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Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 415 records · Page 23Linked to original sources

[Adrenal incidentaloma--report of 14 operated cases and analysis of 4-year autopsy series of Japan].

During the last 7 years, operation was performed for 94 cases of adrenal tumor in our series, of which 14 were incidentally found by abdominal computed tomography or echography. They included 9 cases of pheochromocytoma, 1 of Cushing's syndrome, 3 of ganglioneuroma and 1 of cortical adenoma. Five of 9 pheochromocytoma cases were devoid of hypertension, but all 9 cases had abnormally high levels of urinary catecholamines and/or their metabolites. The 4-year autopsy series of Japan (1980-1983) included about 153,000 cases. Except the metastatic tumors, the following lesions were incidentally found in the adrenal gland: 310 of cortical adenoma, 153 of cortical hyperplasia, 39 of pheochromocytoma and 17 cases of neurogenic tumors. Some of the cortical adenomas are presumed to be more than 1 cm in diameter. So, they are expected to be found incidentally, more frequently in the future. Surgery is not necessary for most of them, except for functioning tumors. Most of the pheochromocytomas are presumed to be hormonally active, and should be treated surgically. It is probable that these functioning tumors had been missed clinically, especially in the elderly persons. Neurogenic tumors and myelolipomas may be left in place, when malignancy can be ruled out.

Adenoma↗

Production of monoclonal antibody to thyroglobulin from malignant thyroid carcinoma.

In this study, the production of anti-human thyroglobulin (Tg) monoclonal antibodies was attempted to detect Tg levels in serum and to study the localization of thyroid metastases in patients with thyroid-gland ablation. As a result four clones of hybridoma cell lines were obtained. By means of enzyme immunoassay (EIA) and immunohistochemical method, it was found that one of them, 2G4, produced a monoclonal antibody recognizing a malignant structural change of Tg and other three clones produced monoclonal antibodies recognizing not only the normal human Tg but also the malignant Tg. Our monoclonal antibody, 2G4, will be a hopeful reagent for the diagnosis in thyroid carcinoma.

Antibodies, Monoclonal↗

Suppression of catecholamine-induced abnormal pacemaker activities by magnesium ion in guinea pig cardiac muscle cells.

The effect of magnesium ion on the abnormal pacemaker activity of guinea pig ventricular muscle cells depolarized by 27 mM K+ was studied. Isoproterenol produced a small depolarization in the resting membrane and elicited automatic repetitive action potentials at higher concentrations in the presence of 0.2 mM Ba2+. This model was used to assess the antiarrhythmic effect of magnesium ion on cardiac muscle cells. Isoproterenol concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as a basis for evaluation. The responsiveness of muscle cells to isoproterenol was suppressed significantly by increasing the magnesium concentration. It is concluded that magnesium ion may have an antiarrhythmic effect on partially depolarized cardiac muscle cells.

Animals↗

Mucin-like antigens in a human pancreatic cancer cell line identified by murine monoclonal antibodies SPan-1 and YPan-1.

The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we describe the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4-1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive beta-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by boiling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.

Animals↗

Electron paramagnetic resonance study of ferrous cytochrome P-450scc-nitric oxide complexes: effects of 20(R),22(R)-dihydroxycholesterol and reduced adrenodoxin.

Electron paramagnetic resonance (EPR) spectra of ferrous-nitric oxide (14NO and 15NO) cytochrome P-450scc complexed with 20(R),22(R)-dihydroxycholesterol were measured at 77 K with X-band (9.35 GHz) microwave frequency. The EPR spectra clearly showed the spin system to have rhombic symmetry (gx = 2.068, gz = 2.001, gy = 1.961, and Az = 1.89 mT for 14NO) and were distinct from those of 20(S)-hydroxycholesterol complexes. The unique nature of the 20(S)-hydroxycholesterol complexes indicates that 20(S)-hydroxycholesterol is not a proper intermediate in the cholesterol side-chain cleavage reaction. In addition, among various steroid complexes of ferrous-NO species having rhombic symmetry, the EPR spectra of 20(R),22(R)-dihydroxycholesterol complexes were significantly different from those of 22(R)-hydroxycholesterol complexes, suggesting that upon 20S-hydroxylation of 22(R)-hydroxycholesterol the conformation of the active site changes so as to facilitate subsequent cleavage of the C20-C22 bond of the cholesterol side chain. Addition of reduced adrenodoxin to the ferrous-NO cytochrome P-450scc complex in the presence of cholesterol caused a complete shift of the gx = 2.070 signal to gx = 2.075, indicating a reorientation of cholesterol in the substrate-binding site of the enzyme upon adrenodoxin binding. Without reduced adrenodoxin, the process of reorientation of cholesterol in the substrate-binding site was very slow, requiring more than 50 h of incubation at 0 degrees C. The present observations suggest that adrenodoxin may have another positive role in the cholesterol side-chain cleavage reaction, in addition to transferring an electron to the heme of cytochrome P-450scc.

Adrenal Cortex↗

A new 5-lipoxygenase selective inhibitor derived from Artocarpus communis strongly inhibits arachidonic acid-induced ear edema.

Natural compounds isolated from the Indonesian plant, Artocarpus communis, inhibit 5-lipoxygenase of cultured mastocytoma cells. One of five compounds, AC-5-1, strongly inhibits 5-lipoxygenase with a half-inhibition dose of 5 +/- 0.12 X 10(-8) M. However, prostaglandin synthesizing activity is not inhibited until 10(-5) M. AC-5-1 is a highly selective inhibitor for 5-lipoxygenase. The AC-5-1 at 10(-5) M inhibits 96% of leukotriene C4 synthesis of mouse peritoneal cells facilitated by calcium-ionophore. Arachidonic acid-induced ear edema of mice, an in vivo inflammatory model, involving leukotriene induction, is strongly inhibited by AC-5-1 in a dose-dependent manner. The inhibition is the strongest of any inhibitors of 5-lipoxygenase reported previously. Since the natural compound AC-5-1 can selectively inhibit 5-lipoxygenase and affect in vivo inflammation, it will be interesting to investigate the role of leukotrienes on inflammation and other physiological processes.

Animals↗

Triacylglycerol lipase-mediated release of arachidonic acid for renal medullary prostaglandin synthesis.

The effect of triacylglycerol lipase or triarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. Prostaglandin E2 generation was enhanced by exogenous triacylglycerol lipase, indicating that arachidonic acid released from medullary triacylglycerols is readily available for prostaglandin biosynthesis. Triarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. Moreover, the kidney medulla slices showed triacylglycerol lipase activity using trimargarin as substrate. The addition of mepacrine made the stimulatory effect of triarachidonin on prostaglandin E2 formation more pronounced. Studies utilizing EGTA and p-bromophenacyl bromide revealed that triacylglycerol lipase of kidney medulla is independent of Ca2+ and sensitive to a sulfhydryl inhibitor. These results suggest the presence of triacylglycerol lipase and triacylglycerol as a possible candidate for providing free arachidonic acid to cyclooxygenase in kidney medulla.

5,8,11,14-Eicosatetraynoic Acid↗

Human placental dipeptidyl aminopeptidase III: hydrolysis of enkephalins and its stimulation by cobaltous ion.

The degradation of enkephalin and related peptides by highly purified dipeptidyl aminopeptidase III (EC 3.4.14.4) was studied. The enzyme releases the N-terminal dipeptide units from substrates greater in length than the tetrapeptide. The enzyme exhibits an optimum of pH 7.5, Km of 81 microM and Vmax of 0.043 mumole/min for Leu-enkephalin. Its activity was markedly stimulated by Co2+, with both the Km and Vmax being increased. Among the enkephalin-related peptides examined, des-Tyr1-Leu-enkephalin was the most rapidly hydrolyzed with Co2+, but only slight stimulation was observed with Co2+.

Cations, Divalent↗

A compound adrenal medullary tumor (pheochromocytoma and ganglioneuroma) and a cortical adenoma in the ipsilateral adrenal gland. A case report with enzyme histochemical and immunohistochemical studies.

Neoplasms of all the adrenal parenchymatous elements [i.e., a compound adrenal medullary tumor (MT) consisting of pheochromocytoma (Pheo) and ganglioneuroma (GN) and a cortical adenoma] were found in the right adrenal gland of a 53-year-old man. A mature GN element was predominant in the MT, and nodules of small polygonal Pheo cells were scattered in GN. No neuroblastomatous element or malignant Pheo was found. The cortical adenoma consisted of compact cells and clear cells; it showed 3 beta hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, and succinate dehydrogenase activity. The nonneoplastic cortex was slightly atrophic and showed weaker activity of the enzymes, suggesting that the adenoma was cortisol-producing. The cortex surrounding the MT was invaded and replaced by either GN or Pheo. In some places, however, hypertrophic compact cells constituted the cortex and were in contact with ACTH-immunoreactive chromaffin cells. A few of the latter were also positive for other proopiomelanocortin (POMC)-derived peptides. Pheo cells in the other parts were negative for POMC-derived peptides.

Adenoma↗

Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats.

Spontaneous occurrence of placental glutathione S-transferase (GST-P)-positive foci was observed in the livers of 5-month-old LEC rats. Quantitative studies revealed that GST-P foci appeared after the onset of hepatitis. The number and size of GST-P foci increased with age and more foci were induced in males than in females. No sex difference, however, was found in the incidence of hepatitis. Although hepatitis is necessary for the induction of GST-P foci, it is insufficient for their further growth. Since hereditary hepatitis first appears at around 4 months of age, leading to a high incidence of hepatocellular carcinomas in later life, the spontaneous occurrence of the foci may be related to the development of hepatocellular carcinoma.

Animals↗

Elevation of serum alpha-fetoprotein and proliferation of oval cells in the livers of LEC rats.

Alpha-fetoprotein (AFP) in the sera of 35 LEC (Long-Evans with a cinnamon-like coat color) rats between 7 and 25 weeks of age was evaluated by enzyme-linked immunosorbent assay (ELISA). Elevation of serum AFP and proliferation of oval cells in the liver were observed in most LEC rats, which suffered from acute hepatitis. On the other hand, the serum AFP level was within the normal range before the onset of hepatitis. Immunohistochemical staining for AFP revealed that some of the proliferating oval cells produced AFP. Morphometric analysis of AFP-positive cells and ELISA for serum AFP demonstrated that there was a statistically significant correlation between the number of AFP-positive cells in the liver and the concentration of AFP in the serum. Histological examination revealed the transition and differentiation of the oval cells to small hepatocytes. These results suggested that the phenomena which occurred in LEC rats suffering from acute hepatitis were similar to those that occurred during the early stage of azo dye hepatocarcinogenesis, although the extent of the oval cell proliferation and the elevation of serum AFP in LEC rats were not as great as those in rats treated with azo dye. This is the first report on a rat strain with proliferation of AFP-producing oval cells during its natural history.

Animals↗

IgG-kappa-producing primary plasmacytoma of the thyroid gland with preoperative serum M protein.

A case of primary plasmacytoma of the thyroid gland which occurred in a 63-year-old woman is reported. Histologic and ultramicroscopic examination revealed that the excised thyroid tumor was plasmacytoma superimposed on lymphocytic thyroiditis. Immunohistological study showed that the tumor cells produced intracytoplasmic immunoglobulin (IgG-kappa). Electrophoretic and immunoelectrophoretic studies disclosed the presence of monoclonal immunoglobulin (IgG-kappa) in samples of the patient's serum which had been obtained preoperatively. After completion of irradiation therapy to the neck following tumor removal, the serum monoclonal immunoglobulin disappeared. The patient is currently alive and well without any evidence of the tumor three years after surgery.

Blood Proteins↗

Effect of tiopronin on prostaglandin synthesis in rabbit kidney medulla slices.

The effect of 2-mercaptopropionylglycine (tiopronin), which is widely used for the treatment of various hepatic disorders, on the generation of medullary prostaglandins (PG) E2 and F2 alpha has been examined. Tiopronin had a potent inhibitory effect on PG E2 formation. Simultaneously, PG F2 alpha production was increased. In the presence of tiopronin the net increased amount of PG F2 alpha was much smaller than the net decreased amount of PG E2 (6-20%). These results suggest that tiopronin has the potential to modulate PG E2 and F2 alpha synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase and that this effect may represent some pharmacological action of the drug.

Animals↗