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T Suda

Publications and source records attributed to T Suda.

At least 163 records · Page 9Linked to original sources
PubMed2000

[Compensatory growth of residual lung after pneumonectomy in childhood].

Though pneumonectomy proved to be a potent stimulus to compensatory growth in the animal model, the literature on this subject in human patients is sparse. We report a rare case of compensatory growth after pneumonectomy in childhood. A 17-year-old man was admitted to our hospital because of chest pain. He had been capable of normal exercise despite a history of pneumonectomy at the age of 4. Chest radiography showed pneumothorax and a displaced heart. In a chest CT scan, both pleural spaces were filled with the enlarged left lung. Since thoracoscopic examination showed a bulla at the surface of S3, bullectomy was performed. The specimen resected from the lung showed slight dilatation of the alveoli. It is considered that the enlargement of the residual lung had occurred as a result of alveolar multiplication rather than by dilatation of the existing alveoli. This case demonstrates lung regeneration in childhood.

Adolescent↗
PubMed2000

[Continuous hepatic arterial infusion of 5-fluorouracil with leucovorin for unresectable liver metastases from colorectal cancer].

Twenty-three patients with liver metastases from colorectal cancer were treated by continuous hepatic arterial infusion chemotherapy with 5-FU and Leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/body of Leucovorin was administered continuously for 5 days, followed by no medication for 16 days. The effect of this therapy was evaluated and the relationship between this therapy and the overexpression of vascular endothelial growth factor (VEGF) or microvessel density (MVD) was also studied. Complete response was obtained in 4 patients and partial response in 3 patients; the response rate was 32%. The response rate was 60% in patients who underwent more than 7 courses. The response rate was 44% in patients with positive VEGF and 33% in patients with negative VEGF. The response rate was 50% in patients with an MVD of more than 30 and 33% in patients with an MVD of less than 30. The 3-year survival rate for patients who underwent more than 7 courses was 37.5%. This therapy had to be abandoned in 6 patients due to occlusion of the catheter. Skillful maintenance of the catheter is necessary for a high response rate and satisfactory prognosis using this therapy.

Aged↗
PubMed2000

[Safety of and untoward reactions to 23-valent pneumococcal vaccine: a prospective study].

The study objective was to demonstrate the safety of Streptococcus pneumoniae vaccine in 430 geriatric patients at high risk of infection. The reactions after inoculation were classified as follows: (1) Grade 1: slight pain at the site of injection; mild systemic fatigue to improve within 3 days. (2) Grade 2: symptoms of swelling, erythema, or pain lasting for more than 3 days; inability to move upper limb due to pain; systemic symptoms such as a temperature above 38 degrees centigrade. (3) Grade 3: reactions requiring immediate medical therapy. Seventy patients (16.3%) showed inoculation reactions, and 360 (83.7%) were asymptomatic. Of the symptomatic reactions, 50 (11.6%) were grade 1.17 (4.0%) grade 2, and 3 (0.7%) grade 3. About 5% of the patients with grade 1 and 2 reactions needed special management. One chronic heart failure patient complained of severe heart failure symptoms after inoculation.

Adult↗
PubMed1999

Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor kappaB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms(+)RANK(-)) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms(+)RANK(+)) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK-RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

Animals↗
PubMed1999

Novel association of the src family kinases, hck and c-fgr, with CCR3 receptor stimulation: A possible mechanism for eotaxin-induced human eosinophil chemotaxis.

The chemokine eotaxin is a potent and relatively eosinophil-specific chemoattractant implicated in the cell migration to inflammatory sites in allergic diseases. Eotaxin exerts its activity solely through the CCR3 receptor, but the signaling pathways are poorly defined. In this study, we show that eotaxin induces an increase in tyrosine phosphorylation of multiple cellular proteins in normal human eosinophils. Eotaxin-dependent tyrosine phosphorylation was detected 1 min after stimulation and increased for at least 15 min with kinetics similar to those of eotaxin-induced cell shape changes. Herbimycin A, a tyrosine kinase inhibitor, blocked both eotaxin-induced tyrosine phosphorylation and cell shape changes as well as chemotaxis. Immunofluorescence microscopy analyses showed that eotaxin-induced cell shape changes were accompanied by redistribution of tyrosine-phosphorylated proteins and F-actin reorganization that were sensitive to herbimycin A. Coimmunoprecipitation studies revealed that binding of eotaxin to CCR3 greatly enhanced association of the Src family kinases, Hck and c-Fgr, with CCR3 after internalization of CCR3. These results may indicate that recruitment of Hck and c-Fgr to CCR3 in a compartment triggers tyrosine phosphorylation, leading to rapid cell shape changes required for cell migration.

Benzoquinones↗
PubMed1999

In vitro effects of angiopoietins and VEGF on hematopoietic and endothelial cells.

To investigate the role of TIE-2/angiopoietins (Angs) in postnatal hematopoiesis, we cultured bone marrow cells in the presence of Ang-1 and -2 with or without VEGF. While either Ang-1 or Ang-2 alone had hematopoietic effects on unseparated bone marrow cells and no effect on proliferation of endothelial cells, both enhanced the growth of endothelial cells and hematopoietic progenitor cells in the presence of VEGF. FACS analysis showed that Lin(-)TIE-2(+)Flk-1(+) cells cocultured with OP9 stromal cells gave rise to endothelial and hematopoietic cells in the presence of VEGF and Ang-1. Ang-1 promoted the adhesion of sorted primary Lin(-)TIE-2(+) cells to fibronectin, and this adhesion enhanced proliferation of hematopoietic progenitor cells synergistically with stem cell factor (SCF). Our findings suggest that TIE-2/angiopoietins may act as critical regulators of proliferation of hematopoietic progenitors and endothelial cells in a synergistic manner.

Angiopoietin-1↗
PubMed1999

Evidence that physiological levels of circulating leptin exert a stimulatory effect on luteinizing hormone and prolactin surges in rats.

Increasing evidence suggests that leptin, an adipocyte-derived hormone, may positively regulate the reproductive axis, and serve as a critical metabolic signal linking nutrition and the reproductive function. However, along this line there remains an as-of-yet unresolved important issue whether physiological levels of circulating leptin exert a stimulatory effect on the reproductive axis. It is also unknown whether hyperleptinemia affects the reproductive function. In this study, we attempted to examine these unexplored issues, employing as an indicator the estradiol/progesterone-induced luteinizing hormone (LH) and prolactin (PRL) surges in ovariectomized female rats. Experiments were performed on normally fed, 3-day starved, 3-day starved + murine leptin (100 microg/kg/day), and normally fed + murine leptin (300 microg/kg/day) groups. Leptin was administered utilizing osmotic minipumps during 3 days immediately before experimentation. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation completely abolished both LH and PRL surges, but 3-day starved + leptin (100 microg/kg/day) group, whose plasma leptin levels (3.7 +/- 0.4 ng/ml) were similar to those in normally fed group (3.4 +/- 0.5 ng/ml), showed a significant recovery of the hormonal surges. On the other hand, the magnitudes of LH and PRL surges in normally fed + leptin (300 microg/kg/day) group, whose leptin levels were 10.8 +/- 1.5 ng/ml, were statistically the same as those in normally fed group. These results indicate for the first time that physiological concentrations of circulating leptin exert a stimulatory effect on the steroid-induced LH and PRL surges in the rat. It was also suggested that mild hyperleptinemia of 3 days' duration may not significantly affect the hormonal surges.

Animals↗
PubMed1999

C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression.

Eosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA-binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.

Base Sequence↗
PubMed1999

Endothelial growth factor receptors in human fetal heart.

BACKGROUND: Endothelial receptor tyrosine kinases include 3 members of the vascular endothelial growth factor receptor (VEGFR) family and 2 members of the angiopoietin receptor (Tie) family. In addition, the VEGF(165) isoform binds to neuropilin-1 (NP-1), a receptor for collapsins/semaphorins. The importance of these receptors for vasculogenesis and angiogenesis has been shown in gene-targeted mice, but so far, little is known about their exact expression patterns in the human vasculature. METHODS AND RESULTS: Frozen sections of human fetal heart were stained immunohistochemically with receptor-specific monoclonal (VEGFR, Tie) or polyclonal (NP-1) antibodies. The following patterns were observed: The endocardium was positive for VEGFR-1, VEGFR-2, NP-1, Tie-1, and Tie-2 but negative for VEGFR-3. The coronary vessels were positive for Tie-1, Tie-2, VEGFR-1, and NP-1 and negative for VEGFR-2 and VEGFR-3. Myocardial capillaries and epicardial blood vessels stained for VEGFR-1, VEGFR-2, NP-1, and Tie-1; myocardial capillaries and epicardial veins weakly for Tie-2; and epicardial lymphatic vessels for VEGFR-2 and VEGFR-3, weakly for Tie-1 and Tie-2, but not for VEGFR-1 or NP-1. CONCLUSIONS: The results demonstrate differential expression of the endothelial growth factor receptors in distinct types of vessels in the human heart. This information is useful for the understanding of their roles in physiological and pathological processes and for their diagnostic and therapeutic application in cardiovascular medicine.

Capillaries↗
PubMed1999

Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3-1alpha-hydroxylase gene in normocalcemic rats.

Regulation of vitamin D metabolism has long been examined by using vitamin D-deficient hypocalcemic animals. We previously reported that, in a rat model of chronic hyperparathyroidism, expression of 25-hydroxyvitamin D3-1alpha-hydroxylase (CYP27B1) mRNA was markedly increased in renal proximal convoluted tubules. It is believed that the major regulator for the expression of renal CYP27B1 is parathyroid hormone (PTH). However, in the normocalcemic state, the mechanism to regulate the renal CYP27B1 gene could be different, since plasma levels of PTH are very low. In the present study, the effect of PTH and calcitonin (CT) on the expression of renal CYP27B1 mRNA was investigated in normocalcemic sham-operated rats and normocalcemic thyroparathyroidectomized (TPTX) rats generated by either PTH or CaCl2 infusion. A single injection of CT dose-dependently decreased the expression of vitamin D receptor mRNA in the kidney of normocalcemic sham-TPTX rats. Concomitantly, CT greatly increased the expression of CYP27B1 mRNA in the kidney of normocalcemic sham-TPTX rats. CT also increased the expression of CYP27B1 mRNA in the kidney of normocalcemic TPTX rats. Conversion of serum [3H]1alpha,25(OH)2D3 from 25-hydroxy[3H]vitamin D3 in vivo was also greatly increased by the injection of CT into sham-TPTX rats and normocalcemic TPTX rats, but not into hypocalcemic TPTX rats. In contrast, administration of PTH did not induce the expression of CYP27B1 mRNA in the kidney of vitamin D-replete sham-TPTX rats and hypocalcemic TPTX rats. PTH increased the expression of renal CYP27B1 mRNA only in vitamin D-deficient hypocalcemic TPTX rats. These results suggest that CT plays an important role in the maintenance of serum 1alpha,25(OH)2D3 under normocalcemic physiological conditions, at least in rats.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

Decreased expression of Th2 type cytokine mRNA contributes to the lack of allergic bronchial inflammation in aged rats.

Sensitized Brown Norway rats are known to develop eosinophilic bronchial inflammation and airway hyperresponsiveness after Ag exposure. However, we have previously observed that sensitized aged rats of the same strain failed to develop such allergic inflammation. In the present study, we investigated age-associated changes of cytokine mRNA expression in bronchoalveolar lavage (BAL) cells. Both young (8- to 10-wk-old) and aged (100- to 120-wk-old) Brown Norway rats were sensitized with OVA, and BAL was performed 24 h after OVA inhalation challenge. Semiquantitative RT-PCR analysis of BAL cells showed that the cells from aged rats preferentially expressed Th1 type cytokine (IFN-gamma) mRNA, whereas cells from young animals expressed more Th2 type cytokine mRNAs including those for IL-4 and IL-5. Decreased expression of Th2 type cytokine transcripts in aged animals was further confirmed by quantitative analysis, competitive RT-PCR of BAL cells, and in situ hybridization. The age-associated changes of cytokine profile were not restricted to BAL cells but were a general feature of lymphocytes, as shown by examination of popliteal lymph nodes draining the site of sensitization. These findings suggest that decreased allergic inflammation in aged animals is attributable to age-dependent impairment of Th2 generation in response to Ag.

Age Factors↗
PubMed1999

Osteoclast differentiation factor acts as a multifunctional regulator in murine osteoclast differentiation and function.

Osteoclast differentiation factor (ODF), a novel member of the TNF ligand family, is expressed as a membrane-associated protein by osteoblasts/stromal cells. The soluble form of ODF (sODF) induces the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. Here, the effects of sODF on the survival, multinucleation, and pit-forming activity of murine osteoclasts were examined in comparison with those of M-CSF and IL-1. Osteoclast-like cells (OCLs) formed in cocultures of murine osteoblasts and bone marrow cells expressed mRNA of RANK (receptor activator of NF-kappaB), a receptor of ODF. The survival of OCLs was enhanced by the addition of each of sODF, M-CSF, and IL-1. sODF, as well as IL-1, activated NF-kappaB and c-Jun N-terminal protein kinase (JNK) in OCLs. Like M-CSF and IL-1, sODF stimulated the survival and multinucleation of prefusion osteoclasts (pOCs) isolated from the coculture. When pOCs were cultured on dentine slices, resorption pits were formed on the slices in the presence of either sODF or IL-1 but not in that of M-CSF. A soluble form of RANK as well as osteoprotegerin/osteoclastogenesis inhibitory factor, a decoy receptor of ODF, blocked OCL formation and prevented the survival, multinucleation, and pit-forming activity of pOCs induced by sODF. These results suggest that ODF regulates not only osteoclast differentiation but also osteoclast function in mice through the receptor RANK.

Acid Phosphatase↗
PubMed1999

A common signaling pathway via Syk and Lyn tyrosine kinases generated from capping of the sialomucins CD34 and CD43 in immature hematopoietic cells.

The sialomucin CD34 is a useful marker for hematopoietic stem/progenitor cells. However, the role of CD34 remains poorly understood. Here we investigate the functions of CD34 and another sialomucin CD43 coexpressed on hematopoietic stem/progenitor cells. Stimulation of undifferentiated hematopoietic KG1a cells with anti-CD34 or anti-CD43 induced homotypic cytoadhesion, accompanied by formation of a long-lived cap of CD34 and CD43 respectively, which colocalized with F-actin. Stimulation with either antibody specifically increased tyrosine phosphorylation of the identical set of proteins of Lyn, Syk, pp60, pp69, and pp77 at the capping site. These events were similar to those observed in monocytic U937 cells ectopically expressing CD34. After stimulation of KG1a cells, coimmunoprecipitation of Lyn with pp69 and pp77 and of Syk with pp37 was detected in the membrane fraction. Blockade of antibody-induced cap formation by treatment with cytochalasin D leads to inhibition of tyrosine phosphorylation of Syk and pp77 and homotypic cytoadhesion. Moreover, normal human CD34(+) bone marrow cells showed cap formation of CD34 or CD43 after stimulation. These results suggest that crosslinking of either CD34 or CD43 activates the same signaling pathway for cytoadhesion through Lyn, Syk, and the novel tyrosine-phosphorylated proteins within hematopoiesis.

Antigens, CD↗
PubMed1999

Induction of cell shape changes through activation of the interleukin-3 common beta chain receptor by the RON receptor-type tyrosine kinase.

The RON receptor-type tyrosine kinase, a member of the hepatocyte growth factor receptor family, is a receptor for macrophage-stimulating protein (MSP). Recently, we observed that MSP induces morphological changes in interleukin (IL)-3-dependent Ba/F3 cells ectopically expressing RON. We show here that stimulation of those cells with either MSP or IL-3 increases tyrosine phosphorylation of proteins of 130, 110, 90, 62, and 58 kDa and induces similar morphological changes, accompanied by unique nuclear shape and redistribution of F-actin. A tyrosine kinase inhibitor, genistein, blocked both the increase in tyrosine phosphorylation and morphological changes. Upon stimulation with either MSP or IL-3, prominent tyrosine-phosphorylated pp90 was similarly co-immunoprecipitated with the common beta chain of IL-3 receptor (betac). Unlike IL-3, stimulation with MSP increased tyrosine phosphorylation of betac without activation of JAK2, resulting in morphological changes with modest cell growth. Confocal immunofluorescence analyses showed colocalization of RON, betac, and tyrosine-phosphorylated proteins. In vitro kinase assays revealed that autophosphorylated RON phosphorylated betac. These results suggest that the signaling pathway for morphological changes through betac and its associated protein pp90 is distinct from the pathway for cell growth in the IL-3 signal transduction system.

Actins↗
PubMed1999

A detailed study on the role of sex steroid milieu in determining plasma leptin concentrations in adult male and female rats.

We examined the effects of sex steroid milieu on plasma leptin levels in adult male and female rats. Since the body weight is known to influence leptin concentrations, the hormone was measured in rats with a very similar body weight (about 250 g) throughout this study. Plasma leptin levels were significantly higher in female than in male rats. Orchidectomy (ODX) caused a significant rise in leptin, and replacement of a physiological dose of testosterone (T) completely abolished the effect of ODX. Since the effect of tamoxifen (estrogen antagonist) coadministered with T on leptin levels in ODX rats was the same as that of T alone, it was suggested that the suppressive effect of T on leptin may be mediated by the androgenic potency of T, but not by its aromatized product, estradiol. In female rats, plasma leptin concentrations did not change significantly during the estrous cycle. Furthermore, leptin levels were not affected either by ovariectomy alone or by the administration after ovariectomy of physiological doses of estradiol, progesterone, or both. This is the first study to demonstrate in rats with a very similar body weight the existence of a clear sexual difference in plasma leptin levels, and also a suppressive action of T on the adipocyte hormone concentrations.

Animals↗
PubMed1999

Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis.

CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

Animals↗
PubMed1999

The melanocortin 4 receptor mediates leptin stimulation of luteinizing hormone and prolactin surges in steroid-primed ovariectomized rats.

We have previously reported that leptin, the product of the obese (ob) gene, may play a physiologically relevant role in the generation of estradiol/progesterone-induced luteinizing hormone (LH) and prolactin (PRL) surges in female rats. In the present study, we examined whether the stimulatory effect of leptin on the hormonal surges is mediated through the melanocortin (MC) 4 receptor in the brain, as is leptin's effect on feeding behavior. We also explored whether the MC4 receptor participates in tonic stimulation of steroid-induced LH and PRL surges. Experiments were performed on both normally fed and 3-day starved rats, which were ovariectomized and primed with estradiol and progesterone. At 11:00 h on the day of the experiments, the normally fed rats received an intracerebroventricular administration of artificial cerebrospinal fluid (vehicle), SHU 9119 (a nonselective MC3/MC4 receptor antagonist, 1.0 nmol), or HS014 (a selective MC4 receptor antagonist, 1.0 nmol). The 3-day starved rats were given vehicle, recombinant mouse leptin (0.3 nmol), leptin (0.3 nmol) + SHU9119 (1.0 nmol), or leptin (0.3 nmol) + HS014 (1.0 nmol). From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation completely abolished both LH and PRL surges, but leptin significantly reinstated these hormonal surges. Both SHU9119 and HS014 significantly decreased the magnitude of LH and PRL surges in normally fed rats and also significantly blocked the leptin stimulation of the hormonal surges in starved rats. These results suggest that the MC4 receptor may be the pivotal subtype of MC receptors mediating the leptin stimulation of LH and PRL surges. The data also suggest that endogenous MC(s) may tonically stimulate the hormonal surges in normally fed rats via the MC4 receptor. This is the first report describing a physiological role of a specific MC receptor in regulating the reproductive axis.

Animals↗