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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 19 recordsLinked to original sources

The localization of mutarotase in rat kidney.

The localization of mutarotase in rat kidney was investigated by fluorescein-labelled and peroxidase-labelled antibody techniques, and by method of isolation of the nuclei and cytoplasm in non-aqueous solvents. In these immunohistochemical studies, mutarotase was almost exclusively recognized in the nuclei of epithelial cells of renal tubules and glomeruli in rat. The specific activity of mutarotase was found to be 1.5 times higher in the nuclei (122 units/g dry wt) than that in the cytoplasm (80 units/g dry wt) isolated with non-aqueous solvents. These results suggest that mutarotase may be involved in the metabolism of D-glucose in nuclei.

Animals

Determination of plasma testosterone by mass fragmentography using testosterone-19-d3 as an internal standard. Comparison with radioimmunoassay.

Analytical procedures for the measurement of testosterone by mass fragmentography (MF) using trideuterated testosterone (testosterone-19,19,19-d3) are described. For the calculation of plasma testosterone, peak height ratios were measured by MF performed on the molecular ions of the TFA derivative of testosterone (m/e 480) and testosterone-19,19,19-d3 (m/e 483). The sensitivity of the method was judged from the lower limit of detection of the mass spectrometer which was at 10 pg. For the measurement of the precision, the inter- and intra-assay coefficients of variation (C.V.) were calculated by using a pooled plasma sample; they were 3.15% and 1.79%, respectively. The specificity was investigated by the use of 5 alpha-dihydrotestosterone and the MF method was found to afford a highly selective technique. These results obtained by MF have been compared with the results obtained by a radioimmunoassay method.

Gas Chromatography-Mass Spectrometry

Studies on drug metabolism by use of isotopes. XXIV-Determination of 3-phenylpropyl carbamate metabolites using stable isotope labelling with deuterium or carbon-13.

Metabolism of 3-phenylproply carbamate was investigated by using a stable isotope tracer technique. 3-Phenylpropanol, 3-hydroxy-3-phenylpropanol, 3-hydroxy-3-phenylpropyl carbamate, 2,3-dihydroxy-3-phenylproply carbamate, benzoic acid and hippuric acid were identified as the rat urinary metabolites. Using the dilution analysis, the amounts of metabolites in urine and faeces in rat and man were determined. In rats, 2,3-dihydroxy-3-phenylproply carbamate and 3-phenylpropanol glucuronide were excreted into the urine as the major metabolites of this drug. On the other hand, in man, the major metabolite was hippuric acid and about 30% of the administered dose was excreted as hippuric acid in the 24 h urine. The tracer technique using a singly labelled drug with carbon-13 employed in the present study provided a reliable methods for the analysis of drug metabolites and was comparable with the tracer technique using a multilabelled drug with deuterium.

1-Propanol

Discrepancies between the doses of cholecystokinin or caerulein-stimulating exocrine and endocrine responses in perfused isolated rat pancreas.

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.

Amylases

Effect of caerulein on exocrine and endocrine pancreas in the rat.

The secretion of insulin, glucagon, pancreatic juice, and amylase in response to a 20-min iv infusion of synthetic caerulein were studied simultaneously in the anesthetized rat. Caerulein, a chemical analogue of cholecystokinin, was used in doses of 1-1000 ng/kg.min. The maximum stimulatory effect of caerulein on pancreatic juice volume and amylase output was obtained with doses of 10 ng/kg.min. With increasing doses, the effect decreased progressively. On the other hand, the release of insulin and glucagon was stimulated only by supramaximal doses of caerulein, which had little or no effect on pancreatic exocrine secretions. These results raised the question of whether, under physiological conditions, cholecystokinin regulates the secretory activity of the endocrine pancreas.

Amylases

Insulin and glucagon relationships during aging in rats.

Oral glucose tolerance tests were performed under pentobarbital anesthesia in 43 male Wistar rats 2 to 18 months of age in order to determine if insulin and glucagon secretion are altered with aging. Although any linear correlation was not demonstrated between aging and blood glucose, plasma insulin or glucagon levels, post-glucose levels of blood glucose were significantly suppressed and those of plasma glucagon were significantly elevated at 4 to 6 months of age. No significant difference was found between young (2 months of age) and aged rats (12 to 14 and 17 to 18 months of age) in either blood glucose or plasma insulin levels during oral glucose load. On the other hand, post-glucose plasma glucagon levels of the aged rats were significantly higher than those of the young ones. Furthermore, comparisons of various kinds of indices among the different age groups, such as insulinogenic index, insulin/glucagon and so forth during oral glucose tolerance tests also indicate the significant alteration of glucagon secretion during aging process. It is concluded from the present data that glucose tolerance does not apparently deteriorate during aging process in rats but that glucagon responses to oral glucose administration are elevated with aging.

Aging

Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide.

Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Post-glucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation. In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumor-bearing rats were significantly lower than those of body weight adjusted controls. It is inferred from the study that secretory activity of pancreatic A-cells of tumor-bearing rats is restrained by excess insulin released from islet cell tumors.

Adenoma, Islet Cell

High concentration of gamma-aminobutyric acid in pancreatic beta cells.

The gamma-aminobutyric acid (GABA) concentration of pancreatic islets in rats treated with streptozotocin (STZ) and of human insulinoma tissue was studied. Seven hours after the administration of 65 mg/kg body weight of STZ, a distinct increase in serum insulin concentration and at the same time a decrease in blood glucose level were seen. Twenty-four hours after the injection of STZ, however, the level of serum insulin decreased much, whereas that of blood glucose increased considerably. On the other hand, the GABA concentration of the islet was reduced dramatically to about one-tenth the control level after both 7 and 24 h. The histologic investigations of the islets revealed the destruction of B cells but no changes in A and D cells 7 and 24 h after the treatment of STZ. Nerve fibers and nerve endings in the islets were preserved intact all through the study. The GABA and insulin contents of the two cases of human insulinoma were determined. One insulinoma, which was compactly occupied with B cells according to its histologic features, contained a high concentration of GABA. The other tumor, having a rather sparse distribution of B cells in it as compared with the former case, possessed a lower concentration of GABA, but it was still high compared with that of its surrounding tissues. The present observations indicate that a large amount of GABA is available in the B cells of the pancreatic islets.

Adenoma, Islet Cell

Studies on the biotransformation of paeonol by means of isotope tracer techniques.--Synthesis and physicochemical properties of carbon-13 and deuterium labeled compounds--.

In order to perform the metabolic study of paeonol (I) in human and animals by using isotope tracer techniques, synthesis of I and its urinary metabolites labeled with carbon-13 or deuterium was investigated. 2-Hydroxy-4-methoxy[d3]acetophenone, 2,5-dihydroxy-4-methoxy[d3]acetophenone, and resacetophenone[acetyl-13C2] were synthesized from methyl iodide-d3, dimethyl sulfate-d6, and acetic acid-1,2-13C2, respectively. Physicochemical studies by IR and NMR spectra showed that stable isotope was not eliminated during the synthetic process of each compound. For the quantification of the metabolites by GC-MS analysis, isotope effect on gas chromatography and fragmentation was studied.

Acetophenones