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Biomedical subjects

T Fukushima

Publications and source records attributed to T Fukushima.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. AIMS: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. RESULTS: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. CONCLUSION: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

Adenocarcinoma↗
PubMed2006

Functionalization of multilayered DNA-coatings with bone morphogenetic protein 2.

The focus of the present study was to functionalize multilayered DNA-coatings with the osteoinductive factor bone morphogenetic protein 2 (BMP-2) using different loading modalities. The multilayered DNA-coatings were built up from either poly-d-lysine (PDL) or poly(allylamine hydrochloride) (PAH) and DNA using electrostatic self-assembly (ESA). The amounts of BMP-2 loaded into the multilayered DNA-coatings and its subsequent release characteristics were determined using radiolabeled BMP-2. Additionally, the effect of BMP-2 functionalized multilayered DNA-coatings on the in vitro behavior of bone marrow-derived osteoblast-like cells was evaluated in terms of proliferation, differentiation, mineralization, and cell morphology. The results demonstrate the feasibility of multilayered DNA-coatings to be functionalized by embedding BMP-2 according to three different loading modalities: superficial (s), deep (d), and double-layer (dl). BMP-2 was incorporated proportionally into the multilayered DNA-coatings as: s+(4*d)=dl. All differently loaded multilayered DNA-coatings showed an initial burst release followed by an incremental sustained release of the remaining BMP-2. In vitro experiments demonstrated that the loaded factor remained biologically active, as an accelerated calcium deposition was observed on s- and dl-loaded multilayered DNA-coatings, without affecting cell proliferation. In contrast, d-loaded multilayered DNA-coatings influenced osteoblast-like cell behavior by decreasing the deposition of calcium.

Alkaline Phosphatase↗
PubMed2006

Antifungal activity of DNA-lipid complexes and DNA-lipid films against Candida species.

In this study amphiphilic lipids, DNA-lipid complexes, and DNA-lipid films were prepared, and their antifungal activity against Candida species was examined. The amphiphilic lipids were synthesized from a reaction of glycine or L-alanine with n-alkyl alcohol in the presence of p-toluene sulfonic acid. DNA-lipid complexes, which were prepared by the simple mixing of DNA and amphiphilic lipids, were insoluble in water. Self-standing, water-insoluble DNA-lipid films were prepared by casting the DNA-lipid complexes from a chloroform/ethanol solution. The antifungal activities of the lipids and DNA-lipid complexes against the Candida species were evaluated by minimum inhibitory concentrations (MICs); those of DNA-lipid films were evaluated by the disk diffusion method. The seven kinds of lipids, DNA-lipid complexes, and DNA-lipid films showed antifungal activity, and no differences were seen in the antifungal activities between glycine and L-alanine derivatives. The lipids, DNA-lipid complexes, and DNA-lipid films, which have shorter alkyl chain length in lipids, showed antifungal activity against all Candida species. However, the effect of antifungal activity against Candida species decreased with increased alkyl chain length in lipids. In this study, it was found that lipids, DNA-lipid complexes, and films with a decyl or dodecyl group exhibit more favorable antifungal activity.

Animals↗
PubMed2006

MRI and SPECT studies of dural arteriovenous fistulas presenting as pure progressive dementia with leukoencephalopathy: a cause of treatable dementia.

We report two patients with dural arteriovenous fistulas (DAVFs) who presented with pure progressive dementia. Both patients showed only slowly progressive dementia, without headache, papilledema and other neurologic signs associated with diffuse white matter changes in MRI. MR cerebral angiography showed sigmoid sinus DAVFs that were mainly supplied by the occipital artery, together with retrograde filling of the superior sagittal and straight sinus and dilated cortical veins. SPECT studies showed extensive blood flow reduction in the occipital and parieto-occipital areas and right temporal lobe in one patient. Selective embolization for treatment of the DAVF improved cognitive function associated with the abnormal white matter MRI signal. MRI and SPECT showed that severity of dementia correlated with diffuse white matter changes and regional cerebral blood flow. Our cases suggest that gradually impaired cerebral circulation due to venous hypertensive encephalopathy could be involved in slowly progressive dementia with leukoencephalopathy resulting from a DAVF. DAVFs may be particularly important for differential diagnosis in elderly patients with pure progressive dementia. Thus, early diagnosis of DAVFs and treatment by endovascular surgery is important as treatable or reversible dementia.

Central Nervous System Vascular Malformations↗
PubMed2006

Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease).

A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and spinal cord involvement is described. Magnetic resonance imaging (MRI) of the optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted images after intravenous meglumine gadopentetate infusion. On T2 weighted sagittal images, a sawtooth pattern was observed over seven vertebral segments of the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the left optic nerve was seen, with thrombotic obstruction of the central retinal artery. Spongy degeneration was observed in all levels of the spinal cord, with patchy and motheaten patterns caused by thromboses and endothelial proliferation in subarachnoid vessels. Findings on MRI were consistent with findings on pathological examination.

Atrophy↗
PubMed2006

Anti-Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy.

A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti-Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti-Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease-like presentation.

Adult↗
PubMed2006

Runoff and loads of nutrients and heavy metals from an urbanized area.

To investigate the run-off characteristics of dissolved and particulate substances from a heavily urbanized area (basin area: 95 ha, percentage of impervious surfaces: 60%), sensors for measuring water level, water temperature, DO, pH, electric conductivity (EC), turbidity and ammonium ion were placed in the channel connecting storm sewers and natural river, together with water sampling for analyzing SS, nutrients and metals. While both turbidity and EC showed apparent "first flush", the peaks of EC were always earlier than those of turbidity. In a similar manner, dissolved nutrients and metals exhibited earlier "first flush" compared with particulate nutrients and acid-extractable metals. Significantly positive correlations between EC and dissolved substances as well as those between turbidity and particulate (acid-extractable minus dissolved) substances were usually observed, and two distinct different regressions were found between the two datasets separated before and after the concentration peaks. Using these relationships, the total loads during the respective rainfall events were calculated on the basis of EC and turbidity changes. The total loads of nitrogen, zinc, etc. were nearly proportional to the lengths of non-rainfall periods before the events, indicating that these loads derived from the atmospheric deposition.

Cities↗
PubMed2006

Dispersion and dry and wet deposition of PAHs in an atmospheric environment.

The atmospheric concentration and dry and wet deposition were measured for particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) from August to December in Higashi-Hiroshima City, Japan. PM concentration of fine particles (0.6-7 microm) was 5.7-75.1 micro m(-3), and coarse particles (> 7 microm) was 2.2-22.3 microg m(-3). Total PAHs concentration of fine particles was 0.14-16.3 ng m(-3), and coarse particles was 0.01-0.77 ng m(-3). Their concentration increased on non-rainy days and decreased rapidly on rainy days. For seasonal fluctuations of PAHs, their concentrations decreased from summer to winter, and the rate of decrease was more distinct for fine particles. For total (dry + wet) depositions, the PM flux was 1.9-11.2 mg m(-2) d(-1), and the total PAHs flux was 1.9-97.2 ng m(-3) d(-1). From these measurements, the yearly total loading of PAHs was estimated for the particle phase. Total loading was 28 microg m(-2) y(-1) for the dry deposition and 52 mg m(-2) y(-1) for the wet deposition. The loading of the wet deposition was comparable to those of the dry deposition for all ring numbers.

Air Movements↗
PubMed2006

A nosocomial parvovirus B19 infection-induced transient aplastic crisis in a patient with chronic renal failure.

A male patient aged 67 years with chronic renal failure (CRF), who had undergone hemodialysis since June 3, complained of dyspnea while walking on June 23, 1998. Rapidly progressive anemia and severe reticulocytopenia were noted. Serological tests showed that parvovirus B19- (B19) specific IgM antibody, but not IgG antibody, was present in the patient's serum. B19 DNA was detected in the patient's serum by the polymerase chain reaction (PCR). Therefore, a definite diagnosis of transient aplastic crisis induced by B19 was made. On June 10, prior to the appearance of this case, a female nurse aged 27 years working in our hemodialysis center, complained of cough, fever and arthralgia. Another female nurse, aged 35 years, developed similar symptoms on July 3. Both nurses had a positive IgM titer against B19, but were negative for IgG, indicating an acute B19 infection. These findings led us to suspect that this series of B19 infection was spread by nosocomial transmission. Although some cases of B19 infection have been reported to occur in laboratory staffs, the B19 nosocomial infection has not been described in the literature. We also suggest that a transient aplastic crisis due to B19 infection could lead to severe anemia in cases of CRF whose erythropoiesis is maintained by a recombinant human erythropoietin.

Aged↗
PubMed2006

Expression and mutation of SMAD4 in poorly differentiated carcinoma and signet-ring cell carcinoma of the colorectum.

Poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig) are rare but highly malignant types of colorectal cancer. To explore their genetic backgrounds we investigated TGF-beta type II receptor (TGF-beta RII) and SMAD4 in the TGF-beta signaling pathway, and to identify their mutator phenotype we examined microsatellite instability (MSI) status. Loss of SMAD4 expression was significantly more frequent in Por (12 of 38; 31%) and Sig (4 of 5; 80%) tumors than in well (Well) and moderately differentiated (Mod) carcinomas (p = 0.04, 0.003, respectively). Mutation of the SMAD4 gene was detected in 2 of 26 Por tumors. MSI was positive in 14 of the 38 Por tumors and in 1 of the 5 Sig tumors, but in none of the Well or Mod tumors examined. We also found mutation of TGF-beta RII, a putative target of MSI, in 10 of 35 Por tumors (28.6%), but in none of 3 Sig tumors. As a whole, about 50% of the Por tumors and 80% of the Sig tumors showed abnormalities of either TGF-beta RII or SMAD4 expression. This suggests that disruption of the TGF-beta signaling pathway may play a central role in the pathogenesis of Por and Sig tumors of the colorectum.

Adenocarcinoma↗
PubMed2005

Dynamic gadolinium-enhanced fat-suppressed T1-weighted MRI (chemical shift selective images) for remitting seronegative symmetrical synovitis with pitting edema.

A 75-year-old man suddenly suffered from polyarthralgia and pitting edema in his distal extremities. Laboratory tests revealed inflammation, negative rheumatoid factor, and positive B7 human leukocyte antigen typing. Severe synovitis was observed in dynamic gadolinium-enhanced fat-suppressed (DGEFS) T1-weighted images of his right hand. Our diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS(3)PE syndrome). He responded dramatically to low-dose corticosteroids, after which his synovitis remarkably improved as observed with DGEFS imaging. DGEFS imaging is useful for distribution of synovitis in patients with RS(3)PE syndrome as well as assessing the efficacy of treatment.

Aged↗
PubMed2005

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3' Untranslated Regions↗
PubMed2005

Comparison of susceptibility to SIVmac239 infection between CD4(+) and CD4(+)8(+) T cells.

CD4-bearing T cells are the primary targets for human immunodeficiency virus type 1(HIV-1)/simian immunodeficiency virus (SIV) infection. However, it is unclear whether the susceptibility of CD4-bearing T cells including CD4 single positive and CD4/8 double positive T cells to HIV/SIV infection is the same or not. In this study, we compared the susceptibility to SIV infection between CD4(+) and CD4(+)8(+) T cells, using Herpesvirus saimiri (HVS)-transformed CD4(+) and CD4(+)8(+) T cells established from peripheral blood mononuclear cells (PBMC) of rhesus macaques. Although there was little difference between the two CD4-bearing T cell population in the expression level of CD4 molecules and chemokine receptors such as CXCR4 and CCR5, SIV replicated more efficiently in CD4(+)8(+) T cells than in CD4(+) T cells. Moreover, we found that reverse transcription initiated more efficiently in CD4(+)8(+) T cells than in CD4(+) T cells and that the cell lysates from CD4(+) T cells impaired the RT activity more strongly than that from CD4(+)8(+) T cells. These findings suggest that intracellular environment in CD4(+) 8(+) T cells is better for reverse transcription and that the infection of those CD4(+)8(+) T cells might play critical and different roles in HIV-1/SIV infection and dissemination.

Animals↗
PubMed2005

A case of perforation and fistula formation resulting from metallic stent for sigmoid colon stricture in Crohn's disease.

A 52-year-old male was diagnosed with Crohn's disease at the age of 25 years. Thereafter, he underwent three operations for intestinal strictures or fistula. A self-expanding metallic stent was inserted into the sigmoid colon stricture endoscopically in November 1999. Thirty two months later, he presented left lower abdominal pain. Endoscopic and radiographic examinations demonstrated perforation of the stent and ileosigmoid fistula. Laparotomy revealed an inflammatory mass around the sigmoid colon, and the wire frame of the metallic stent had penetrated the colonic wall and had fistulized to the ileum. The affected sigmoid colon was resected and low anterior resection and ileostomy were performed. Metallic stent for intestinal stricture of Crohn's disease with active ulceration may postpone surgery temporarily but can be a potentially dangerous procedure.

Colon, Sigmoid↗
PubMed2005

Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct peripheral T-cell neoplasm that is highly resistant to chemotherapy. Several groups, including ours, have reported encouraging results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with ATLL. To confirm our previous report and to establish the basis for a phase II clinical study, we analyzed 40 allo-HSCT for acute and lymphoma types of ATLL in seven institutions in Japan between 1997 and 2002. All evaluable cases entered complete remission (CR) after allo-HSCT and the median survival time was 9.6 months for all patients. The estimated 3-year overall and relapse-free survival, and disease relapse were 45.3, 33.8 and 39.3%, respectively. Among 10 cases with ATLL relapse, five cases achieved CR again: three by the reduction or cessation of immunosuppressive agents, which suggested a graft-versus-ATLL (GvATLL) effect. However, univariate or multivariate analysis did not show any benefit of graft-versus-host disease (GVHD) on the prevention of relapse. These results suggested that allo-HSCT was effective for some patients with aggressive ATLL, and that the GvATLL effect could be achieved even without GVHD. A new phase II trial to test the efficacy of allo-HSCT for ATLL is warranted.

Adult↗
PubMed2005

Osteopontin/Eta-1 upregulated in Crohn's disease regulates the Th1 immune response.

BACKGROUND AND AIMS: The pathogenesis of Crohn's disease (CD), a chronic inflammatory bowel disease characterised by a Th1 immune response, remains unclear. Osteopontin (OPN) is a phosphoprotein known as an adhesive bone matrix protein. Recent studies have shown that OPN plays an important role in lymphocyte migration, granuloma formation, and interleukin 12 (IL-12) production. The present study investigated expression and the pathophysiological role of OPN in CD. METHODS: Plasma OPN concentration was measured by enzyme linked immunosorbent assay. Expression of OPN in human intestinal mucosa was determined using reverse transcription-polymerase chain reaction and western blot, and localisation of OPN was examined by immunohistochemistry. Expression of integrin beta3, an OPN receptor, on lamina propria mononuclear cells (LPMC) was assessed by flow cytometry. Functional activation of OPN in LPMC was investigated by measuring the production of cytokines. RESULTS: Plasma OPN concentration was significantly higher in patients with CD compared with normal controls or patients with ulcerative colitis (UC). OPN was upregulated in intestinal mucosa from UC and CD patients. OPN producing cells were epithelial or IgG producing plasma cells, or partial macrophages. OPN was detected in areas surrounding granuloma from mucosa in CD. Integrin beta3 expressing macrophages infiltrated inflamed mucosa in UC and CD; in contrast, there was no expression of integrin beta3 on intestinal macrophages in normal mucosa. OPN induced production of IL-12 from LPMC in CD but not in normal controls or UC. CONCLUSIONS: Increased OPN expression facilitates cytokine production and is closely involved in the Th1 immune response associated with CD.

Biomarkers↗
PubMed2004

Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus.

The authors identified two Japanese spinocerebellar ataxia (SCA) families characterized by postural and action tremor and a very slow progression rate. A genome-wide linkage analysis revealed linkage to chromosome 3p26.1-25.3 with the highest multipoint lod score at D3S3728 (Zmax = 3.31 at theta = 0.00). The candidate region was 14.7 cM flanked by D3S1620 and D3S3691, which was partly overlapping with the locus of SCA15 characterized by pure cerebellar ataxia. Despite the difference in phenotypes, there remains a possibility that the causative gene for these Japanese SCA is allelic to SCA15.

Adult↗