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Biomedical subjects

H Nakagawa

Publications and source records attributed to H Nakagawa.

At least 19 recordsLinked to original sources
PubMed2007

Taxane-induced scleroderma.

We report five women who presented with scleroderma due to taxanes, mimicking systemic sclerosis. All five patients had received taxane chemotherapy for the treatment of metastatic breast cancer. Marked oedema began first, followed by skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months after the administration of taxane in all patients. Skin biopsies showed full-layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic cell infiltration. These cases resemble systemic sclerosis in terms of their clinical course and histological findings. However, clinical findings including Raynaud's phenomenon and pulmonary fibrosis as well as immunological abnormalities associated with systemic sclerosis were not detected in any of the patients. Although the mechanisms have not been clarified, it should be noted that taxane is causally involved in the formation of scleroderma-like skin conditions.

Adult↗
PubMed2006

A case of glossopharyngeal zoster diagnosed by detecting viral specific antigen in the pharyngeal mucous membrane.

Glossopharyngeal nerve paralysis caused by varicella zoster virus reactivation is rare. We present a case of glossopharyngeal zoster confirmed by direct immunofluorescence staining for virus antigens. A 35-year-old man presented with right-sided, severe swallowing pain and dysgeusia. Physical examination showed a loss of ipsilateral gag reflex. White spots on the posterior wall of the right pyriform sinus were seen by laryngofibroscopy, and a loss of taste on the right posterior part of the tongue was confirmed by gustometry using the filter paper disc method. The varicella zoster virus antigen was revealed by direct immunofluorescence staining by fluorescein isothiocyanate labelled mouse monoclonal antibody specific for varicella zoster virus glycoprotein, using samples obtained from the mucosal lesion by abrasion with a cotton swab. The patient was treated by intravenous administration of acyclovir. His throat pain and dysgeusia completely resolved. We discuss the advantages of direct immunofluorescence staining for varicella zoster virus antigen for the diagnosis of glossopharyngeal zoster.

Acyclovir↗
PubMed2006

AKT induces senescence in primary esophageal epithelial cells but is permissive for differentiation as revealed in organotypic culture.

Epidermal growth factor receptor (EGFR) overexpression and activation is critical in the initiation and progression of cancers, especially those of epithelial origin. EGFR activation is associated with the induction of divergent signal transduction pathways and a gamut of cellular processes; however, the cell-type and tissue-type specificity conferred by certain pathways remains to be elucidated. In the context of the esophageal epithelium, a prototype stratified squamous epithelium, EGFR overexpression is relevant in the earliest events of carcinogenesis as modeled in a three-dimensional organotypic culture system. We demonstrate that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, and not the MEK/MAPK (mitogen-activated protein kinase) pathway, is preferentially activated in EGFR-mediated esophageal epithelial hyperplasia, a premalignant lesion. The hyperplasia was abolished with direct inhibition of PI3K and of AKT but not with inhibition of the MAPK pathway. With the introduction of an inducible AKT vector in both primary and immortalized esophageal epithelial cells, we find that AKT overexpression and activation is permissive for complete epithelial formation in organotypic culture, but imposes a growth constraint in cells grown in monolayer. In organotypic culture, AKT mediates changes related to cell shape and size with an expansion of the differentiated compartment.

Cell Differentiation↗
PubMed2006

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment.

OBJECTIVES: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. METHODS: A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary beta2-MG (microglobulin) > or =1000 microg/gCr. Mortality risk analysis was performed using Cox's proportional model to compare mortality between subjects with urinary beta2-MG > or =1000 and <1000 microg/gCr, and to investigate the relationship between the degree of urinary beta2-MG and mortality. RESULTS: Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary beta2-MG > or =1000 microg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary beta2-MG > or =1000 microg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary beta2-MG > or =1000 microg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary beta2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary beta2-MG > or =10000 microg/gCr in both sexes. CONCLUSION: Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Aged↗
PubMed2006

Histone deacetylase inhibitor FK228 suppresses the Ras-MAP kinase signaling pathway by upregulating Rap1 and induces apoptosis in malignant melanoma.

Histone deacetylase (HDAC) inhibitors are expected to be effective for refractory cancer because their mechanism of action differs from that of conventional antineoplastic agents. In this study, we examined the effect of the HDAC inhibitor FK228 on malignant melanoma, as well as its molecular mechanisms. FK228 was highly effective against melanoma compared with other commonly used drugs. By comparing the gene expression profiles of melanoma cells and normal melanocytes, we defined a subset of genes specifically upregulated in melanoma cells by FK228, which included Rap1, a small GTP-binding protein of the Ras family. The expression of Rap1 mRNA and protein increased in FK228-treated melanoma cells in both a dose- and a time-dependent manner. A decrease in the phosphorylation of c-Raf, MEK1/2, and ERK1/2 was accompanied by an increase in Rap1 expression in both FK228-treated and Rap1-overexpressing cells. Inhibition of Rap1 upregulation by small interfering RNA (siRNA) abrogated the induction of apoptosis and suppression of ERK1/2 phosphorylation in FK228-treated melanoma cells. These results indicate that the cytotoxic effects of FK228 are mediated via the upregulation of Rap1. Furthermore, we found that Rap1 was overexpressed and formed a complex with B-Raf in melanoma cell lines with a V599E mutation of B-Raf. The siRNA-mediated abrogation of Rap1 overexpression increased the viability of these cells, suggesting that Rap1 is also an endogenous regulator of Ras-MAP kinase signaling in melanomas.

Animals↗
PubMed2006

Retinoic acid-inducible gene-I is induced in gingival fibroblasts by lipopolysaccharide or poly IC: possible roles in interleukin-1beta, -6 and -8 expression.

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH family of proteins, and little is known of its biological function in the oral region. We previously reported that interleukin 1beta (IL-1beta) induced RIG-I expression in gingival fibroblasts. In this study, we studied the mechanism of RIG-I expression induced by lipopolysaccharide (LPS) or double-stranded RNA (dsRNA) in gingival fibroblasts. We also addressed the role of RIG-I in the expression of IL-1beta, IL-6 and IL-8 in gingival fibroblasts stimulated with LPS or dsRNA. We stimulated cultured human gingival fibroblasts with LPS or dsRNA, and examined the expression of RIG-I mRNA and protein. The effect of cycloheximide, a protein synthesis inhibitor, on RIG-I induction by these stimuli was examined. The expression of IL-1beta, IL-6 and IL-8 in gingival fibroblasts transfected with RIG-I cDNA stimulated with LPS or dsRNA was examined. LPS or dsRNA induced the expression of mRNA and protein for RIG-I in concentration- and time-dependent manners. We also examined the localization of RIG-I, and found that it was expressed in cytoplasm. Cycloheximide did not suppress the LPS or dsRNA-induced RIG-I expression. Introduction of RIG-I cDNA into gingival fibroblasts resulted in enhanced expression of IL-1beta, IL-6 and IL-8; moreover, overexpression of RIG-I stimulated with LPS or dsRNA synergistically increased expression of IL-1beta, IL-6 and IL-8. RIG-I may have important roles in the innate immune response in the regulation of IL-1beta, IL-6 and IL-8 expression in gingival fibroblasts in response to LPS and dsRNA.

Blotting, Western↗
PubMed2006

G-protein beta3 subunit variant C825T is a risk factor for hypertension in Japanese females--a prospective cohort study over 5 years.

The relationship between the G-protein beta3 subunit variant C825T and risk of hypertension was examined in a prospective cohort study of Japanese workers. This study included observations over a 5-year period from 1997 to 2002 on 878 males and 692 females who were normotensive at entry. Hypertension was defined as systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg, or taking antihypertensive medication. Pooled logistic regression analyses were performed using C825T genotype, age, body mass index, lifestyle, and the result of blood chemistries as the covariates. Multivariate pooled logistic regression analysis showed the risk of hypertension was 2.31 times higher in females with the TT genotype than in females with the CC genotype (95% confidence interval: 1.07-4.96), after adjustment for the effects of other potential covariates. In contrast, no significant risk of hypertension was observed with the TT genotype in male subjects. This study indicates that the 825T allele is an independent risk factor for hypertension in Japanese females, and suggests that this polymorphism may be a beneficial prognostic marker for hypertension in the general Japanese female population.

Adult↗
PubMed2006

Diffusion anisotropy and diffusivity of white matter tracts within the temporal stem in Alzheimer disease: evaluation of the "tract of interest" by diffusion tensor tractography.

PURPOSE: Our aim was to determine whether diffusion anisotropy and diffusivity of white matter tracts of the temporal stem in patients with Alzheimer (AD) can be evaluated independently by using diffusion tensor tractography. MATERIALS AND METHODS: Subjects included 15 patients with AD (11 women and 4 men; mean age, 74 years) and 15 age-matched control subjects (11 women and 4 men; mean age, 72 years). Diffusion tensor images were acquired by using echo-planar imaging. We drew tractographies of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop, with diffusion tensor analysis software. We measured diffusion anisotropy, diffusivity, and the number of voxels along the "tracts of interest" and used the Student t test to compare results between patients with AD and controls. RESULTS: Values of diffusion anisotropy of the bilateral uncinate fasciculus and left inferior occipitofrontal fasciculus were significantly lower for patients with AD than for controls. Also, values of diffusivity in the bilateral uncinate fasciculus were significantly greater for patients with AD than for controls. There was no significant difference in diffusion anisotropy or diffusivity along Meyer's loop between the 2 groups. There was no significant difference in the number of voxels included in all constructed tracts between patients with AD and controls. CONCLUSION: White matter tracts of the temporal stem can be evaluated independently by using diffusion tensor tractography, which appears to be a promising technique for determining changes in white matter in degenerative diseases.

Aged↗
PubMed2005

Immunohistochemistry of symptomatic hypertrophy of the posterior longitudinal ligament with special reference to ligamentous ossification.

STUDY DESIGN: Immnunohistochemical staining of the thickened posterior longitudinal ligament of the cervical spine. OBJECTIVES: To clarify the histological characteristics of hypertrophy of the posterior longitudinal ligament (HPLL) of the cervical spine and the relationship between HPLL and ossification of the posterior longitudinal ligament (OPLL). SETTING: Aichi Medical University, Aichi, Japan. METHODS: Eight specimens of HPLL and two of OPLL were obtained during anterior decompressive surgery on the cervical spine from patients with myelopathy. Hematoxylin and eosin staining, alcian blue staining and immunohistochemical staining with antibodies against bone morphogenetic protein (BMP), transforming growth factor (TGF)-beta, proliferating cell nuclear antigen (PCNA), alkaline phosphatase (ALP) and osteopontin (OPN) were carried out on the specimens. RESULTS: HPLL showed hyalinoid degeneration, the proliferation of chondrocytes and fibroblast-like spindle cells, infiltration of vessels and small ossification. In four cases, chondroid tissue was prominent with chondrocytes, which were expressed by ALP and OPN. The cells in HPLL were weakly or moderately stained by BMP, TGF-beta and PCNA. Their expression was similar to that of OPLL. Immunohistochemical staining was negative for all cells in the control cases. CONCLUSIONS: Histological and biochemical evidence supports the hypothesis that HPLL transforms into OPLL. The positive expression of BMP and TGF-beta in HPLL cells of myelopathic patients, and their similarity to OPLL, suggest that these cells have the potential to differentiate into osteogenic cells. Of note, neither BMP nor TGF-beta was demonstrated in the PLL of control subjects. Furthermore, the expression of chondrocytes by ALP and OPN in cartilage-prominent HPLL suggests that the cartilage can be replaced by new bone.

Aged↗
PubMed2005

Flowering response of rice to photoperiod and temperature: a QTL analysis using a phenological model.

In this study we have attempted to quantify the thermal and photoperiodical responses of rice (Oryza sativa L.) flowering time QTLs jointly by a 'date-of-planting' field experiment of a mapping population, and a 'phenological model' analysis that separately parameterizes the two responses, based on daily temperature, daily photoperiod and flowering date. For this purpose, the 'three-stage Beta model', which parameterizes the sensitivity to temperature (parameter alpha), the sensitivity to photoperiod (parameter beta), and earliness under optimal conditions (10 h photoperiod at 30 degrees C) (parameter G), was applied to 'Nipponbare' x 'Kasalath' backcross inbred lines that were transplanted on five dates. QTLs for the beta value were detected in the four known flowering time QTL (Hd1, Hd2, Hd6 and Hd8) regions, while QTLs for the G value were detected only in the Hd1 and Hd2 regions. This result was consistent with previous reports on near-isogenic lines (NILs) of Hd1, Hd2 and Hd6, where these loci were involved in photoperiod sensitivity, and where Hd1 and Hd2 conferred altered flowering under both 10 and 14 h photoperiods, while Hd6 action was only affected by the 14 h photoperiod. Hd8 was shown to control photoperiod sensitivity for the first time. Interestingly, Hd1 and Hd2 were associated with a QTL for the alpha value, which might support the previous hypothesis that the process of photoinduction depends on temperature. These results demonstrate that our approach can effectively quantify environmental responses of flowering time QTLs without controlled environments or NILs.

Flowers↗
PubMed2005

Intraoperative electrical stimulation of the pelvic splanchnic nerves during nerve-sparing radical hysterectomy.

OBJECTIVES: This study sought to determine whether intraoperative electrical stimulation (IES) of pelvic splanchnic nerves (PSNs) while monitoring bladder contraction was useful to predict postoperative bladder function during conventional nerve-sparing radical hysterectomy. METHODS: Seventeen patients with stage Ib or IIa cervical cancer underwent conventional radical hysterectomy. IES was performed in all cases, stimulating the roots of PSN, the posterior sheath of the vesicouterine ligament (PVL) and the dorsal area of the ligament. After resection of the uterus, the PSN roots were stimulated again. Bladder function was evaluated by urodynamic study (UDS) preoperatively and 3 months after surgery. RESULTS: The results of IES were consistent with bladder function evaluated by postoperative UDS. In 13 of 17 cases, an increased intravesical pressure was observed with IES of the PSN roots after uterus resection. Nine of 13 cases showed marked detrusor contraction with UDS 3 months after surgery and were able to void without using abdominal pressure except in one case. In the remaining 4 of 17 cases, no response could be detected to IES on either side. Three cases voided using abdominal pressure and one used clean intermittent self-catheterization without spontaneous voiding. CONCLUSIONS: IES while monitoring intravesical pressure during radical hysterectomy represents a technically simple and useful procedure for the prediction of postoperative bladder function.

Adenocarcinoma↗
PubMed2005

Postmortem study of the spinal cord showing snake-eyes appearance due to damage by ossification of the posterior longitudinal ligament and kyphotic deformity.

UNLABELLED: CLINICAL DESIGN: A case report. OBJECTIVES: To elucidate the clinical role of snake-eyes appearance in this case, correlation between radiological, clinical and postmortem study was performed. SETTING: Aichi, Japan. CASE REPORT: A 73-year-old man developed weakness and pain in the upper limbs due to kyphotic deformity secondary to laminectomy for cervical ossification of the posterior longitudinal ligament. Axial magnetic resonance imaging revealed snake-eyes appearance from C4 to C6. He died of acute myocardial infarction 3 months after anterior decompressive surgery. RESULTS: A postmortem examination of the cervical spinal cord showed small cystic six necrotic areas at the junction of the central gray matter and the ventrolateral posterior column, one in the right and one in the left, in association with neuronal loss in the anterior horn. CONCLUSIONS: Bilateral small intramedullary high-signal areas known as 'snake-eyes appearance' located around the central gray matter and the ventrolateral posterior column, are associated with neuronal loss in the compressed anterior horn that played an important role in worsening weakness of the upper limbs.

Aged↗
PubMed2005

Organic matter released from activated sludge bacteria cells during their decay process.

Organic matter released from activated sludge bacteria is a considerable issue in the wastewater reclamation process. In this study, we focused 2-keto-3-deoxyoctulosonic acid in the Lipopolysaccharide existed in the gram-negative bacterial cell wall as an index of organic matter released from bacteria, and investigated the fate of 2-keto-3-deoxyoctulosonic acid in the aerated and ultrasonicated activated sludge samples. The results shows 1) 2-keto-3-deoxyoctulosonic acid concentration in the hydrolyzed sample was higher than non-hydrolyzed sample, and this implied that 2-keto-3-deoxyoctulosonic acid existed in the water phase as a monomer and also as a polymer such as Lipopolysaccharide form and their fragments; 2) the value of (2-keto-3-deoxyoctulosonic acid)/(dissolved organic carbon) ratio did not change in the sludge sonication process and was approximately 0.0006, on the other hand, in the bacteria decay process, the ratio varied from zero to approximately 0.0012; 3) the linear relationship was observed between the degraded heterotrophic biomass and the generated 2-keto-3-deoxyoctulosonic acid; and 4) 2-keto-3-deoxyoctulosonic acid might be considered as an index of organic matter originated from activated sludge bacteria cell.

Gram-Negative Bacteria↗