Biomedical subjects
Publications and source records attributed to T Ito.
Ovarian Brenner tumor is an uncommon epithelial tumor that accounts for 1.5% to 2.5% of all ovarian neoplasms. These tumors are usually benign. Whereas the magnetic resonance imaging features of benign Brenner tumors have been described, reports of malignant findings are limited. We report a case of borderline malignant Brenner tumor that imaged as a cystic lesion with papillary projections and solid elements.
The sequences of the 3'-terminal 1306 and 2160 nucleotides of RNAs 1 and 2 of a virus serologically related to Satsuma dwarf virus (SDV) from Hyuganatsu ( Citrus tamurana Hort. ex Tan.) were determined, respectively. We found that the partial RNA-dependent RNA polymerase region in RNA1 and the coat proteins (CPs) region in RNA2 of the virus tentatively named Hyuganatsu virus (HV) have 78.3-84.0% and 76.9-80.7% amino acid sequence identities to those of known SDV-related viruses (SDV-RVs), i.e., SDV, Citrus mosaic virus, and Navel orange infectious mottling virus. Sequence analyses show that HV is classifiable as a new SDV-RV species.
The midbrain periaqueductal gray (PAG) is the area promoting emotional motor responses, reproductive behaviors and analgesia. Recent studies suggest that neurons in the PAG may be crucial for regulating the micturition reflex in both experimental animals and humans. We examined single neuronal activities in the PAG and the adjacent area in response to isovolumetric spontaneous micturition reflexes in 20 supracollicular decerebrated cats. In total, 84 neurons were recorded in the PAG that were related to urinary storage/micturition cycles. Of the neurons recorded, the most common were tonic storage neurons (43%), followed by tonic micturition neurons (29%), phasic storage neurons (15%) and phasic micturition neurons (13%). In addition to the tonic/phasic as well as storage/micturition classification, the neurons showed diverse discharge patterns: augmenting, constant and decrementing, with the constant discharge pattern being most common. Of the 16 neurons located within the PAG that had similar discharge patterns to those just ventral to the PAG, the micturition neurons were distributed in a broader area, whereas the storage neurons seemed to be concentrated in the middle part of the PAG (P0-1, Horsley-Clarke coordinate). High-frequency stimulation (HFS; 0.2-ms duration, 100 Hz) applied in the PAG elicited inhibition of the micturition reflex. Effective amplitude of the electrical stimulation for evoking inhibitory responses was less than 50 microA. In conclusion, the results of the present study showed that HFS of the PAG inhibited the micturition reflex and there were micturition-related neuronal firings in the PAG in cats, suggesting that the PAG is involved in neural control of micturition.
The number of pancreas transplants reached 16,043 worldwide in October 2001, with 1800 performed in 2000. Since the introduction of cyclosporine (CyA) in 1979, a regimen consisting of CyA, azathioprine, and steroids has been shown to improve long-term survival of clinical transplants. In Japan, the first simultaneous pancreas-kidney transplantation was performed in 1984, using organs from a brain-dead donor. This procedure was followed by 14 pancreas transplantations from cardiac arrest donors. All cases utilized a CyA-based regimen with antilymphocyte globulin or OKT3 induction. Six of the 15 recipients required less insulin postoperatively. Under a new transplant law enforced in 1997, 10 pancreas/pancreas-kidney transplantations were performed in patients diagnosed with end-stage renal failure due to diabetes mellitus type 1. In 1 patient, the graft failed due to venous thrombosis, but the other 9 recipients achieved an increased quality of life without the need for insulin or for dialysis. Pancreas transplantation represents an effective treatment worldwide and in Japan, due to the availability of CyA or tacrolimus in combination with other agents such as antilymphocyte globulin, OKT3, or mycophenolate mofetil. This investigation presents the results of pancreas-kidney transplantation in Japan, in comparison with those worldwide, and describes a recent case in Japan.
The Pancreas Transplantation (tx) Program under the Japanese Organ Transplant Act was started in 2000. PTx is indicated for type 1 diabetic patients on hemodialysis therapy. As of April 2003 93 patients are listed as candidates. Ten cases of PTx with enteric or bladder-drained technique were performed during the last 3 years as well as nine SPK and one PAK. Of 10 cases, nine recipients are insulin-free with HbA1c values ranging from 4.4% to 5.7%, although exogenous insulin was required in six cases temporarily, namely for a median 63 days (12 to 225 days). One case was lost due to pancreatic graft thrombosis. All 10 kidney grafts are functioning. Based on the experiences with 14 cases of pancreas tx using non-heart-beating (NHB) donors, we defined the criteria of NHB donor as: age younger than 40 years and cessation of respiratory support. One case of SPK with graft of NHB donor was done, and the recipient is off insulin. Pancreas and kidney are allocated for SPK if the recipient shares at least one HLA-DR antigen. Marginal donors were defined as higher mean donor age, median 37 (range 18 to 58 years); mean 38 +/- 12 years), and no death cause of by trauma. The revascularization of gastroduodenal artery to the pancreatic graft was performed in eight cases to minimize the risk of ischemic injury to the pancreatic graft and technical failure in cases of marginal donor.
BACKGROUND: The recurrence rate of IgA nephropathy (IgAN) in transplanted kidneys has been reported to be >50%. Although recurrent IgAN has a benign clinical course, recent data suggest that it leads to graft loss in a substantial number of patients. METHODS: We performed a retrospective single-center analysis of 34 renal transplant recipients, with biopsy-proven IgAN as the cause of end-stage renal failure. RESULTS: Renal allograft biopsies were performed in 30 patients, of whom 24 did and 6 did not have biopsy-confirmed recurrent transplant IgAN. Recurrent transplant IgAN was more often detected in men and at later timepoints after post-transplantation. Four patients with recurrent transplant IgAN progressed to graft failure. Progression to graft failure was associated with worsened renal function, higher systolic blood pressure, and the lack of presenation of angiotensin-converting enzyme inhibitors (ACEs) at the time of allograft biopsy. Immunologic factors such as frequency of acute rejection, HLA typing, and immunosuppression did not show a relation to recurrence or graft loss. CONCLUSIONS: Recurrent transplant IgAN increased with long-term graft survival and risk factors for graft loss due to recurrent IgAN were similar to those among IgAN in native kidneys.
Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is characterized by abnormal accumulation of inosine triphosphate. We describe the first Japanese case with ITPase deficiency and demonstrate that the deficiency of ITPase activity is not only found in erythrocytes but also in white blood cells.
The recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop acute graft-versus-host disease (aGVHD), which is closely related to morbidity and mortality. However, the essential part of the immune responses elicited in aGVHD remains largely unknown. We attempt to determine if peripheral blood dendritic cells (PBDCs) are altered in aGVHD, and find that the number of PBDCs (both myeloid and lymphoid DCs) is significantly decreased. Immunohistochemical staining of the biopsied skin from patients with aGVHD demonstrates that a number of fascin(+) cells with dendritic projections infiltrate the dermis of the skin. Based on these findings, we hypothesize that the PBDCs are recruited to the affected tissues and may thus play important roles in immune responses elicited in aGVHD.
Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.
CYP3A5 expression is regulated by single-nucleotide polymorphisms (SNPs). The CYP3A5 genotype might contribute to a marked interindividual variation in CYP3A-mediated metabolism of drugs. Nifedipine is a typical substrate of CYP3A4 and CYP3A5 in vitro. The aim of this study was to elucidate the influence of the CYP3A5 genotype on nifedipine disposition in healthy subjects. A single capsule containing 10 mg of nifedipine was administered to 16 healthy male Japanese subjects (eight subjects: CYP3A5(*)1/(*)3; eight subjects: CYP3A5(*)3/(*)3). Blood samples were collected to analyze the pharmacokinetics of serum nifedipine and nitropyridine metabolite (M-I). The area under the plasma concentration-time curve (AUC), the peak plasma concentration (C(max)) and the terminal half-life (t(1/2)) of nifedipine, and the ratio of the nifedipine AUC to M-I AUC showed large intragroup variations, but no significant differences between the two genotypes. Based on the present findings, the functional relevance of CYP3A5 polymorphism should be re-evaluated in clinical trials.
AIMS: It has been reported that 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors increase bone mineral density (BMD) in vivo. We investigated the effect of HMG-CoA reductase inhibitors on BMD in patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: We selected 122 patients with Type 2 diabetes, who were not taking active vitamin D preparations. Their mean age was 67.3 +/- 9.2 years. They were divided into a control group (n=63) without HMG-CoA reductase inhibitor therapy and an HMG-CoA group (n=59) who were treated with these drugs. The BMD of the distal one-third of the radius was measured by dual-energy X-ray adsorptiometry at baseline and after 2 years. RESULTS: There were no significant differences between the control and HMG-CoA groups at baseline with respect to age, gender, body mass index, duration of diabetes, haemoglobin A1c, fasting plasma glucose, adjusted calcium, serum phosphorus, alkaline phosphatase, albumin excretion rate and radial BMD. However, there was a significantly smaller annual decrease of the radial BMD in the HMG-CoA group. Multiple regression analysis with a forward elimination procedure revealed a positive correlation of the radial BMD Z-score with body mass index, while there was a negative correlation with alkaline phosphatase and albumin excretion rate. In addition, the annual rate of change of the radial BMD showed a positive correlation with HMG-CoA reductase inhibitor therapy. CONCLUSIONS: These findings suggest that HMG-CoA reductase inhibitors may prevent bone loss in patients with Type 2 diabetes.
BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown aetiology. It has been suggested that T helper type 1 (Th1) polarisation is associated with the pathophysiology of sarcoidosis, but the mechanism of skewing towards Th1 has not been elucidated. Dendritic cells (DCs) are known to regulate immune responses. This study was performed to determine whether DCs are involved in the aetiology of sarcoidosis. METHODS: The numbers of peripheral blood DCs in 24 patients with sarcoidosis were analysed and biopsy specimens from four patients were stained immunohistochemically using monoclonal antibodies. RESULTS: The numbers of both myeloid and lymphoid DC subsets were significantly decreased in the blood and mature DCs were found in the granulomas of patients with sarcoidosis. A number of interferon-gamma (IFN-gamma) producing T cells were also detected in the sarcoid granuloma, as well as many interleukin (IL)-4 producing T cells. Double staining of the biopsy specimen using anti-fascin and anti-CD3 antibodies showed an anatomical interaction between DCs and T cells. CONCLUSIONS: These findings suggest that the blood DC subsets may migrate into the affected tissues, contributing to the formation of the granulomas in sarcoidosis. It is hypothesised that the migrating DCs may regulate the T cell response in sarcoidosis, at least in the granulomatous lesions.
Muon spin relaxation and magnetic susceptibility measurements have been performed on the pure and diluted spin 1/2 kagomé system (CuxZn(1-x))3V2O7(OH)2 2H2O. In the pure x=1 system we found a slowing down of Cu spin fluctuations with decreasing temperature towards T approximately 1 K, followed by slow and nearly temperature-independent spin fluctuations persisting down to T=50 mK, indicative of quantum fluctuations. No indication of static spin freezing was detected in either of the pure (x=1.0) or diluted samples. The observed magnitude of fluctuating fields indicates that the slow spin fluctuations represent an intrinsic property of kagomé network rather than impurity spins.
The community structure of sulfate-reducing bacteria (SRB) and the contribution of SRB to carbon mineralization in a wastewater biofilm growing under microaerophilic conditions were investigated by combining molecular techniques, molybdate inhibition batch experiments, and microelectrode measurements. A 16S rDNA clone library of bacteria populations was constructed from the biofilm sample. The 102 clones analyzed were grouped into 53 operational taxonomic units (OTUs), where the clone distribution was as follows: Cytophaga- Flexibacter- Bacteroides (41%), Proteobacteria (41%), low-G+C Gram-positive bacteria (18%), and other phyla (3%). Three additional bacterial clone libraries were also constructed from SRB enrichment cultures with propionate, acetate, and H(2) as electron donors to further investigate the differences in SRB community structure due to amendments of different carbon sources. These libraries revealed that SRB clones were phylogenetically diverse and affiliated with six major SRB genera in the delta-subclass of the Proteobacteria. Fluorescent in situ hybridization (FISH) analysis revealed that Desulfobulbus and Desulfonema were the most abundant SRB species in this biofilm, and this higher abundance (ca. 2-4x10(9) cells cm(-3) and 5x10(7) filaments cm(-3), respectively) was detected in the surface of the biofilm. Microelectrode measurements showed that a high sulfate-reducing activity was localized in a narrow zone located just below the oxic/anoxic interface when the biofilm was cultured in a synthetic medium with acetate as the sole carbon source. In contrast, a broad sulfate-reducing zone was found in the entire anoxic strata when the biofilm was cultured in the supernatant of the primary settling tank effluent. This is probably because organic carbon sources diffused into the biofilm from the bulk water and an unknown amount of volatile fatty acids was produced in the biofilm. A combined approach of molecular techniques and batch experiments with a specific inhibitor (molybdate) clearly demonstrated that Desulfobulbus is a numerically important member of SRB populations and the main contributor to the oxidation of propionate to acetate in this biofilm. However, acetate was preferentially utilized by nitrate-reducing bacteria but not by acetate-utilizing SRB.
The anisotropic Hall effect and magnetization have been investigated for single crystals of Nd2Mo2O7 under high magnetic fields up to 27 T and at low temperatures down to 50 mK. The magnetization curves indicate that the Nd moments with strong Ising anisotropy are coupled antiferromagnetically with the Mo spins and show field-induced flipping on the respective sites. The Hall resistivity changes its sign with increasing field applied along the [111] direction, while it monotonously approaches zero with the field applied along the [100] or [110] direction. This behavior is in accord with the prediction by the Berry phase theory and is interpreted in terms of the field-induced reversal of spin chirality on the pyrochlore lattice.
Inelastic neutron scattering was used to probe edge states in a quantum spin liquid. The experiment was performed on finite length antiferromagnetic spin-1 chains in Y2BaNi1-xMgxO5. At finite fields, there is a Zeeman resonance below the Haldane gap. The wave-vector dependence of its intensity provides direct evidence for staggered magnetization at chain ends, which decays exponentially towards the bulk [xi=8(1) at T=0.1 K]. Continuum contributions to the chain-end spectrum indicate interchain segment interactions. We also observe a finite size blueshift of the Haldane gap.
The oncogene function in primary epithelial cells is largely unclear. Recombination organ cultures in combination with the stable and transient gene transfer techniques by retrovirus and electroporation, respectively, enable us to transfer oncogenes specifically into primary epithelial cells of the developing avian glandular stomach (proventriculus). In this system, the epithelium and mesenchyme are mutually dependent on each other for their growth and differentiation. We report here that either stable or transient expression of v-src in the epithelium causes budding and migration of epithelial cells into mesenchyme. In response to the transient expression of v-Src or a constitutive active mutant of MEK, we observed immediate downregulation of the Sonic hedgehog gene and subsequent elimination of E-cadherine expression in migrating cells, suggesting the involvement of MAP kinase signaling pathway in these processes. v-src-expressing cells that were retained in the epithelium underwent apoptosis (anoikis) and detached from the culture. Continuous expression of v-src by, for example, Rous sarcoma virus (RSV) was required for the epithelial cells to acquire the ability to express type I collagen and fibronectin genes (mesenchymal markers), and finally to establish the epithelial-mesenchymal transition. These observations would partly explain why RSV does not apparently cause carcinoma formation, but induces sarcomas exclusively.
We retrospectively investigated the efficacy and feasibility of concurrent chemoradiotherapy for patients with severe dysphagia caused by oesophageal squamous cell carcinoma. Concurrent chemoradiotherapy was performed in 57 patients with T3 or T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU) 400 mg m(-2) 24 h(-1) on days 1-5 and 8-12, combined with 2-h infusion of cisplatin (CDDP) 40 mg m(-2) on days 1 and 8. Radiation treatment at a dose of 30 Gy in 15 fractions of the mediastinum was administered concomitantly with chemotherapy. A course schedule with 3-week treatment and a 1 to 2-week break was applied twice, with a total radiation dose of 60 Gy, followed by two or more courses of 5-FU and CDDP. In all, 24 patients (42%) achieved a complete response, and the 3-year survival rate was 19%. Major toxicities were leukocytopenia and oesophagitis, and there were two (4%) treatment-related deaths. In contrast, 22 patients with T3 disease survived longer than 35 patients with T4 disease (P=0.001); however, the survival rate in 15 patients with M1 LYM disease did not differ significantly from that in 42 patients without M1 LYM disease (P=0.3545). Our results indicate that definitive chemoradiotherapy is potentially curative for locally advanced oesophageal carcinoma with malignant stricture. The efficacy and survival of patients treated with this regimen are related to the T factor.