Publications by authors named "Tomohiro Iwasaki"

28 Publications

  • Page 1 of 1

Carcinoma showing thymus-like differentiation (CASTLE) of the salivary gland: Report of 2 cases of a hitherto under-recognized extrathyroid counterpart.

Pathol Res Pract 2021 Nov 8;227:153646. Epub 2021 Oct 8.

Department of Anatomic Pathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.

Carcinoma showing thymus-like differentiation (CASTLE) outside the thyroid gland is extremely rare. Here we report two cases of CASTLE of the major salivary gland. The tumors occurred in the parotid gland of a 31-year-old female (Case 1) and in the submandibular gland of a 40-year-old female (Case 2). Both tumors showed a lobulated growth pattern, and were histologically composed of a nested or sheet-like proliferation of carcinoma cells with round- to oval-shaped nuclei, distinct nucleoli and pale eosinophilic cytoplasm, accompanied by various degrees of lymphocytic infiltration. Immunohistochemical staining revealed that the tumors were positive for pan-cytokeratin, p40, CD5, CD117 and bcl-2. In addition, PD-L1 expression was seen in 10-90% of tumor cells. After the initial surgery, Case 1 remained tumor-free for 20 months, while Case 2 suffered lymph node recurrence at 4 months, followed by lung metastasis, which was treated with chemoradiotherapy and anti-PD-1 immune checkpoint inhibitor, resulting in a partial response. The present findings indicate that an extrathyroid counterpart of CASTLE can occur as a primary salivary gland neoplasm. Salivary CASTLEs seem to show a wide range of biological behavior, and long-term follow-up may be needed. Immune checkpoint inhibitor targeting PD-1 might become a promising treatment option in patients with CASTLE; however, further study with a larger number of cases is necessary to establish the optimal therapeutic strategy and prognostic factors for this rare cancer.
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http://dx.doi.org/10.1016/j.prp.2021.153646DOI Listing
November 2021

Periostin expression and its supposed roles in benign and malignant thyroid nodules: an immunohistochemical study of 105 cases.

Diagn Pathol 2021 Sep 25;16(1):86. Epub 2021 Sep 25.

Department of Pathology, Shizuoka General Hospital, Shizuoka, Japan.

Background: Thyroid tumors are often difficult to histopathologically diagnose, particularly follicular adenoma (FA) and follicular carcinoma (FC). Papillary carcinoma (PAC) has several histological subtypes. Periostin (PON), which is a non-collagenous extracellular matrix molecule, has been implicated in tumor invasiveness. We herein aimed to elucidate the expression status and localization of PON in thyroid tumors.

Method: We collected 105 cases of thyroid nodules, which included cases of adenomatous goiter, FA, microcarcinoma (MIC), PAC, FC, poorly differentiated carcinoma (PDCa), and undifferentiated carcinoma (UCa), and immunohistochemically examined the PON expression patterns of these lesions.

Results: Stromal PON deposition was detected in PAC and MIC, particularly in the solid/sclerosing subtype, whereas FA and FC showed weak deposition on the fibrous capsule. However, the invasive and/or extracapsular regions of microinvasive FC showed quite strong PON expression. Except for it, we could not find any significant histopathological differences between FA and FC. There were no other significant histopathological differences between FA and FC. Although PDCa showed a similar PON expression pattern to PAC, UCa exhibited stromal PON deposition in its invasive portions and cytoplasmic expression in its carcinoma cells. Although there was only one case of UCa, it showed strong PON immunopositivity. PAC and MIC showed similar patterns of stromal PON deposition, particularly at the invasive front.

Conclusions: PON may play a role in the invasion of thyroid carcinomas, particularly PAC and UCa, whereas it may act as a barrier to the growth of tumor cells in FA and minimally invasive FC.
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http://dx.doi.org/10.1186/s13000-021-01146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465710PMC
September 2021

A Case of Colonic Micropapillary Carcinoma with a High Frequency of Apoptosis.

J Gastrointest Cancer 2021 Jul 24. Epub 2021 Jul 24.

Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan.

Colorectal micropapillary carcinoma (MPC) exhibits aggressive biological characteristics, with empty spaces and reversed polarity, similar to the poorly differentiated clusters (PDCs) formed from detached cancer cells. Epithelial-mesenchymal transition, which is involved in the cancer cell acquisition of apoptosis resistance, is closely linked with histological findings of MPC, PDCs, and tumor buds (TBs), with MPC and TBs considered as apoptosis-resistant features. However, we encountered a case of colonic MPC with frequent apoptosis. We examined the case using immunohistochemistry. In many of the tumor glands (TGs) of the MPC, empty spaces and tumor cell detachment toward the gland interior were observed. Moreover, TG ruptures were scattered, with PDCs adjacent to them. Apoptosis occurred mainly at the TG and PDC peripheries in the middle and deep tumor layers, and transforming growth factor beta 1 (TGF-β1) positivity was evident in those tumor cells. Cells positive for apoptosis-related M30 were distributed mainly in the deep layer with a significant PDC and TB presence. However, apoptosis and M30 positivity were low in the TBs. Non-tumorous bud components, especially those in the deep layer, had poor ability to promptly acquire apoptosis resistance. No nuclear β-catenin positivity was found in any of the tumor cells. Apoptosis has the potential to reciprocally produce MPC, PDCs, and TBs, with TGF-β1 involvement.
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http://dx.doi.org/10.1007/s12029-021-00674-2DOI Listing
July 2021

Long Spinal Cord Lesions Caused by Venous Congestive Myelopathy Associated with Intravascular Large B-cell Lymphoma.

Intern Med 2021 Jun 19. Epub 2021 Jun 19.

Department of Neurology, Tsubame Rosai Hospital, Japan.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of B-cell lymphoma, characterized by lymphoma cell proliferation within small blood vessels. We herein describe a rare case with long spinal cord lesions caused by venous congestive myelopathy associated with IVLBCL. An 81-year-old man presented with paraplegia of the lower limbs and sensory disturbances. Magnetic resonance imaging revealed intramedullary longitudinal T2-hyperintensity lesions in the thoracic cords. The patient died three months after disease onset, and a neuropathological analysis revealed predominantly atypical B-lymphocytes located sparsely in the veins of the spinal cord. IVLBCL should be considered in the differential diagnoses of long spinal cord lesions.
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http://dx.doi.org/10.2169/internalmedicine.6717-20DOI Listing
June 2021

Rare paraneoplastic syndromes in digestive systems caused by lung cancer.

BMJ Case Rep 2021 Feb 5;14(2). Epub 2021 Feb 5.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University, Niigata, Japan.

We observed a rare case of two different digestive paraneoplastic syndromes that improved with the treatment of the neoplasms. The first syndrome was chronic intestinal pseudo-obstruction (CIPO), which is a subtype of paraneoplastic syndromes called a paraneoplastic neurological syndrome (PNS). The second was Stauffer's syndrome, which is a unique paraneoplastic syndrome characterised by non-metastatic intrahepatic cholestasis associated with neoplasms. Here, we report the case of a 55-year-old man who presented with two concurrent paraneoplastic syndromes in the digestive system. The intestinal pseudo-obstruction and elevated biliary enzyme levels improved as the lung cancer responded to chemotherapy. In this case, CIPO as a PNS led to the detection of lung cancer. To our knowledge, this is the first report of Stauffer's syndrome caused by lung adenocarcinoma.
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http://dx.doi.org/10.1136/bcr-2020-240161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871262PMC
February 2021

Salivary Duct Carcinoma With Rhabdoid Features-No or Aberrant Expression of E-cadherin and Genetic Changes in CDH1: Immunohistochemical and Genetic Analyses of 17 Cases.

Am J Surg Pathol 2021 04;45(4):439-449

Department of Pathology, Shizuoka General Hospital, Shizuoka City.

Salivary duct carcinoma is a relatively uncommon malignancy of the salivary glands; however, it frequently occurs as a carcinomatous component of carcinoma ex pleomorphic adenoma. We previously reported salivary duct carcinoma with rhabdoid features (SDCRF) as an extremely rare subtype of salivary duct carcinoma, and that it occurred as a salivary counterpart of pleomorphic lobular carcinoma of the breast (PLCB). We collected new cases of SDCRF for this study, in which we examined a total of 17 cases immunohistochemically and genetically. As it is known that PLCB exhibits loss of or aberrant E-cadherin expression and carries nonsense/missense mutations in or deletion of the CDH1 gene, we examined the CDH1 gene status of our SDCRF cases. All of the examined SDCRF cases involved the diffuse proliferation of large ovoid cells with eosinophilic cytoplasm and eccentric nuclei, which displayed reduced cell-cell adhesion. Most cases were positive for pan-cytokeratin, androgen receptor, gross cystic disease fluid protein-15, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1, and WI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4, whereas they were negative for vimentin. No and decreased/cytoplasmic E-cadherin expression was observed in 11 and 4 of 17 cases, respectively, whereas no and decreased/cytoplasmic β-catenin expression were observed in 10 and 5 of 17 cases, respectively. Among the 11 cases that could be genetically analyzed, a nonsense mutation (1 case), missense mutations (6 cases), and insertions (1 case) were detected in the CDH1 gene. In conclusion, we propose that SDCRF is the salivary counterpart of PLCB due to its morphology and immunophenotype, and the genetic status of CDH1.
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http://dx.doi.org/10.1097/PAS.0000000000001672DOI Listing
April 2021

Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis.

World J Surg Oncol 2020 Nov 7;18(1):289. Epub 2020 Nov 7.

Department of Gastroenterological Surgery, Shizuoka General Hospital, 4-27-1 Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan.

Background: Tumor budding (TB) and poorly differentiated clusters (PDCs) are a sequence of histologic findings that predict worse prognosis and node metastasis in colorectal cancer (CRC). TB and PDC (TB/PDC) are caused by cancer cell detachment and are distinguished by the number of cancer cells that constitute a cell cluster. In short, PDC is regarded as the previous step of TB. TB/PDC and epithelial-mesenchymal transition (EMT) are closely linked, but its pathogenic mechanisms are still unclear. S100A10, a member of the S100 protein family, forms a heterocomplex with annexin A2 (ANX A2) and then translocates to cell membrane from the cytoplasm and plays various roles in cell dynamics, including plasminogen activation. S100A10 is the activation modulator of the heterocomplex and promotes cell invasion. S100A10 is involved in the remodeling of both actin and extracellular matrix (ECM), which is also associated with EMT.

Case Presentation: In two representative cases of conventional advanced CRC, we immunohistochemically examined S100A10 and ANX A2 expressions in which both TB and PDC were prominent. Both CRCs metastasized to multiple regional lymph nodes. In both cases, a membranous positivity for S100A10 was diffusely found in both tumor buds and PDCs and was observed in the tumor cells protruding toward the stroma, giving rise to TB/PDC. However, even in tumor glands with TB/PDC, the tumor cells with a smooth border around the stroma showed either cytoplasmic fine-granular expression or no positivity. The immunoreactivity for ANX A2 was almost the same as that for S100A10. In the main tumor components without TB/PDC, no distinct positivity was detected at their smooth borders.

Conclusions: During oncogenesis, membranous S100A10 has the potential to be related to TB of CRC. This may be due to plasminogen activation, actin remodeling, and interaction with an altered ECM. However, further study is required to confirm this hypothesis.
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http://dx.doi.org/10.1186/s12957-020-02075-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648945PMC
November 2020

Involvement of Annexin A2 Expression and Apoptosis in Reverse Polarization of Invasive Micropapillary Carcinoma of the Breast.

Case Rep Pathol 2020 10;2020:9242305. Epub 2020 Jul 10.

Department of Clinical Research, Shizuoka General Hospital, Shizuoka, Japan.

Invasive micropapillary carcinoma (IMPC) is characterized by pseudopapillary tumor-cell clusters with a reverse polarity (RP) floating in lacunar spaces, with aggressive biological characteristics. The RP prevention is considered to inhibit IMPC, but its pathogenic mechanisms remain unclear. Annexin A2 (ANX A2), a cell-polarity protein, is known to be involved in lumenogenesis. ANX A2 expression is immunohistochemically examined, as well as both epithelial membrane antigen (EMA) and mucin-1 glycoprotein (MUC-1), the gold-standard markers for luminal differentiation, in the background tumor components of a case of IMPC. The following findings were noticed: (1) Apoptosis was scattered with peripheral apoptotic vacuolar change; (2) EMA and MUC-1 expressions were found, rimming the peripheral apoptotic vacuoles (including the contact surface with neighboring tumor cells), and these positions corresponded to the ones with a distinct ANX A2 positivity; and (3) partially detached tumor cells showed distinct positivity of three proteins at the stroma-facing surface, which is consistent with a RP. Taken together, frequent apoptosis in tumor cells with membranous accumulation of ANX A2 is considered to be indispensable for the reverse polarization of IMPC, and that secondary necrosis following apoptosis induces the cell-polarity disorder and creates detached tumor cells with a RP.
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http://dx.doi.org/10.1155/2020/9242305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368959PMC
July 2020

Annexin A2 Expression in the Aerogenous Spread of Pulmonary Invasive Mucinous Adenocarcinoma with Gastric Lineage.

Case Rep Oncol Med 2020 18;2020:2492636. Epub 2020 May 18.

Department of Clinical Research, Shizuoka General Hospital, Japan.

Spread through air spaces (STAS) is a unique form of lung cancer progression associated with a worse prognosis. However, the mechanisms underlying STAS and the associated proteins remain unclear. Annexin A2 (ANX A2), which is a membrane-binding protein involved in cell adhesion, is known to promote cancer invasion. In this report, we describe the immunohistochemical analysis of ANX A2 expression in an invasive mucinous adenocarcinoma (IMAC) resected from a 63-year-old man in whom the tumor cells had detached from the alveolar wall and exhibited STAS. At the detachment site, we observed cytoplasmic ANX A2 positivity on the basal side and in the exfoliative gap, as well as reduced collagen IV positivity expression. This biomarker pattern suggested an IMAC with gastric lineage. We hypothesize that ANX A2 is secreted from the basal sides of tumor cells and induces tumor cell detachment by degrading the basement membrane. A further comparison of this case with an IMAC with nongastric lineage suggested the following probabilities: (1) ANX A2 likely contributes to STAS in a manner that is dependent on its subcellular localization. (2) Both the subcellular localization of ANX A2 and the detachment site depend on tumor cell characteristics, including the biomarker immunophenotype.
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http://dx.doi.org/10.1155/2020/2492636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254091PMC
May 2020

A case of small hepatocellular carcinoma with malignant ductular reaction.

Int J Clin Exp Pathol 2020 1;13(5):1073-1080. Epub 2020 May 1.

Department of Pathology, Shizuoka General Hospital No. 4-27-1, Kita-Ando, Aoi-ku, Shizuoka 420-8527, Japan.

Herein reported is the unique case of a small hepatocellular carcinoma (HCC) with several foci of a minor (10% in area) component of "malignant ductular reactions". The patient was 51-year-old man who was a drinker. HBV/HCV were negative. The tumor was small (12×10×11 mm), solid, expansile and reddish-brown, and contained fibrous septa. The background was cirrhotic without alcoholic features. Histologically, the tumor was well differentiated HCC, and, besides the HCC, it contained several small foci consisting of the following four biliary epithelial elements: clusters of small cells (CSC), ductules (D), ductular hepatocytes (DH), and bile ducts (BD). The proportion of area was as follows: HCC 90%, CSC 3%, D 3%, DH 2%, and BD 2%. These non-HCC elements were intimately admixed and formed several foci that were characteristically located in the fibrous septa (FS), except for CSC which were situated among HCC cells close to FS. There were gradual merges between HCC and CSC, CSC and D, D and DH, and D and BD, respectively. Cells of CSC and D resembled rat oval cells. Cells of these four elements had atypical features regarded as malignant. Immunohistochemically (IHC), HCC were positive for arginase, HepPar1, and less frequently CK7. CSC were positive for CK7. D were positive for arginase, HepPar1, CK7, CK19, EMA, and EpCAM. DH were positive for arginase, HepPar1, and CK7. BD were positive for CK7, CK19, EMA, EpCAM and mucin. Although such tumors as this have been termed stem cell-related cancers, our case lacked definite evidence for stem cell origin in histology as well as in the IHC that showed negativity for KIT, CD34, and OCT3/4. The above findings suggest that CSC, D, DH and BD are analogous to the ductular reaction seen in hepatic inflammation. Therefore, we termed the phenomenon "malignant ductular reaction". It is suggested in the present tumor that at first only HCC developed, and then HCC cells in the interface with FS transformed to CSC, like a fetal ductal plate. Then, the CSC gave rise to D, which in turn led to DH and BD in FS, all findings of which are most likely sequential considering embryonic biliary development. The idea that the present tumor was at first D carcinoma and then D developed on one hand into CSC and HCC, and on the other into DH and BD seems possible, but its probability appears low because the vast majority of the present tumor had the phenotype of HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270666PMC
May 2020

A case of small well-differentiated hepatocellular carcinoma with marked lymphocytic infiltrate.

Int J Clin Exp Pathol 2020 1;13(3):624-633. Epub 2020 Mar 1.

Department of Pathology, Shizuoka General Hospital No. 4-27-1, Kita-Ando, Aoi-ku, Shizuoka, Shizuoka 420-8527, Japan.

We herein report a case of well-differentiated small hepatocellular carcinoma (HCC) with severe lymphocytic infiltrate (SLI) in a 55-year-old male patient with HCV-related cirrhosis. The patient had been followed-up because of HCV-related cirrhosis. He was found to have two small nodules in S8 by imaging techniques, and he underwent S8 segmentectomy. The resected liver showed two small nodules. Both were encapsulated, well-defined, solid, reddish and expansive nodules with fibrous septa. They measured 8 × 8 mm and 15 × 10 mm, respectively. Histologically, both tumours were pure HCC; the smaller showed SLI with lymphocytes/HCC cells ratio over 20, while the larger showed mild lymphocytic infiltration with lymphocytes/HCC cells ratio of 0.8. The smaller HCC was well-differentiated (trabecular thickness <3) HCC-SLI with Edmondson II = I cytologic atypia, while the larger was moderately-differentiated (trabeculae >3) HCC (Edmondson II>III>I). Extremely well-differentiated Edmondson I HCC or adenomatous hyperplasia areas were seen in the periphery of both HCCs. The patterns of SLI could be classified into the following three: sinusoids (S) type, portal tract (PT) type, lymph follicle (LF) type. In S-type, lymphocytes were infiltrated between the trabeculae. In PT-type, SLI was found to arise from extension from already inflamed PT within HCC or neighboring PT. The HCC cells frequently exhibited moth-eaten or piece meal necrosis in PT-type. In LF-type, lymphocytes were activated, and nuclear dusts were noted. It appeared that LF-type has arisen from preexisting S-type and/or PT-type. We speculated that the entry of SLI was from S in S-type, from incorporated inflamed PT in PT-type, and from both in LF-type. The approximate overall positive ratios of lymphoid cells among inflammatory cells were as follows: CD20 50%, CD3 70%, CD4 50%, CD8 30%, CD138 3%, CD163 40%, granzyme B 2%, smooth muscle actin (SMA) 30%, CD31 30%, CD21 2%, S100 3%, bcl-2 10%, CK19 1%, CD10 1%, CD30 0%, CD56 0% and Ki67 labeling index = 5%. EBV-ISH and HPV IHC were negative. Interestingly, Kupffer cells had myofibroblastic antigen in addition to macrophage antigens, and stellate cells expressed macrophage antigens aside from myofibroblastic antigens. These data suggest that, in the present case, pan-B-cells, pan-T-cells, helper T-cells, cytotoxic T-cells, plasma cells, macrophages, Kupffer cells, stellate cells, myofibroblasts, fibroblasts, endothelial cells, dendritic cells, Langerhans cells, and toxic molecules may play roles in tumour immunology.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137018PMC
March 2020

Membranous overexpression of S100A10 is associated with a high-grade cellular status of breast carcinoma.

Med Mol Morphol 2020 Jun 15;53(2):104-114. Epub 2019 Nov 15.

Department of Diagnostic Pathology, Hamamatsu University Hospital, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.

S100A10 promotes tumor invasion in various cancers. Although genetic studies on S100A10 in breast carcinoma (BC) have been used for molecular biological classification, immunohistochemical studies are lacking. We aimed to identify the correlation between S100A10 expression in BC and various pathological parameters, including morphological features to determine histological grade (HG). Immunostained serial paraffin-embedded tissue sections from 176 cases of resected BC or normal mammary ducts (controls) were assessed for the membrane expression of S100A10. Of the 176 cases, 125 conventional infiltrating ductal carcinomas were chosen, comprising 67 (53.6%) S100A10-positive tumors, whereas normal mammary ducts were S100A10-negative. S100A10 immunoreactivity in ductal carcinoma in situ (n = 51) was similar to that of invasive carcinoma. The distinct membrane-immunopositivity was correlated with high HG, severe nuclear pleomorphism, frequent mitotic counts, high Ki-67 labeling index, HER2/neu overexpression, and low estrogen receptor status (P < 0.05), but not with tubular formation, pT categories, node metastasis, vessel permeation, and pStage. Membrane overexpression of S100A10 in BC correlates with the high-grade morphological and molecular status of the carcinoma cell rather than stromal invasion and architectural deviation. Evidence points to the use of S100A10 as a biomarker representing a high-grade cellular status of BC.
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http://dx.doi.org/10.1007/s00795-019-00236-3DOI Listing
June 2020

Postnatal relative adrenal insufficiency results in methylation of the glucocorticoid receptor gene in preterm infants: a retrospective cohort study.

Clin Epigenetics 2018 18;10:66. Epub 2018 May 18.

2Division of Pediatrics, Juntendo University School of Medicine, 3-1-3, Hongo, Bunkyo, 113-8421 Japan.

Background: To investigate the relationship between early-life stress and glucocorticoid receptor (GR) gene methylation, which may result in long-lasting neurodevelopmental impairment, we performed a longitudinal analysis of the methylation ratio within the GR gene promoter 1F region using next-generation sequencing in preterm infants.Cell-free DNA was extracted from the frozen serum of 19 preterm birth infants at birth and at 1 and 2 months after birth. All were admitted to the neonatal intensive care unit of Juntendo University Shizuoka Hospital between August 2014 and May 2016 and suffered from chronic lung disease (CLD).Through bisulfite amplicon sequencing using an Illumina Miseq system and Bismark-0.15.0 software, we identified the rate of cytosine methylation.

Results: Patients' sex and body weight standard deviation were extracted as the associated independent variables at birth. Sex, glucocorticoid administration for treating CLD, and postnatal invasive procedures (surgical operation and blood sampling) were extracted as the associated independent variables at 1 month. Methylation rates increased significantly between postnatal 1 and 2 months at 9 of the 39 CpG sites. Postnatal glucocorticoid administration to treat circulatory collapse was the most-associated independent variable with a positive regression coefficient for a change in methylation rate at these nine CpG sites. It also influenced the methylation ratio at 22 of the 39 CpG sites at 2 months of age. The standard deviation (SD) score at birth was extracted as an independent variable, with a negative regression coefficient at 9 of the 22 CpG sites together with glucocorticoid administration.

Conclusions: The results of this study indicate that a prenatal environment that results in intrauterine growth restriction and postnatal relative adrenal insufficiency requiring glucocorticoid administration leads to GR gene methylation. That, in turn, may result in neurodevelopmental disabilities.
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http://dx.doi.org/10.1186/s13148-018-0497-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960186PMC
May 2019

Bleeding from a Small-Intestinal Ulcer Associated with Chronic Hepatitis C.

Am J Case Rep 2018 Mar 3;19:234-237. Epub 2018 Mar 3.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata, Japan.

BACKGROUND Hepatitis C virus infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide. Extrahepatic manifestations are well recognized among patients with chronic HCV infection. CASE REPORT We report a case of melena occurring in a 69-year-old Japanese man who had been diagnosed with CHC and who was treated with antiviral therapy. CONCLUSIONS Finally, he was diagnosed with multiple small intestine ulcers in a short time. We herein report the case of HCV with rapidly developing small intestine ulcers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844191PMC
http://dx.doi.org/10.12659/ajcr.908594DOI Listing
March 2018

Case of severe alcoholic hepatitis treated with granulocytapheresis.

World J Clin Cases 2016 Nov;4(11):369-374

Yukari Watanabe, Kenya Kamimura, Hiroyuki Abe, Shunsaku Takahashi, Ken-ichi Mizuno, Manabu Takeuchi, Shuji Terai, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Severe alcoholic hepatitis (AH) has a high mortality, and it is associated with encephalopathy, acute renal failure, sepsis, gastrointestinal bleeding, and endotoxemia. The 28-d mortality remains poor (34%-40%), because no effective treatment has been established. Recently, corticosteroids (CS) have been considered effective for significantly improving the prognosis of those with AH, as it prevents the production of pro-inflammatory cytokines. However, CS are not always appropriate as an initial therapeutic option, such as in cases with an infection or resistance to CS. We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria (), and was successfully treated with granulocytapheresis monotherapy without using CS. The experience of this case will provide understanding of the disease and information treating cases without using CS.
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http://dx.doi.org/10.12998/wjcc.v4.i11.369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112357PMC
November 2016

Localized Hepatic Tuberculosis with Imaging Changes Caused by the Progression of Tuberculosis.

Intern Med 2016 15;55(6):613-6. Epub 2016 Mar 15.

Department of Internal Medicine, Tsubame Rosai Hospital, Japan.

Localized hepatic tuberculosis (LHTB) is difficult to diagnose preoperatively, and most cases of LHTB are diagnosed based on pathological findings. A relationship between imaging features and the pathological stage of hepatic tuberculosis (TB) has recently been reported, which could aid in the diagnosis of hepatic TB. We herein present a case study of a patient with LHTB diagnosed postoperatively who demonstrated imaging changes due to the progression of TB. An awareness of the presence of LHTB might have permitted a preoperative diagnosis. This is the first report of an LHTB patient who exhibited imaging changes during the course of the disease.
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http://dx.doi.org/10.2169/internalmedicine.55.5607DOI Listing
September 2016

A low-pungency S3212 genotype of Capsicum frutescens caused by a mutation in the putative aminotransferase (p-AMT) gene.

Mol Genet Genomics 2015 Dec 6;290(6):2217-24. Epub 2015 Jun 6.

Graduate School of Agriculture, Shinshu University, 8304 Minami-minowa, Kami-ina, Nagano, 399-4598, Japan.

The purpose of this study was to identify the genetic mechanism underlying capsinoid biosynthesis in S3212, a low-pungency genotype of Capsicum frutescens. Screening of C. frutescens accessions for capsaicinoid and capsiate contents by high-performance liquid chromatography revealed that low-pungency S3212 contained high levels of capsiate but no capsaicin. Comparison of DNA coding sequences of pungent (T1 and Bird Eye) and low-pungency (S3212) genotypes uncovered a significant 12-bp deletion mutation in exon 7 of the p-AMT gene of S3212. In addition, p-AMT gene transcript levels in placental tissue were positively correlated with the degree of pungency. S3212, the low-pungency genotype, exhibited no significant p-AMT transcript levels, whereas T1, one of the pungent genotypes, displayed high transcript levels of this gene. We therefore conclude that the deletion mutation in the p-AMT gene is related to the loss of pungency in placental tissue and has given rise to the low-pungency S3212 C. frutescens genotype. C. frutescens S3212 represents a good natural source of capsinoids. Finally, our basic characterization of the uncovered p-AMT gene mutation should contribute to future studies of capsinoid biosynthesis in Capsicum.
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http://dx.doi.org/10.1007/s00438-015-1071-1DOI Listing
December 2015

Bcl11b SWI/SNF-complex subunit modulates intestinal adenoma and regeneration after γ-irradiation through Wnt/β-catenin pathway.

Carcinogenesis 2015 Jun 31;36(6):622-31. Epub 2015 Mar 31.

Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Chuo-ku, Niigata 951-8510, Japan, Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae-shi, Tokyo, 201-8511, Japan, Brain Research Institute, Niigata University, Asahimachi 1-757, Chuo-ku, Niigata 951-8510, Japan, Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan and RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

SWI/SNF chromatin remodeling complexes constitute a highly related family of multi-subunit complexes to modulate transcription, and SWI/SNF subunit genes are collectively mutated in 20% of all human cancers. Bcl11b is a SWI/SNF subunit and acts as a haploinsufficient tumor suppressor in leukemia/lymphomas. Here, we show expression of Bcl11b in intestinal crypt cells and promotion of intestinal tumorigenesis by Bcl11b attenuation in Apc (min/+) mice. Of importance, mutations or allelic loss of BCL11B was detected in one-third of human colon cancers. We also show that attenuated Bcl11b activity in the crypt base columnar (CBC) cells expressing the Lgr5 stem cell marker enhanced regeneration of intestinal epithelial cells after the radiation-induced injury. Interestingly, BCL11B introduction in human cell lines downregulated transcription of β-catenin target genes, whereas Bcl11b attenuation in Lgr5(+) CBCs increased expression of β-catenin targets including c-Myc and cyclin D1. Together, our results argue that Bcl11b impairment promotes tumor development in mouse and human intestine at least in part through deregulation of β-catenin pathway.
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http://dx.doi.org/10.1093/carcin/bgv044DOI Listing
June 2015

Complete Genome Sequence of Ralstonia pickettii DTP0602, a 2,4,6-Trichlorophenol Degrader.

Genome Announc 2013 Oct 31;1(6). Epub 2013 Oct 31.

Department of Environmental Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.

Ralstonia pickettii strain DTP0602 utilizes 2,4,6-trichlorophenol as its sole carbon and energy source. Here, we report the complete genome sequence of strain DTP0602, which comprises three chromosomes and no plasmids. We also found that the two had gene clusters responsible for the degradation of 2,4,6-trichlorophenol are located on the 2.9-Mb chromosome 2.
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http://dx.doi.org/10.1128/genomeA.00903-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814637PMC
October 2013

Simple and rapid synthesis of magnetite/hydroxyapatite composites for hyperthermia treatments via a mechanochemical route.

Int J Mol Sci 2013 Apr 29;14(5):9365-78. Epub 2013 Apr 29.

Department of Chemical Engineering, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai, Osaka 599-8531, Japan.

This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix. We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates. When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration. For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s. These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments.
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http://dx.doi.org/10.3390/ijms14059365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676787PMC
April 2013

A case of Lemierre's syndrome in association with liver abscess without any other metastatic lesions.

Intern Med 2012 1;51(11):1419-23. Epub 2012 Jun 1.

Department of Internal Medicine, Nanbugo General Hospital, Japan.

Lemierre's syndrome (LS) is characterized by pharyngitis followed by septicemia, internal jugular vein thrombophlebitis, and metastatic embolization in general. LS is commonly caused by Fusobacterium necrophorum. Herein, we present a case of LS with liver abscesses that presented as a sole metastatic lesion. We were not able to diagnose LS until Fusobacterium necrophorum was isolated due to the lack of the common involvement. Doripenem was effective against the pathologic features including the liver abscesses. LS should be taken into consideration when clinicians find liver abscesses following pharyngitis even when the common complications of LS are not detected.
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http://dx.doi.org/10.2169/internalmedicine.51.7364DOI Listing
November 2012

Japanese case of Budd-Chiari syndrome due to hepatic vein thrombosis successfully treated with liver transplantation.

Hepatol Res 2012 Feb;42(2):213-8

Division of Gastroenterology and Hepatology Division of Digestive and General Surgery Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences Department of Clinical Laboratory, Niigata University Medical and Dental Hospital, Niigata, Japan.

A 22-year-old Japanese woman was found to have severe esophageal varices and then suffered from hepatic encephalopathy. She was diagnosed with Budd-Chiari syndrome (BCS) due to hepatic vein (HV) thrombosis accompanied by portal vein thrombosis without inferior vena cava (IVC) obstruction. Latent myeloproliferative neoplasm (MPN) lacking the JAK2-V617F mutation was considered to be the underlying disease. Liver transplantation was strikingly effective for treating the clinical symptoms attributable to portal hypertension. Although thrombosis of the internal jugular vein occurred due to thrombocythemia, which manifested after transplantation despite anticoagulation therapy with warfarin, the thrombus immediately disappeared with the addition of aspirin. Neither thrombosis nor BCS has recurred in more than 4 years since the amelioration of the last thrombotic event, and post-transplant immunosuppression with tacrolimus has not accelerated the progression of MPN. In Japan, IVC obstruction, which was a predominant type of BCS, is suggested to have decreased in incidence with recent improvements in hygiene. The precise diagnosis of BCS and causative underlying diseases should be made with attention to the current trend of the disease spectrum, which fluctuates with environmental sanitation levels. Because the stepwise strategy, including liver transplantation, has been proven effective for patients with pure HV obstruction in Western countries, this strategy should also be validated for utilization in Japan and in developing countries where HV obstruction potentially predominates.
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http://dx.doi.org/10.1111/j.1872-034X.2011.00913.xDOI Listing
February 2012

Development of a novel tablet machine for a tiny amount of powder and evaluation of capping tendency.

Chem Pharm Bull (Tokyo) 2011 ;59(12):1518-22

Department of Chemical Engineering, Osaka Prefecture University, Sakai, Osaka, Japan.

A novel single punch tablet machine was developed for a tiny amount of powder sample. This tablet machine mainly consists of upper and lower punches, single die, and conical powder feeder equipped with micro-vibrators. By using the powder feeder, mass of discharged powder can be maintained constant even if a tiny amount of powder having poor flowability is used. Motions of both upper and lower punches can be set arbitrarily. Thus, this machine enables us to prepare tablets with a tiny amount of powder sample under the same compression mechanism as conventional rotary tablet machines. Performance of the developed tablet machine was evaluated in a continuous direct tableting using a model powder with poor flowability. Thirty-four tablets (195 mg×34) having acceptable properties can be successfully prepared using no more than 10.0 g of a powder sample. We then proposed a novel in-die evaluation method of capping tendency. A new phase diagram consisting of the elastic recovery energy and the plastic deformation energy was proposed. These energies were calculated from a force-displacement profile, continuously monitored by the developed tablet machine. The results indicate that by using the new diagram the capping tendency of tablets prepared from various model powders can be well discriminated. The developed tablet machine and proposed evaluation method can contribute to a significant cost reduction and speeding up of formulation studies of oral dosage form.
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http://dx.doi.org/10.1248/cpb.59.1518DOI Listing
March 2012

Adhesive cell cultivation on polymer particle having grafted epoxy polymer chain.

Tissue Cell 2011 Apr 23;43(2):115-24. Epub 2011 Feb 23.

Department of Chemical Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.

In this study, we synthesized a new cell immobilization support having poly(glycidyl methacrylate) as a graft polymer chain and used this support for cell cultivation. Base polymer particle was synthesized by suspension polymerization and epoxy polymer chain was extended from particle surface on graft polymerization. Produced polymer particles had broad particle size distribution ranging from 20 to 1000 μm and the degree of polymerization of grafted polymer chain was ranged from 500 to 1000. The effects of various factors, such as grafted polymer chain length and its surface density, composition of base polymer network and graft polymer chain, on the cell growth of murine fibroblast cell line (MS-5 cell) on polymer particle were studied. This polymer particle could cultivate not only fibroblast cell line but also epidermal cell line (HeLa cell), osteoblast cell line (MC3T3E1 cell), and chondrocyte cell line (ch-8 cell) on its surface. Growth rate is almost the same as that of cells using poly(styrene) tissue culture dish. To apply this cell cultivation system for examination of cell co-culture, HeLa cell immobilized on 100 μm of polymer particle was successfully co-cultured with MS-5 cell immobilized on 300 μm of polymer particle for four weeks.
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http://dx.doi.org/10.1016/j.tice.2010.12.007DOI Listing
April 2011

[Case of visceral varicella-zoster virus infection after autologous peripheral blood stem cell transplantation in which severe abdominal pain preceded the skin rash].

Nihon Shokakibyo Gakkai Zasshi 2010 Dec;107(12):1947-55

Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, Japan.

We report a 54-year-old man who developed visceral varicella-zoster virus (VZV) infection after autologous peripheral blood stem cell transplantation (auto-PBSCT) without using immunosuppressive agents for multiple myeloma. He suffered from severe abdominal pain 2 months after auto-PBSCT, and morphine chloride was needed to control it. Since the characteristic skin rash of VZV infection appeared over his entire body on the seventh hospital day, aciclovir was immediately started with favorable results. It is extremely difficult to diagnose VZV infection when severe abdominal pain proceeds and the eruptions characteristic of VZV infections are absent. This may also result in devastating delays in effective antiviral treatment. The increase in fat density around the celiac trunk and the root of the superior mesenteric artery on computed tomography shown in this case may has contributed to the correct diagnosis of visceral VZV infection.
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December 2010

Improvement of dissolution property of poorly water-soluble drug by supercritical freeze granulation.

Chem Pharm Bull (Tokyo) 2009 Oct;57(10):1040-4

Drug Formulation Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Fujieda, Shizuoka 426-8646, Japan.

The dissolution property of the poorly water-soluble drug, flurbiprofen (FP) was improved by a novel supercritical freeze granulation using supercritical carbon dioxide. Supercritical freeze granulation was defined as a production method of the granulated substances by using the dry ice to generate intentionally for the rapid atomization of the supercritical carbon dioxide to the atmospheric pressure. This process utilized a rapid expansion of supercritical solutions (RESS) process with the mixture of the drug and lactose. In the supercritical freeze granulation, needle-like FP fine particles were obtained which adhered to the surface of lactose particles, which did not dissolve in supercritical carbon dioxide. The number of FP particles that adhered to the surface of particles decreased with an increase in the ratio of lactose added, leading to markedly improve the dissolution rate. This improvement was caused not only by the increase in the specific surface area but also the improvement of the dispersibility of FP in water. It is thus concluded that the supercritical freeze granulation is a useful technique to improve the dissolution property of the poorly water-soluble flurbiprofen.
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http://dx.doi.org/10.1248/cpb.57.1040DOI Listing
October 2009

Improvement of dissolution property of poorly water-soluble drug by novel dry coating method using planetary ball mill.

Chem Pharm Bull (Tokyo) 2008 Sep;56(9):1243-7

Drug Formulation Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd, Fujieda, Shizuoka, Japan.

The dissolution property of a poorly water-soluble drug, flurbiprofen (FP), was improved by a novel dry coating method using a planetary ball mill. Several mixtures composed of water-soluble additives (D-mannitol, lactose, and erythritol), light anhydrous silicic acid, and flurbiprofen were prepared. These mixtures and several starches were co-ground in a planetary ball mill, and the surface of the starches was dry coated with the mixtures. The size, appearance, yield, and drug dissolution property of the dry coated preparations were evaluated, and the optimal formulation which improved the dissolution property of poorly water-soluble flurbiprofen was determined. The dissolution rate of FP was increased by dry coating of the surface of starches with microparticulated FP. It was further increased by co-grinding of FP, starch, and a water-soluble additive, or dry coating of the starch surface with microparticulated FP and light anhydrous silicic acid, as a glidant. These co-ground and dry coated preparations could be recovered from the pot of the planetary ball mill readily without adhesion to the inside wall of the pot. These are considered to be novel, industrially applicable methods for improving the dissolution rate of poorly water-soluble drugs.
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http://dx.doi.org/10.1248/cpb.56.1243DOI Listing
September 2008

Numerical simulation of film coating process in a novel rotating fluidized bed.

Chem Pharm Bull (Tokyo) 2006 Jun;54(6):839-46

Department of Chemical Engineering, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.

In this study, numerical simulation of film coating process in a novel rotating fluidized bed (RFB) was conducted by using a Discrete Element Method (DEM)-Computational Fluid Dynamics (CFD) coupling model. Particle movements and fluid motions in a centrifugal force field were simulated at three-dimensional cylindrical coordinate, and this model was applied to film coating process. Film coating process in a RFB was numerically analyzed by using a simplified assumption that a particle was coated only when a particle existed within a spray zone. The experiments were also conducted and uniformity of sprayed material was evaluated by investigating color difference of the coated particles. As a result of the numerical simulation, three-dimensional bubble movements and particle circulation could be well simulated. In addition, mass of the sprayed material on a single particle in a RFB could be visualized by using our proposed model. The relationship between distribution of the sprayed material and the coating time was also analyzed. Calculated mass distributions of the sprayed material could be expressed by a normal distribution function, showing qualitative good agreement with the previous studies. Effect of the operating parameters, such as gas velocity and centrifugal acceleration, on the uniformity of the sprayed material was also investigated by both numerical and experimental approaches. Comparison of the coating process in a RFB with that in a conventional fluidized bed was also conducted by the numerical simulation. The result showed that uniformity of the sprayed material was greatly improved in a RFB due to the much smaller circulation time.
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http://dx.doi.org/10.1248/cpb.54.839DOI Listing
June 2006
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