Biomedical subjects

K Takenaka

Publications and source records attributed to K Takenaka.

At least 19 recordsLinked to original sources

PubMed2001

Cytokine characteristics of jaundice in mouse liver.

OBJECTIVE: The aim of this study is to clarify the perioperative cytokine changes and their mechanism in jaundiced liver. MATERIALS AND METHODS: Obstructive jaundice was induced using a common bile duct ligation (CBDL) and a two-thirds hepatectomy (HEP) was performed in six- to seven-week-old male C3H/HeN mice. When hepatectomy was added to CBDL, it was carried out 2 to 5 days after CBDL. The serum interleukin 6 (IL-6) levels and heat shock protein (HSP)-70 expression were evaluated. One mg per mouse of methylprednisolone (MPL) was intraperitonealy administered in some mice of CBDL+HEP group. RESULTS: The post-hepatectomy IL-6 values at 2 and 3 days after CBDL were significantly lower than those in the HEP group, while those at 5 days after CBDL were significantly higher than those in HEP group. The serum IL-6 value of the steroid group was significantly lower than that of non-steroid group in HEP group. However, no steroid effects were recognized on post-hepatectomy IL-6 values at 3 days after CBDL, steroid inhibited post-hepatectomy IL-6 production at 5 days after CBDL. No expression of HSP70 protein was observed in the control group, but HSP70 protein was expressed in both the hepatocytes and Kupffer cells 3 days after CBDL, then at 5 days after CBDL, no HSP70 protein was expressed in the Kupffer cells. CONCLUSIONS: In the early period of obstructive jaundice, the IL-6 level after hepatectomy did not increase in comparison to HEP group, and steroid had no effect on IL-6 level. According to the progression of obstructive jaundice, the IL-6 level after hepatectomy increased to a higher level than before, and the effect of MPL was restored. HSP70 is thus suggested to have an important role in cytokine production.

Animals↗

PubMed2001

Prevention of murine acute graft-versus-host disease by staphylococcal enterotoxin B treatment.

Retroviral superantigens such as minor lymphocyte stimulating (Mls) antigen play an important role in the pathogenesis of acute graft-versus-host disease (GVHD). However, it remains unclear how exogenous bacterial superantigens modulate acute GVHD. In this study, we tested the effects of staphylococcal enterotoxin B (SEB) on the development of acute GVHD in a model involving the systemic transfer of parental C57Bl/6 spleen cells into BDF1 mice. SEB treatment suppressed the expansion of donor-derived T cells and blocked the decrease in the number of host cells. Impaired haematopoiesis was actually rescued by treatment with SEB. In SEB-treated mice, both spontaneous proliferation and IL-2 production in T cells were suppressed on day 2 after parental cell infusion. On day 21, the number of donor-derived CD4+ Vbeta8+ T cells markedly decreased in the spleen of SEB-treated mice. Donor-derived CD4+ T cells failed to proliferate in response to host alloantigens, and both donor- and host-derived T cells were unable to produce IL-2 in response to concanavalin A stimulation, suggesting that SEB treatment induced a general immunosuppressive state. Our results indicate that SEB treatment prevents the development of acute GVHD by leading to unresponsiveness of donor-derived T cells against host alloantigens in a Vbeta-restricted and unrestricted manner.

Acute Disease↗

PubMed2001

Initial experience with nifekalant hydrochloride (MS-551), a novel class III antiarrhythmic agent, in patients with acute extensive infarction and severe ventricular dysfunction.

Nifekalant hydrocholoride, a novel class III antiarrhythmic agent, was used as the treatment in 4 patients with extensive anterior infarction and severe ventricular dysfunction. The malignant ventricular tachyarrhythmia was effectively suppressed at a relatively low dose, without compromising the hemodynamics, indicating that this potent K+ channel blocker has therapeutic potential for acute myocardial infarction.

Aged↗

PubMed2000

Anisotropic optical spectra of PrBa2Cu4O8: possible Tomonaga-Luttinger liquid response of the quasi-one-dimensional metallic CuO double chains.

The optical spectra of PrBa2Cu4O8 show large in-plane anisotropy. For the a polarization (E perpendicular chain), the spectrum is characterized by a gap of 1.4 eV, indicating the charge-transfer insulating nature of the CuO2 planes. For the metallic chain direction (E // b), the spectrum deviates from a simple Drude response; reflectivity R(b)(omega) shows a sharp edge at approximately 1 eV but it also shows a dip at approximately 15 meV, which splits the conductivity spectrum into two parts--a zero-energy mode with small weight and a pronounced 40 meV mode. These features are discussed in terms of a Tomonaga-Luttinger liquid in a doped 1D Mott insulator and compared with 1D Bechgaard salts.

Journal Article↗

PubMed2000

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗

PubMed2000

Dominant negative isoform of the Ikaros gene in patients with adult B-cell acute lymphoblastic leukemia.

Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.

Adolescent↗

PubMed2000

Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells.

Ceramide has recently been regarded as a potential mediator of apoptosis. In the present study, the effects of Bcl-2 and Bax on the ceramide-mediated apoptotic pathways were examined in glioma cells overexpressing Bcl-2 or Bax. Etoposide, cisplatin and tumor necrosis factor-alpha induced apoptosis of C6 rat glioma cells which was associated with ceramide formation due to activation of neutral sphingomyelinase, followed by release of mitochondrial cytochrome c into the cytosol and activation of caspases-9 and -3. The growth of C6 cells stably overexpressing either Bcl-2 or Bax was almost equal to that of the vector-transfected cells. Bax overexpression enhanced etoposide-induced apoptosis through acceleration of cytochrome c release and caspases activation. However, Bax had no effect on ceramide formation. Similar findings were obtained in C6 cells and U87-MG human glioblastoma cells which were transiently overexpressed with Bax. In contrast, Bcl-2 overexpression resulted in a retardation of the apoptotic process via prevention of cytochrome c release and caspases activation, and ceramide formation was also blocked when Bcl-2 was highly overexpressed in glioma cells. In addition, transient overexpression of Bcl-xL also exerted inhibitory effects on ceramide formation and apoptotic cell death induced by etoposide. These results indicate that Bax promotes apoptosis regardless of ceramide formation and that Bcl-2 or Bcl-xL prevents ceramide formation by repressing neutral sphingomyelinase as well as ceramide-induced cytochrome c release. Oncogene (2000) 19, 3508 - 3520

Animals↗

PubMed2000

Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training.

BACKGROUND: Calcineurin may play a pivotal role in the signaling of cardiac hypertrophy; since this hypothesis was first put forward, controversial reports have been published using various experimental models. This study was designed to compare the physiological left ventricular hypertrophy (LVH) induced by voluntary exercise with LVH induced by aortic constriction and to determine whether calcineurin participates in the signaling of exercise-induced LVH. METHODS AND RESULTS: Wistar rats were assigned to 1 of the following 5 groups: 10 weeks of voluntary exercise (EX), a sedentary regimen, a 1-week (AC1) or 4-week (AC4) ascending aortic constriction period, or a sham operation. EX rats ran 2.4+/-0.7 km/day voluntarily in specially manufactured cages; this was associated with an increase of LV diastolic dimension and stroke volume. Myocardial calcineurin activity markedly increased in EX rats (46.4+/-8.3 versus 18.4+/-0.5 pmol. min(-1). mg(-1) in sedentary rats; P<0.001) and in AC1 rats (44.9+/-6.7 versus 22.1+/-3.7 pmol. min(-1). mg(-1) in sham-operated rats; P<0.001), but not in AC4 rats (29.0+/-3.4 pmol. min(-1). mg(-1)). Treatment with cyclosporin A completely inhibited the development of LVH in EX rats, but it only partially attenuated the development of LVH in AC4 rats. CONCLUSIONS: Calcineurin was activated in exercise-induced physiological LVH and in the developing phase of LVH (AC1), but not in decompensated pressure-overload hypertrophy (AC4). Cyclosporin therapy for the prevention of LVH may be harmful because it does not block the development of pathological hypertrophy but rather that of favorable adaptive hypertrophy.

Animals↗

PubMed2000

MEK and Cdc2 kinase are sequentially required for Golgi disassembly in MDCK cells by the mitotic Xenopus extracts.

At the onset of mitosis, the Golgi apparatus, which consists of several cisternae, disperses throughout the cell to be partitioned into daughter cells. The molecular mechanisms of this process are now beginning to be understood. To investigate the biochemical requirements and kinetics of mitotic Golgi membrane dynamics in polarized cells, we have reconstituted the disassembly of the Golgi apparatus by introducing Xenopus egg extracts into permeabilized Mardin-Darby canine kidney (MDCK) cells. We used green fluorescence protein (GFP)-tagged galactosyltransferase-expressing MDCK cells to analyze the morphological changes of the Golgi membrane in the semi-intact system. Analyses by fluorescence and electron microscopies showed that the Golgi disassembly can be dissected into two elementary processes morphologically. In the first process, the perinuclear Golgi stacks break into punctate structures, intermediates, which are comprised of mini-stacks of cisternae associating with apical microtubule networks. In the second process, the structures fragment more thoroughly or substantially relocate to the ER. Our analyses further showed that cdc2 kinase and mitogen-activated protein kinase kinase (MAPKK = MEK) are differently involved in these two processes: the first process is mainly regulated by MEK and the second mainly by cdc2.

Animals↗

PubMed2000

A new surgical strategy for cirrhotic patients with hepatocellular carcinoma and hypersplenism. Performing a hepatectomy after a laparoscopic splenectomy.

BACKGROUND: Hepatectomy for cirrhotic patients with hypersplenism is a high-risk operative procedure. We report herein a new strategy for high-risk patients with hepatocellular carcinoma (HCC). METHODS: Six cirrhotic patients with HCC and hypersplenism received a partial hepatectomy after first undergoing a laparoscopic splenectomy. We then compared the variables for these patients before splenectomy and before hepatectomy. RESULTS: The platelet count and the white blood cell count were found to be significantly elevated before hepatectomy. The ammonia value decreased significantly before hepatectomy. The albumin value tended to be elevated before hepatectomy. Furthermore, the Child's classification of all patients improved significantly before hepatectomy. However, other variables-such as the indocyanine green dye excretion test at 15 min and the bilirubin value-did not change after splenectomy. For hepatectomy patients who first underwent a laparoscopic splenectomy, operation time ranged from 265 to 440 min (average time, 361 min), and blood loss ranged from 500 to 2,200 ml (median volume, 1,300 ml). Four of six patients did not require any blood transfusion; furthermore, no patient needed a platelet-rich plasma transfusion. All but one patient, who suffered postoperatively from an intractable duodenal ulcer, had an uneventful postoperative course. CONCLUSION: Partial hepatectomy after an initial laparoscopic splenectomy is a new and effective choice of treatment for cirrhotic patients with HCC and hypersplenism.

Aged↗

PubMed2000

Ikaros expression in human hematopoietic lineages.

The Ikaros gene has been implicated in lymphoid development and proliferation from the results of gene targeting studies in mice. Recently we reported that the Ikaros gene may be involved in the disease progression of chronic myelogenous leukemia (CML). In this report, we investigated Ikaros isoforms in human non-lymphoid leukemia cell lines and normal granulocyte/macrophage (CFU-GM) and erythroid (BFU-E)-derived colonies. We evaluated Ikaros gene expression by RT-PCR, Southern blotting, sequencing analysis, Northern blotting, and immunoblotting.Ikaros isoforms Ik-1 and Ik-2, 3 were predominantly expressed in human non-lymphoid leukemia cell lines. Ik-4 and Ik-8 were also detectable as a minor population. In contrast to the previous report in mice, multiple Ikaros isoforms were expressed in human CFU-GM and BFU-E-derived colonies, and the dominant-negative isoform Ik-6 was not detectable. We also showed that human Ikaros isoforms contained an additional coding sequence in the N-terminal region, which was highly homologous to the sequence reported in mice. These observations suggest that the Ikaros gene may play some role in the development of human non-lymphoid lineage hematopoiesis. Moreover, the finding that the dominant-negative isoform Ik-6, which was overexpressed in patients with blast crisis of CML, was rarely detectable in non-lymphoid lineages supports its pathogenetic role in human hematologic malignancies.

Animals↗

PubMed2000

Allogeneic peripheral blood stem cell transplantation for the treatment of chronic active Epstein-Barr virus infection.

The prognosis of chronic active Epstein-Barr virus infection (CAEBV) is very poor. We describe a 24-year-old male with severe CAEBV who was treated with allogeneic peripheral blood stem cell transplantation (allo-PBSCT). On admission, EBER-1 in lymphocytes infiltrating the liver, EBV-DNA in peripheral blood mononuclear cells (PBMC) and monoclonal NK cell proliferation were confirmed. After unsuccessful chemotherapy, he received an allo-PBSCT from his HLA-identical sister. Although he died of pulmonary hemorrhage on day +19, EBV-DNA was undetectable by PCR in PBMC, and the post-mortem liver showed no EBER-1-positive lymphocytes. This experience suggests that EBV-positive lymphocytes in CAEBV may be eradicated by allo-PBSCT, thereby raising the possibility of a new treatment modality. Bone Marrow Transplantation (2000) 26, 805-808.

Adult↗

PubMed2000

Ordering of ceramide formation, caspase activation, and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells.

Etoposide (VP-16) a topoisomerase II inhibitor induces apoptosis of tumor cells. The present study was designed to elucidate the mechanisms of etoposide-induced apoptosis in C6 glioma cells. Etoposide induced increased formation of ceramide from sphingomyelin and release of mitochondrial cytochrome c followed by activation of caspase-9 and caspase-3, but not caspase-1. In addition, exposure of cells to etoposide resulted in decreased expression of Bcl-2 with reciprocal increase in Bax protein. z-VAD.FMK, a broad spectrum caspase inhibitor, failed to suppress the etoposide-induced ceramide formation and change of the Bax/Bcl-2 ratio, although it did inhibit etoposide-induced death of C6 cells. Reduced glutathione or N-acetylcysteine, which could reduce ceramide formation by inhibiting sphingomyelinase activity, prevented C6 cells from etoposide-induced apoptosis through blockage of caspase-3 activation and change of the Bax/Bcl-2 ratio. In contrast, the increase in ceramide level by an inhibitor of ceramide glucosyltransferase-1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol caused elevation of the Bax/Bcl-2 ratio and potentiation of caspase-3 activation, thereby resulting in enhancement of etoposide-induced apoptosis. Furthermore, cell-permeable exogenous ceramides (C2- and C6-ceramide) induced downregulation of Bcl-2, leading to an increase in the Bax/Bcl-2 ratio and subsequent activation of caspases-9 and -3. Taken together, these results suggest that ceramide may function as a mediator of etoposide-induced apoptosis of C6 glioma cells, which induces increase in the Bax/Bcl-2 ratio followed by release of cytochrome c leading to caspases-9 and -3 activation.

Animals↗

PubMed2000

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro.

Precursor cells that migrate into the thymus are still multipotent. Therefore, thymic epithelial cells (TECs) may provide microenvironments not only for T-cell development, but also for maintenance of multipotent precursor cells until they undergo T-cell commitment. In the present study, we performed long-term cultures of CD34+ bone-marrow (BM) cells on TEC lines that were derived from cortical epithelial cells of post-natal thymus, to investigate whether human TECs could maintain long-term nonlymphoid haematopoiesis. Haematopoietic cells maintained in direct contact with established TEC lines were able to generate clonogenic progeny to both myeloid and erythroid cells for periods in excess of 5 weeks. Their abilities to support colony-forming units of granulocytes-macrophages (CFU-GM) and burst-forming units of erythroids (BFU-E) were almost equal to those of BM stromal cells. We observed similar results by using cloned TEC lines derived by limiting dilution, as well as those by using parental TEC lines. Colony-forming activities were maintained even when haematopoietic progenitor cells were physically separated from TEC lines and cultured on microporous membrane. These observations indicate that haematopoiesis maintained in TEC-contact long-term cultures may depend on soluble factors produced by TEC lines. Our results suggest that thymic cortical epithelial cells have the ability to support not only the differentiation of haematopoietic cells, but also long-term survival of clonogenic myeloid/erythroid progenitor cells.

Antigens, CD34↗

PubMed2000

Growth factor-induced promoter activation of murine phospholipase C delta4 gene.

Phospholipase C delta4 (PLCdelta4) is one of the delta-type PLC isozymes, the expression of which is induced in nuclei by treatment with serum and also in some cancer cells. We isolated and analyzed a promoter region of the murine PLCdelta4 gene. DNA sequence analysis showed that this region is GC-rich and has no TATA box, and the region from -143 to -127 was found, by luciferase activity and gel mobility-shift assay, to be essential for transcription of PLCdelta4. We also found that the promoter activity of PLCdelta4 was stimulated by treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca2+ ionophore in addition to serum. In parallel, we detected PLCdelta4 mRNA induction and an increase in complex formation of the promoter region and nuclear protein from HeLa cells on stimulation with these growth factors. Finally, we found that trapping the growth factor-induced cytoplasmic Ca2+-inhibited activation of the promoter activity and protein induction in nuclei. These results show that PLCdelta4 may have an important role in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+.

Animals↗

PubMed2000

Two cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) following diffuse large B-cell lymphoma.

Histiocytic necrotizing lymphadenitis (HNL) is often mistaken for malignant lymphoma clinically and is also sometimes difficult to differentiate from lymphoma even histopathologically. In this report, we describe the first 2 reported cases of HNL following non-Hodgkin's lymphomas. The patients were 27- and 30-year-old women who developed cervical and axillary lymph node swellings, respectively, in the course of remission of diffuse large B-cell lymphoma. The affected lymph nodes showed the typical histology of HNL: irregular-shaped "necrotic" foci with histiocytes engulfing apoptotic bodies intermingled with large-sized blastic lymphocytes. These findings mimicked the partial involvement of large-cell lymphoma. However, the blastic cells were almost exclusively T cells, and numerous apoptotic bodies were present, which excluded the possibility of recurrence of diffuse large B-cell lymphoma.

Adult↗

PubMed2000

Elevation of mRNA levels of tissue-type plasminogen activator and urokinase-type plasminogen activator in hippocampus and cerebral cortex following middle cerebral artery occlusion in rats.

Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) have been used for thrombolitic therapy. In contrast, it is suggested that these compounds might be involved in neuronal cell damage. The activation and the function of tPA and uPA are less understood in ischemic brain tissue. Therefore, changes in tPA and uPA mRNA in rat brain tissue after MCA occlusion and in the neuronal cell line, PC12 cells, during the hypoxic stimulation were examined. Permanent middle cerebral artery (MCA) occlusion was induced by advancing a filament into the internal carotid artery in 36 adult male Sprague-Dawley rats. The ischemic cerebral cortex and contralateral cortex of MCA area, and bilateral hippocampus were collected at 0 (controls), 1, 3, 6, 12 and 24 h after occlusion. Hypoxia was induced in PC12 cells with a multigas incubator (set to 1% O2). The quantitative reverse transcription-polymerase chain reaction acted as a measurement of alteration in mRNA levels. The mRNA levels of tPA and uPA were significantly increased after MCA occlusion in the ischemic cerebral cortex. The magnitude of the increase in tPA and uPA mRNA in 24 h after occlusion was twice the value in sham-operated rat (0 h). The increases of tPA mRNA were time-dependent in insult and contralateral hippocampus. The increase of uPA mRNA was also seen in the hippocampus bilaterally, although the increase was more significant on the ipsilateral side. In PC12 cells, necrotic (approximately 35%) and apoptotic cells (approximately 65%) could be distinguished by hypoxic stimulus for 24 h, and the mRNA for tPA was significantly increased for 6 h-12 h, while the mRNA for uPA was not detected at any point in the study. Our results suggest that focal ischemia might result in the activation of these proteases not only in the insult but also in the contralateral brain tissue.

Animals↗

PubMed2000

Diagnostic utility of CSF soluble CD27 for primary central nervous system lymphoma in immunocompetent patients.

The aim of this study is to determine the diagnostic utility of cerebrospinal fluid (CSF) soluble CD27 (sCD27) as a tumor marker for primary central nervous system lymphoma (PCNSL) in immunocompetent patients. A total of 93 CSF samples were collected from the following four patient groups: the PCNSL group, 13 patients (26 samples) with PCNSL, 12 samples obtained at initial diagnosis, 10 during therapy, four at complete remission; the other brain tumors (OBT) group, 30 patients (30 samples) with other brain tumors; the other neurological diseases (OND) group, 25 (25 samples) with other neurological diseases; the inflammatory neurological diseases (IND) group, 12 patients (12 samples) with inflammatory neurological diseases. sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value was found to be 15 U ml-1. The CSF sCD27 levels were over 15 U ml-1 in 23 of the 26 PCNSL samples and were significantly higher than those in the OBT and OND groups in which all samples were below 15 U ml-1. Elevated CSF sCD27 levels were also observed in 11 of 12 IND samples. In the two PCNSL patients whose CSF sCD27 levels were studied longitudinally, the sCD27 levels correlated very well with remission and relapse of the disease. CSF sCD27 is useful as a tumor marker for PCNSL in immunocompetent patients, and is also useful to evaluate the effect of various types of treatment. Although there was a large cross-reactivity in the CSF sCD27 levels between PCNSL and IND group, white blood cell count in the CSF is helpful to distinguish these two diseases.

Adult↗