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Biomedical subjects

H Kawaguchi

Publications and source records attributed to H Kawaguchi.

At least 19 recordsLinked to original sources
PubMed2006

Renal adenocarcinoma in a ferret.

A spontaneous case of renal tumor was observed in a 7-year-old ovariectomized female pet ferret (Mustela putorius furo). Clinical signs included exhaustion, emaciation, anorexia, and stooping position. At necropsy, a solid and cystic mass replaced the left kidney and adrenal gland. The tumor was composed of pleomorphic epithelial cells with a large number of giant cells. Metastases were recognized in the lung, liver, greater omentum, right renal pelvis, and systemic lymph nodes. Immunohistochemical stains revealed that the tumor cells were positive for CD10, cytokeratin (CAM 5.2), and Ki-67 (MIB-1). On the basis of morphologic and immunohistochemical features, the tumor was diagnosed as a pleomorphic renal adenocarcinoma. This type of neoplasm is very rare in all species and has never been reported in a ferret.

Adenocarcinoma↗
PubMed2005

Osteoarthritis development in novel experimental mouse models induced by knee joint instability.

OBJECTIVE: Although osteoarthritis (OA) is induced by accumulated mechanical stress to joints, little is known about the underlying molecular mechanism. To apply approaches from mouse genomics, this study created experimental mouse OA models by producing instability in the knee joints. METHODS: The models were of four types: severe, moderate, mild, and medial, depending on the severity and direction of instability imposed by combinations of ligament transection and menisectomy. OA development was evaluated by X-ray and histology by Safranin-O staining, and quantified using our original gradings. Expressions of type II, IX and X collagens and matrix metalloproteinase (MMP)-2, -3, -9 and -13 were further examined by immunohistochemistry and in situ hybridization (ISH). RESULTS: The severe, moderate and mild models exhibited OA development in the posterior tibial cartilage. The severe model showed cartilage destruction at 2 weeks and osteophyte formation at 4-8 weeks after surgery; however, the mild model showed only a partial cartilage destruction at 8 weeks. The grading confirmed that the OA disorders progressed depending on the severity of joint instability. In the medial model, the OA development in the medial tibial cartilage was similar to that in the posterior cartilage of the mild model. Among the collagens and MMPs, type X collagen and MMP-13 were markedly induced and colocalized in the early stage OA cartilage. CONCLUSION: We established four types of mouse models exhibiting various speeds of OA progression. By applying a mouse genomics approach to the models, molecular backgrounds in various stages of OA development can be clarified.

Animals↗
PubMed2004

Resolution of spinal epidural haematoma without surgery in a haemophilic infant.

Non-traumatic spinal epidural haematoma is a rare complication of haemophilia. We report a seven-month-old boy who presented with symptomatic spinal epidural haematoma. He was found to have a hemophilia B trait, and after factor IX replacement, his neurological signs were stabilized and follow-up MRI demonstrated rapid resolution of the haematoma. This illustrative case suggests that surgical intervention can be deferred as the first step in treating spinal epidural haematoma in a haemophilic infant.

Factor IX↗
PubMed2003

Preventive effects of sequential treatment with alendronate and 1 alpha-hydroxyvitamin D3 on bone mass and strength in ovariectomized rats.

Because accumulating evidence has shown that bisphosphonates are unable to maintain their bone-sparing effects after the withdrawal of the drug, a replacement treatment is needed when bisphosphonate treatment cannot be continued for some reason. The present study investigated the preventive effects of alendronate followed by 1alpha(OH)D3 on the mass and mechanical strength of trabecular and cortical bones in ovariectomized rats. Sprague-Dawley rats were ovariectomized or sham-operated at 48 weeks of age. Ovariectomized rats treated with vehicle alone (OVX group) showed significant decreases in bone mineral density (BMD) and mechanical strength of the lumbar vertebra and the midfemur during a 20-week period after the operation as compared with sham-operated rats. These decreases were prevented by continuous treatment with alendronate (0.5 mg/kg/day, po) for 20 weeks (ALN-C group), whereas the values reverted to those of the OVX group when alendronate was withdrawn at 10 weeks (ALN-W group). The sequential treatment with alendronate and 1alpha(OH)D3 (0.05 microg/kg/day, po) for 10 weeks each (ALN --> 1alpha group) resulted in higher BMD and mechanical strength of the lumbar vertebra and the midfemur in this group than in the OVX and ALN-W groups. The increase in mechanical strength was proportional to that in BMD at both sites, suggesting that the stimulatory effects of these treatments on bone strength were due to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the preventive effects of the sequential treatment. Therefore, we propose that 1alpha(OH)D3 may be a good choice to replace alendronate when alendronate treatment cannot be continued for some reason.

Aging↗
PubMed2002

The validity of upright myelography for diagnosing lumbar disc herniation.

Although computed tomographic (CT) myelography and magnetic resonance imaging (MRI) are used for assessing lumbar disc herniations (LDH), they cannot provide images when patients are standing or walking, whose CT myelograms and MRI images show only slight disc bulging. The purpose of this study was to evaluate the usefulness of upright myelography. We examined by myelography in both an upright and a lying position for 50 patients with LDH at L4-5 and L5-S1 to assess the difference in disc bulge size. Lateral myelogram was used for evaluating the difference quantitatively. In 29 patients with damage at L4-5, 21 (72.4%) had increased disc bulging when upright, and 22 (75.9%) showed subligamentous LDH. In 21 patients with damage at L5-S1, fewer patients showed increased disc bulging when upright than showed unchanged disc bulging. This upright myelographic technique could show increased disc bulging in patients with mild compression at L4-5 whose sciatica increased in an upright position. Upright myelography seems to be the only method for assessing patients with LDH, especially at the L4-5 level, whose neurological symptoms develop during standing or walking.

Adolescent↗
PubMed2002

Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women.

Based on the fact that the klotho-deficient mouse exhibits multiple aging phenotypes, including osteopenia and subchondral sclerosis of joints, we explored the possibility of whether human klotho gene polymorphism is associated with two major age-related skeletal disorders: osteoporosis and spondylosis. Analysis of the CA repeat sequence downstream of the final exon of the klotho gene identified ten types of alleles in Japanese postmenopausal women (n = 377). We investigated the association of this microsatellite polymorphism with bone density and spondylosis score of the lumbar spine. None of the genotypes was associated with bone density in the overall population (n = 377; 754 alleles) nor in the subpopulation at not more than 10 years after menopause ( 20 years after menopause (n = 102; 204 alleles, p = 0.024). The type 7 allele was associated with high bone density in women more than 20 years after menopause (p = 0.042). The association study with spondylosis of postmenopausal women (n = 221) revealed that another distinct allele, type 8, was significantly associated with low spondylosis score at L-4/5 (p = 0.019) and L-5/S-1 (p = 0.048) levels in the subpopulation equal to or younger than the average age (<or=63 years old, n = 119; 238 alleles), but not in the older subpopulation. These findings indicate that the klotho gene may be a candidate for the genetic regulation of common age-related diseases like osteoporosis and spondylosis, and we provide the first evidence suggesting that this gene may be involved in the etiology of human diseases.

Adult↗
PubMed2002

Chronic active Epstein-Barr virus infection (CAEBV) successfully treated with allogeneic peripheral blood stem cell transplantation.

We report a pediatric case of CAEBV and T cell-based Hodgkin's-like disease successfully treated with allo PBSCT from an HLA-matched sibling. The diagnosis of CAEBV was made from clinical signs and the presence of the EBV genome in PBMC and tumor cells. Conditioning with busulfan (BU) + etoposide (VP16) + cyclophosphamide (CY) was effective and well tolerated. EBV was totally eradicated by 3 months after allo PBSCT. Although she suffered from chronic GVHD of the liver, she has been well and free of disease for 47 months since PBSCT. We suggest allo PBSCT for CAEBV as a potent therapeutic strategy for eradication of the EBV genome and allowing immunological reconstitution.

Antineoplastic Agents↗
PubMed2002

An unusual reduction technique prior to surgical treatment for traumatic spondylolisthesis in the lower cervical spine.

Traumatic spondylolisthesis in the lower cervical spine is rare and only a few cases have been reported. We present a 56-year-old man who had severe C6-C7 spondylolisthesis without major neurological complications, caused by a traffic accident. Plain CT images showed a pedicular fracture on the right side and a laminar fracture on the left side at C6, but magnetic resonance images revealed no spinal cord compression. Application of a halo brace and maintaining the neck in slight flexion without traction resulted in reduction of the spondylolisthesis to nearly normal alignment. Anterior fusion using an autogeneous bone graft and a plate was easily performed without loss of correction. We suggest that preoperative reduction using a halo brace in slight flexion without longitudinal skull traction is useful and effective for severe traumatic spondylolisthesis in the lower cervical spine.

Cervical Vertebrae↗
PubMed2001

Alkynethiolato and alkyneselenolato ruthenium half-sandwich complexes: synthesis, structures, and reactions with (eta(5)-C(5)H(5))(2)Zr.

Alkynethiolato and alkyneselenolato complexes of ruthenium, CpRu(PPh(3))(2)(EC(triple bond)CR) (Cp = eta(5)-C(5)H(5); E = S, R = Ph (1a), SiMe(3) (1b), (t)Bu (1c); E = Se, R = Ph (2a), SiMe(3) (2b)), were synthesized by the reactions of CpRuCl(PPh(3))(2) with corresponding lithium alkynechalcogenolates in THF. An analogous reaction of Cp*RuCl(PEt(3))(2) (Cp* = eta(5)-C(5)Me(5)) with LiSC(triple bond)CPh produced Cp*Ru(PEt(3))(2)(SC(triple bond)CPh) (3). Complexes 1a and 2a were allowed to react in THF with "Cp(2)Zr", generated in situ from Cp(2)ZrCl(2) and 2 equiv of n-BuLi, from which the S-bridged Ru-Zr dinuclear complexes CpRu(PPh(3))(C(triple bond)CPh)(mu-S)ZrCp(2) (4a) and CpRu(PPh(3))(C(triple bond)CPh)(mu-Se)ZrCp(2) (4b) were isolated, respectively. In these complexes, C-S(Se) bond cleavage of the alkynechalcogenolate ligands was promoted by "Cp(2)Zr", and the Zr atom was oxidized from II to IV. Treatment of 4a and 4b in THF under 1 atm CO gave rise to CpRu(CO)(C(triple bond)CPh)(mu-E)ZrCp(2) (E = S (5a), Se (5b)), while addition of tert-butyl isocyanide to a THF solution of 4b afforded CpRu(CN(t)()Bu)(C(triple bond)CPh)(mu-Se)ZrCp(2) (6). The crystal structures of 1a, 1c, 2a, 2b, 3, 4a, 4b, and 5b were determined by X-ray diffraction analysis.

Journal Article↗
PubMed2001

ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts.

We recently reported that angiotensin II (Ang II) induced IL-6 mRNA expression in cardiac fibroblasts, which played an important role in Ang II-induced cardiac hypertrophy in paracrine fashion. The present study investigated the regulatory mechanism of Ang II-induced IL-6 gene expression, focusing especially on reactive oxygen species (ROS)-mediated signaling in cardiac fibroblasts. Ang II increased intracellular ROS in cardiac fibroblasts, and the increase was completely inhibited by the AT-1 blocker candesartan and the NADH/NADPH oxidase inhibitor diphenyleneiodonium (DPI). We first confirmed that antioxidant N-acetylcysteine, superoxide scavenger Tiron, and DPI suppressed Ang II-induced IL-6 expression. Because we observed that exogenous H(2)O(2) also increased IL-6 mRNA, the signaling pathways downstream of Ang II and exogenous H(2)O(2) were compared. Ang II, as well as exogenous H(2)O(2), activated ERK, p38 MAPK, and JNK, which were significantly inhibited by N-acetylcysteine and DPI. In contrast with exogenous H(2)O(2), however, Ang II did not influence phosphorylation and degradation of IkappaB-alpha/beta or nuclear translocation of p65, nor did it increase NF-kappaB promoter activity. PD98059 and SB203580 inhibited Ang II-induced IL-6 expression. Truncation and mutational analysis of the IL-6 gene promoter showed that CRE was an important cis-element in Ang II-induced IL-6 gene expression. NF-kappaB-binding site was important for the basal expression of IL-6, but was not activated by Ang II. Ang II phosphorylated CREB through the ERK and p38 MAPK pathway in a ROS-sensitive manner. Collectively, these data indicated that Ang II stimulated ROS production via the AT1 receptor and NADH/NADPH oxidase, and that these ROS mediated activation of MAPKs, which culminated in IL-6 gene expression through a CRE-dependent, but not NF-kappaB-dependent, pathway in cardiac fibroblasts.

Angiotensin II↗
PubMed2001

Connection between B lymphocyte and osteoclast differentiation pathways.

Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another osteoclast differentiation pathway closely connected with B lymphocyte differentiation. Recently the TNF family molecule osteoclast differentiation factor/receptor activator of NF-kappaB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating osteoclast differentiation. We demonstrate that B-lymphoid lineage cells are a major source of endogenous ODF/RANKL in bone marrow and support osteoclast differentiation in vitro. In addition, B-lymphoid lineage cells in earlier developmental stages may hold a potential to differentiate into osteoclasts when stimulated with M-CSF and soluble ODF/RANKL in vitro. B-lymphoid lineage cells may participate in osteoclastogenesis in two ways: they 1) express ODF/RANKL to support osteoclast differentiation, and 2) serve themselves as osteoclast progenitors. Consistent with these observations in vitro, a decrease in osteoclasts is associated with a decrease in B-lymphoid cells in klotho mutant mice (KL(-/-)), a mouse model for human aging that exhibits reduced turnover during bone metabolism, rather than a decrease in the differentiation potential of osteoclast progenitors. Taken together, B-lymphoid lineage cells may affect the pathophysiology of bone disorders through regulating osteoclastogenesis.

Aging↗
PubMed2001

Cholesteryl ester transfer protein deficiency causes slow egg embryonation of Schistosoma japonicum.

In our attempt to discover a potential cause for accumulation of cholesteryl ester transfer protein (CETP) deficiency in Eastern Asia, we studied the association of CETP deficiency with pathogenesis of Schistosoma japonicum, a life-threatening parasite peculiar to this region. The eggs of S. japonicum showed slow embryonation when cultured in CETP-deficient human plasma. Restoration of CETP to the deficient plasma rescued it, while inhibition of CETP in normal plasma did not cause slow embryonation of the cultured eggs. The egg embryonation was also retarded in the liver but not in the intestine of wild-type mice in comparison to the CETP-transgenic mice. The granulomatous lesion around the parasite eggs in the liver was less in the wild-type than in the CETP-transgenic mice. Thus, CETP deficiency may act against Schistosomiasis japonica by retarding egg embryonation, a potential cause of liver granulomatosis. It does not seem directly due to the lack of CETP activity in plasma but to abnormal lipoprotein generated by chronic CETP deficiency.

Animals↗
PubMed2001

Ganglioside G(D2) in small cell lung cancer cell lines: enhancement of cell proliferation and mediation of apoptosis.

Expression levels of gangliosides and glycosyltransferase genes responsible for their syntheses in human lung cancer cell lines and a normal bronchial epithelial cell line were analyzed. Both non-small cell lung cancers and small cell lung cancers (SCLCs) mainly expressed G(M2) and G(M1), whereas only SCLCs expressed b-series gangliosides, such as G(D2), G(D1b), and G(T1b). Accordingly, many SCLC cell lines showed up-regulation of the G(D3) synthase gene. Consequently, we introduced G(D3) synthase cDNA into a SCLC line with low expression of b-series gangliosides and analyzed the effects of newly expressed gangliosides on tumor phenotypes. The transfectant cells expressing high levels of G(D2) and G(D3) exhibited markedly increased growth rates and strongly enhanced invasion activities. Addition of anti-G(D2) monoclonal antibodies into the culture medium of these cells resulted in the marked growth suppression of G(D2)-expressing cell lines with reduced activation levels of mitogen-activated protein kinases but not of nonexpressants, suggesting that G(D2) plays important roles in cell proliferation. Moreover, G(D2)-expressing cells treated with anti-G(D2) antibodies showed features of apoptotic cell death at 30 min after addition of antibodies, i.e., shrinkage of cytoplasm, binding of Annexin V, and staining with propidium iodide, followed by DNA fragmentation. This G(D2)-mediated apoptosis was associated with caspase-3 activation and partly inhibited by a caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone. The finding that anti-G(D2) antibodies suppressed the cell growth and induced apoptosis of SCLC cells strongly suggested the usefulness of G(D2) as a target for the therapy of disastrous cancer, although the precise mechanisms for apoptosis remain to be clarified.

Antibodies, Monoclonal↗
PubMed2001

Expression of IL-1 beta and IL-8 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans.

The interaction between epithelial cells and microorganisms is the most important step in bacterial infections. Epithelial cells in response to exposure to pathogenic bacteria produce cytokines that initiate inflammation. However, little is known about the cytokine response of gingival epithelial cells to periodontopathogenic bacteria. Actinobacillus actinomycetemcomitans is thought to play a significant role in the initiation of periodontitis because of its bacteriological characteristics. In the present study, we investigated the cytokine induction by human gingival epithelial cells (HGEC) following exposure to A. actinomycetemcomitans in comparison with human gingival fibroblasts (HGF) in culture. Northern blot analysis showed that mRNAs of interleukin 1beta (IL-1beta) and IL-8, but not IL-6, in HGEC were induced in response to A. actinomycetemcomitans. Secretion of IL-8 by HGEC was also increased following A. actinomycetemcomitans challenge, whereas production of IL-1beta could not be detected. The levels of IL-8 and its mRNA were increased depending on the concentration of A. actinomycetemcomitans. The co-culture with HGF and A. actinomycetemcomitans resulted in an increase in the levels of IL-6 and IL-8 mRNA in HGF. However, HGF exposed to A. actinomycetemcomitans, showed no expression of IL-1beta mRNA. These findings demonstrated that HGEC and HGF stimulated with A. actinomycetemcomitans have different profiles in cytokine mRNA expression. Furthermore, A. actinomycetemcomitans may play an important role in amplifying the local immune response and in initiating inflammatory reaction through release of IL-8 from gingival epithelial cells.

Aggregatibacter actinomycetemcomitans↗
PubMed2001

Pure atmospheric pressure promotes an expression of osteopontin in human aortic smooth muscle cells.

Although the types of pathophysiological stimulation that initiate an overexpression of OPN have yet to be determined, we hypothesized that mechanical stress is one of the candidates which initiates OPN expression in vascular smooth muscle cells. Cell proliferation assay indicated that a pure atmospheric pressure of 160 mmHg activated cell proliferation by 11% in human aortic smooth muscle cells (HASMC) compared to nonpressurized controls. Immunoblot analysis probed with an anti-OPN antibody demonstrated a 50% increase in OPN. Dual-luciferase reporter assay demonstrated that OPN promoter, corresponding to the -771 through -1 region of OPN gene, was highly responsive to pure atmospheric pressure by ten times that of the control. From these observations, we concluded that pure atmospheric pressure directly promotes an expression of OPN in HASMC, with these results also suggesting that high blood pressure-mediated mechanical compression is involved in the process of atherosclerosis and remodeling via OPN expression in HASMC.

Animals↗
PubMed2001

Separation of signal and noise from in vivo optical recording in Guinea pigs using independent component analysis.

Optical recording in vivo severely suffers from the interference of heartbeat noise. So far, heartbeat noise has been minimized by subtracting from each experimental trial an average of interlaced control recordings. This method, however, is time-consuming and increases tissue damage due to phototoxicity. Here we applied independent component analysis (ICA) to in vivo optical recordings, for separation of auditory signals and noises. Our results show that ICA can be successfully used to separate sound-evoked signals and heartbeat noises. Compared with the previous method, ICA has a comparable power of separation and does not require background recordings.

Acoustic Stimulation↗
PubMed2001

Prognostic significance of lymphocyte infiltration following preoperative chemoradiotherapy and hyperthermia for esophageal cancer.

PURPOSE: Lymphocyte infiltration (LI) around cancerous lesions is an important immune response. The purpose of this study is to evaluate the prognostic significance of LI after preoperative treatment for esophageal cancer. METHODS AND MATERIALS: Preoperative chemoradiotherapy (CR therapy), either bleomycin 30 mg or cisplatin 120 mg/m(2) plus radiation 30 Gy, was performed on 51 cases with esophageal cancer, while hyperthermo-chemoradiotherapy (HCR therapy) was also indicated in 71 cases. Using resected specimens, both the histopathologic effectiveness and degree of LI to cancerous lesions were evaluated. RESULTS: The incidences of the cases in which preoperative treatment was effective were 56% and 92.3% in LI (-) and LI (++) group (p < 0.05). The presence of LI resulted in favorable prognosis; the 5-year survival rates of LI (++) and LI (+) patients were 75.5% and 46.1%, both of which were significantly better than LI (-) (27.8%, p < 0.05 and p < 0.01, respectively). Especially among cases whose preoperative treatment was moderately effective, a multivariate analysis revealed LI to be a favorable prognostic factor independent of other clinicopathologic factors (p = 0.0171). Regarding the preoperative treatment, the incidence of LI (++) was higher in the HCR group (16.9%) than in the CR group (2.0%, p < 0.01). CONCLUSIONS: LI appears to be a prognostic predictor after preoperative CR therapy while, in addition, simultaneous hyperthermia may stimulate LI in cases with esophageal cancer.

Analysis of Variance↗