Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 19 recordsLinked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

[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↗

PubMed1992

Serum levels of lipids and apolipoproteins in angiographically assessed coronary artery disease in Japanese patients.

Serum total cholesterol (T-CHO), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo A-I, A-II, B, C-II, C-III and E) values were determined in 143 Japanese subjects undergoing coronary angiography. Among the factors measured, T-CHO, TG, apo B and C-III levels were significantly higher in patients with coronary artery disease (CAD) than in those without CAD. The HDL-C/T-CHO ratio was also significantly lower in patients with CAD. Although no parameters show differences between the group without CAD and the group of single vessel disease, T-CHO and apo B were significantly higher in the groups with double and triple vessel disease, and TG and apo C-III were also higher in the group with triple vessel disease compared with the normal group. Furthermore, the HDL-C/T-CHO ratio was significantly lower in the double and triple vessel groups, and HDL-C was lower only in the triple vessel group. The results indicate that changes in these parameters suggest a high likelihood of multiple vessel disease, and that an increase in TG and apo C-III levels is also one of the important indicators for CAD even in Japanese patients.

Aged↗

PubMed1992

[Mechanism to induce scoliosis in Duchenne muscular dystrophy--a study of paraspinal muscle by X-ray computed tomography].

We studied mechanism to induce scoliosis in Duchenne muscular dystrophy (DMD) by use of X-ray computed tomography (CT) of paraspinal muscles. CT examination of paraspinal muscles was performed on 15 DMD patients at the following six levels; 1. Th3 vertebrae (upper thoracic spine level) 2. Th6 vertebrate (middle thoracic spine level) 3. Th10 vertebrae (lower thoracic spine level) 4. L1 vertebrae (upper lumbar spine level) 5. L3 vertebrae (middle lumbar spine level) 6. L5 vertebrae (lower lumbar spine level). We evaluated the degeneration of paraspinal muscle by a decrease in radio-density of the muscle which indicates infiltration of fatty tissue. The degeneration of the lateral portion of paraspinal muscle was more marked than that of the medial portion. The muscle was most severely affected at the middle lumbar spine level, showing a tendency to increase degeneration at the lower level of the spine. In cases showing laterality of the degeneration of paraspinal muscle, the less affected muscle on CT was located at the convex site of scoliosis. We speculate that the scoliosis occurs when DMD patients have asymmetrical paraspinal muscle degeneration, leading them to take compensatory posture.

Adolescent↗

PubMed1992

[A new method of gait analysis in Duchenne muscular dystrophy].

We assessed gait in Duchenne muscular dystrophy (DMD) mainly by determining alteration of foot pressure using a new gait analyzing procedure. DMD patients showed a characteristic foot pressure pattern according to their degree of dysfunction. In stage I disease, the observed pattern was the same as that of normal controls. In stage II, the period during which the center of foot pressure was seen in the front part of the foot was prolonged. This change became more marked in stage III. In stage IV, the center of foot pressure began at the head of the ossis metatarsalis primi and moved back and toward the lateral side. Thereafter, the center of foot pressure again moved forward along the outside of the foot. These changes were considered to be the result of talipes equinus and waddling gait, which are commonly demonstrated in patients with DMD.

Adolescent↗

PubMed1992

The effects of arachidonic acid and its CoA ester on the catabolism of prostaglandin E2 in rabbit kidney cortex.

The effects of arachidonic acid and arachidonoyl CoA on the catabolism of prostaglandin E2 in a 105000 x g supernatant fraction from rabbit kidney cortex were examined. Arachidonic acid reduced the 15-hydroxy prostaglandin dehydrogenase activity by 50% at 20 microM, while arachidonoyl CoA showed weak inhibition for the enzyme activity (15% at 20 microM). However, arachidonoyl CoA strongly inhibited the prostaglandin delta 13 reductase activity, the concentration required for 50% inhibition being about 3 microM. The dehydrogenase inhibition by arachidonic acid was non-competitive with regard to NAD+ and prostaglandin E2, respectively. Arachidonoyl CoA was also a non-competitive inhibitor for the reductase with regard to NADH and 15-keto prostaglandin E2, respectively. These results suggest that arachidonic acid and arachidonoyl CoA can be important modulating factors in prostaglandin catabolism by the kidney cortex.

15-Oxoprostaglandin 13-Reductase↗

PubMed1992

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: experience by a single surgical team in Japan.

Nineteen patients were surgically treated for hyperparathyroidism associated with multiple endocrine neoplasia type 1 syndrome. Fourteen patients (74%) had removal of three or more parathyroid glands at the first operation, and five (26%) by removal of 2 1/2 or fewer glands. Two patients had recurrent hypercalcemia during the mean follow-up period of 65 months. One had a recurrence 10 years after subtotal parathyroidectomy. Reexploration in this patient revealed enlargement of the remaining tissue in the neck and an enlarged supernumerary gland in the aorticopulmonary window. The other patient had persistent hypercalcemia after removal of two hyperplastic parathyroid glands until after another 1 1/2 more glands were removed. After reoperation the patient was normocalcemic for 10 years before hypercalcemia was again noticed. The patient subsequently died from renal carcinoma metastases, which might have been the cause of the hypercalcemia before death.

Adult↗

PubMed1992

[A caruncular oxyphilic adenoma with an appearance of apocrine type secretion].

The histopathological and cytological findings of a caruncular oxyphilic adenoma (oncocytoma) in a 85 year-old male is described. The columnar or polygonal tumor cells contained numerous eosinophilic fine granules (mitochondria). They showed papillary proliferation and cyst formation. Electron microscopically, some tumor cells contained amorphous cytoplasm and small numbers of mitochondria in their apical snout, and secreted the contents in the extracellular spaces. It seemed that the tumor cells originated from the ductal epithelia in the caruncle and microscopically some cells simulated apocrine type secretion.

Adenoma↗

PubMed1992

Acidic tripeptidyl aminopeptidase in rat liver tritosomes: partial purification and determination of its primary substrate specificity.

We have found the enrichment in rat liver tritosomes of an enzyme which hydrolyzed the synthetic substrate, Ala-Ala-Phe-pNA, under acidic conditions. The enzyme cleaved the substrate in an exopeptidolytic manner, releasing Ala-Ala-Phe. The enzyme was solubilized from tritosomes and partially purified. Beside Ala-Ala-Phe-pNA, the obtained enzyme was shown to cleave angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) and des-1Tyr-dynorphin A 1-8 (Gly-Gly-Phe-Leu-Arg-Arg-Ile) with tripeptide units. The results obtained suggested that the enzyme preferred an aromatic amino acid at the third position of a substrate peptide.

Acids↗