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Biomedical subjects

M Nakada

Publications and source records attributed to M Nakada.

At least 19 recordsLinked to original sources
PubMed2006

The characteristics of simple muscle power by gripping: gender differences and reliability of parameters using various loads.

AIM: There are few studies on muscle power during local muscle contractions with a small range of motion such as in gripping. The purposes of this study were to clarify the properties of the developmental phase based on time series of muscle power output, the reliability of the parameters, their relationships and the load intensity derived peak power by gender differences, and to examine the possibility of evaluating muscle power using gripping. METHODS: Fifteen young males and 15 females participated in this study. Based on a crossover experimental design, each subject carried out 2 explosive grips at 20%, 30%, 40% and 50% loads of maximal using a voluntary grip contraction (MVC). The grip contraction velocities, sampled at 100 Hz, were measured accurately using a power instrument with an accelerometer. Muscle power curves were drawn from the product of the velocity and the set-up load. RESULTS: The cross-correlation coefficients between the trials for the average curve of the time-series moving distance, the velocity, and the power in any load were very high (over 0.95) in both genders. The reliability of each parameter was mostly good in both genders (intraclass correlation coefficient, ICC>0.75). The peak power curve differed between genders, and the curve around the peak value in females was irregular. CONCLUSIONS: A gender difference was found in the maximal power and the properties of the power curve. The maximal muscle power appeared at 30-50% MVC in males, and at 20-40% MVC in females. The peak power during the whole contraction, and the time to peak may reflect the conditions throughout the whole of the contraction. The new device used in this study to evaluate local regional muscle power (grip) is a very reliable and useful tool.

Adult↗
PubMed2003

Recurrent intracranial esthesioneuroblastoma outside the initial field of radiation with progressive dural and intra-orbital invasion.

A 55-year-old man presented with esthesioneuroblastoma in the right paranasal sinuses and orbita, extending into the right anterior and middle cranial fossa. He received a partial resection of tumour and post-operative radiotherapy, which was set with a central focus on the right orbit. Five years later, he came to our hospital with a complaint of left exophthalmos. Neuro-imaging revealed that the tumour recurred on the opposite side of the primary lesion, which was out side the irradiated field, with progressive invasion of the left temporal dura. The residual tumour in the irradiated field had reduced in size. He received gross total resection and post-operative radiotherapy. We would like to emphasize that radiotherapy is an important adjuvant therapy for esthesioneuroblastoma, and that the field setting for radiation therapy is extremely important.

Brain Neoplasms↗
PubMed2001

Suppression of membrane-type 1 matrix metalloproteinase (MMP)-mediated MMP-2 activation and tumor invasion by testican 3 and its splicing variant gene product, N-Tes.

Using expression cloning to screen a human fetal kidney cDNA library for regulator(s) of pro-matrix metalloproteinase (MMP)-2 processing mediated by membrane-type (MT) 1 MMP, we isolated a cDNA whose product interfered with pro-MMP-2 activation. It encodes the NH(2)-terminal 313-amino acid region of a calcium-binding proteoglycan, testican 3, with a 3-amino acid substitution at the COOH terminus and thus was named N-Tes. N-Tes comprises a signal peptide, a unique domain, a follistatin-like domain, and a Ca(2+)-binding domain but lacks a COOH-terminal thyroglobulin domain and two putative glycosaminoglycan attachment sites of testican 3. Pro-MMP-2 activation by MT3-MMP was also inhibited by the coexpression of N-Tes. Immunoprecipitation analysis demonstrated direct interaction of N-Tes with either MT1-MMP or MT3-MMP. Expression of testican 1 or testican 3 but not testican 2 also inhibited pro-MMP-2 activation by either MT1-MMP or MT3-MMP. Deletion and substitution of amino acids residues in N-Tes revealed that the unique NH(2)-terminal domain of N-Tes is responsible for the inhibition of pro-MMP-2 activation by MT-MMPs. Expression of N-Tes and testican 3 was detected in normal brain but down-regulated in glioma tissues. Transfection of either the N-Tes or testican 3 gene into U251 glioma cells or Madin-Darby canine kidney cells transformed by erbB2 suppressed their invasive growth in collagen gel. These results suggest that both N-Tes and testican 3 would interfere with tumor invasion by inhibiting MT-MMPs.

Alternative Splicing↗
PubMed2001

Expression of dominant-negative form of Ets-1 suppresses fibronectin-stimulated cell adhesion and migration through down-regulation of integrin alpha5 expression in U251 glioma cell line.

Ets transcription factors are associated with tumor malignancy. We reported previously that the stable transfection of the dominant-negative form of Ets-1 (Ets-DN) in the glioma cell line U251 induced down-regulation of urokinase-type plasminogen activator mRNA expression and invasiveness (M. Nakada et al., J. Neuropathol. Exp. Neurol., 58: 329-334, 1999). Here we analyzed effects of Ets-DN expression on cell adhesion, migration, and phosphorylation of focal adhesion kinase. U251 cells expressing Ets-DN (U251-DN) showed reduced cell adhesion, spreading, and extension of actin stress fibers on dishes coated with fibronectin but not on dishes coated with collagen. Migration of U251-DN cells was found to be significantly inhibited compared with that of parental cells when examined by wound-induced migration assay on fibronectin-coated dishes. Phosphorylation levels of focal adhesion kinase in U251-DN cells were also attenuated on dishes coated with fibronectin. Reduced expression level of integrin alpha5 subunit in U251-DN cells was demonstrated by semiquantitative reverse transcription-PCR analysis. Semiquantitative reverse transcription-PCR of surgical samples of brain tumors revealed that the expression level of Ets-1 mRNA correlated with that of integrin alpha5 mRNA in glioma. The experimental metastatic ability of U251-DN cells examined in chick embryo was considerably lower than that of parental cells. These results suggest that Ets-1 contributes to glioma malignancy by up- regulating expression of the integrin alpha5 subunit, which composes integrin alpha5beta1 and mediates intracellular signaling and the subsequent acceleration of the invasive process, including cell adhesion and migration.

Animals↗
PubMed2001

Differential role of CD80 and CD86 molecules in the induction and the effector phases of allergic rhinitis in mice.

Selective involvement of CD80 and/or CD86 in the differentiation of T-helper (Th)1 and Th2 was seen in several diseases. In this study, we sought to determine the differential roles of CD80 and CD86 in the induction and effector phase of allergic rhinitis using Schistosoma mansoni egg antigen (SEA) as a specific Ag. Intranasal sensitization with SEA in BALB/c mice elicited a strong Th2 response including SEA-specific IgE production, nasal eosinophilia, and IL-4 and IL-5 production by nasal lymphocytes after Ag challenge. Blockade of CD80 at the induction phase significantly inhibited these manifestations, whereas no effect was observed by CD86 blockade. In contrast, the simultaneous blockade of both CD80 and CD86 during the effector phase partially inhibited IgE and IgG(1) production and nasal eosinophilia, although either blockade of CD80 or CD86 during the phase failed to inhibit these responses. Flow cytometric analysis on nasal mononuclear cells showed that CD80 but not CD86 was preferentially expressed on non-B cells by in vitro SEA stimulation in unsensitized mice. However, both CD80 and CD86 expression were significantly augmented by in vitro SEA stimulation in sensitized mice. Our results suggest the differential roles and expression of CD80 and CD86 in the development of allergic rhinitis.

Animals↗
PubMed2001

Homologous-pairing activity of the human DNA-repair proteins Xrcc3.Rad51C.

The human Xrcc3 protein is involved in the repair of damaged DNA through homologous recombination, in which homologous pairing is a key step. The Rad51 protein is believed to be the only protein factor that promotes homologous pairing in recombinational DNA repair in mitotic cells. In the brain, however, Rad51 expression is extremely low, whereas XRCC3, a human homologue of Saccharomyces cerevisiae RAD57 that activates the Rad51-dependent homologous pairing with the yeast Rad55 protein, is expressed. In this study, a two-hybrid analysis conducted with the use of a human brain cDNA library revealed that the major Xrcc3-interacting protein is a Rad51 paralog, Rad51C/Rad51L2. The purified Xrcc3.Rad51C complex, which shows apparent 1:1 stoichiometry, was found to catalyze the homologous pairing. Although the activity is reduced, the Rad51C protein alone also catalyzed homologous pairing, suggesting that Rad51C is a catalytic subunit for homologous pairing. The DNA-binding activity of Xrcc3.Rad51C was drastically decreased in the absence of Xrcc3, indicating that Xrcc3 is important for the DNA binding of Xrcc3.Rad51C. Electron microscopic observations revealed that Xrcc3.Rad51C and Rad51C formed similar filamentous structures with circular single-stranded DNA.

Base Sequence↗
PubMed2001

Roles of membrane type 1 matrix metalloproteinase and tissue inhibitor of metalloproteinases 2 in invasion and dissemination of human malignant glioma.

OBJECT: Acquisition of invasive and metastatic potentials through proteinase expression is an essential event in tumor progression. Among proteinases, matrix metalloproteinases (MMPs) are thought to play a key role in tumor progression through the degradation of the extracellular matrix. In the present study, the authors examined the role of MMP-2 (gelatinase A) and membrane type 1 MMP (MT1-MMP), an activator of the zymogen of MMP-2, proMMP-2, together with tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in the invasion of astrocytic tumors in humans. METHODS: Analyses performed using sandwich enzyme immunoassays demonstrated that the production levels of pro-MMP-2 and TIMP-1, but not TIMP-2, are significantly higher in glioblastomas multiforme than in other grades of astrocytic tumors. Quantitative reverse transcription-polymerase chain reaction indicated that MT1-MMP is expressed predominantly in glioblastoma tissues, and its expression levels are significantly enhanced as tumor grade increases. In addition, the expression levels and proMMP-2 activation ratio were remarkably higher in glioblastomas associated with cerebrospinal fluid (CSF) dissemination than in those not associated with CSF dissemination. In contrast, an examination of TIMP-2 levels showed a reverse correlation. Like MT1-MMP, TIMP-1 and TIMP-2 were immunolocalized to neoplastic cells in glioblastoma samples. To study the roles of these molecules in the invasion of astrocytic tumors more fully, stable transfectants expressing the MT1-MMP gene were developed in a U251 human glioblastoma cell line. The MT1-MMP transfectants displayed prominent activation of proMMP-2 and invasive growth in three-dimensional collagen gel; however, mock transfectants and parental cells displayed noninvasive growth without the activation. The invasion and gelatinolytic activity of the transfectants were completely inhibited by addition of recombinant TIMP-2, but not recombinant TIMP-1. CONCLUSIONS: These results indicate that MT1-MMP may contribute to tumor invasion and CSF dissemination of glioblastoma cells on the basis of an imbalance of TIMP-2.

Astrocytoma↗
PubMed2000

Preparation of novel synthons, uniquely functionalized tetrahydrofuran and tetrahydropyran derivatives.

The dianion of the acetoacetic ester reacts with epibromohydrin derivatives to afford a mixture of (Z)-2-alkoxycarbonylmethylidenetetrahydrofuran derivative and (E)-2-alkoxycarbonylmethylidenetetrahydropyran derivative. The selective formation of the tetrahydrofuran derivative is achieved by the use of LiClO4 as the additive. The preparation of the optically active tetrahydrofuran derivatives and tetrahydropyran derivatives is also examined, and the optical purity and absolute configuration of the products is elucidated.

Furans↗
PubMed1999

Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors.

Three different membrane-type matrix metalloproteinases (MT1-, MT2-, and MT3-MMPs) are known to activate in vitro the zymogen of MMP-2 (pro-MMP-2, progelatinase A), which is one of the key MMPs in invasion and metastasis of various cancers. In the present study, we have examined production and activation of pro-MMP-2, expression of MT1-, MT2-, and MT3-MMPs and their correlation with pro-MMP-2 activation, and localization of MMP-2, MT1-MMP, and MT2-MMP in human astrocytic tumors. The sandwich enzyme immunoassay demonstrates that the production levels of pro-MMP-2 in the anaplastic astrocytomas and glioblastomas are significantly higher than that in the low-grade astrocytomas (P<0.05 and P<0.01, respectively), metastatic brain tumors (P<0.05), or normal brains (P<0.01). Gelatin zymography indicates that the pro-MMP-2 activation ratio is significantly higher in the glioblastomas than in other astrocytic tumors (P<0.01), metastatic brain tumors (P<0.01), and normal brains (P<0.01). The quantitative reverse transcription polymerase chain reaction analyses demonstrate that MT1-MMP and MT2-MMP are expressed predominantly in glioblastoma tissues (17/17 and 12/17 cases, respectively), and their expression levels increase significantly as tumor grade increases. MT3-MMP is detectable in both astrocytic tumor and normal brain tissues, but the mean expression level is approximately 50-fold lower compared with that of MT1-MMP and MT2-MMP in the glioblastomas. The activation ratio of pro-MMP-2 correlates directly with the expression levels of MT1-MMP and MT2-MMP but not MT3-MMP. In situ hybridization indicates that neoplastic astrocytes express MT1-MMP and MT2-MMP in the glioblastoma tissues (5/5 cases and 5/5 cases, respectively). Immunohistochemically, MT1-MMP and MT2-MMP are localized to the neoplastic astrocytes in glioblastoma samples (17/17 cases and 12/17 cases, respectively), which are also positive for MMP-2. In situ zymography shows gelatinolytic activity in the glioblastoma tissues but not in the normal brain tissues. These results suggest that both MT1-MMP and MT2-MMP play a key role in the activation of pro-MMP-2 in the human malignant astrocytic tumors and that the gelatinolytic activity is involved in the astrocytic tumor invasion.

Adenocarcinoma↗
PubMed1999

The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb.

BACKGROUND/PURPOSE: The type of renal dysplasia resulting from obstructive uropathy depends on the completeness of the obstruction and its timing with respect to the stage of glomerulogenesis at the time of the obstruction. The authors created a successful obstructive uropathy model in the female fetal lamb to demonstrate the differing pathogenesis of renal dysplasia. METHODS: Female fetal lambs at 60 and 90 days' gestation had their urethra and urachus ligated transabdominally and were delivered by cesarean section at 145 days (full term). Kidney length and cortical thickness were measured, and samples were examined histologically. In the lambs operated on at 90 days, the urine was collected at delivery and Na and CI were measured and compared with the results obtained from normal full-term lambs. RESULTS: Seven of 10 female lambs had hydronephrosis or dysplastic kidneys. The cortext to kidney length ratio was 10+/-3% in the 90-days hydronephrotic group versus 29+/-6% in the controls (P<.001). Morphologically, the 90-day model had dilatation of the collecting tubules with normal glomerular numbers. The 60-day model had tubular cysts with fibromuscular cuffing and reduced glomerular numbers. The fetal urine Na was 47+/-3.3 mmol/L in controls versus 78+/-24 mmol/L in the hydropnephrotic lambs (P<.05). The urine CI in these lambs was 38+/-8.6 mmol/L in controls versus 55+/-14.5 mmol/L in the hydronephrotic lambs (P<.05). CONCLUSIONS: An obstructive uropathy model was created in female fetal lambs. There were no dysplastic changes in the kidneys in lambs operated on at 90 days' gestation, but there were definite dysplastic changes in those operated on at 60 days. Concentrations of Na and CI in the fetal urine are higher than normal in the 90-day model.

Animals↗
PubMed1999

CD80 (B7-1) and CD86 (B7-2) antigens on house dust mite-specific T cells in atopic disease function through T-T cell interactions.

BACKGROUND: CD80 (B7-1) and CD86 (B7-2) play an important role in antigen presentation to effector cells. Recent studies have demonstrated that these costimulatory molecules are also expressed on activated T cells. However, the functional role of CD80 and CD86 expressed on allergen-specific T cells in atopic diseases has not yet been clarified. OBJECTIVE: We sought to determine the functional role of CD80 and CD86 expressed on allergen-specific T cells in atopic diseases. METHODS: We assayed the expression of CD80 and CD86 on allergen-specific T-cell lines from patients with perennial allergic rhinitis stimulated by Dermatophagoides farinae-crude (Der f-c) antigen, 1 of the major allergens causing house dust mite allergy. T-cell proliferation induced by Der f-c-specific T-T cell interactions was measured, and the role of CD80 and CD86 in this proliferation was examined. In addition, we compared the proportion of CD45RO+CD86(+) T cells in primary culture of PBMCs stimulated by Der f-c antigen between patients with perennial allergic rhinitis and control subjects. RESULTS: On T-cell activation, CD86 antigen was upregulated earlier than CD80. Both CD80 and CD86 expressed on Der f-c-specific T cells could provide costimulatory signals to induce allergen-specific T-cell proliferation that was partially inhibitable by both anti-CD80 and anti-CD86 mAbs. The proportion of CD45RO+CD86(+) T cells in primary culture from atopic patients was significantly higher than that from control subjects. CONCLUSION: These results suggest that costimulatory molecules, such as CD80 and CD86, expressed on allergen-specific T cells may be involved in the amplification of allergen-specific immune responses through T-T cell interactions in atopic diseases.

Adult↗
PubMed1999

Active oxygen species generation and cellular damage by additives of parenteral preparations: selenium and sulfhydryl compounds.

We investigated the relationship between active oxygen species (AOS) generation and cultured vascular endothelial cellular damage caused by simultaneous exposure to selenium compounds and sulfhydryl compounds such as cysteine (Cys) or reduced glutathione (GSH). Selenium compounds, selenite, selenate or selenomethionine (SeMet), are added to total parenteral nutrition (TPN) and intravenously administered. We confirmed by luminol dependent chemiluminescence, an indicator of AOS generation, that selenite generates AOS in the presence of clinical concentrations of sulfhydryl compounds, 0.5 mM Cys or 0.5 mM GSH, and that the amount of AOS generated reaches the maximum when their mole ratio is 1:50. However, AOS generation was not observed after simultaneous administration of various concentrations of selenate or SeMet with sulfhydryl compounds. Moreover, simultaneous exposure to 10 microM selenite and sulfhydryl compounds was found to result in significant increases in the [3H]-adenine and lactate dehydrogenase (LDH) release rates from cells, a significant decrease in the amount of cellular protein, and enhancement of cellular damage as compared with after exposure to selenite alone. However, simultaneous exposure to 10 microM selenate or 10 microM SeMet together with sulfhydryl compounds did not induce cellular damage. These findings revealed that selenite generates AOS and causes cellular damage in the presence of sulfhydryl compounds. Accordingly, it seems better to choose selenate or SeMet instead of selenite when a selenium compound is to be added to TPN.

Adenine↗
PubMed1999

Prevalence and prediction of allergic rhinitis using questionnaire and nasal smear examination in schoolchildren.

Allergic rhinitis is a common condition among schoolchildren. However, little is known about the prevalence of nasal eosinophilia. We investigated the prevalence of rhinitis via questionnaire and nasal smears for eosinophils. The questionnaire was administered in 1992 and 1995. Complete responses were obtained from 1044 and 431 schoolchildren, respectively, of whom 26.5% and 22.5% claimed to have nasal symptoms. Nasal smears were taken in 1992, 1993 and 1994, and 415, 285 and 384 samples were collected, respectively. Positive eosinophilia were seen in 39.8%, 35.1% and 35.9% children in 1992, 1993 and 1994, respectively. In 1992, we utilized both questionnaire and nasal smears simultaneously to evaluate 415 schoolchildren. Of 415 schoolchildren, 72 (17.3%) had both nasal symptoms and nasal eosinophilia. Interestingly, those who showed positive eosinophilia in 1992, especially those who had eosinophilia with nasal symptoms, had significantly higher incidence of nasal symptoms three years later in 1995 than those who showed negative eosinophilia in 1992. These results suggest that nasal eosinophilia in schoolchildren are associated with subsequent nasal symptoms, and that nasal smear examination may be a potentially valuable test to predict prolonged or recurrent allergic rhinitis.

Adolescent↗
PubMed1999

Ets-1 positively regulates expression of urokinase-type plasminogen activator (uPA) and invasiveness of astrocytic tumors.

Acquisition of invasive/metastatic potential through protease expression is an essential event in tumor progression. Urokinase-type plasminogen activator (uPA) is often expressed in human tumors including astrocytic tumors. To elucidate the possible regulation mechanism of uPA gene expression in astrocytic tumors, quantitative RT-PCR was performed to monitor the gene expression of uPA and the transcription factor Ets-1. Expression of uPA and Ets-1 genes was up-regulated in astrocytic tumors, but was not detected in normal brain. Expression levels of uPA correlated with those of Ets-1, and also with the degree of malignancy of the tumors. Glioma cell lines U251, U87, and T98G also expressed both uPA and Ets-1 genes. Expression of a dominant negative mutant of Ets-1, which competitively inhibits Ets-1 function, abolished uPA expression in U251 cells. Parental U251 cells showed invasive growth in 3-dimensional collagen gel, however, cells expressing dominant negative Ets-1 failed to grow invasively in the collagen gel. Treatment of U251 cells with the uPA inhibitor aprotinin also inhibited spreading of cells into collagen gel. These results suggest that Ets-1 plays an essential role in regulation of uPA gene expression, which in turn contributes to the invasive growth of astrocytic tumors.

Brain Neoplasms↗
PubMed1998

The cluster of arachnoid diverticula in the occipital bone: report of two cases with literature review.

The authors report two cases of multicentric osteolytic lesions in the occipital bone without any history of head trauma. The excisional biopsy of the first case revealed that the lesion was multicentric but a continuous cavity with the subarachnoid space through various sizes of dural defect, and the cavities were covered by arachnoid lining. Together with the previously reported similar 5 cases, the characteristic common feature is multicentric osteolytic lesions in the occipital bone at advanced age without marginal sclerosis. "The cluster of arachnoid diverticula in the occipital bone (CADOB)" is probably the most appropriate term for these non-traumatic lesions with the following characteristics: elderly patients, occipital bone, midline, multiple, intact outer table, nonsclerotic margin and without history of trauma. Operation may not be indicated because of its non-progressive and benign nature.

Aged↗
PubMed1998

Efficacy of exogenous fibronectin in wound healing in malnourished rats.

BACKGROUND/PURPOSE: Fibronectin (FN) plays an important role in fibrin matrix formation during the wound healing process. The authors investigated whether exogenous FN increases the bursting strength (BS) of surgical wounds in malnourished rats. METHODS: Ninety rats were grouped according to three nutritional conditions (n = 30 in each group). All animals underwent a transverse celiotomy after 3 weeks of feeding, and FN (2 mg/body/day) was given postoperatively to 15 rats in each of the three groups. Wound BS was measured on postoperative days (PODs) 3, 5, and 7 after removal of the sutures. RESULTS: BS in normally nourished rats (group N; 142.6+/-23.4 mmHg) was significantly higher than that in protein malnourished rats (group PM, 110.2+/-11.2 mm Hg) and protein/ calorie (Cal)-malnourished rats (group PCM, 76.5+/-10.7 mm Hg) on POD 7 (P<.01). However, BS values for groups PM + FN (147.0+/-21.1 mmHg) and PCM + FN (115.1+/-28.9 mm Hg) were intensified significantly in comparison with groups PM and PCM (P<.01). Plasma FN levels in rats of the three FN nontreated groups were similarly decreased on POD 3 or 5, but returned to the preoperative level on POD 7, whereas those for the other three FN-treated groups increased after POD 3. CONCLUSION: Intravenous administration of FN might strengthen the weakened wounds of malnourished animals.

Abdominal Injuries↗