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Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 19 recordsLinked to original sources

Peculiar nuclear clearing composed of microfilaments in papillary carcinoma of the thyroid.

BACKGROUND: Papillary carcinoma of the thyroid frequently occurs in young women. Four cases of papillary carcinoma were found in women in their 20s, and the disease was characterized by unusual morphologic and clinical features. METHODS: Four cases were analyzed clinically, grossly, microscopically, ultrastructurally, and immunohistochemically and compared with control cases of papillary carcinoma. RESULTS: The tumors histologically showed various appearances with trabecular, solid cribriform, follicular, and papillary patterns. A striking finding was that stratified cancer cell nests with prominent nuclear clearings were scattered in the tumors. Ultrastructurally, the nuclear clearings were composed of fine thread-like fibrils, and they were bound unselectively to various antibodies against hormones and intermediate filaments. The four patients also had common clinicopathologic features as follows: they were all women in their 20s and their preoperative serum thyroglobulin levels were all normal despite the large size of their thyroid tumors. The tumors were grossly well encapsulated, and there was no lymph node metastasis, except in one patient who had only one positive node. CONCLUSIONS: The peculiar nuclear features were distinct from intranuclear cytoplasmic inclusions or ground-glass nuclei, and these have not been reported previously to the authors' knowledge in conventional thyroid neoplasms. These tumors might represent another subtype of papillary thyroid carcinoma.

Actin Cytoskeleton

Analysis of thyroid carcinoma based on material registered in Japan during 1977-1986 with special reference to predominance of papillary type.

BACKGROUND: As geographic differences have been observed in the characteristics of thyroid carcinoma, an analysis was made on thyroid carcinoma in the iodine rich country of Japan. METHODS: A total of 10,973 patients with histologically confirmed thyroid carcinoma registered in Japan from 1977-1986 were analyzed. Cases detected incidentally at autopsy and cases of nonepithelial tumor were excluded. This series included approximately 27% of all thyroid carcinoma cases in Japan. RESULTS AND CONCLUSIONS: Histologic distribution showed that papillary carcinoma accounted for 78.4% of cases, follicular carcinoma accounted for 17.2%, medullary carcinoma for 1.4%, squamous cell carcinoma for 0.3%, and anaplastic carcinoma for 2.7%. There is a tendency in Japan to diagnose papillary carcinoma as follicular carcinoma and to diagnose malignant lymphoma as anaplastic carcinoma. It was considered that the percentage of papillary carcinoma was higher and the percentage of follicular carcinoma and anaplastic carcinoma was lower than foregoing values. The characteristics of thyroid carcinoma in Japan were described, and the low incidence of nonpapillary carcinoma compared with papillary carcinoma was discussed in relation to iodine excess as an etiologic factor.

Adolescent

Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells.

Synaptotagmin (p65) is an abundant synaptic vesicle protein of neurons and contains regions similar to the regulatory domain of protein kinase C. These domains are thought to be involved in calcium-dependent interaction with membrane phospholipids during exocytosis. To assess the functional role of synaptotagmin, synaptotagmin-deficient clonal variants of PC12 cells were isolated. All of the variant cells released catecholamine and adenosine triphosphate in response to elevated intracellular concentrations of calcium, which suggests that synaptotagmin is not essential for secretion of catecholamine and adenosine triphosphate from PC12 cells.

Adenosine Triphosphate

Highly conserved hexamer, octamer and nonamer motifs are positive cis-regulatory elements of the wheat histone H3 gene.

Base substitution mutations were introduced into the promoter region of the wheat histone H3 gene, and promoter activity was assayed in stably transformed sunflower calli or in wheat protoplasts transfected transiently. At least four positive regulatory elements, a hexamer motif (ACGTCA), two octamer(-like) motifs of a direct (CcCGGATC) and a reverse (aATCCGCG) form, and a nonamer motif (CATCCAACG) were identified within the -185 region of the H3 promoter. Analyses of the type I element (CCACGTCACCaATCCGCG) consisting of the hexamer and reverse-oriented octamer motifs, and which is conserved in other plant histone genes as well, predicted the presence of an octamer-binding protein(s).

Base Sequence

Low frequency of p53 gene mutation in tumors induced by aflatoxin B1 in nonhuman primates.

Aflatoxin B1 has been suggested as a causative agent for a G to T mutation at codon 249 in the p53 gene in human hepatocellular carcinomas from southern Africa and Qidong in China. To test this hypothesis, nine tumors induced by aflatoxin B1 in nonhuman primates were analyzed for mutations in the p53 gene. These included four hepatocellular carcinomas, two cholangiocarcinomas, a spindle cell carcinoma of the bile duct, a hemangioendothelial sarcoma of the liver, and an osteogenic sarcoma of the tibia. None of the tumors showed changes at the third position of codon 249 by cleavage analysis of the HaeIII enzyme site at codon 249. A point mutation was identified in one hepatocellular carcinoma at the second position of codon 175 (G to T transversion) by sequencing analysis of the four conserved domains (II to V) in the p53 gene. These data suggest that mutations in the p53 gene are not necessary in aflatoxin B1 induced hepatocarcinogenesis in nonhuman primates. The occurrence of mutation in codon 249 of the p53 gene in selective samples of human hepatocellular cancers may indicate involvement of environmental carcinogens other than aflatoxin B1 or that hepatitis B virus-related hepatitis is a prerequisite for aflatoxin B1 induction of G to T transversion in codon 249.

Adenoma, Bile Duct

Two-dimensional electrophoretic analysis of transformation-sensitive polypeptides during chemically, spontaneously, and oncogene-induced transformation of rat liver epithelial cells.

Recently, we described the establishment of a computerized database of rat liver epithelial (RLE) cellular polypeptides (Wirth et al., Electrophoresis, 1991, 12, 931-954). This database has now been expanded to include the analysis of cellular polypeptide alterations during chemically (aflatoxin B1; AFB), spontaneously, and oncogene (v-Ha-ras, v-raf, and v-myc/v-raf)-induced transformation of RLE cells. Two-dimensional mapping of [35S]methionine-labeled whole cell lysate, cell-free in vitro translation products and [32P]orthophosphate-labeled polypeptides revealed subsets of polypeptides specific for each transformation modality. A search of the RLE protein database indicated the specific subcellular location for the majority of these transformation-sensitive proteins. Significant alterations in the expression of the extracellular matrix protein, fibronectin, as well as tropomyosin- and intermediate filament-related polypeptides (vimentin, beta-tubulin, the cytokeratins, and actin) were observed among the various transformant cell lines. Immunoprecipitation and Western immunoblot analysis of tropomyosin expression in four individual AFB-, as well as four spontaneously induced, and each of the oncogene-transformed cell lines indicated that five major tropomyosin (Tm 1-5) isoforms were variably expressed in the various cell lines, including one polypeptide tentatively identified as Tm6. Whereas alterations in tropomyosin expression appeared to be transformation-specific, alterations in the individual intermediate filament polypeptides were related more to the differentiation state of the individual cell lines rather than to the transformation phenotype. These studies extend our earlier efforts toward the establishment of a comprehensive computerized database of RLE cellular proteins and demonstrates how such a database may serve as a useful source for studies concerning the regulation of growth and differentiation as well as transformation of RLE cells.

Actins

Purification and characterization of new arginine esteropeptidase from the soluble fraction of human submaxillary glands.

An arginine esteropeptidase was completely purified from the soluble fraction of human submaxillary glands. The molecular weight was calculated to be 12,000, having 2 species of subunits. The study of the effect of inhibitors confirmed the enzyme's serine protease-like characteristics. The best ester and amide substrates were Tos-Arg-OMe and D-Ile-Pro-Arg-pNA, respectively.

Amino Acid Sequence

Detection and separation of some arginine amidases including tissue kallikrein from human seminal plasma.

A plasminogen/plasmin like substance (AHSAA-1), with affinity to lysine column was separated from DEAE-cellulose adsorbed human seminal plasma. Two forms of acidic arginine amidase with different affinities to LBTI (AHSAA-2) and aprotinin columns (AHSAA-3) were separated from the DEAE-cellulose adsorbed preparation and AHSAA-3 was identified as tissue kallikrein. Two basic arginine amidase preparations having affinity to LBTI (BHSAA-1) and aprotinin column were also separated from the CM-cellulose adsorbed human seminal plasma. Three basic arginine amidases with different molecular mass (BHSAA-2 to 4) were separated by Cellulofine GCL-2000 gel filtration from aprotinin adsorbed material and some of their properties were examined.

Amino Acid Sequence

A silicone prosthesis for covering a large tracheal defect in patients who underwent surgery for locally recurrent aggressive thyroid cancer.

Following the usual sleeve or window resection of the trachea, reconstruction of the trachea can be carried out without difficulty in patients with aggressive thyroid cancer. When the cancer recurs locally in those patients, reoperation often yields a large tracheal defect, for which a commercially available tracheostomy cannula or a silicone-tube does not fit. By using a technique in the maxillofacial prosthetic field, it has become possible to make a new type of prosthesis which is more comfortable and acceptable to the patients with a large tracheal defect. A new type of silicone rubber prosthesis is made individually from the mold of each patient. Several appointments are required for adjustments by the chair side. It must tightly obstruct the tracheostomy stoma so that the patient can easily breathe, speak and take oral fluids. Patients can easily remove and replace this device by themselves and care of the prosthesis is easy. The practical use of this type of prosthesis in three patients is reported herein.

Adenocarcinoma

Effect of 22R-hydroxycholesterol on the action of sphingomyelinase from Bacillus cereus toward bovine erythrocytes.

The incorporation of 22R-hydroxycholesterol [(22R)-5-cholestene-3 beta,22-diol] into the bovine erythrocyte membranes remarkably enhanced the degradation of sphingomyelin in erythrocyte membranes by the action of sphingomyelinase from Bacillus cereus, causing much faster hemolysis of erythrocytes. The stimulative effect of 22R-hydroxycholesterol on the breakdown of sphingomyelin was maximal in the presence of Mg2+. On the other hand, in spite of the presence of 22R-hydroxycholesterol, the breakdown of sphingomyelin was inhibited by increasing concentrations of Ca2+. Also, the incorporation of 22R-hydroxycholesterol into the erythrocyte membranes facilitated the specific adsorption of the enzyme onto the surface of the erythrocyte membranes. The specific adsorption of sphingomyelinase amounted to 20-40% of the total activity in the presence of Mg2+ and the absence of divalent metal ions. In the presence of Ca2+, the incorporation of 22R-hydroxycholesterol enhanced the enzyme adsorption, exceeding more than 90% of the total activity. Therefore, the incorporation of 22R-hydroxycholesterol into bovine erythrocyte membranes remarkably accelerates the breakdown of sphingomyelin in the presence of Mg2+, and the specific adsorption of sphingomyelinase onto erythrocytes in the presence of Ca2+.

Adsorption

Inhibition of prostaglandin delta 13 reductase activity in rabbit kidney cortex by glutathione disulfide.

t-Butyl hydroperoxide and H2O2-Fe(2+)-EDTA-glutathione system which produces hydroxyl radicals did not affect the 15-hydroxy prostaglandin dehydrogenase activity in rabbit kidney cortex. On the other hand, H2O2-Fe(2+)-EDTA-glutathione system inhibited the prostaglandin delta 13 reductase activity. Mannitol, a scavenger of hydroxyl radicals, had no effect on the inhibitory action of this system, indicating that the effect of H2O2-Fe(2+)-EDTA-glutathione system on the prostaglandin delta 13 reductase may not be due to produced hydroxyl radicals. As a result of further investigation, it was shown that glutathione disulfide, which is synthesized concomitantly with hydroxyl radicals from H2O2-Fe(2+)-EDTA-glutathione, inhibited the prostaglandin delta 13 reductase activity. These results suggest that hydroperoxides and hydroxyl radicals may not be likely candidates for the modulator of the catabolism of prostaglandins in the kidney cortex, and that glutathione disulfide has the potential to modulate the prostaglandin catabolism by affecting the prostaglandin delta 13 reductase activity.

15-Oxoprostaglandin 13-Reductase

The superior cervical ganglion: origin of sympathetic fibers in the facial and hypoglossal nerves in the cat.

Location of superior cervical ganglion (SCG) neurons, sending axons into the facial and hypoglossal nerves, was investigated in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). After wheat germ agglutinin conjugated HRP (WGA-HRP) was injected into these nerves, many retrogradely labeled neurons were found widely in the ipsilateral SCG, particularly around the caudal half of the SCG. These neurons were round or oval in shape and 70-80% of these were medium in size. In fluorescent experiments, fast blue (FB) was used in combination with diamidino yellow (DY). After injections of FB into the facial nerve and DY into the hypoglossal nerve, a few FB-DY double-labeled neurons occurred in the SCG ipsilaterally.

Adrenergic Fibers

Effect of tert-butyl hydroperoxide on cyclooxygenase and lipoxygenase metabolism of arachidonic acid in rabbit platelets.

The effect of tert-butyl hydroperoxide (t-BOOH) on the formation of thromboxane (TX) B2, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid (AA) in washed rabbit platelets was examined. t-BOOH enhanced TXB2 and HHT formation at concentrations of 8 microM and below, and at 50 microM it inhibited the formation, suggesting that platelet cyclooxygenase activity can be enhanced or inhibited by t-BOOH depending on the concentration. t-BOOH inhibited 12-HETE production in a dose-dependent manner. When the platelets were incubated with 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) instead of AA, t-BOOH failed to inhibit the conversion of 12-HPETE to 12-HETE, indicating that the inhibition of 12-HETE formation by t-BOOH occurs at the lipoxygenase step. Studies utilizing indomethacin (a selective cyclooxygenase inhibitor) and desferrioxamine (an iron-chelating agent) revealed that the inhibitory effect of t-BOOH on the lipoxygenase is not mediated through the activation of the cyclooxygenase and that this effect of t-BOOH is due to the hydroperoxy moiety. These results suggest that hydroperoxides play an important role in the control of platelet cyclooxygenase and lipoxygenase activities.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

Effects of fatty acyl-coenzyme A esters on prostaglandin synthesis in rabbit kidney medulla microsomes.

The effects of fatty acyl-coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl-CoA) on the synthesis of prostaglandins (PGs) in rabbit kidney medulla microsomes were examined. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the formed PGE2, PGF2 alpha and PGD2 were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce PGE2 mainly. The addition of fatty acyl-CoA esters inhibited total PG formation (the sum of PGE2, PGF2 alpha and PGD2) in a dose-dependent manner. Palmitoyl-, stearoyl- and oleoyl-CoA were about 10 times more potent than linoleoyl- and arachidonoyl-CoA as inhibitors of total PG formation. Linoleic acid was slightly more effective than linoleoyl-CoA, while palmitic acid had no influence on PG formation. All the fatty acyl-CoA esters inhibited the formation of PGE2. Simultaneously, the production of PGF2 alpha and PGD2 was increased. These results suggest that the CoA derivatives of palmitic, stearic and oleic acids have the potential to modulate PGE2, PGF2 alpha and PGD2 synthesis by affecting the activities of both-cyclooxygenase and endoperoxide E2 isomerase.

Acyl Coenzyme A

Experimental study on adrenal autografts in rats to preserve normal adrenocortical function after bilateral adrenalectomy.

In order to establish a technique for successful adrenal tissue autotransplantation, we conducted an experimental study with rats, in which we investigated the effects of the total amount of grafted tissue and the size of each graft piece. Three 'amount' factor levels (1/4 of a gland and 1 and 2 glands) and two 'size' factor levels (1-mm3 fragments and a paste-like mince) were studied. The total amount of grafted adrenal tissue affected the amount of steroid secreted. Autografting of 1/4 of a gland resulted in corticosterone secretion at the normal basal level, but grafting of more than 1 gland enabled the rats to withstand stress better. The take of the grafts with the two different size levels did not differ.

Adrenal Glands

[Formation and removal of active oxygen species and lipid peroxides in biological systems].

The mechanisms of formation and removal of active oxygen species and lipid peroxides in biological systems have been briefly reviewed. Cytotoxic active oxygen species can be classified into two types: (a) radical species such as O2-. (superoxide) and HO. (hydroxyl radical) and (b) non-radical species such as H2O2 (hydrogen peroxide) and 1O2 (singlet oxygen). The direct or indirect attack of active oxygen species on polyunsaturated fatty acids, essential constituents of biological membranes, has been shown to result in the formation of a number of peroxidative lipid breakdown-products: LOOH (lipid hydroperoxide), LOO. (lipid peroxyl radical) and LO. (lipid alkoxyl radical). The lipid peroxide decomposition is probably dependent on the presence of ferric-ferrous ions. These processes are called lipid peroxidation reactions. In recent years, there has been a renewed interest in the role played by lipid peroxidation in many disease states. The multiple lines of defense against toxic oxygen intermediates consist of enzymatic systems, glutathione peroxidase, catalase and superoxide dismutase, and furthermore involves antioxidant capacities such as those of vitamin E and vitamin C. In biological systems, there are naturally occurring lipid-soluble (vitamin E and ubiquinone) and water-soluble (vitamin C, reduced glutathione and uric acid) antioxidants. Therefore, so long as homeostasis is maintained between the rate of radical generation and the rate of radical dissipation, the cellular generation of radicals may not be harmful. In contrast, this balance can be disturbed if cellular defenses are decreased or if there is a significant increase in the flux of radical generation. Once lipid peroxidation is initiated, the reactive intermediate formed induces cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Serum intact parathyroid hormone concentration measured by a two-site immunoradiometric assay in normal subjects and patients with various parathyroid disorders.

Serum intact parathyroid hormone (PTH) concentration was measured by a two-site immunoradiometric assay (IRMA) in normal subjects and patients with various parathyroid disorders. Serum intact PTH levels were all within the detection limit of the IRMA in normal subjects, and there was a significant negative correlation between serum calcium (Ca) and intact PTH levels. Although 3 out of 26 patients (11.5%) with primary hyperparathyroidism had a normal serum intact PTH concentration, these patients could be readily discriminated from normal subjects by plotting serum intact PTH against the serum Ca concentration. In contrast, serum intact PTH was undetectable in 16 out of 17 patients (94.1%) with idiopathic hypoparathyroidism. Patients with pseudohypoparathyroidism (PHP) type I, mostly under treatment with active vitamin D, exhibited wide distribution of serum intact PTH concentration, and appeared to belong to two distinct subgroups. One group of patients demonstrated a similar relationship between serum intact PTH and Ca levels to normal subjects. The other exhibited much higher serum intact PTH levels despite a normal serum Ca concentration, and no obvious relationship could be observed between the two parameters. These results demonstrate that an inverse relationship between serum Ca and intact PTH can be demonstrated in normal subjects with normocalcemia, that most of the parathyroid disorders can be diagnosed by measuring serum Ca and the intact PTH concentrations simultaneously, and that patients with PHP can be divided into two subgroups: one with a normal relationship between serum Ca and intact PTH, and the other with a high serum PTH level in the face of normocalcemia.

Adolescent

Calcitonin release from medullary thyroid carcinoma by thyrotropin-releasing hormone: comparison with calcium injection.

The effects of thyrotropin-releasing hormone on the release of calcitonin were investigated in 15 normal subjects and 12 patients with medullary thyroid carcinoma. The present study also compared the effect of TRH stimulation with calcium infusion test on calcitonin release in patients with medullary thyroid carcinoma. In normal subjects, calcitonin increased from a basal value of 7.5 +/- 2.5 pmol/l to a peak value of 9.4 +/- 3.0 pmol/l (p less than 0.01) after iv injection of synthetic TRH (500 micrograms). Basal calcitonin values in patients with medullary thyroid carcinoma were high (1216 +/- 2230 pmol/l, p less than 0.05), and TRH induced a further increase in calcitonin to 1842 +/- 3149 pmol/l in all the patients (p less than 0.05). They had a peak value of 7891 +/- 13,528 pmol/l after the calcium infusion, which was significantly higher than the basal value of 1463 +/- 2630 pmol/l (p less than 0.05). All medullary thyroid carcinoma patients displayed a marked calcitonin increase after TRH and calcium stimulation. Although the increase in serum calcitonin after TRH injection was lower than that after calcium injection (1.6-fold vs 5.4-fold, p less than 0.05), there was no significant difference in mean peak calcitonin value following TRH and calcium injection in patients with medullary thyroid carcinoma. These results indicated that TRH could stimulate calcitonin release from the thyroid C-cells in both normal subjects and patients with medullary thyroid carcinoma.

Adult