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Biomedical subjects

T Takenouchi

Publications and source records attributed to T Takenouchi.

At least 19 recordsLinked to original sources
PubMed2006

The effects of FasL on inflammation and tumor survival are dependent on its expression levels.

The apoptosis-inducing Fas ligand (FasL) is expressed in a variety of human cancers and has been implicated in tumor immune evasion. Paradoxically, ectopic expression of FasL in experimental tumors triggers a neutrophil-mediated inflammatory response and tumor rejection. To resolve these conflicting findings, we have established B16 melanoma and P29 Lewis lung carcinoma lines expressing different levels of FasL and examined their tumorigenicity in vivo. While tumors with a high level of FasL were rapidly rejected as previously reported, those expressing a low level of FasL were not rejected but grew faster than did FasL-negative parental cells. The growth enhancement of FasL(low) tumors was not observed in T-cell-deficient nude mice, suggesting that FasL expressed in tumors at low levels counteracted against T-cell-dependent antitumor responses. In support of this notion, FasL(low) tumors were found to grow faster than parental cells in mice that had acquired tumor-specific immunity. Furthermore, histological examinations revealed apoptosis of lymphocytes in tissue sections of FasL(low) tumors. These results collectively suggest that FasL on tumors is a double-edged sword: at high levels it triggers tumor rejection whereas at low levels it facilitates tumor growth possibly by suppressing antitumor immune responses.

Animals↗
PubMed2006

Low-energy electrodynamics of superconducting diamond.

Heavily boron-doped, diamond films can become superconducting with critical temperatures Tc well above 4 K. Here we first measure the reflectivity of such a film down to 5 cm(-1), by also using coherent synchrotron radiation. We thus determine the optical gap 2Delta, the field penetration depth lambda, the range of action of the Ferrell-Glover-Tinkham sum rule, and the electron-phonon spectral function alpha2F(omega). We conclude that diamond behaves as a dirty BCS superconductor.

Journal Article↗
PubMed2005

Origin of the metallic properties of heavily boron-doped superconducting diamond.

The physical properties of lightly doped semiconductors are well described by electronic band-structure calculations and impurity energy levels. Such properties form the basis of present-day semiconductor technology. If the doping concentration n exceeds a critical value n(c), the system passes through an insulator-to-metal transition and exhibits metallic behaviour; this is widely accepted to occur as a consequence of the impurity levels merging to form energy bands. However, the electronic structure of semiconductors doped beyond n(c) have not been explored in detail. Therefore, the recent observation of superconductivity emerging near the insulator-to-metal transition in heavily boron-doped diamond has stimulated a discussion on the fundamental origin of the metallic states responsible for the superconductivity. Two approaches have been adopted for describing this metallic state: the introduction of charge carriers into either the impurity bands or the intrinsic diamond bands. Here we show experimentally that the doping-dependent occupied electronic structures are consistent with the diamond bands, indicating that holes in the diamond bands play an essential part in determining the metallic nature of the heavily boron-doped diamond superconductor. This supports the diamond band approach and related predictions, including the possibility of achieving dopant-induced superconductivity in silicon and germanium. It should also provide a foundation for the possible development of diamond-based devices.

Journal Article↗
PubMed2004

Primary malignant peripheral nerve sheath tumor of the cauda equina in a child case report.

STUDY DESIGN: A case report of primary malignant peripheral nerve sheath tumor (MPNST) of the cauda equina in a child is presented, and the literature is reviewed. OBJECTIVE: To discuss the problems involved in the treatment of primary intradural MPNSTs. SETTING: A department of orthopaedic surgery in Japan. METHODS: A 4-year-old boy complained of low-back pain radiating to the left calf. MRI revealed an intradural tumor at L3-L5 level. Following laminectomy of L3, L4 and L5, the tumor was removed en bloc. Based on pathological and immunohistological findings, the tumor was diagnosed as an MPNST. RESULTS: Although adjuvant chemotherapy was administered local recurrence and cerebral and spinal metastases of the tumor were found 6 months after the operation. Following additional incomplete removal of the recurrent tumor, radiation therapy was administered. Although recurrent and metastatic tumors disappeared or diminished in size by radiation, tumors increased in size thereafter, despite additional adjuvant chemotherapy. At 21 months after the first operation, he died of pneumonia. CONCLUSIONS: Reported clinical outcomes for patients with primary intradural MPNST are very poor. Although no gold standard for the treatment of tumors has been established yet, surgical removal of tumors combined with postoperative high-dose radiation may be recommended.

Brain Neoplasms↗
PubMed2002

Experimental Helicobacter pylori gastric infection in miniature pigs.

An experimental Helicobacter pylori infection in miniature pigs was developed and investigated. Eighteen miniature pigs were inoculated with an H. pylori strain that has high virulence in mice at c. 5 x 10(10) cfu. H. pylori infection in miniature pigs was achieved by the administration of agar 1% in brucella broth with fetal bovine serum 10% just before inoculation. The bacterial colonisation and distribution were analysed by mapping of viable cell counts in the stomach in pigs of three different ages. The mapping assay was achieved on post-infection day 3 for the 5-day-old and 2-week-old pigs, and between days 41 and 43 for 3-month-old pigs. The highest cell counts were observed in 5-day-old pigs, which averaged 4.9 x 10(6) cfu/g of mucosa (n = 4). The bacteria were colonised mainly in the cardiac and fundus gland region in the 5-day-old and 2-week-old pigs, whereas the colonisation sites did not depend on the region in the 3-month-old pigs. Biopsy assay of the antral mucosa of a 3-month-old pig after H. pylori infection showed that this infection persisted for >22 months. Serum antibody against H. pylori was detected in the infected pigs but not in the uninfected animal. Immunostaining demonstrated the presence of bacteria on the epithelial surface of the infected pigs. A microscopic finding common to all the infected pigs, focal gastritis with infiltration of lymphocytes detected on the lesser curvature of the stomach, resembled the microscopic appearance in H. pylori-infected human patients. These results suggest that miniature pigs might be a suitable model for studying H. pylori infection.

Age Factors↗
PubMed2001

Reduced neuritic outgrowth and cell adhesion in neuronal cells transfected with human alpha-synuclein.

Since recent reports have suggested that alpha-synuclein might play a role in neuronal plasticity, the main objective of this study was to determine the effects of alpha-synuclein on neuritic outgrowth. We stably transfected either human (h) alpha- or beta-synuclein cDNA in B103 rat neuronal cells. Expression of h(alpha)-synuclein resulted in reduced neurite extension and weak adhesion compared to vector-transfected and h(beta)-synuclein expressing cells. To investigate the potential pathways involved, we studied the effects of reagents known to modulate B103 proliferation and differentiation. Neither phorbol 12-myristate 13-acetate nor forskolin or antioxidants (catalase, superoxide dismutase, or vitamin E) were able to restore the reduced length of neurites in h(alpha)-synuclein-expressing cells. These results suggest that reduced neuritic activity in the h(alpha)-synuclein-expressing cells might be due, in part, to alterations in cell adhesion capacity. This might be attributed to alpha-synuclein affecting a signal transduction pathway distinct from protein kinase C and protein kinase A.

Animals↗
PubMed2001

Factors influencing the linear depth of invasion of primary basal cell carcinoma.

BACKGROUND: Predicting subclinical growth of basal cell carcinoma (BCC) is important for clinicians to determine adequate surgical margins. However, few attempts to predict the depth of invasion of BCC prior to surgery have been done. OBJECTIVE: To identify the factors significantly influencing the depth of invasion of primary BCC. METHODS: In 235 primary BCCs treated with surgical excision, maximum vertical diameter, designated as "invasion index," from the surrounding skin surface to the bottom of the tumor was measured. Multiple linear regression analysis was used to identify the factors significantly influencing the invasion index. Seven variables including age, sex, duration, anatomic location, tumor horizontal diameter, histologic subtypes, and ulceration were entered into the model. RESULTS: Among seven variables, male sex (P = 0.0003), larger tumor diameter (P = 0.0011), and histologic subtypes including infiltrative, morpheic, and micronodular subtypes (P = 0.0019) had significant strength of influence for the invasion index. CONCLUSION: The three predictive factors positively related to the linear depth of invasion in this study are important, but not sufficient, considerations at planning of surgery and for postoperative follow-up of BCC.

Aged↗
PubMed2000

alpha-synuclein promotes mitochondrial deficit and oxidative stress.

Abnormal accumulation of the presynaptic protein alpha-synuclein has recently been implicated in the pathogenesis of Alzheimer's and Parkinson's diseases. Because neurodegeneration in these conditions might be associated with mitochondrial dysfunction and oxidative stress, the effects of alpha-synuclein were investigated in a hypothalamic neuronal cell line (GT1-7). alpha-Synuclein overexpression in these cells resulted in formation of alpha-synuclein-immunopositive inclusion-like structures and mitochondrial alterations accompanied by increased levels of free radicals and decreased secretion of gonadotropin-releasing hormone. These alterations were ameliorated by pretreatment with anti-oxidants such as vitamin E. Taken together these results suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial alterations that may result in oxidative stress and, eventually, cell death.

Animals↗
PubMed2000

A case of localized follicular hamartoma: an ultrastructural and immunohistochemical study.

We report the case of a 22-year-old woman with a nevoid plaque that we termed localized follicular hamartoma. The plaque was noticed at puberty on a unilateral site of the face and scalp. Clinically, it revealed numerous, skin-colored to light brown papules alone and in groups, occasionally bearing a single hair. Histologically, branched epithelial nests of squamoid and/or basaloid cells were revealed in connection with the interfollicular epidermis and the upper portions of hair follicles, of which the lower portions showed normal structures. Immunohistochemically, the epithelial nests showed the keratin expression consisted with that of the infundibular epithelium. S-100-positive cells were found in the epithelial nests and the stroma. Factor XIIIa-positive dendritic cells were numerous in adjacent to the epithelial nests. Ultrastructurally, immature melanocytes with a small number of premelanosomes and Merkel cells were found in the nests. Stromal dendritic cells showed the adherent features of the cytoplasmic processes to anchoring fibrils or basal lamina of the epithelial nests. From these findings, our case is a hamartoma, which seems to be an abortive growth of secondary hair germs with a limited differentiation to the upper follicular portion.

Adult↗
PubMed2000

Two cases of vulval pigmented extramammary Paget's disease: histochemical and immunohistochemical studies.

We describe two Japanese female patients with pigmented extramammary Paget's disease (EMPD); one patient had a dark brown plaque and the other had a reddish patch with a pigmented area, both affecting the vulval region. Histochemical and immunohistochemical examinations confirmed EMPD with melanocyte colonization; plump tumour cells with a large nucleus and pale cytoplasm that were positive for CAM 5.2 and CEA proliferated singly or in nests in the epidermis, and scattered among the tumour cells were many dendritic cells with a large amount of melanin that were positive for HMB-45 and S-100 protein. Fontana-Masson (FM) stain showed many positive cells with well-developed dendritic processes within and around tumour nests. Histochemical and immunohistochemical studies of non-pigmented EMPD cases on the same region showed that HMB-45 positive cells were sparse or not detected at all, and that also FM staining-positive cells were decreased or not detected, and their dendritic processes were poorly formed. The present study suggests that there might be heterogeneity in EMPD in terms of relationships between Paget's cells and melanocytes.

Aged↗
PubMed1999

Isolation and characterization of Cox17p from porcine heart by determining its survival-promoting activity in NIH3T3 cells.

We have found that the gel filtration fraction of porcine heart extract clearly promoted the survival of NIH3T3 fibroblast cells in the serum-free medium condition. A structural analysis showed that the active fraction contained a novel peptide, porcine Cox17p (p-Cox17p), which was recently reported by Chen et al. as dopuin (Z. W. Chen et al., Eur. J. Biochem. 249 (1997) 518-522). Porcine Cox17p/dopuin possesses high sequence homology to the product of human COX17 gene (h-Cox17p). Although Cox17p has been implied to be involved in copper recruitment to mitochondria and in the functional assembly of cytochrome oxidase in yeast, its role in mammalian cells is unknown. In this study, we chemically synthesized p-Cox17p to investigate its biological effects. Refolding experiments of synthesized linear p-Cox17p revealed the existence of mostly one pattern of three intrachain disulfide bridges similar to that of native p-Cox17p, because the main oxidized p-Cox17p was completely co-eluted with the natural product. The addition of heavy metal ions such as copper, zinc and cadmium significantly inhibited the formation of the oxidized form, suggesting that reduced p-Cox17p may interact directly with these metal ions. The reduced and oxidized forms of p-Cox17p were also confirmed to promote the survival of NIH3T3 cells in serum-free medium as observed with the natural product, indicating that Cox17p may be a bioactive peptide.

3T3 Cells↗
PubMed1999

Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease.

alpha-Synuclein is a major component of aggregates forming amyloid-like fibrils in diseases with Lewy bodies and other neurodegenerative disorders, yet the mechanism by which alpha-synuclein is intracellularly aggregated during neurodegeneration is poorly understood. Recent studies suggest that oxidative stress reactions might contribute to abnormal aggregation of this molecule. In this context, the main objective of the present study was to determine the potential role of the heme protein cytochrome c in alpha-synuclein aggregation. When recombinant alpha-synuclein was coincubated with cytochrome c/hydrogen peroxide, alpha-synuclein was concomitantly induced to be aggregated. This process was blocked by antioxidant agents such as N-acetyl-L-cysteine. Hemin/hydrogen peroxide similarly induced aggregation of alpha-synuclein, and both cytochrome c/hydrogen peroxide- and hemin/hydrogen peroxide-induced aggregation of alpha-synuclein was partially inhibited by treatment with iron chelator deferoxisamine. This indicates that iron-catalyzed oxidative reaction mediated by cytochrome c/hydrogen peroxide might be critically involved in promoting alpha-synuclein aggregation. Furthermore, double labeling studies for cytochrome c/alpha-synuclein showed that they were colocalized in Lewy bodies of patients with Parkinson's disease. Taken together, these results suggest that cytochrome c, a well known electron transfer, and mediator of apoptotic cell death may be involved in the oxidative stress-induced aggregation of alpha-synuclein in Parkinson's disease and related disorders.

Acetylcysteine↗
PubMed1999

Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus.

We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM(1) antibody did not affect loss of tumorigenicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-2, but not beta-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.

Animals↗
PubMed1999

The surgical management of sacrococcygeal chordoma.

BACKGROUND: Complete excision of sacrococcygeal chordoma is necessary at initial surgery due to its poor sensitivity to radiotherapy and chemotherapy. However, due to the anatomic characteristics of this tumor, intralesional excision tends to be employed, resulting in local recurrences in many patients. METHODS: The clinical features and results of surgical treatment of 13 patients with sacrococcygeal chordoma who were treated at the Chiba Cancer Center and Chiba University beginning in 1972 were analyzed. RESULTS: Intralesional excision was performed in eight patients, marginal excision in two patients, and wide excision in three patients. Local recurrence was observed in six patients, with a high proportion occurring in the gluteal muscles attached to the sacrum (the gluteus maximus muscle and piriform muscle). Seven patients died of their disease and six patients were alive with no evidence of disease. The 5-year survival rate was 81.8% and the 10-year survival rate was 29.1%. CONCLUSIONS: It is highly possible that residual chordoma infiltrating the gluteal muscles accounts mainly for the local recurrences. Therefore, a precise preoperative assessment of the tumor infiltration into the gluteal muscles by magnetic resonance imaging is important for the prevention of local recurrence. For complete tumor removal, a radical wide posterior surgical margin of the gluteal muscles should be employed. A less radical anterior surgical margin is sufficient because there is a firm presacral fascia anterior to the sacrum. The appropriate surgical margin for the complete removal of the chordoma differs according to the location of the tumor and tissues involved.

Adult↗
PubMed1999

Structure, tissue distribution, and pharmacological characterization of Xenopus orexins.

We isolated the Xenopus gene encoding prepro-orexin to predict the structures of orexins in submammalian chordates. Putative mature Xenopus orexin-A and -B are highly similar to each mammalian counterpart. Especially, the C-terminal 10 residues were highly conserved among these species and isopeptides. Immunohistochemical examination of Xenopus brain revealed that orexin-containing neurons were highly specifically localized in the ventral hypothalamic nucleus. A rich network of immunoreactive fibers was found in various regions of the Xenopus brain. The distribution was similar to that of mammalian orexins. Xenopus orexin-A and -B specifically bind and activate human orexin receptors expressed in Chinese hamster ovary cells. Of interest, Xenopus orexin-B had several-fold higher affinity to human OX2R compared with human orexins. These results suggest that Xenopus orexin-B might be a useful pharmacological tool as an OX2R selective high-affinity agonist.

Amino Acid Sequence↗
PubMed1999

Biological actions of the epidermal growth factors-like domain peptides of mouse schwannoma-derived growth factor and human amphiregulin.

Several members of the epidermal growth factor (EGF) family of growth factors that contain EGF-like units at their carboxy portion have been isolated and characterized. Schwannoma-derived growth factor (SDGF) and amphiregulin (AR) are members of this family. SDGF has high sequence homology to AR, and is known to be not only a potent mitogen for astrocytes and fibroblasts but also a neurotrophic factor. We previously confirmed that the synthetic EGF-like peptides SDGF(38-80) and AR(44-84), corresponding to the EGF-like domain of mouse SDGF and human AR, respectively, formed similar disulfide bond patterns to that of EGF. In the present study, we further investigated the biological actions of these two EGF-like peptides on several cultured cell lines. We found that SDGF(38-80) and AR(44-84) have weak mitogenic activity in NIH/3T3 cells and weak binding affinity to the EGF receptor on the surface of A431 cells compared with EGF. However, SDGF(38-80) and EGF induced short neurite outgrowth in PC12 h cells, a subclone of PC12 cells, at 100 nM. In addition, a significant increase in acetylcholinesterase (AChE) activity induced by SDGF(38-80) was observed at a concentration similar range to that of EGF, which is known as a differentiation marker of these cells. The effect of AR(44-84) in PC12 h cells was weaker than those of SDGF(38-80) and EGF, but the AChE activity was significantly increased by the addition of 100 nM AR(44-84), which did not stimulate NIH/3T3 cell growth. These results also suggest that SDGF(38-80) and AR(44-84) may be effective for neuronal differentiation rather than proliferation.

3T3 Cells↗
PubMed1999

Detection of gyrA mutations among 335 Pseudomonas aeruginosa strains isolated in Japan and their susceptibilities to fluoroquinolones.

gyrA point mutations in 335 clinical Pseudomonas aeruginosa isolates were examined mainly by nonisotopic single-strand conformation polymorphism analysis and direct sequencing. Seven types of missense gyrA mutations were observed in 70 of 335 strains (20.9%), and ciprofloxacin MICs were > or = 3.13 micrograms/ml for 63 of 70 strains (90.0%). These included two double point mutations and three novel mutations (Ala-67-->Ser plus Asp-87-->Gly, Ala-84-->Pro, and Gln-106-->Leu). Thr-83-->Ile mutants were predominantly observed (63 of 70 mutants) and showed high-level fluoroquinolone resistance (ciprofloxacin MIC at which 50% of isolates are inhibited, 25 micrograms/ml).

Anti-Infective Agents↗