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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 883 records · Page 49Linked to original sources

Correlation between stable E-rosette formation and induction of alloantigen specific MLR suppressor cells in human mixed lymphocyte culture.

The induction kinetics of human suppressor cells in unidirectional mixed lymphocyte culture (MLC) and the E-receptor of the suppressor cells were studied. Suppressor cell function was measured by the degree of suppression of mixed lymphocyte reaction (MLR). MLR suppressor cells appeared 3 days after priming MLC was started, and maintained the same suppressive effect until the 11th day. These suppressor cells were allo-antigen specific and resistant to x-irradiation up to 1000 rad, but susceptible to 1500 rad or to mitomycin C treatment. MLR suppressor cells which were obtained from priming MLC after 3 to 8 days formed rosettes with sheep erythrocytes at 37 degrees C.

Epitopes↗

Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl type 2 chain polylactosamine.

The quantity of tumor-associated antigens carrying type 2 chain polylactosamines with four types of fucosyl determinants, LeX (X-hapten), poly-LeX, sialyl LeX, and LeY (Y-hapten), present in sera of patients with various malignant and non-malignant disorders, as well as the qualitative chemical properties of the carrier molecules in sera, have been investigated using four monoclonal antibodies, each of which defines one of these determinants. The following findings are of particular importance: the serum levels of LeX defined by antibody FH2 and poly-LeX defined by ACFH18 in patients with cancer were occasionally high (incidence about 10%); however, the majority of patients did not show elevated levels; the serum level of the antigen, defined by monoclonal antibody FH6 (termed sialyl LeX-i since this determinant is carried by i antigen), was significantly high in patients with cancers originating from organs from which adenocarcinomas often develop. For example, among various types of lung cancer, only adenocarcinoma but not squamous cell carcinoma, small cell carcinoma, or large cell carcinoma showed a high level of sialyl LeX-i antigen in sera. The incidence of high antigen levels in sera of patients with adenocarcinomas of lung was as high as 76% of the observed cases; the serum level of Ley (Y-hapten) was frequently high in patients with hepatoma (incidence, 34%); sialyl LeX-i antigen was separated on gel filtration as a glycoprotein with an average molecular weight greater than 10(6). It was characterized by its susceptibility to basehydrolysis, Pronase digestion, and sialidase and endo-beta-galactosidase treatment and is assumed to be a high molecular weight mucin-type glycoprotein; sialyl LeX-i antigen expressed in sera of patients with cancer was soluble in perchloric acid, while the same antigen in sera of patients with noncancerous diseases and normal subjects was mostly insoluble in perchloric acid. LeX, a poly-LeX, and essentially all LeY antigens in sera of patients with cancer were perchloric acid-insoluble.

Antibodies, Monoclonal↗

[Combination chemotherapy with etoposide, mitomycin C, and cyclophosphamide in advanced non-small cell lung cancer].

Forty-three patients with advanced non-small cell lung cancer were treated with a combination chemotherapy regimen comprising etoposide 100 mg/m2 p.o. days 1-5, mitomycin C 10 mg/m2 i.v. day 1 and cyclophosphamide 500 mg/m2 i.v. day 1, every 4 weeks. The median age was 61, and the median initial PS-2. Fourteen patients had received prior therapy. The response rates in previously untreated patients were 25% (5/20) for adenocarcinoma, 0% (0/4) for squamous cell carcinoma, 0% (0/3) for large cell carcinoma, and 18.5% (5/27) for all patients. There were no responders among the pretreated patients. The median survival time was 7 months for previously untreated patients, 4 months for pretreated patients and 6 months for all patients. Patients with adenocarcinoma survived significantly longer (8 months) than those with squamous cell carcinoma (4 months) and large cell carcinoma (3 months). Toxicity consisted of leukopenia (74%), anemia (74%), nausea or vomiting (55%) and alopecia (94%).

Adenocarcinoma↗

Possible mechanisms of elevation of serum secretory immunoglobulin A in liver diseases.

In order to investigate possible mechanisms of elevation of serum secretory immunoglobulin A (sIgA) in liver diseases, human liver specimens were applied to immunohistochemical study of immunoglobulin A, secretory component, and J chain, which are components of sIgA. In the cases of chronic hepatitis with high serum sIgA levels, these antigens were present in dilated bile canaliculi of hepatocytes and they were continuously stained on the lateral plasma membrane of hepatocytes from the bile canaliculus to the space of Disse over the junctional complexes. Furthermore, in liver cirrhosis and extrahepatic cholestasis, they were also detected in intraportal bile ductules and intercellular spaces of degenerated cholangiocytes. These results suggest that at least two pathways might allow elevation of serum sIgA: through the communication of the bile canaliculus with the space of Disse over junctional complexes and through the bile ductule into the portal blood vessel.

Bile Canaliculi↗

Immunohistochemical studies on structural changes of the hepatic lobules in chronic liver diseases.

Liver biopsy specimens were examined immunohistochemically to clarify structural changes of the hepatic lobules in chronic liver diseases. In normal liver carbohydrate antigen 19-9 was located in the biliary ductular epithelium, whereas factor VIII-related antigen was observed in the endothelium of portal veins, hepatic arteries, and central veins. This antigen was not detected in the sinusoidal endothelium. In contrasts, monoclonal antibody OKM5 was reactive with the sinusoidal endothelium but was unreactive with the endothelium of the portal blood vessels or central veins. In chronic active hepatitis and liver cirrhosis, both carbohydrate antigen 19-9 positive biliary ductular cells and factor VIII-related antigen positive endothelial cells were not only observed in the enlarged portal area but also extended into the parenchyma. They were occasionally accompanied by fibers. These findings suggest that fibrosis, ductular epithelial, and blood vascular proliferation in the portal space and their invasion into the parenchyma might gradually cause structural changes of the hepatic lobules in chronic liver disease.

Antigens↗

[Study on the clinical application of plasma and tissue carcinoembryonic antigen to cases with bile duct carcinoma].

Plasma CEA (P-CEA) in 50 cases with bile duct carcinoma and tissue CEA (T-CEA) detected by PAP method in 46 resected cases with carcinoma were examined. The mean level of P-CEA was 4.4 +/- 0.6 ng/ml and the positive rate was 68%. It was considered that a factor of vessel invasion was closely related to the increasing factor of P-CEA. Concerning the relationship between P-CEA and prognosis of the patient, the level of P-CEA seemed to be useful as a parameter of recurrence of carcinoma during the follow up periods. T-CEA in the cancerous lesion was positive in 76%. There were no relations between the histology of the carcinoma and the ability to produce CEA. Conclusively, the histological type invasion of the carcinoma was detected clearly and easily by using the PAP method for T-CEA. To examine the T-CEA in the resected margin seemed to be useful as an additional diagnostic method for carcinoma in the residual bile duct.

Adult↗

Intraluminal fibrosis in interstitial lung disorders.

The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are involved. Under these circumstances, intraluminal organization can mediate the fusion of adjacent alveolar structures by intraluminal connective tissue.

Alveolitis, Extrinsic Allergic↗

Electron microscopic analysis of amacrine and bipolar cell inputs on Y-, X-, and W-cells in the cat retina.

In the cat retina, bipolar and amacrine cell inputs were analyzed electron microscopically in 5 ganglion cells (two Y-cells, two X-cells and one W-cell) that were well-isolated and had clear morphological features. For Y- and X-cells, subtypes of a and b were further identified according to the sublamina of the inner plexiform layer in which their dendrites extended. Y-a and Y-b ganglion cells had large somas, thick axons, and several thick dendrites that branched extensively with a large dendritic field. X-a and X-b cells had medium-sized somas, medium-sized axons and extremely narrow dendritic fields. The W-cell studied had a medium-sized soma, a medium-sized axon, and extremely thin dendrites that extended widely. For each of the 5 ganglion cells, ultrathin serial sections were made to study relative occurrence of amacrine and bipolar synapses in whole length of dendrites. About 50% of the terminals were bipolar in the Y-a and Y-b cell dendrites, 36-38% in the X-a and X-b cell dendrites, whereas only 19.7% were bipolar in the W cell dendrites. Bipolar terminals tended to make synaptic contacts with the distal dendrites of Y- and W-cells.

Animals↗

Metabolism of 2-oxoaldehydes in yeasts. Purification and characterization of lactaldehyde dehydrogenase from Saccharomyces cerevisiae.

NAD-dependent lactaldehyde dehydrogenase, catalyzing an oxidation of lactaldehyde to lactate, was purified approximately 70-fold from cell extracts of Saccharomyces cerevisiae with a 28% yield of activity. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The relative molecular mass of the enzyme was estimated to be 40 000 on Sephadex G-150 column chromatography and on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme was most active at pH 6.5, 60 degrees C and specifically oxidized L-lactaldehyde to L-lactate in the presence of NAD. The Km values for L-lactaldehyde and NAD were 10 mM and 2.9 mM, respectively. The purest enzyme was extremely unstable and almost completely inactivated during storage at -20 degrees C, pH 7.5. For the reactivation of the enzyme, halide ions such as Cl-, I- and Br- were required.

Aldehyde Oxidoreductases↗

Mode of reinnervation in neonatally denervated lamina of the cat's lateral geniculate nucleus.

Physiological properties of relay cells were studied in the lateral geniculate nucleus (LGN) of neonatally one-eye-removed adult cats. Most of the relay cells recorded from the denervated lamina (lamina A1) were still classifiable into either Y- or X-cells, like those recorded from the non-denervated lamina (lamina A). However, receptive field centers of both Y- and X-cells in the denervated lamina were slightly over twice as large as those of the corresponding classes in the non-denervated lamina. These data indicate that reinnervated relay cells may receive excessive convergent inputs from either Y or X type retinal axons which have grown translaminarly.

Animals↗

Metabolism of 2-oxoaldehyde in yeasts. Purification and characterization of NADPH-dependent methylglyoxal-reducing enzyme from Saccharomyces cerevisiae.

An enzyme catalyzing the reduction of methylglyoxal was isolated from Saccharomyces cerevisiae and its enzymatic properties were analyzed. The enzyme, specifically eluted from a blue-dextran--Sepharose CL-6B column by the substrate, methylglyoxal, was homogeneous on polyacrylamide gel electrophoresis. The enzyme consisted of single polypeptide chain with a relative molecular mass of 43 000. The enzyme was glycoprotein and contained 6.6% carbohydrate. NADPH was specifically required for activity and the Km for NADPH was 2.0 X 10(-7) M. The enzyme was active on various glyoxals such as glyoxal, methylglyoxal (Km = 5.88 mM) and phenylglyoxal (Km = 1.54 mM). The reaction catalyzed by the enzyme was virtually irreversible. The activity was inhibited by sulfhydryl agents and activated by reducing agents such as glutathione. Intermediates in glycolysis, nucleosides, nucleotides, polyamines and various metal ions showed little inhibitory or activating effects on enzyme activity. Tricarboxylic acids showed a slight inhibitory effect. The activity of the enzyme was strongly inhibited by anionic detergents. The enzyme was rapidly inactivated by incubating with the substrates probably because of the non-enzymatic interaction between glyoxals and NH2 groups in arginine residues in the enzyme. NADP, one of the reaction products, also inhibited the enzyme activity and the Ki for NADP was about 0.07 mM. We tentatively designated the enzyme methylglyoxal reductase.

Alcohol Oxidoreductases↗

Characterization of methylglyoxal synthase in Saccharomyces cerevisiae.

Methylglyoxal synthase in Saccharomyces cerevisiae was purified approximately 300 folds from cell extracts with 20% of activity yield. During purification procedures, polymorphic behaviours of the enzyme were observed. The purified enzyme was homogeneous on polyacrylamide gel electrophoresis and consisted of a single polypeptide chain of Mr = 26,000. The enzyme was most active at pH 9.5-10.5 and strictly specific to dihydroxyacetone phosphate with Km = 3 mM. Phosphoenolpyruvate, glyceraldehyde-3-phosphate, orthophosphate and thiol compounds were potent inhibitors of the enzyme.

Carbon-Oxygen Lyases↗

Axonal projections of X-cells to the superior colliculus and to the nucleus of the optic tract in cats.

Axonal projections of ganglion cells to the superior colliculus (SC) and to the nucleus of the optic tract (NOT) were re-examined physiologically in the cat's retina. Taking care to minimize current spreads around the stimulating electrodes placed in the NOT or the SC, we reached a conclusion that a substantial proportion of X-cells project to the NOT while a small but definite proportion of them project to the SC.

Animals↗

Origin of immature teratoma of the ovary.

Six cases of immature teratoma of the ovary were karyotyped and analyzed for chromosomal heteromorphisms, enzyme polymorphisms, and HLA specificities to determine their mechanism of origin. Three cases were chromosomally abnormal, with karyotypes of 48,XX, +14, +21; 47,XX, +20; and 47,XXX, respectively. The tumors with 48,XX, +14, +21 and 47,XX, +20 karyotypes were heterozygous for chromosomal heteromorphisms which were identical to those of their host and therefore originated from a premeiotic cell or failure of meiosis I. Both had a poor prognosis. The 47,XXX tumor and the three cases with normal karyotypes were homozygous for chromosome heteromorphisms and either homozygous or heterozygous for enzyme and HLA markers and therefore originated from a failure of meiosis II or duplication of a mature haploid ovum. All four had an uneventful postoperative course. These observations show that immature teratomas are like cystic teratomas in having at least three separate mechanisms of origin. However, they are unlike cystic teratomas in having a high proportion with chromosome abnormalities and a high rate of malignant transformation.

Adult↗

Measurement of immunoreactive leukotriene C4 in blood of asthmatic children.

Peptide leukotriene (LT) such as LTC4, LTD4, LTE4 have been considered to be major mediators of immediate type hypersensitivity reaction such as asthma. We have developed a rapid and simple extraction method using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay (i-LTC4). In this extraction method, 91% LTC4 was recovered in a final methanol fraction. The identity was confirmed by the recovery test and by the dilution method. The amount of i-LTC4 in plasma from asthmatic patients was determined by radioimmunoassay after the extraction. The order of the plasma level of i-LTC4 was; severe asthma greater than slight or moderate asthma greater than asthmatic patient without attack greater than healthy adult. The highest level of LTC4 was 0.27 +/- 0.11 pmol/ml in severe asthmatic plasma.

Adult↗