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Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 1,099 records · Page 61Linked to original sources
PubMed1991

[Controversies in early detection of colorectal cancer].

In recent years, a great advance has been brought in an early detection of colorectal cancer, especially early colorectal cancer. But some controversies are present as follows: 1. Mass screening for colorectal cancer. Immunologic tests for fecal occult blood increased the sensitivity and specificity for detecting colorectal neoplasia without a question. However, this screening method has not proven to get the effectiveness in decreasing mortality of colorectal cancer, although a case control study is under way in our department. 2. Adenoma-carcinoma sequence or de nov carcinoma. These two theories on histogenesis of colorectal cancer are on "hot" discussion to be better understood. 3. Strip biopsy for colorectal lesions. This method is now begun to be introduced to apply for small type-II lesions of colon. 4. Others (barium enema or endoscopy, a new method of colonic preparation which replaces Brown's method, tumor marker in colorectal cancer etc.). Today's status and future prospects were made on these matters.

Biomarkers, Tumor↗
PubMed1991

[Manometrical study of the pharynx and the pharyngoesophageal sphincter in patients with polymyositis].

The purposes of this paper are to evaluate degree of dysphagia at the pharyngeal stage of swallowing in patients with polymyositis. A catheter with three diode transducers 5 cm apart was swallowed through the nose into the upper esophagus. Firstly a patient was commanded to drink water of 2 ml at about five second intervals, and the swallowing pressures were recorded on condition that the speed of paper recording and catheter pull-through is the same 1 mm/sec. Secondly the swallowing pressures were recorded on condition that the middle transducer is fixed at the level of the upper esophageal sphincter and the speed of paper recording is 5 mm/sec. Thirdly the resting pressure of upper esophageal sphincter was recorded on the same condition of the first recording. The results were as follows: (1) All eight patients showed extremely low swallowing pressure at the all level of the pharynx compared with healthy men. (2) Four patients showed poor relaxation of the upper esophageal sphincter. (3) The resting pressure of the upper esophageal sphincter was low in seven. In polymyositis manometrical study of the pharynx and the pharyngoesophageal sphincter is a useful method for evaluating swallowing function.

Adult↗
PubMed1990

[A double-blind, cross-over clinical trial of recombinant human G-CSF on neutropenia induced by chemotherapy for non-Hodgkin's lymphoma].

A double-blind, placebo-controlled, cross-over clinical trial of recombinant human granulocyte colony-stimulating factor (rG-CSF), produced by Chinese hamster ovary cells, was conducted in 46 patients receiving intensive chemotherapy for non-Hodgkin's lymphoma. Each patient received 2 cycles of CHOP therapy. rG-CSF (2 micrograms/kg/day) or its placebo was given subcutaneously to each patient for 14 days from 2 days after initiation of the chemotherapy, in a cross-over fashion. rG-CSF significantly increased the absolute neutrophil counts (ANC) at nadir, and reduced the number of days with ANC less than 1,000/mm3 and also the number of days for recovery to ANC greater than or equal to 2,000/mm3. Bone marrow examination showed a significant increase in the number of myeloid cells after rG-CSF treatment. 12 infective episodes were observed during placebo cycles, while 6 infective episodes were observed during rG-CSF cycles. No serious side effects were observed. We concluded that rG-CSF was effective in neutropenia induced by intensive chemotherapy for non-Hodgkin's lymphoma.

Adult↗
PubMed1990

Isolation of a gene for a regulatory 15-kDa subunit of mitochondrial F1F0-ATPase and construction of mutant yeast lacking the protein.

A gene coding for yeast 15-kDa protein, a regulatory factor of mitochondrial F1F0-ATPase, was isolated. The cloned gene was disrupted in vitro and mutant strains that did not contain the 15-kDa protein were constructed by transformation of yeast cells with the disrupted gene. The ATP-synthesizing activity of the mutant mitochondria was the same as that of wild-type cells, suggesting that the 15-kDa protein is not required for mitochondrial oxidative phosphorylation. Collapse of the membrane potential induced ATP-hydrolyzing activity of F1F0-ATPase of the mutant mitochondria but not of normal mitochondria. Activation of the enzyme was also observed during incubation of submitochondrial particles from mutant cells, but not of those from wild-type cells. Thus, it is inferred that the 15-kDa protein supports the action of an intrinsic ATPase inhibitor of the ATP-hydrolyzing activity of the enzyme upon de-energization of mitochondrial membranes.

Amino Acid Sequence↗
PubMed1990

Induction of tumor necrosis factor-alpha and its receptors during differentiation in myeloid leukemic cells along the monocytic pathway. A possible regulatory mechanism for TNF-alpha production.

We examined the characteristics of tumor necrosis factor (TNF) receptors expressed on immature mouse myeloid leukemic cells (M1), M1 cells induced to differentiate into macrophages, and macrophage cells (Mm1 cells) by binding studies with radioiodinated TNF. Scatchard analysis of TNF binding revealed that a single class of high affinity receptor was present and that 750-1,100 receptors were expressed on each immature M1 cell. The number of TNF receptors was increased 1.5-2-fold on differentiated M1 cells and 4-5-fold on Mm1 cells with no change in affinity. The addition of interferon-gamma (IFN-gamma) up-regulated the expression of TNF receptors in differentiated M1 cells and Mm1 cells, while immature M1 cells were insensitive to IFN-gamma. The number of TNF receptors on the differentiated cells was increased 4-5-fold by the treatment with IFN-gamma with no change in the binding constant. The affinity of TNF receptors to human TNF-alpha (Kd = 1.7-2.8 nM) was lower than that to murine TNF-alpha (Kd = 0.2-0.7 nM). The assays for cell growth and [3H]thymidine incorporation suggested that no relation exists between the sensitivity of the cells to TNF-alpha and the number of TNF receptors. Enhancement of TNF-mediated cytotoxicity by the treatment with IFN-gamma did not correlate with increases in the number of TNF receptors. Cytolytic assays using L929 cells demonstrated that the amount of constitutive and lipopolysaccharide (LPS)-induced secretion of TNF-alpha was markedly increased during differentiation. Both the constitutive expression and IFN-gamma-mediated superinduction of TNF receptors, and the constitutive and LPS-induced secretion of TNF-alpha were closely related to the extent of cellular differentiation along the monocytic pathway. The time course of LPS-induced TNF-alpha activity showed a rise-and-decline profile with a peak at 2 h. On the other hand, the time course of the number of cell surface TNF receptors showed a decline-and-rise profile, a mirror image of the TNF-alpha activity time course profile in the supernatant. Anti-TNF-alpha antibody treatment blocked the LPS-induced down-regulation of TNF receptors and increased TNF-alpha mRNA accumulation. We discussed "an autoinhibitory system" in which an internalization of secreted TNF-alpha mediated by its own receptors is involved not only in decreasing TNF-alpha activity in the supernatant but also in reducing TNF-alpha mRNA expression.

Animals↗
PubMed1990

A small GTP-binding protein (G protein) recognized by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G protein in human platelet cytosol.

We have recently purified from bovine brain cytosol a novel type of regulatory protein for smg p25A, named smg p25A GDP dissociation inhibitor (GDI), that regulates the GDP/GTP exchange reaction of smg p25A by inhibiting the dissociation of GDP from and thereby the subsequent binding of GTP to it. This smg p25A GDI is inactive for other ras p21/ras p21-like small GTP-binding proteins (G proteins) including c-Ha-ras p21, smg p21, rhoA p21 and rhoB p20. In human platelet membranes, smg p25A was not detected but a G protein with an apparent Mr value of 24,000 (24KG) was recognized by smg p25A GDI and the dissociation of GDP from and the binding of GTP to 24KG were inhibited by smg p25A GDI. The doses of smg p25A GDI necessary for these activities for both 24KG and smg p25A were the same. This 24KG was not recognized by an anti-smg p25A monoclonal antibody. The GDI activity for human platelet 24KG and smg p25A was detected in human platelet cytosol. This human platelet GDI was recognized by an anti-smg p25A GDI polyclonal antibody. These results indicate that there is a 24KG-24KG GDI system similar to a smg p25A-smg p25A GDI system in human platelets.

Animals↗
PubMed1990

Participation of the peroxisomal beta-oxidation system in the chain-shortening of PCA16, a metabolite of the cytosine arabinoside prodrug, YNKO1, in rat liver.

When PCA16, a metabolite of the cytosine arabinoside prodrug YNKO1, was incubated with isolated rat hepatocytes, time-dependent H2O2 generation was found. When the hepatocytes obtained from clofibrate-treated rat liver were used as an enzyme source, PCA16-dependent production of H2O2 was increased by around 6-fold. The activity of peroxisomal beta-oxidation for PCA16 assayed by H2O2 generation was 3-fold higher than that for palmitic acid, whereas the activity of mitochondrial beta-oxidation for PCA16 assayed by ketone body production was much less than that for palmitic acid. A subcellular distribution study revealed that the distribution of the activities of beta-oxidation and fatty acyl-CoA oxidase for PCA16-CoA coincided with those of cyanide-insensitive palmitoyl-CoA-dependent beta-oxidation and catalase, a marker enzyme of peroxisomes. The profile of the cofactor requirement for beta-oxidation of PCA16-CoA in isolated peroxisomes was similar to that for palmitoyl-CoA oxidation, and the reaction was not inhibited by KCN. The formation of CoA derivative prior to beta-oxidation reaction was essential. HPLC analysis of metabolites after incubation of PCA16-CoA with isolated peroxisomes demonstrated the production of four metabolites, two of which were identified as PCA14 and PCA12 by fast atomic bombardment-mass spectrometry. These results indicate that peroxisomal beta-oxidation participates in the shortening of the alkyl-side chain of PCA16 and plays an important role in the formation of antileukemic cytosine arabinoside from YNKO1.

Animals↗
PubMed1990

Activation of ATP hydrolysis by an uncoupler in mutant mitochondria lacking an intrinsic ATPase inhibitor in yeast.

An intrinsic ATPase inhibitor and 9-kDa protein are regulatory factors of mitochondrial ATP synthase in Saccharomyces cerevisiae. A gene encoding the ATPase inhibitor was isolated from a yeast genomic library with synthetic oligonucleotides as hybridization probes and was sequenced. The deduced amino acid sequence showed that the precursor protein contains an amino-terminal presequence of 22 amino acid residues. Mutant strains that did not contain the inhibitor and/or the 9-kDa protein were constructed by transformation of cells with their in vitro disrupted genes. The disruption of the chromosomal copy in recombinant cells was verified by Southern blot analysis, and the absence of the proteins in the mutant cells was confirmed by Western blot analysis. All the mutants could grow on a nonfermentable carbon source and the oxidative phosphorylation activities of their isolated mitochondria were the same as that of normal mitochondria. However, an uncoupler, carbonylcyanide-m-chlorophenylhydrazone, induced marked ATP hydrolysis in the inhibitor-deficient mitochondria, but not in normal mitochondria. These observations suggest that the ATPase inhibitor inhibits ATP hydrolysis by F1F0-ATPase only when the membrane potential is lost.

Adenosine Triphosphate↗
PubMed1990

Rat liver nuclei protein kinase C is the isozyme type II.

Rat liver nuclei protein kinase C is identified as type II isozyme employing monospecific antibodies obtained against each three types of rat brain protein kinase C isozymes. (Yoshida, Y., Huang, F. L., Nakabayashi, H., and Huang, K-P. (1988) J. Biol. Chem. 263, 9868-9873). A major immunoreactive protein band at 80 kDa was revealed by type II isozyme antibodies at each step of purification, nuclear extract included. The nuclear protein kinase C has been purified to apparent homogeneity as revealed by silver nitrate staining on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showing a single 80 kDa protein band. It does seem that 66 kDa protein (Masmoudi, A., Labourdette, G., Mersel, M., Huang, F. L., Huang, K.-P., Vincendon, G., and Malviya, A. N. (1989) J. Biol. Chem. 264, 1172-1179) is a major contaminant devoid of any protein kinase activity. The ratio obtained between protein kinase C enzymatic activity over phorbol dibutyrate bound, at various purification steps, indicates that the nuclear enzyme is a phorbol ester receptor. When isolated nuclei were incubated with 12-O-tetradecanoyl phorbol-13-acetate, endogenous protein kinase C activity was elevated about 8-10-fold suggesting the existence of phorbol ester signaling pathway at the level of nucleus. The role of nuclear protein kinase C is delineated in the regulation of inducible gene transcription

Animals↗
PubMed1990

Developmental expression of protein kinase C isozymes in rat cerebellum.

Previously we showed that protein kinase C (PKC) isozymes (types I, II, and III) have distinctive neuronal localizations in cerebellum. In the present study, we followed the different appearances of these isozymes during the postnatal development of cerebellum. By immunoblot analysis, type I PKC was found to be low within 2 weeks after birth; an abrupt increase was observed between 2 and 3 weeks and leveled off afterwards. By immunofluorescent staining, the type I PKC-specific antibody recognized the cell bodies and dendrites of Purkinje cells. The increase of this isozyme between 2 and 3 weeks of age correlates with the spreading of Purkinje cell arborization, at which time bulk of synaptogenesis between dendritic spines and axons of granule cells occurs. Both type II and III PKCs were present in granule cells. At birth, the level of type II PKC was relatively high compared to that of type III PKC, and the type II PKC-specific antibody stained the granule cell precursors in the external layer more heavily than did the type III PKC-specific antibody. The level of type II PKC declined slightly after birth and increased again at one week and plateaued after three weeks, whereas that of type III PKC increased gradually until leveling off after three weeks. Throughout the development, the type III PKC-specific antibody also stained the cell bodies of Purkinje cells but not their dendrites. These results demonstrate that the developmental expression of PKC isozymes is under separate control, and their distinct cellular and subcellular localizations suggest their unique functions in the cerebellum.

Aging↗
PubMed1990

Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14 alpha-demethylase (cytochrome P-45014DM): a model study with stereoisomers of triadimenol and purified cytochrome P-45014DM from yeast.

The effect of the four triadimenol stereoisomers on the purified yeast lanosterol 14 alpha-demethylase (cytochrome P-45014DM), the primary target of azole antifungal agents, was studied. (1S,2R)-Triadimenol was the most potent demethylase inhibitor and bound quantitatively to the enzyme below 0.05 microM. This isomer also interfered with the chemical reduction of cytochrome P-45014DM and the binding of CO to the cytochrome. The other isomers showed a lower inhibitory effect on the enzyme, and the order of activity was (1R,2R) greater than (1R,2S) greater than or equal to (1S,2S). Based on these findings and the reported preferred conformations for the triadimenol stereoisomers (Anderson, N.H. et al., Pestic. Sci. 15:310-316, 1984), it is predicted that orientation of the hydrophobic tert-butyl and p-chlorophenyl groups relative to the azole nitrogen is important to fit the antifungal agent in the active site of the demethylase.

Azoles↗
PubMed1990

Elemental analysis of hair among hydrofluoric acid exposed workers.

The concentrations of fluorine (F), sodium (Na), magnesium (Mg), aluminum (Al), potassium (K), phosphorus (P), calcium (Ca), iron (Fe), nickel (Ni), zinc (Zn) and iodine (I) in the hair of 142 hydrofluoric acid (HF) exposed workers and 273 control subjects were analyzed by wavelength dispersive X-ray fluorescence spectrometry. Postshift urine and serum specimens were also collected for the determination of fluoride. To determine whether external contamination influences hair analysis, the control hair samples were kept in the work environment for one week. With the exception of lower K and Fe values, the levels of F and other elements in the hair of HF workers were higher than in the control subjects. The concentrations of F in hair and in postshift urine were in good correlation (r = 0.65). In the hair of HF workers F and Ca, F and Mg, F and P, F and Al were well correlated with each other (r greater than 0.6). F concentration in the hair increased after the sample was retained, however, it decreased to the reference value after washing. The levels of Ca, Mg and other elements did not change during the experiment.

Adult↗
PubMed1990

Regulatory proteins of F1F0-ATPase: role of ATPase inhibitor.

An intrinsic ATPase inhibitor inhibits the ATP-hydrolyzing activity of mitochondrial F1F0-ATPase and is released from its binding site on the enzyme upon energization of mitochondrial membranes to allow phosphorylation of ADP. The mitochondrial activity to synthesize ATP is not influenced by the absence of the inhibitor protein. The enzyme activity to hydrolyze ATP is induced by dissipation of the membrane potential in the absence of the inhibitor. Thus, the inhibitor is not responsible for oxidative phosphorylation, but acts only to inhibit ATP hydrolysis by F1F0-ATPase upon deenergization of mitochondrial membranes. The inhibitor protein forms a regulatory complex with two stabilizing factors, 9K and 15K proteins, which facilitate the binding of the inhibitor to F1F0-ATPase and stabilize the resultant inactivated enzyme. The 9K protein, having a sequence very similar to the inhibitor, binds directly to F1 in a manner similar to the inhibitor. The 15K protein binds to the F0 part and holds the inhibitor and the 9K protein on F1F0-ATPase even when one of them is detached from the F1 part.

Adenosine Diphosphate↗
PubMed1990

Antitumor effect of combination of murine recombinant interferon beta, murine recombinant interferon gamma and human recombinant interleukin-2 in MethA-bearing mice.

We have previously reported that the combination of murine recombinant interferon beta (Mu-rIFN beta) with murine recombinant interferon gamma (Mu-rIFN gamma) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFN beta with Mu-rIFN gamma on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 x 10(3) U or 5 x 10(4) U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 x 10(5) U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 x 10(3) U and 5 x 10(5) U) in addition to the combination of IFN beta and IFN gamma showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFN beta and IFN gamma had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFN beta and gamma was effective for cancer treatment.

Animals↗