly increased. The abnormal responses of ammonia and hypoxanthine were normalized 3 months after treatment with 1 alpha-hydroxyvitamin D3. These findings suggest that excess purine degradation occurred in exercising muscles of patients with idiopathic hypoparathyroidism.

Adult↗
PubMed1987

[Immunohistological analysis of infiltrating lymphocyte subpopulations in gliomas and metastatic brain tumors].

Subpopulations of infiltrating lymphocytes were studied by immunohistological method using monoclonal antibodies in gliomas and metastatic brain tumors. Thirteen specimens from 8 glioma patients, and 7 specimens from 3 metastatic brain tumor patients were used. No special therapy for brain tumor had been performed in these cases, but 3 glioma patients and all metastatic brain tumor patients had received steroid hormone. Frontal lobe obtained from the autopsy case of chest trauma was served as a normal control. Frozen sections were stained with avidin-biotin peroxidase complex method using Leu-series monoclonal antibodies for pan T-cells (Leu-1), cytotoxic/suppressor T-cells (Leu-2 a), helper/inducer T-cells (Leu-3 a) and B-cells (Leu-12). Lymphocyte infiltrates were quantitated by counting positively stained cells in 13 glioma and 7 metastatic brain tumor specimens. In normal frontal lobe, only a few T-cells infiltrated around several blood vessels in the parenchyma and subarachnoid space. But in the cases of glioma, many perivascular lymphocytic infiltrates were found and in the cases of metastatic brain tumor, many lymphocytes were found diffusely in the interstitial area between nests of tumor cells. Most of these lymphocytes were T-cells and B-cells were scarce, and Leu-2 a and Leu-3 a positive cells intermingled with each other. Len-3 a/2 a ratio ranged from 0.2 to 0.9 in the half of gliomas and 1.5 to 3.6 in another half of gliomas, three of which were treated with steroid hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗