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Biomedical subjects

T Katagiri

Publications and source records attributed to T Katagiri.

At least 127 records · Page 7Linked to original sources
PubMed1998

Correlation between myocardial blood flow and fasting glucose metabolism in ischemic heart disease. Quantitative assessment by nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose positron emission tomography.

Ischemic myocardium avidly incorporates fluorine-18 fluorodeoxyglucose (F-18 FDG) in the fasting state, in contrast to the relative absence of F-18 FDG uptake in normal myocardium with sufficient blood flow in the fasting state. Although many studies have attempted to use F-18 FDG uptake to discriminate ischemic but viable myocardium from scarred myocardium, little is known clinically about the correlation between blood flow and F-18 FDG uptake in ischemic myocardium. We studied the critical level of blood flow that causes avid F-18 FDG uptake in myocardium in 9 patients. All patients had angiographically proven ischemic heart disease but no diabetes. Regional myocardial blood flow (RMBF) was measured quantitatively by positron emission tomography (PET) using nitrogen-13 ammonia in the resting state, in which the normal value was 80.2 +/- 13.0 ml/min/100 cm3. The F-18 FDG uptake in myocardium was assessed with the differential uptake ratio (DUR) scale. We constructed circumferential profiles of radioactivity uptake in myocardium for each study, and chose 780 sections of myocardium in which the relation between the two factors could be analyzed. In moderately ischemic to normal myocardium with RMBF of 50 to 90 ml/min/100 cm3, RMBF and F-18 FDG uptake were negatively correlated (r = -0.44, p < 0.01). When RMBF was 50 to 60 ml/min/100 cm3 (n = 121), the peak DUR value of F-18 FDG uptake was 4.0 +/- 2.0. The two factors were not correlated when RMBF was less than 50 ml/min/100 cm3 or 90 ml/min/100 cm3 or higher. Our results suggest that RMBF and F-18 FDG uptake values as measured with PET may provide valuable information on the possible benefit of intervention in ischemic heart disease.

Aged↗
PubMed1998

Simultaneous evaluations of contractility and energy metabolism of stunned myocardium using 31P magnetic resonance spectroscopy.

A canine model of postischemic myocardial dysfunction (15 min ischemia, 60 min reperfusion) was used to evaluate the relationship between energy metabolism and myocardial contractile function by on-line measurements of ECG, left ventricular pressure, coronary blood flow and regional segment shortening (%SS) with the continuous acquisition of 31PMR spectra. Two groups emerged from these studies; the first (n = 7) in which regional myocardial %SS remained significantly depressed after 60 min of reperfusion (stunned) and the second (n = 5) in which regional %SS returned to control levels after 60 min of reperfusion (non-stunned). Both groups exhibited rapid, similar decreases in %SS and parallel rapid decreases in the phosphocreatine to inorganic phosphate (PCr/Pi) ratio with the onset of ischemia. The PCr/ATP ratio exceeded control levels in the stunned group immediately upon reperfusion and remained significantly above control after 60 min of reperfusion. Measurements of tissue myocardial creatine kinase (CK) revealed a significant decrease in total tissue CK activity in stunned myocardium compared to control. A significant inverse relationship (r = -0.904, p < 0.003) was found between myocardial tissue CK specific activity and the PCr/ATP ratios. We postulate that the elevated PCr/ATP ratio caused by the impairment of energy transfer to the contractile apparatus constitutes a contractile dysfunction in the postischemic heart.

Animals↗
PubMed1998

[Induction of Ph-negative normal clone and long-term survival by combined treatment with G-CSF plus middle dose cytosine arabinoside for patients with chronic myeloid leukemia in blastic transformation].

Three patients with chronic myeloid leukemia (CML) in blastic transformation were treated with G-CSF plus middle dose cytosine arabinoside (Ara-C). G-CSF was administered (150 mg, s.c. or 300 mg, d.i.v./day) 24 hr prior to Ara-C (2-3 g/body, 6 hour d.i.v. for 2-5 days) and continued until the peripheral neutrophil count rose above 1,000/microlitre. As a supplement, VP-16 (80 mg/m2, for 2 days) was administered as warranted to control the growth of blastic cells. All 3 patients survived for more than 12 months with a favorable performance status. Normal karyotypes were detected in 2 of the patients after chemotherapy. One of those patients in paticular demonstrated normal bone marrow findings with the almost complete disappearance of the Ph-positive clone. In vitro cultures of peroxidase-negative CML blastic cells revealed that G-CSF stimulated the induction of blastic cells into the cell cycle and that blastic cell apoptosis was more pronounced in cells cultured with G-CSF plus Ara-C than with G-CSF or Ara-C alone. G-CSF plus middle dose Ara-C therapy appears to be a strong candidate for the treatment of CML in blastic transformation with a poor prognosis.

Adult↗
PubMed1998

Multiple possible sites of BRCA2 interacting with DNA repair protein RAD51.

To investigate the biological consequences of aberrant BRCA2 protein during mammary carcinogenesis, we attempted to identify proteins that normally interact with BRCA2. By using a yeast two-hybrid system with a hybrid protein that contained residues 639-1,508 of BRCA2 protein fused to the GAL4 DNA-binding domain, we isolated five independent cDNA clones that encoded parts of RAD51 protein, a human homolog of bacterial RecA. In vitro experiments using anti-RAD51 antibody confirmed interaction of BRCA2 with RAD51. The RAD51-binding region of BRCA2 detected in the present study was distinct from the region reported recently. Further studies using smaller portions of BRCA2 defined at least two additional RAD51-binding domains, residues 982-1,066 and 1,139-1,266. Our results suggest that BRCA2 can interact with RAD51 through multiple sites of BRCA2 and that control of mitotic and meiotic recombination and/or of genomic integrity through binding to RAD51 may be a crucial mechanism by which BRCA2 suppresses abnormal proliferation of mammary cells.

Amino Acid Sequence↗
PubMed1998

[Assessment of myocardial perfusion with second harmonic imaging--using intravenous injection of Albunex and Levovist].

The objection of this study was to determine whether a method of harmonic imaging could improve the myocardial contrast after injection of Albunex and Levovist. Two dogs were imaged harmonic mode from transdiaphragm approach (transmit at 2.5 MHz and received at 5.0 MHz). Albunex (0.22 ml/kg) and Levovist (400 mg/ml x 2 ml) was injected intravenously for each dog. Venous injection of Albunex coupled with harmonic imaging produced only coronary flow. Venous injection of Levovist coupled with harmonic imaging produced myocardial opacification. It is possible that venous injection of Levovist coupled with harmonic imaging method will also useful in studying myocardial perfusion.

Albumins↗
PubMed1998

Molecular cloning of a novel interferon regulatory factor in Japanese flounder, Paralichthys olivaceus.

A complementary DNA library was constructed in lambda ZAP II using messenger RNA from the leukocytes of some heterocloned Japanese flounder, Paralichthys olivaceus, that had been artificially infected with Hirame rhabdovirus (HRV). A cloned flounder interferon regulatory factor (designated fIRF) cDNA was found to be 1746 bp in length, with an open reading frame of 297 amino acids. The overall amino acid sequence of fIRF had approximately 40% identity with the previously reported avian and mammalian IRF-1s and IRF-2s. The fIRF sequence was most similar to that recorded for the chicken IRF-1. Amino acid sequence identities between the DNA-binding domain of the fIRF and that of both chicken IRF-1 and chicken IRF-2 were 72.3%. The DNA-binding domain of fIRF contained the repeated tryptophan motif that is characteristic of members of the IRF family. The mRNA of fIRF was detected in various tissues by reverse transcription-polymerase chain reaction (RT-PCR). The fIRF was transcribed mainly in the intestine, ovary, muscle, liver, heart and spleen, while it was minimally transcribed in the brain and kidney. When Japanese flounder were injected with HRV, the relative expression of fIRF mRNA was found to increase and peak 3 days after injection. The quantities of the fIRF mRNA increased to levels that were 7.5-fold higher than those of noninjected fish. In addition, when Japanese flounder were injected with Edwardsiella tarda, the expression of fIRF mRNA showed increases 2, 3, and 4 days after injection. The quantities of the fIRF mRNA on those days represented approximately 6-, 15-, and 14-fold increases, respectively, over the levels in noninjected fish.

Amino Acid Sequence↗
PubMed1998

[A case developing tetraplegia due to systemic lupus erythematosus which was remitted by a steroid].

The case reported here was a 58-year-old woman who was diagnosed as having systemic lupus erythematosus (SLE) in 1985 because she had erythema in the cheeks arthritis, a hematological abnormality (decreased white blood cell count), an immunological abnormality (LE-positive cells), and a positive result of antinuclear antibody test. Although the patient was once remitted by treatment with prednisolone (PSL) at 60 mg/day, and continuously received PSL at a maintenance dose of 2.5 mg/day, she was admitted in June 1996 by our hospital with chief complaints of fever and decreased muscular strength in the four extremities. At admission, she had symmetrical tetraplegia, which was peripherally predominant and severer in the lower extremities, and hypoesthesia accompanied by numbness. She was negative for anti-phospholipid antibody and showed no abnormality in cerebrospinal fluid examination. No lesions responsible for tetraplegia were detected at brain MRI, spinal MRI, or myelography. Because fever, multiple arthralgia, an increased erythrocyte sedimentation rate, a decreased lymphocyte count, hypocomplementemia, and a high immune complex level indicated the active stage of SLE (recurrence), she was given PSL at dose increased to 60 mg/day. After about 2 months, SLE was remitted and her tetraplegia and hypoesthesia was gradually improved thereafter. Although tetraplegia associated with peripheral nervous disorder, in which angitis occurring as a symptom of the active stage of SLE was thought to be Involved, was remitted by a steroid in out patient, no such cases have been reported in Japan, to our knowledge. Thus our patient was thought to be a very rare case of value.

Anti-Inflammatory Agents↗
PubMed1997

SHP-1 is involved in neuronal differentiation of P19 embryonic carcinoma cells.

Accumulating evidence suggests that tyrosine phosphorylation plays an important role in the development of the central nervous system and in the differentiation of neuronal cells. To identify protein tyrosine phosphatases (PTPs) that might regulate signaling events leading to neuronal cell differentiation, we cloned PTP genes from the murine P19 embryonic carcinoma cell line and examined the change of their expression during differentiation. P19 cells are known to be pluripotent and the aggregate formation and subsequent replating in the presence of retinoic acid (RA) induce growth arrest and neuronal differentiation. The results demonstrated that among several PTP genes expressed in P19 cells, a cytosolic Src homology region 2 domain-containing PTP, SHP-1, is expressed highly in undifferentiated P19 cells, but is reduced to an undetectable level at day 3 after replating in the presence of RA. Further, SHP-1 was tyrosine-phosphorylated and activated at day 1 after replating. When ectopic SHP-1 was constitutively expressed, P19 cells continued to proliferate and failed to differentiate upon stimulation with RA. Collectively, these results suggest that the regulated expression and activity of SHP-1 may be involved in the neuronal differentiation of P19 cells.

Animals↗
PubMed1997

Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts.

Bone morphogenetic protein-2 (BMP-2) inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A., and Suda T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the possible involvement of Smad proteins, vertebrate homologues of Drosophila Mothers against decapentaplegic, in the BMP effects on the differentiation of C2C12 myoblasts. C2C12 cells expressed Smad1, Smad2, Smad4, and Smad5 mRNAs, and expression levels were not altered by treatment with BMP-2 or TGF-beta1. When Smads were transiently transfected into C2C12 cells, both Smad1 and Smad5 induced alkaline phosphatase (ALP) activity and decreased the activity of myogenin promoter/chloramphenicol acetyltransferase (myogenin-CAT) without BMP-2. When C-terminal-truncated Smad1 and Smad5 were transfected into constitutively active BMP receptor type IB (BMPR-IB)-expressing C2C12 cells, BMP signals were blocked, resulting in an increase in myogenin-CAT activity. On the other hand, Smad1 and Smad5 decreased myogenin-CAT activity but did not induce ALP activity in MyoD-transfected NIH3T3 fibroblasts. These results suggest that both Smad1 and Smad5 are involved in the intracellular BMP signals which inhibit myogenic differentiation and induce osteoblast differentiation in C2C12 cells, and that the conversion of the two differentiation pathways is regulated independently at a transcriptional level.

Animals↗
PubMed1997

Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand in C2C12 myoblasts.

Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-beta superfamily, inhibits the terminal differentiation of C2C12 myoblasts and changes their differentiation pathway into cells expressing osteoblast phenotypes such as alkaline phosphatase (ALP) activity and osteocalcin production (Katagiri et al., 1994, J. Cell Biol. 127, 1755-1766). Two type I receptors for BMP-2 (BMPR-IA and BMPR-IB) have been cloned, but the role of the respective receptors in signal transduction is not clear. In the present study, we examined the signal transduction of BMP-2 in C2C12 cells using constitutively activated mutant BMPR-IA and BMPR-IB. C2C12 cells expressed BMPR-IA and BMPR-II mRNAs, but not BMPR-IB mRNA at detectable levels in Northern blotting. When mutated BMPR-IA and BMPR-IB were transiently transfected into C2C12 cells, both BMPR-IA and BMPR-IB similarly induced ALP activity in the absence of BMP-2. We also established subclonal cell lines of C2C12 cells by stably transfecting mutated BMPR-IB. When the mutated BMPR-IB-transfected cells were cultured in medium with low serum (differentiation medium) without BMP-2, the cells differentiated into ALP-positive mononuclear cells and not into myosin heavy chain-positive myotubes. These mutated BMPR-IB-transfected cells expressed ALP activity and osteocalcin mRNA in a time-dependent manner, but neither muscle creatine kinase nor myogenin mRNAs. These results indicate that the mutated BMP-2 type I receptors can constitutively transduce BMP-2 signals in the absence of the ligand in C2C12 cells.

Alkaline Phosphatase↗
PubMed1997

Suppression of autoimmune disease and of massive lymphadenopathy in MRL/Mp-lpr/lpr mice lacking tyrosine kinase Fyn (p59fyn).

MRL/Mp-lpr/lpr (MRL/lpr) mice suffer from a generalized autoimmune disease that includes autoantibody production and glomerulonephritis and develop massive lymphadenopathy characterized by an expanded population of CD4- CD8- B220+ T cells that is derived from autoreactive T cells in the periphery. Some of us previously reported that these atypical T cells overexpressed a gene for tyrosine kinase p59fyn (Fyn). To define the role of Fyn in the renal disease and lymphadenopathy in MRL/lpr mice, we have generated Fyn-deficient MRL/lpr mice whose fyn gene is replaced by the gene for beta-galactosidase. Fyn-deficient MRL/lpr mice developed markedly limited disease and lived more than twice as long as the conventional MRL/lpr mice. In the mutant mice, the production of IgG3 anti-DNA autoantibody was significantly (p < 0.005%) reduced, and glomerular deposits of IgG3 and C3 were remarkably diminished. Ag receptor-mediated proliferative responses of Fyn-deficient splenic T cells were markedly impaired. The mutant mice showed delayed accumulation of the atypical CD4- CD8- B220+ T cells that exhibited a significantly lower activity of ZAP-70 compared with those in the conventional MRL/lpr mice. These data demonstrated that Fyn is involved as a positive regulator in the disease of MRL/lpr mice. Fyn provides a signal for both the expansion of autoreactive T cells and the production of IgG3 anti-DNA autoantibody by B cells. Thus, manipulation of Fyn may improve systemic autoimmune disease in humans.

Animals↗
PubMed1997

A kinase domain-truncated type I receptor blocks bone morphogenetic protein-2-induced signal transduction in C2C12 myoblasts.

Members of the transforming growth factor (TGF)-beta superfamily bind the transmembrane serine/threonine kinase complex consisting of type I and type II receptors. Their intracellular signals are propagated via respective type I receptors. Bone morphogenetic protein (BMP)-2, a member of the TGF-beta superfamily, induces ectopic bone formation when implanted into muscular tissues. Two type I receptors (BMPR-IA and BMPR-IB) have been identified for BMP-2. We have reported that BMP-2 inhibits the terminal differentiation of C2C12 myoblasts and converts their differentiation pathway into that of osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A. and Suda, T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the involvement of functional BMP-2 type I receptors in signal transduction in C2C12 cells, which expressed mRNA for BMPR-IA, but not for BMPR-IB in Northern blotting. TGF-beta type I receptor (TbetaR-I) mRNA was also expressed in C2C12 cells. Subclonal cell lines of C2C12 that stably expressed a kinase domain-truncated BMPR-IA (DeltaBMPR-IA) differentiated into myosin heavy chain-expressing myotubes but not into alkaline phosphatase (ALP)-positive cells, even in the presence of BMP-2. In contrast, the differentiation of the DeltaBMPR-IA-transfected C2C12 cells into myotubes was suppressed by TGF-beta1, as in the parental C2C12 cells. BMP-2 did not efficiently suppress the mRNA expression of muscle-specific genes such as muscle creatine kinase, MyoD, and myogenin, nor did it induce the expression of ALP mRNA in the DeltaBMPR-IA-transfected C2C12 cells. In contrast, TGF-beta1 inhibited mRNA expression of the muscle-specific genes in those cells. When wild-type BMPR-IA was transiently transfected into the DeltaBMPR-IA-transfected C2C12 cells, a number of ALP-positive cells appeared in the presence of BMP-2. Transfection of wild-type BMPR-IB or TbetaR-I failed to increase the number of ALP-positive cells. These results suggest that the BMP-2-induced signals, which inhibit myogenic differentiation and induce osteoblast differentiation, are transduced via BMPR-IA in C2C12 myoblasts.

Affinity Labels↗
PubMed1997

Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin.

Bone morphogenetic protein (BMP) is a family of cytokines that induce ectopic bone formation when implanted into muscular tissues. We reported that BMP-2 inhibits the terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A., and Suda, T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the molecular mechanism of the inhibitory effect of BMP-2 on terminal differentiation of myogenic cells. When either MyoD or myogenin cDNA was introduced into C3H10T1/2 (10T1/2) cells with a muscle-specific CAT reporter containing four copies of the right E-box of muscle creatine kinase (MCK) enhancer, the CAT activity was dose-dependently suppressed by BMP-2. Furthermore, BMP-2 inhibited the terminal differentiation of these subclonal 10T1/2 cells that stably expressed MyoD or myogenin into mature myotubes that expressed myosin heavy chain and troponin T. The differentiation of a subclone of the MyoD-transfected NIH3T3 cells into mature muscle cells was also inhibited by BMP-2. BMP-2 induced alkaline phosphatase activity in 10T1/2-derived, but not in NIH3T3-derived MyoD-transfected cells. These cells constitutively expressed exogenous MyoD and myogenin, which were localized exclusively in the nuclei irrespective of the presence and the absence of BMP-2. However, these cells failed to express the mRNAs of endogenous myogenic factors and MCK when cultured with BMP-2. In the electrophoresis mobility shift assay using nuclear extracts of the myogenic cells, MyoD and myogenin bound to the right E-box in the enhancer region of the MCK gene even in the presence of BMP-2. These results suggest that BMP-2 inhibits the terminal differentiation of myogenic cells by suppressing the transcriptional activity of the myogenic factors.

3T3 Cells↗
PubMed1997

Changes in microsomal membrane phospholipids and fatty acids and in activities of membrane-bound enzyme in diabetic rat heart.

Diabetes mellitus is associated with alterations in lipid metabolism and cardiac dysfunction despite an absence of coronary arteriosclerotic changes. To investigate mechanisms of cardiac dysfunction in diabetic cardiomyopathy, we studied the relation between activities of membrane-bound enzymes and surrounding phospholipids in rats with diabetes induced with a single intravenous injection of streptozotocin (65 mg/kg). We found that total phospholipid content of sarcoplasmic reticulum membrane increased significantly 8 weeks after treatment with streptozotocin owing to increases in phosphatidylcholine and phosphatidylethanolamine, a decrease in arachidonic acid, and an increase in docosahexaenoic acid in the early stage of diabetes. Sarcolemmal Na+/K(+)-ATPase activity and the number of receptors decreased in isolated cardiomyocytes of diabetic rats 8 weeks after streptozotocin administration. The Ca2+ uptake of both sarcoplasmic reticulum and mitochondria decreased simultaneously in permeabilized, isolated cardiomyocytes from diabetic rats. The depression of membrane-bound enzyme activities was correlated with alterations in phospholipids, which are closely related to the microenvironment of membrane-bound enzymes and influence intracellular Ca2+ metabolism. Because these changes in phospholipids and fatty acids were reversible with insulin therapy, they are diabetes-specific and might be a cause of cardiac dysfunction in diabetes.

Animals↗
PubMed1997

Immunohistochemical detection of bone morphogenetic protein-2 and transforming growth factor beta-1 in tracheopathia osteochondroplastica.

Tracheopathia osteochondroplastica (TO) is an unusual condition characterized by cartilaginous or bony submucosal nodules in the tracheobronchial tree. Bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-beta 1) are potent inducers for new bone formation. We studied the precise localization of BMP-2 and TGF-beta 1 in two autopsied cases of TO, using immunohistochemical methods. Positive BMP-2 immunoreactivity was detected in numerous mesenchymal cells and chondroblasts lining the nodules in the tracheal submucosa. BMP-2 was not found in mature lamellar bony nodules. TGF-beta 1 was not seen in mesenchymal cells, though it did appear in chondrocytes and osteocytes in the nodules. These results suggest that BMP-2 plays an important role in nodule formation and acts synergistically with TGF-beta 1 to promote the nodules inductive cascade in the tracheal submucosa.

Aged↗
PubMed1997

Spontaneous lesions of nasal cavity in aging F344 rats and BDF1 mice.

The outline of spontaneous lesions of the nasal cavity that were commonly observed in F344 rats and BDF1 mice used as untreated control groups in ten 2-year carcinogenicity studies were presented. In rats, the common spontaneous lesions were eosinophilic change of the respiratory epithelium and the olfactory epithelium, respiratory metaplasia of glands and the olfactory epithelium, foreign body inflammation, deposit of calcium, and thrombus. In mice, the common spontaneous lesions were eosinophilic change of the respiratory epithelium and olfactory epithelium, and respiratory metaplasia of glands and the olfactory epithelium. Some of these lesions revealed either species or sex-related differences of incidence.

Aging↗