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S Kakuta

Publications and source records attributed to S Kakuta.

At least 19 recordsLinked to original sources
PubMed2001

Calbindin-D28k and calretinin immunoreactive neurons in the olfactory bulb of the musk shrew, Suncus murinus.

The distribution, morphological features, and postnatal development of calbindin-D28k (CB) and calretinin (CR) immunoreactive neurons in the main olfactory bulb (MOB) of the musk shrew, Suncus murinus, were studied by immunostaining to determine the degree of colocalization of CB and CR, and the relationship of CB and CR to neuron development in the MOB of animals of the order Insectivora. In adults, CB-positive neurons were identified as periglomerular and perinidal cells in the periglomerular region, as superficial short-axon cells in the external plexiform layer, and as four types of interneurons (Cajal, horizontal, Golgi, and bitufted cells) in the mitral cell, internal plexiform, and granule cell layers. CR-positive neurons were identified as projection neurons (tufted and mitral cells) and interneurons (periglomerular, perinidal, and granule cells). On postnatal days 1 and 3, CB-positive neurons revealed numerous processes finely arborized near the somata, and were morphologically unidentifiable. At the same time, CR-positive neurons were identified as young periglomerular and granule cells, and as migrating bipolar cells extending leading processes with growth cones in each layer of the MOB and the subependymal layer between the anterior lateral ventricle and the center of the MOB. On postnatal day 28, mature CB-positive and CR-positive interneurons were distributed in their corresponding layers, whereas migrating CR-positive bipolar cells were rarely detected. No cells colocalized CB and CR. The results suggest that perinidal cells in the shrew MOB may develop postnatally, together with glomerular and granule cells. We suggest that CB is associated with mechanisms of the outgrowth of neuronal processes, whereas CR is involved in mechanisms of cell migration and outgrowth of neuronal processes, in some types of neurons in the developing stage of the shrew MOB.

Age Factors↗
PubMed2001

Cloning of a novel 2',5'-oligoadenylate synthetase-like molecule, Oasl5 in mice.

The 2',5'-oligoadenylate synthetase (2-5OAS) is a enzyme that catalyzes synthesis of 2',5'-oligoadenylates (2-5A) in a dsRNA-dependent manner, and known as a major component of the IFN-induced host defense mechanisms against microbial infections. Here, we report the presence of a novel 2-5OAS-like molecule, termed Oasl5, in mice. The size of Oasl5 cDNA was about 2 kb and encoded a protein consisting of 362 aa. The amino acid sequence showed 76% similarity to the mouse 2-5OAS, however, several motifs being important for the enzyme activity were not conserved. The Oasl5 mRNA was most significantly expressed in the brain, and relatively weak expression was found in other organs such as the spleen, kidney, ovary and testis. It was also expressed in embryonic stem (ES) cells. The Oasl5 mRNA expression in ES cells was elevated 5-fold after treatment with IFN and about 2-fold in the brain when stimulated with IFN inducer, polyinosinic-polycytidylic acid (poly[I:C]). In situ hybridization analysis revealed that Oasl5 is expressed in neurons in the central nervous system in adult mice. When Oasl5 was expressed in E. coli, it yielded 42 kDa protein that binds to dsRNA, but it did not show oligoadenylate synthetase activity. These findings suggest a novel function of Oasl5, which are independent of oligoadenylate synthetase activity, in the brain and developing embryos.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Differential immunolocalization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat.

In this study, to identify the precise localization of m2 and m3 muscarinic receptors in the anteroventral and anterodorsal thalamic nuclei of the rat, we used receptor-subtype-specific antibodies and characterized their immunolocalization patterns by light and electron microscopy. Many m2-positive neurons were distributed throughout these nuclei. Ultrastructural analysis showed that more than 30% of m2-positive dendritic profiles in these nuclei are proximal dendritic shafts. Moreover, a few m2-positive fiber terminals were found only in the anterodorsal thalamic nucleus. These m2-positive terminals were large (1.10+/-0.30 microm in diameter) and formed asymmetrical synapses with dendritic profiles. The m3-positive neurons were also distributed in both nuclei, and the m3-positive neuropil exhibited a significant staining gradient, with the most intense staining in the ventrolateral part of the anteroventral thalamic nucleus. This region receives the densest cholinergic input originating from the dorsal tegmental region. At the ultrastructural level, the majority of m3-positive dendritic profiles were more distal regions of the dendrites compared to the m2 receptors in the anteroventral thalamic nucleus. However, no significant difference in the intradendritic distribution pattern between m2 and m3 receptors was found in the anterodorsal thalamic nucleus, which receives no cholinergic input. These findings show the differential localization of m2 and m3 receptors in the anteroventral and anterodorsal thalamic nuclei, and suggest that the m3 receptors are spatially more closely associated with ascending cholinergic afferent fibers in the anteroventral thalamic nucleus.

Animals↗
PubMed2001

Requirement for natural killer T (NKT) cells in the induction of allograft tolerance.

In this study, we investigated the role of Valpha14 natural killer T (NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not Valpha14 NKT cell-deficient mice. Adoptive transfer with Valpha14 NKT cells restored long-term acceptance of allografts in Valpha14 NKT cell-deficient mice. The critical role of Valpha14 NKT cells to mediate immunosuppression was also observed in vitro in mixed lymphocyte cultures in which lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions were blocked. Experiments using IL-4- or IFN-gamma-deficient mice suggested a critical contribution of IFN-gamma to the Valpha14 NKT cell-mediated allograft acceptance in vivo. These results indicate a critical contribution of Valpha14 NKT cells to the induction of allograft tolerance and provide a useful model to investigate the regulatory role of Valpha14 NKT cells in various immune responses.

Adaptation, Physiological↗
PubMed2001

Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells in vitro, but its physiological role in tumor surveillance remains unknown. Here, we report that TRAIL is constitutively expressed on murine natural killer (NK) cells in the liver and plays a substantial role in suppressing tumor metastasis. Freshly isolated NK cells, but not natural killer T cells or ordinary T cells, from the liver expressed cell surface TRAIL, which was responsible for spontaneous cytotoxicity against TRAIL-sensitive tumor cells in vitro along with perforin and Fas ligand (FasL). Administration of neutralizing monoclonal antibody against TRAIL significantly increased experimental liver metastases of several TRAIL-sensitive tumor cell lines. Such an anti-metastatic effect of TRAIL was not observed in NK cell-depleted mice or interferon-gamma-deficient mice, the latter of which lacked TRAIL on liver NK cells. These findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor.

Animals↗
PubMed2001

Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide.

The glycolipid alpha -galactosylceramide (alpha -GalCer), which is presented by CD1d and specifically activates Valpha 14 NKT cells, exerts a potent anti-metastatic effect when administered in vivo. In this study, we demonstrated that alpha -GalCer administration led to rapid elimination of NKT cells by apoptosis in the liver and spleen, after they produced IFN-gamma and IL-4. In contrast, a more prolonged secretion of IFN-gamma was observed by liver and splenic NK cells after alpha -GalCer administration. Cytotoxic activity of liver mononuclear cells was not augmented 3h after alpha -GalCer administration, but was increased at 24 h when NKT cells were mostly depleted. The alpha -GalCer-induced cytotoxic activity was abolished in IFN-gamma -deficient and NK cell-depleted mice as well as CD1-deficient mice, suggesting that the alpha -Galcer-induced cytotoxicity was mainly mediated by IFN-gamma -activated NK cells. While the alpha -GalCer-induced cytotoxicity in vitro was mostly perforin dependent, anti-metastatic effect of alpha -GalCer was impaired in NK cell-depleted or IFN-gamma -deficient mice but not in perforin-deficient mice. Collectively, these results indicated that the anti-metastatic effect of alpha -GalCer is mainly mediated by NK cells, which are activated secondarily by IFN-gamma produced by alpha -GalCer-activated NKT cells, in a perforin-independent manner.

Animals↗
PubMed2000

Establishment of a cell line with phenotypes of chondrocyte from a human osteogenic sarcoma of the mandible.

We have succeeded in transplanting a human osteogenic sarcoma of the mandible into athymic mice. The transplanted tumor showed marked chondrogenesis and mineralization. Recently, a cell line (USAC) with phenotypes of chondrocyte has been established from the transplanted tumor. USAC cells were stellate or spindle-shaped in sparse culture, but polygonal or spherical at sub-confluency to confluency. In long-term culture, the cells were condensed and calcified nodules were formed. Production of types I, II and X collagen were detected by immunohistochemical staining and Western blot analysis. Type I collagen was strongly expressed in the stellate or spindle-shaped cells. Although type II collagen was usually present in all cells during culture, it was strongly stained in polygonal cells at confluency. Type X collagen was seen in large polygonal cells around calcified nodules. Marked [35S]-sulfate uptake and metachromasia were seen at the confluent stage and in the nodule. The cells around the nodules were positive for alkaline phosphatase, and the center of the nodules was stained with alizarin red. The potentiality of cartilage formation was confirmed by in vivo experiments using a diffusion chamber in athymic mice. These observations indicate that USAC cells maintain characteristics of chondrocyte progenitor cells and thus may serve as a useful model to study the sequential events of chondrogenesis and the process of morbid endochondral calcification. This experiment also demonstrated that transplantation of tumor tissue into athymic mice is a convenient strategy for establishment of a cell line.

Analysis of Variance↗
PubMed2000

Effects of cytokines on the production of nitric oxide in a chondrogenic cell line established from human osteogenic sarcoma.

OBJECTIVES: The purpose of this study was to examine the effects of various cytokines and/or lipopolysaccharide (LPS) on nitric oxide (NO) production from USAC, a newly established clonal cell line derived from human osteogenic sarcoma that expressed chondrocytic phenotypes. MATERIALS AND METHODS: No production was measured by Griess method. Inducible nitric oxide synthase (iNOS) mRNA was detected by PCR analysis. Western blotting analysis and immunocytochemistry was used to detect iNOS protein. RESULTS: Although USAC cells treated without any stimulants produced only small amounts of NO, exposure to cytokines and/or LPS induced iNOS in USAC cells and produced high levels of NO. The stimulatory effects of cytokines and/or LPS on NO production required TNF-alpha. TNF-alpha alone neither induced iNOS in USAC cells nor caused production of NO, but addition of TNF-alpha to USAC cells pretreated with LPS and IFN-gamma enhanced the expression of iNOS mRNA, induced iNOS protein and produced NO. Dexamethasone inhibited the stimulatory effect of TNF-alpha. CONCLUSIONS: The responsiveness of USAC cells to cytokines and/or LPS and steroid hormone on NO production was quite different from that reported for rabbit and human articular cartilaginous cells. The differences in responsiveness between articular cartilaginous chondrocytes and USAC cells might have been because USAC cells were established from a malignant tumor.

Animals↗
PubMed1999

[Marked hypernatremia in suprasellar germinoma lacking a sense of thirst].

We here report a 17-year-old high school boy having suprasellar germinoma who presented marked hypernatremia probably due to damages of both the osmoregulation and thirst centers. He was in good health until July, 1996, when he noticed slight general malaise and complained of dryness of the mouth, but without polyuria. He was found to have hypernatremia of mild degree (serum Na 151 mEq/l), but dropped out from the follow-up. In April, 1997, he was admitted to our hospital with complaints of general malaise and weakness of the upper and lower extremities. Serum Na was high at 202 mEq/l with a plasma osmolality of 390 mOsm/kg H2O. He completely lacked a sense of thirst and polydipsia/polyuria. Computed tomography and magnetic resonance imaging indicated a suprasellar tumor, possibly a germinoma. Hypernatremia was first treated with intravenous infusion of a half-normal saline solution, followed by immediate polyuria of 3 to 6 l/day. Subsequently, nasal administration of desamino-D-arginine vasopressin (DDAVP) induced stabilization of serum Na to a range between 140 and 160 mEq/l. The tumor disappeared following steroid pulse therapy and irradiation of 50 Gy to the brain. At the time of discharge, he and his family were instructed to record the urine volume, amount of water intake, body weight and amount of DDAVP used. The patient was instructed to drink water corresponding to the urine volume while maintaining the dose of DDAVP. One year after treatment, the water balance reverted to a positive direction, leading to a normal range of serum Na probably because of partial recovery of the osmoreceptors and/or trained drinking habit. This case illustrates the so-called adipsic hypernatremia which is attributed to partial osmoreceptor destruction by a suprasellar germinoma.

Adolescent↗
PubMed1998

Involvement of Fas/Fas ligand system-mediated apoptosis in the development of concanavalin A-induced hepatitis.

Concanavalin A (Con A)-induced hepatitis is an experimental hepatitis model in which hepatic injury is caused by the action of cytokines produced by T cells. Using IFN-gamma-deficient mice, we previously demonstrated that IFN-gamma plays a central role in Con A-induced hepatitis. Here, we show that development of the disease is completely suppressed in gld/gld mice, in which Fas ligand is defective. In contrast, suppression of the disease in Ipr/Ipr mice was incomplete, since a small amount of the fas mRNA was produced in these mice. The data indicate that activation of the Fas/Fas ligand system is a necessary step in the development of Con A-induced hepatitis. Furthermore, we found that not only fas but also caspase-1 expression was reduced in IFN-gamma-deficient mice. Since caspase-1 is an integral component of Fas signal transduction, these observations suggest that IFN-gamma-induced activation of both fas and caspase-1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.

Animals↗
PubMed1998

Parvalbumin immunoreactive neurons in the main olfactory bulb of the house musk shrew, Suncus murinus.

The distribution, morphological features, and postnatal development of parvalbumin (PV) immunoreactive neurons in the main olfactory bulb (MOB) of the house musk shrew, Suncus murinus, were studied to report for the first time on PV positive bulbar interneurons in the order Insectivora. In adult animals, PV neurons are distributed in the glomerular layer (GL), the external plexiform layer (EPL), the internal plexiform layer (IPL) and the granule cell layer (GCL) of the MOB. These neurons were identified as a subpopulation of periglomerular cells and perinidal cells [Alonso et al., 1995] in the GL and at the GL-EPL border, respectively, and as bipolar and multipolar neurons in the EPL and four types of the interneurons (horizontal cells, Cajal cells, Golgi cells, and bitufted cells) in the layers deeper than the mitral cell layer. During development of PV neurons, neurons exhibiting extremely faint PV immunoreactivity first appeared in the GCL at postnatal day 14 and increased markedly in number and intensity of their PV immunoreactivity from postnatal days 14 to 28. At postnatal day 21, PV neurons were identified as periglomerular cells in the GL, perinidal cells at the GL-EPL border, and morphologically unidentifiable neurons in the EPL, IPL and GCL. At postnatal day 28, PV neurons exhibited a nearly adult pattern with respect to distribution and structural features. The present results strongly suggest that a wide variety of PV positive neurons in the MOB of the house musk shrew may develop postnatally.

Animals↗
PubMed1998

[Membranoproliferative glomerulonephritis-like lesion with fibrillary deposition associated with multicentric Castleman's disease].

We report a case of a 65-year-old man presenting with multicentric Castleman's disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion with fibrillary deposits. The lesion was characterized by highly organized ultrastructual deposits that were negative for Congo-red stain and for immunoglobulin, light chain and C3. Thus, this renal lesion was considered histologically to be fibrillary glomerulonephritis presenting by light microscopy as mesangiocapillary glomerulonephritis. To our knowledge, among the limited number of cases of renal lesion associated with MCD ever reported, this is the first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6 (IL-6), known as an indicator of MCD activity and as an autocrine growth factor for mesangial cells, was chronologically measured. Augmentation of urinary IL-6 simultaneously with that of extra renal symptoms of MCD and associated renal disease may indicate an underlying role of this cytokine in the present case. Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is derived from extrarenal lymphonodi, and not to an in situ product of the glomeruli. However, it may have been related to glomerular injury.

Aged↗
PubMed1997

Clinical trial of recombinant granulocyte colony-stimulating factor for chemotherapy-induced neutropenia patients with oral cancer.

PURPOSE: This study was undertaken to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in reducing neutropenia in patients with oral cancer undergoing intensive chemotherapy. MATERIALS AND METHODS: Patients with chemotherapy-induced neutropenia (< 1 x 10(9)/L) were divided into two groups: control group (n = 13) and rhG-CSF administration group (n = 16). rhG-CSF was administered subcutaneously at a dose of 75 micrograms/day on consecutive days. Peripheral blood cell counts and oral complications were investigated in each group. RESULTS: The duration of neutropenia and absolute neutrophil nadir counts were significantly improved by administration of G-CSF. No consistent effect on thrombocytopenia was noted. Administration of rhG-CSF also reduced the duration and degree of oral complications associated with chemotherapy-induced neutropenia. Intolerable side effects associated with administration of rhG-CSF were not observed. CONCLUSION: It was concluded that rhG-CSF is effective in shortening the duration of neutropenia after chemotherapy at a dose of 75 micrograms/day.

Adult↗
PubMed1997

[A case of anti-basement membrane (BM) mediated disease presenting renal and pulmonary symptoms by divergent timing].

A case of 49-year-old man with anti-GBM antibody and who manifested pulmonary and renal symptoms at divergent times. Thirty-six years previously, renal disease with unneglectable degree of proteinuria was noticed. One month before admission, he was found by chance to have elevated serum creatine (Scr); 3.4 mg/dl. At admission, his Scr was 13.7 mg/dl and Hb 12.7 g/dl, TP 5.2 g/dl with 3+ proteinuria and no glucosuria. He was a heavy smoker and remained so while admitted. Renal biopsy presented fibrocellular crescents in 100% of glomeruli with striking tubulointerstitial involvement. Immunofluorescence showed linear IgG deposition along the glomerular capillary wall. Hemodialysis was instituted, and after 13 hospital days, anti-GBM antibody at admission was high at 128 U, with negative PANCA. Plasmapheresis was also performed, but on the next day pulmonary hemorrhage occurred with a concomitant rise of anti-GBM to 250 U. Thus, steroid pulse therapy was conducted in combination with plasmapheresis. Pulmonary hemorrhage subsided along with lowering of anti-GBM (48 U), but renal failure persisted. The patient died of septicemia. Based on the clinical course of the case, the term "anti-BM mediated disease" may more properly delineate the entity of the disease rather than the classical eponym "Goodpasture's disease" which requires coexistence of pulmo- and renal manifestations for definition.

Anti-Glomerular Basement Membrane Disease↗
PubMed1994

Expression of collagen species in a cartilaginous tumor derived from a human osteogenic sarcoma.

We have succeeded in transplanting human osteogenic sarcoma into nude mice. Morphologically, the transplanted tumor is chondrosarcoma and manifests calcification, but not ossification. This tumor is thought to be an excellent model for studying the process of morbid endochondral calcification. In this study, we have used in situ hybridization to examine expression of collagen type I, II, and III mRNAs in this tumor. In situ hybridization was carried out using biotinylated DNA probes. Hybridized probes were detected using a streptavidin-biotin-alkaline phosphatase reagent. The results showed that collagen type I and II mRNAs were produced by cells of the transplanted tumor. Collagen type I mRNA was chiefly localized in the marginal region of the tumor. Collagen type II mRNA, which was predominantly found in the premineralized region of the transplanted tumor, gradually decreased toward the mineralized region. Collagen type III mRNA was not expressed in the transplanted tumor. These results suggest that the character of progenitor chondrogenic cells might be transferred to the transplanted tumor, and that the tumor cells may change the expression of collagen genes with the differentiation or maturation.

Animals↗