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Shigeo Mori

Publications and source records attributed to Shigeo Mori.

At least 19 recordsLinked to original sources
PubMed2006

Adenomyoma with goblet and Paneth cells of the ileum.

A case of ileal adenomyoma with goblet and Paneth cells is reported. A 75-year-old man died of ruptured hepatocellular carcinoma. As an incidental finding at autopsy, a 9 x 7 x 6 mm(3)-sized nodule was found in the ileal wall. Histologically, the lesion occupied the submucosa and muscularis propria, and consisted of glandular structures of various sizes and interlacing smooth muscle bundles surrounding the glandular elements. Goblet cells and Paneth cells were interspersed in the glandular element. Immunohistochemically, the glandular element was positive for cytokeratin (CK) 7 and negative for CK 20. This is the first reported case of adenomyoma of the gastrointestinal tract that contained Paneth cells. The result of the immunohistochemical staining favored the heterotopic pancreas theory concerning its pathogenesis. The appearance of goblet and Paneth cells might be the result of metaplasia.

Adenomyoma↗
PubMed2006

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗
PubMed2006

Genetic marking of hematopoietic stem and endothelial cells: identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin-1 domain.

Using an in silico database search, we identified a novel gene encoding a cell surface molecule with a thrombospondin domain, and designated the gene as transmembrane molecule with thrombospondin module (Tmtsp). Expression profiling of Tmtsp using specific monoclonal antibodies and Venus, a variant of yellow fluorescent protein knock-in mice in the Tmtsp locus, demonstrated its specific expression in hematopoietic and endothelial cells. In lymphohematopoietic cells, Tmtsp was predominantly expressed in hematopoietic stem and progenitor cells, and the level of expression gradually declined as the cells differentiated. Venus expression faithfully traced the expression of Tmtsp, and the level of Venus expression correlated well to the in vitro hematopoietic activity as well as the in vivo bone marrow repopulating capacity. Notably, Venus expression marked the development of definitive hematopoiesis in both the extraembryonic yolk sac and the intraembryonic aorta-gonad-mesonephros (AGM) region and, in combination with CD41, strikingly promoted the enrichment of developing progenitors in the CD41(+)Venus(high) fraction at embryonic day 10.5 (E10.5). In this context, Tmtsp is a novel marker gene for primitive hematopoietic cells and endothelial cells, and Tmtsp(Venus/)(+) mice would serve as a valuable mouse model for the analysis of both embryonic and adult hematopoiesis, as well as for vascular biology.

Amino Acid Sequence↗
PubMed2006

Randomized phase II study of concurrent and sequential rituximab and CHOP chemotherapy in untreated indolent B-cell lymphoma.

CHOP combined with rituximab (R-CHOP) is regarded as one of the most effective treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL), however, its optimal combination schedule remains unknown. We performed a randomized phase II study to explore a more promising schedule in untreated, advanced indolent B-NHL. Patients were randomized to receive either six courses of CHOP concurrently with rituximab (Arm C), or six courses of CHOP followed by six courses of weekly rituximab (Arm S). A total of 69 patients received the concurrent (n=34) or sequential (n=35) regimen. Overall response rate (ORR) in Arm C was 94% (95% confidence interval [CI], 79 to 99), including a 66% complete response (CR) compared with 97% (95% CI, 85-100), including a 68% CR in Arm S. Patients in Arm C experienced more grade 4 neutropenia (85%versus 70%) and experienced more grade 3 or greater non-hematological toxicities (21%versus 12%). Both arms were tolerated well. With a median follow-up of 28.2 months, the median progression-free survival (PFS) time was 34.2 months in Arm C, and was not reached in Arm S. R-CHOP is highly effective in untreated indolent B-NHL, either concurrent or in a sequential combination. Both combination schedules deserve further investigation.

Adult↗
PubMed2006

Prevalence of Epstein-Barr virus in Japan: trends and future prediction.

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and some malignancies including EBV-associated-lymphomas. A large portion of adults all over the world are infected with EBV. In children, however, there are geographic variations. Most of the children in Asia and in other developing countries are infected in their early life, before 1 year of age (>90% of 5-9-year-old children are infected), while the age of primary infection is delayed in Western countries (approx. 50% of 5-9-year-old children are infected). The purpose of the present paper was to investigate the recent time trend of the EBV seropositivity among 5-7-year-old children living in Tokyo and its neighboring prefectures. Indirect immunofluorescein study for IgG antibody to viral capsid antigen was performed on 442 archival sera. Before the early 1990s, >80% of 5-7-year-old children were found to be seropositive, while the positivity rate decreased to 59% (P < 0.001) for the years 1995-1999. These results also showed that the delay in the age of primary infection is continuing and that the rate is estimated to be <50% in 2006. This result suggests that the delay will affect the incidence of EBV-associated disorders in Japan.

Adolescent↗
PubMed2006

High expression of eosinophil chemoattractant ecalectin/galectin-9 in drug-induced liver injury.

BACKGROUND: Ecalectin/galectin-9 (ECL/GL9) is an eosinophil chemoattractant isolated from T lymphocytes. Drug-induced liver injury (DILI), often caused by an allergic mechanism, is occasionally accompanied by eosinophilic infiltration. In this study, we intended to determine whether DILI can induce augmentation of ECL/GL9 expression. Further, we investigated whether this augmentation is associated with tissue eosinophilia. METHODS: We examined the expression of ECL/GL9 in biopsy specimens of DILI using the immunohistochemical technique. A rabbit anti-ECL/GL9 antibody was produced by immunizing rabbits with synthetic peptide corresponding to a molecular epitope of ECL/GL9. Thereafter, immunohistochemical staining with the use of this antibody was performed on 16 DILI needle biopsy specimens, and on biopsy specimens of chronic viral hepatitis, liver cirrhosis, and normal liver tissues as controls. RESULTS: In all cases of DILI specimens, but not in control liver specimens, a clear positive staining for ECL/GL9 was observed. Such positive staining was noted on Kupffer cells, fibroblasts, and histiocytes, but not on lymphocytes or hepatocytes. However, the intensity of immunolabeling did not correlate with the extent of eosinophile leukocyte infiltration. CONCLUSION: High expression of ECL/GL9 is suggested to be a specific finding of DILI. However, tissue eosinophilia in DILI cannot be explained by the augmentation of ECL/GL9 expression.

Adult↗
PubMed2005

Phase II study of oral fludarabine phosphate in relapsed indolent B-Cell non-Hodgkin's lymphoma.

PURPOSE: Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. PATIENTS AND METHODS: Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). RESULTS: Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. CONCLUSION: Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

Administration, Oral↗
PubMed2005

Apoptosis in murine lymphoid organs following intraperitoneal administration of dimethyl sulfoxide (DMSO).

A significant increase in lymphocyte apoptosis was detected by the TUNEL method in the thymus, spleen, and Peyer's patches (PP) following intraperitoneal (i.p.) administration of dimethyl sulfoxide (DMSO) (treatment, n = 47; control, n = 8). Interestingly, administration of low doses of DMSO caused apoptosis in only the PP, and suggested that i.p. administration of DMSO induced apoptosis for each lymphoid organ in a dose dependent manner. Moreover, in the early stage during the apoptotic change, a characteristic localization of lymphocytes undergoing apoptosis was observed. Briefly, early apoptosis occurred predominantly in the cortical mid-zone of the thymus, white pulp of the spleen, and germinal centers of PP. With increased time following administration, however, lymphocytes throughout lymphoid tissues, independent of characteristic localization during the early stage, seemed to undergo apoptosis, resulting in the severe loss of lymphocytes. In fact, the relative spleen weight significantly decreased at 24 h following DMSO administration (n = 7; P < 0.001 versus 8 control mice). Taken together, these results showed for the first time that the in vivo administration of DMSO to mice caused apoptosis in lymphoid organs, and also demonstrated that the apoptotic behavior varied between different lymphoid organs.

Animals↗
PubMed2005

Ferroelectricity from iron valence ordering in the charge-frustrated system LuFe2O4.

Ferroelectric materials are widely used in modern electric devices such as memory elements, filtering devices and high-performance insulators. Ferroelectric crystals have a spontaneous electric polarization arising from the coherent arrangement of electric dipoles (specifically, a polar displacement of anions and cations). First-principles calculations and electron density analysis of ferroelectric materials have revealed that the covalent bond between the anions and cations, or the orbital hybridization of electrons on both ions, plays a key role in establishing the dipolar arrangement. However, an alternative model-electronic ferroelectricity-has been proposed in which the electric dipole depends on electron correlations, rather than the covalency. This would offer the attractive possibility of ferroelectric materials that could be controlled by the charge, spin and orbital degrees of freedom of the electron. Here we report experimental evidence for ferroelectricity arising from electron correlations in the triangular mixed valence oxide, LuFe(2)O(4). Using resonant X-ray scattering measurements, we determine the ordering of the Fe(2+) and Fe(3+) ions. They form a superstructure that supports an electric polarization consisting of distributed electrons of polar symmetry. The polar ordering arises from the repulsive property of electrons-electron correlations-acting on a frustrated geometry.

Journal Article↗
PubMed2005

Acceleration of Smad2 and Smad3 phosphorylation via c-Jun NH(2)-terminal kinase during human colorectal carcinogenesis.

Conversion of normal epithelial cells to tumors is associated with a shift in transforming growth factor-beta (TGF-beta) function: reduction of tumor suppressor activity and increase of oncogenic activity. However, specific mechanisms of this functional alteration during human colorectal carcinogenesis remain to be elucidated. TGF-beta signaling involves Smad2/3 phosphorylated at linker regions (pSmad2/3L) and COOH-terminal regions (pSmad2/3C). Using antibodies specific to each phosphorylation site, we herein showed that Smad2 and Smad3 were phosphorylated at COOH-terminal regions but not at linker regions in normal colorectal epithelial cells and that pSmad2/3C were located predominantly in their nuclei. However, the linker regions of Smad2 and Smad3 were phosphorylated in 31 sporadic colorectal adenocarcinomas. In particular, late-stage invasive and metastatic cancers typically showed a high degree of phosphorylation of Smad2/3L. Their extent of phosphorylation in 11 adenomas was intermediate between those in normal epithelial cells and adenocarcinomas. Whereas pSmad2L remained in the cytoplasm, pSmad3L was located exclusively in the nuclei of Ki-67-immunoreactive adenocarcinomas. In contrast, pSmad3C gradually decreased as the tumor stage progressed. Activated c-Jun NH(2)-terminal kinase in cancers could directly phosphorylate Smad2/3L. Although Mad homology 2 region sequencing in the Smad4 gene revealed a G/A substitution at codon 361 in one adenocarcinoma, the mutation did not correlate with phosphorylation. No mutations in the type II TGF-beta receptor and Smad2 genes were observed in the tumors. In conclusion, pSmad3C, which favors tumor suppressor activity of TGF-beta, was found to decrease, whereas c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence.

Adenocarcinoma↗
PubMed2005

Prevalence of ischemic enterocolitis in patients with acute pancreatitis.

BACKGROUND: A considerable number of acute pancreatitis cases have been reported to be complicated by nonocclusive mesenteric ischemia. However, no reports have ever referred to the incidence of ischemic enterocolitis in patients with acute pancreatitis, using a series of autopsy cases. Here, we report our review of autopsy cases of patients with acute pancreatitis to examine the incidence of associated ischemic enterocolitis. METHODS: The intestinal and pancreatic slides of 48 autopsy cases of patients with acute pancreatitis were reviewed and the incidence of ischemic enterocolitis was determined. Clinical case records were also reviewed. RESULTS: Thirteen (27%) of 48 autopsy cases of patients with acute pancreatitis were complicated by ischemic enterocolitis. The frequency of shock was significantly higher in patients with ischemic enterocolitis than in those without ischemic enterocolitis. The intestinal lesion was diffuse in many cases and gangrene was not an unusual finding. CONCLUSIONS: The incidence of ischemic enterocolitis in patients with acute pancreatitis was much higher than that in the previous reports. Clinicians who treat patients with acute pancreatitis should consider ischemic enterocolitis as one of the frequent and severe complications of this condition.

Acute Disease↗
PubMed2005

Transforming growth factor-beta and platelet-derived growth factor signal via c-Jun N-terminal kinase-dependent Smad2/3 phosphorylation in rat hepatic stellate cells after acute liver injury.

After liver injury, transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) regulate the activation of hepatic stellate cells (HSCs) and tissue remodeling. Mechanisms of PDGF signaling in the TGF-beta-triggered cascade are not completely understood. TGF-beta signaling involves phosphorylation of Smad2 and Smad3 at linker and C-terminal regions. Using antibodies to distinguish Smad2/3 phosphorylated at linker regions from those phosphorylated at C-terminal regions, we investigated Smad2/3-mediated signaling in rat liver injured by CCl(4) administration and in cultured HSCs. In acute liver injury, Smad2/3 were transiently phosphorylated at both regions. Although linker-phosphorylated Smad2 remained in the cytoplasm of alpha-smooth muscle actin-immunoreactive mesenchymal cells adjacent to necrotic hepatocytes in centrilobular areas, linker-phosphorylated Smad3 accumulated in the nuclei. c-Jun N-terminal kinase (JNK) in the activated HSCs directly phosphorylated Smad2/3 at linker regions. Co-treatment of primary cultured HSCs with TGF-beta and PDGF activated the JNK pathway, subsequently inducing endogenous linker phosphorylation of Smad2/3. The JNK pathway may be involved in migration of resident HSCs within the space of Disse to the sites of tissue damage because the JNK inhibitor SP600125 inhibited HSC migration induced by TGF-beta and PDGF signals. Moreover, treatment of HSCs with both TGF-beta and PDGF increased transcriptional activity of plasminogen activator inhibitor-1 through linker phosphorylation of Smad3. In conclusion, TGF-beta and PDGF activate HSCs by transmitting their signals through JNK-mediated Smad2/3 phosphorylation at linker regions, both in vivo and in vitro.

Adipocytes↗
PubMed2005

Solid pseudopapillary tumor of the pancreas with metastases to the lung and liver.

Presented herein is the case of a 41-year-old woman who was admitted to Teikyo University Hospital with abdominal and back pain. Clinical examination revealed a large mass of the pancreas and multiple nodules in the liver. After surgical resection of the pancreatic and liver tumors, liver nodules recurred repeatedly, and a solitary mass lesion occurred in the right lung. Grossly, the pancreatic tumor was large and partially cystic. Histologically, small and uniform tumor cells proliferated, having solid and pseudopapillary patterns. These pathological findings enabled a pathological diagnosis of solid pseudopapillary tumor (SPT) of the pancreas to be made. The pathological appearance of the liver and lung tumors was similar to that of the pancreatic tumor. This is the first report of a case of pancreatic SPT that showed lung metastasis. It should be kept in mind that pancreatic SPT may take such an aggressive clinical course, although they are usually benign in nature.

Adult↗
PubMed2005

A case of pure red cell aplasia complicated with diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant: effectiveness of rituximab and implications for a common immunopathogenic role of B lymphocytes.

Diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant (DLBL-TH), is characterized by the presence of neoplastic B cells set in a background containing numerous non-neoplastic T lymphocytes and histiocytes. We report here the case of a patient with DLBL-TH who developed overt pure red cell aplasia (PRCA) following chemotherapy and autologous peripheral blood stem cell transplantation. Posttransplantation bone marrow biopsies revealed the absence of erythroid precursors associated with lymphoid aggregates composed of B cells mixed with numerous T cells and histiocytes. Administration of rituximab has led to complete recovery of erythropoiesis, which was associated not only with B cell depletion but also with a marked reduction in bone marrow T cells and histiocytes. These observations strongly suggest the particular pathogenetic role of the patient's B cells in inducing PRCA and recruiting T cells and histiocytes in situ.

Antibodies, Monoclonal↗
PubMed2005

Accumulation of BCL10 at the perinuclear region is required for the BCL10-mediated nuclear factor-kappa B activation.

OBJECTIVES: The dysregulated overexpression of BCL10 that results from a specific chromosomal translocation t(1;14)(p22;q32) in mucosa-associated lymphoid tissue lymphoma has been shown to activate nuclear factor (NF)-kappaB, which may promote growth and survival in tumor cells. Accordingly, the molecular mechanisms underlying NF-kappaB activation may be responsible for lymphomagenesis. The aim of this study was to determine the molecular mechanisms underlying NF-kappaB activation by BCL10 overexpression. METHODS: HeLa or COS-1 cells were transfected with BCL10, intracellular localization of BCL10 and the activation of NF-kappaB were analyzed. RESULTS: BCL10 expressed at a high level exhibited a filamentous distribution at the perinuclear region, whereas BCL10 at a low level of expression displayed a diffuse cytoplasmic distribution. Furthermore, the BCL10-mediated NF-kappaB activation was efficiently inhibited by a Ca2+ chelating agent or a Ca2+ channel blocker. We also found that amino acids (107-119) of BCL10 are required for the formation of filamentous structures at the perinuclear region and NF-kappaB activation. CONCLUSION: These findings suggest that the filamentous pattern of overexpressed BCL10 at the perinuclear region adjacent to the endoplasmic reticulum is important for the BCL10-mediated NF-kappaB activation.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Non-linear eye movements during visual-vestibular interaction under body oscillation with step-mode lateral linear acceleration.

We investigated visual-vestibular interactions in normal humans, where a constant speed of optokinetic stimulation was combined with whole body oscillation of lateral linear acceleration (10 m stroke). The acceleration mode was not sinusoidal, but rectangular (step). The pure optokinetic reflex (reference OKR) and the OKR under combined stimulation (combined OKR) were induced by a random-dot pattern projected onto a hemispherical dome-screen affixed to a chair on a linear accelerator. The translational vestibulo-ocular reflex (tVOR) was determined separately in the dark during acceleration-step oscillation. Since the tVOR was masked by the OKR under combined stimulation, the interaction was assessed as changes in combined-OKR velocity at two segments of opposing acceleration; in other words, tVOR directions identical to (agonistic) and opposite to (antagonistic) the OKR direction. When a moderate optokinetic stimulus-speed of 40 deg/s was combined with a moderate acceleration of 0.3 G (3.0 m/s2) as in Experiment 1 (N=10), the combined-OKR velocity always increased during the agonistic condition, and the motion of the visual pattern was perceived as slow and clear in this segment. On the other hand, during the antagonistic condition, the combined-OKR velocity either remained unchanged or increased moderately, and the motion of the visual pattern was sensed as fast and unclear. Notably, in most subjects, the velocity difference in combined-OKR between the agonistic and antagonistic conditions was around the value of the tVOR velocity. In five of the ten subjects who completed an additional test session with the acceleration level increased from 0.3 to 0.5 G (4.9 m/s2), similar findings were maintained individually, suggesting independent behavior of tVOR. Therefore, we hypothesized that the interaction could be direction-selective; in other words, both tVOR and OKR are additive during the agonistic condition, but tVOR is suppressed during the antagonistic condition. To extend this hypothesis further, another group of subjects was exposed to three different optokinetic-stimulus speeds of 20, 40 and 60 deg/s combined with an acceleration of 0.3 G (Experiment 2, N=15). Combined stimulation tended to optimize the combined-OKR velocity around the given optokinetic stimulus-speed, especially in those cases where the reference-OKR velocity deviated significantly from the stimulus speed. Changes in combined-OKR velocity were small at 20 deg/s, and were likely to be linear across the agonistic and antagonistic conditions. With increasing optokinetic stimulus-speeds, the direction-selective asymmetry hypothesized above was maintained in more than half of the subjects, while in the other subjects the combined-OKR velocity difference increased remarkably, probably due to an enhancement of the OKR gain. We conclude that tVOR suppression during the antagonistic stimulus-condition and non-linearity in the tVOR-OKR interaction are characteristic of the otolith system, even under moderate-stimulus environments, in contrast to the linear eye-movement interaction in the semicircular canal system.

Acceleration↗
PubMed2004

TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions.

Although hepatocyte growth factor (HGF) can act synergistically or antagonistically with transforming growth factor-beta (TGF-beta) signaling, molecular mechanism of their crosstalk remains unknown. Using antibodies which selectively distinguished receptor-regulated Smads (R-Smads) phosphorylated at linker regions from those at C-terminal regions, we herein showed that either HGF or TGF-beta treatment of normal stomach-origin cells activated the JNK pathway, thereafter inducing endogenous R-Smads phosphorylation at linker regions. However, the phosphorylation at their C-terminal regions was not induced by HGF treatment. The activated JNK could directly phosphorylate R-Smads in vitro at the same sites that were phosphorylated in response to TGF-beta or HGF in vivo. Thus, the linker regions of R-Smads were the common phosphorylation sites for HGF and TGF-beta signaling pathways. The phosphorylation induced by simultaneous treatment with HGF and TGF-beta allowed R-Smads to associate with Smad4 and to translocate into the nucleus. JNK pathway involved HGF and TGF-beta-mediated infiltration potency since a JNK inhibitor SP600125 caused the reduction of invasive capacity induced by HGF and TGF-beta signals. Moreover, a combined treatment with HGF and TGF-beta led to a potent increase in plasminogen activator inhibitor type 1 transcriptional activity through Smad3 phosphorylation at the linker region. In contrast, HGF treatment reduced TGF-beta-dependent activation of p15INK4B promoter, in which Smad3 phosphorylation at the C-terminal region was involved. In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions.

Animals↗