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Biomedical subjects

T Kitagawa

Publications and source records attributed to T Kitagawa.

At least 703 records · Page 39Linked to original sources

Re-elevation of gamma-glutamyl transpeptidase activity in periportal hepatocytes of rats with age.

Changes in the level of gamma-glutamyl transpeptidase (gamma-GTP) in the rat liver with age were studied histochemically and biochemically. A high enzyme activity was seen throughout the hepatic lobule with some predominance in the periportal area in the neonatal rat liver. This enzyme activity disappeared almost completely from the hepatocytes of young adults. However, after 30 weeks of age, there was a gradual re-elevation of the enzyme activity in the periportal hepatocytes, attaining a level similar to that of neonatal liver. Expression of gamma-GTP activity in the rat hepatocytes is associated with not only onconeonatal events but also aging.

Aging↗

Induction of gamma-glutamyl transpeptidase activity by dietary phenobarbital in "spontaneous" hepatic tumors of C3H mice.

Biochemical features of spontaneous hepatic tumors in C3H mice were studied histochemically in comparison with those of neoplastic lesions developed in animals fed dietary phenobarbital (PB) continuously or treated with diethylnitrosamine (DEN) during 11 approximately 14 weeks of age. All 42 spontaneous hepatic tumors that developed in control mice by 74 weeks of age were completely negative for gamma-glutamyl transpeptidase (gamma-GTPase) activity. Dietary phenobarbital enhanced hepatic tumorigenesis remarkably, and 32 out of 43 tumors found at 70 weeks showed multifocal gamma-GTPase activity. DEN induced gamma-GTPase-positive islands of hepatocytes, but 12 out of 13 tumors larger than 5 mm in diameter that developed by 60 weeks were gamma-GTPase-negative. The phenomenon of induction of gamma-GTPase activity by PB in "spontaneous" hepatic tumors appears to be important both for elucidating the mechanism of promotion by PB and also for analyzing multisteps of carcinogenesis.

Animals↗

Correlation between time of partial hepatectomy after a single treatment with diethylnitrosamine and induction of adenosinetriphosphatase-deficient islands in rat liver.

Full-grown Sprague-Dawley rats were given a single i.p. injection of diethylnitrosamine (80 mg/kg) and subjected to partial hepatectomy at various times from 4 hr to 7 days later to induce semisynchronized liver cell proliferation. Then, they were maintained on basal diet containing 0.05% phenobarbital, which is known to promote hepatocarcinogenesis, for 16 weeks. By this method, significant numbers of adenosinetriphosphatase-deficient islands were induced in the liver. These islands are considered to be formed by immediate progeny of "initiated cells" or cell precursors in hepatocarcinogenesis, and they can be used as a marker of carcinogenic activity. Results showed that the number of enzyme-altered islands induced was inversely proportional to the time between carcinogen treatment and subsequent partial hepatectomy. The incidence of enzyme-altered islands was greatest when the two treatments were separated by 4 hr and decreased when they were separated by 7 days. These data suggest that carcinogen-induced DNA damage, if not repaired before cell proliferation, is intimately related to the initiation-fixation process of carcinogenesis.

Adenosine Triphosphatases↗

Mechanisms of inhibition by simultaneously administered phenobarbital of 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in the rat.

The mechanisms of inhibition by simultaneously administered phenobarbital of 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB)-induced hepatocarcinogenesis in the rat were studied. Weanling rats were fed a diet containing 0.06% 3'-Me-DAB or 0.06% 3'-Me-DAB and 0.05% phenobarbital for 3 weeks, followed by either basal diet or a diet containing 0.05% phenobarbital as a promoter. The number and the size of enzyme-altered islands and the number of tumors larger than 5 mm in diameter were scored at week 12 and week 40, respectively. The simultaneous feeding of phenobarbital and 3'-Me-DAB resulted in a significant decrease in the number and size of enzyme-altered islands and in the number of tumors, in comparison with those scored in animals fed 3'-Me-DAB alone. It was concluded that the simultaneous feeding of phenobarbital inhibits both the initiation of carcinogenesis and also the promotive action of the carcinogen resulting from its selective toxicity on the liver tissue.

Animals↗

In vitro carcinogenesis of hepatocytes obtained from acetylaminofluorene-treated rat liver and promotion of their growth by phenobarbital.

The hepatic cells of rats being fed acetylaminofluorene were transferred into culture at various times. Proliferative hepatocytic foci were obtained from animals treated with the carcinogen for more than 9 weeks. These hepatocytic foci became transplantable and capable of growth in soft agar after 4 to 12 months in culture. Phenobarbital markedly enhanced the growth of these hepatocytes in culture.

2-Acetylaminofluorene↗

Quaternary structure-induced photoreduction of haem of haemoglobin.

Spectroscopic studies have provided extensive information on the primary process of visual pigments and photoexcitation of chlorophyll as well as their effects on photoreactivity on the higher-order structures of protein has been observed only rarely. Resonance Raman spectroscopy can reveal the vibrational frequencies of the chromophore in a molecule provided the excitation wavelength is in the absorption band of that molecule. As the visible absorption bands of haemproteins are due to pi pi* transitions of the porphyrin ring, we can selectively observe the vibrational frequencies of iron porphyrin during in situ interactions with immediate amino acid residues of protein when the wavelength of excitation light is close to the Soret or Q band. Correlation of some vibrational frequencies of haem with the oxidation and spin states of the haem iron has been studied in detail and an empirical rules has been established. This method is therefore especially suitable for the study of an effect of higher-order structures of protein on the chromophore. We report here a photoreaction facilitated by a particular quaternary structure of protein--in various haemoglobins resonance Raman spectroscopy showed that reversible photoreduction of haem took place in the T state but not the R state.

Animals↗

Resonance Raman spectra of carbon-13- and nitrogen-15-labeled riboflavin bound to egg-white flavoprotein.

The resonance Raman spectra of [2-13C]-, [4a-13C]-, [4-13C]-8 [10a-13C]-, [2,4,4a, 10a-13C]-, [5-15N]-, [1,3-15N]-, and [1,3,5-15N]riboflavin bound to egg-white proteins were observed for N(3)-H and N(3)-D forms with spontaneous Raman technique by using the 488.0-nm excitation line of an argon ion laser. The fluorescence of riboflavin was quenched by forming a complex with egg-white riboflavin binding protein. The in-plane displacements of the C(2), C(4a), N(1), N(3), and N(5) atoms during each Raman active vibration were calculated from the observed isotopic frequency shifts. The 1252-cm-1 mode of the N(3)-H form was found to involve large vibrational displacements of the C(2) and N(3) atoms and to be strongly coupled with the N(3)-H bending mode. This line can be used as an indicator for state of N(3)-H...protein interaction. The 1584-cm-1 mode, which is known to be resonance-enhanced upon excitation near the 370-nm absorption band, was accompanied by the displacement of the N(5) atom in particular. The 1355-cm-1 mode was most strongly resonance-enhanced by the 450-nm absorption band and involved the displacements of all carbon atoms of ring III. Both lines can be used as structure probes for elucidating the structure of electronically excited states of isoalloxazine.

Egg Proteins↗