Publications by authors named "Kunihiko Maeda"

26 Publications

  • Page 1 of 1

Expression and localization of aromatase in human gastric mucosa : Immunohistochemical study using biopsy materials.

Histochem Cell Biol 2019 Jan 28;151(1):21-28. Epub 2018 Aug 28.

Department of Anatomy and Structural Science, Faculty of Medicine, Yamagata University, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.

Parietal cells in the gastric mucosa are known not only as cells playing major roles in food digestion but also as cells bearing endocrine function. In addition to their production of gastrin and ghrelin, it has been recently revealed that these cells are also involved in the synthesis and secretion of estrogens with their expression of aromatase in experimental animals. Although aromatase activity has been detected in human gastric cancer cells and related cell lines, much less study has been done to ascertain the expression of the enzymatic activity in normal gastric mucosa. It has not been established which cell type is responsible for estrogen production in human gastric glands consisting of epithelial cells of several types. The aim of this study is to define the expression of aromatase by parietal cells in human gastric glands using immunohistochemical techniques. We retrieved formalin-fixed paraffin embedded materials of gastric biopsies from 16 patients (nine men, seven women). Colocalization of aromatase and H/K-ATPase β-subunit indicated that positive cells are parietal cells, but not chief cells and mucous cells. Furthermore, immunoreactivity of aromatase was detected within gastric glands irrespective of age or sex. These results suggest that human parietal cells synthesize estrogens within gastric mucosa and subsequently secrete them to the portal vein via gastric vein, as they do in rats. These estrogens might influence liver functions in humans. The estrogenic effects related to liver dysfunction might also be attributed to them.
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http://dx.doi.org/10.1007/s00418-018-1708-3DOI Listing
January 2019

A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia.

CEN Case Rep 2018 May 11;7(1):55-61. Epub 2017 Dec 11.

Department of Nephrology, Osaka Rosai Hospital, Osaka, Japan.

A 53-year-old man presented with proteinuria and hematuria. No significant abnormality was detected in his physical examination or laboratory tests, including evidence of paraprotein in serum and urine. Renal biopsy revealed mesangial proliferation, thickened glomerular basement membranes, and spike formation. Immunofluorescence revealed deposition of immunoglobulin (Ig) M heavy chain, kappa (κ) light chain, and complement component C3 along capillary walls in the glomeruli. Light chain staining indicated significant restriction, because only κ chain, not lambda chain, was present in glomeruli. Aggregated electron dense deposits were observed in the subepithelial area and within the lamina densa on electron-microscopic examination. Cryoglobulinemia and amyloidosis were ruled out. Clinically, steroid therapy was not initiated due to patient preference, and the only prescribed medication was an angiotensin II receptor blocker. At the approximately 3-year follow-up, estimated glomerular filtration rate had decreased very mildly. The present case demonstrates that deposition of monoclonal IgM-κ may be associated with membranoproliferative glomerulonephritis-like changes in the glomeruli. Although no underlying hematological abnormality or paraproteinemia was observed in this case within the range of limited clinical examination, the patient's condition is consistent with proliferative glomerulonephritis with monoclonal IgM deposits, similar to the recently established proliferative glomerulonephritis with monoclonal IgG deposits. Further elucidation of the pathophysiology and effective treatments of the disorder should be expected in the future through the accumulation of similar cases.
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http://dx.doi.org/10.1007/s13730-017-0291-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886923PMC
May 2018

Epstein-Barr virus clonality and plasmacytosis in a patient with atypical angioimmunoblastic T cell lymphoma.

Ann Hematol 2018 Mar 30;97(3):537-539. Epub 2017 Nov 30.

Department of Hematology, Yamagata Prefectural Central Hospital, Yamagata, 990-2292, Japan.

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http://dx.doi.org/10.1007/s00277-017-3189-1DOI Listing
March 2018

Early Improvement in Marrow Fibrosis Following Haploidentical Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome with Bone Marrow Fibrosis.

Intern Med 2016;55(22):3351-3356. Epub 2016 Nov 15.

Department of Hematology, Hokkaido University Graduate School of Medicine, Japan.

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed.
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http://dx.doi.org/10.2169/internalmedicine.55.6435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173507PMC
February 2017

Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy.

Case Rep Nephrol Dial 2015 Sep-Dec;5(3):204-12. Epub 2015 Dec 15.

Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.

Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN.
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http://dx.doi.org/10.1159/000441715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777904PMC
March 2016

Synchronous Double Malignant Tumors Consisting of Stomach and Hodgkin's Lymphoma with Collision between Gastric Adenocarcinoma and Hodgkin's Lymphoma in the Stomach.

Case Rep Gastroenterol 2012 Sep 22;6(3):797-802. Epub 2012 Dec 22.

Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.

We report the rare case of a 72-year-old man with double cancers (gastric adenocarcinoma and Hodgkin's lymphoma) with collision between gastric adenocarcinoma and Hodgkin's lymphoma. Abdominal computed tomography showed increased wall thickness in the fundus region of the stomach and multiple lymph node swellings in the lesser curvature, periceliac and left cardial regions. Upper gastrointestinal endoscopy showed an ulcer approximately 5 cm in diameter with a malignant appearance in the fundus region of the stomach. On histopathologic examination, two completely different tumors were recognized in the stomach. One tumor was a poorly differentiated adenocarcinoma characterized by poorly developed tubular structures associated with prominent lymphoid infiltration of the stroma. The other tumor was found to have proliferated in the wall of the stomach, with diffuse granulomatous lesions and bordering the adenocarcinoma. Large atypical lymphoid cells with prominent nucleoli and enlarged mononuclei or multinuclei were seen in the latter tumor. Hodgkin's lymphoma was also found in the swollen lesser curvature lymph nodes. As a result, gastric adenocarcinoma and metastasis of Hodgkin's lymphoma were collided in the stomach. In conclusion, this case might be helpful in exploring the occurrence mechanism of tumor collision between lymphoma and carcinoma.
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http://dx.doi.org/10.1159/000346465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551438PMC
September 2012

Myoepithelial carcinoma of the breast with focal rhabdoid features.

Breast J 2013 Jan-Feb;19(1):100-3. Epub 2012 Dec 17.

Department of Diagnostic Pathology, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Myoepithelial carcinoma of the breast is extremely rare and only 33 cases have been reported in the English literature. Herein, we report a case of myoepithelial carcinoma of the breast with focal rhabdoid features. The patient was a 67-year-old woman, who presented with a lump of the left breast that rapidly grew to 3 cm in diameter within 3 months. Lumpectomy revealed a solid and whitish colored tumor, which was composed mainly of elongated spindle-shaped cells with mild atypia, focal necrosis, and infiltrative margin. In a small area of the lesion, ovoid tumor cells exhibited eccentric nuclei with centrally located nucleoli and plump cytoplasm including round eosinophilic inclusions, resembling a rhabdoid tumor. Immunohistochemically, both types of tumor cells exhibited a myoepithelial phenotype. MIB-1 index was 30%. The cytoplasmic inclusion of the ovoid cells exhibited immunopositivity for both vimentin and cytokeratin. From these findings, this tumor was diagnosed as a myoepithelial carcinoma with focal rhabdoid features. Although rhabdoid features have been reported in some types of malignant and benign tumors, this is the first report of such features in myoepithelial carcinoma of the breast.
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http://dx.doi.org/10.1111/tbj.12058DOI Listing
June 2013

Peripheral T-cell lymphoma arising from an intraglandular lymph node in the parotid gland: a case report and literature review.

Pathol Int 2012 Jan 28;62(1):60-4. Epub 2011 Oct 28.

Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.

T/NK-cell lymphoma of the salivary gland is rare. A 58-year-old man complained of a tumor mass in the left parotid gland region and he was diagnosed to have a left parotid tumor. The tumor was subsequently resected, revealing a diffuse growth pattern of medium to large sized atypical cells. The tumor was surrounded by fibrous connective tissue in the form of a capsule, and those were positive for CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8, CD10, CD15, CD20, CD25, CD56, CD79a, CD246, EMA, granzyme B, TdT and TIA-1. There was no molecular evidence of Epstein-Barr virus (EBV) infection. It was diagnosed as peripheral T-cell lymphoma (PTCL) arising from an intraglandular lymph node in the parotid gland. In conclusion, Only 17 cases of primary T/NK-cell lymphoma of the salivary glands have been recorded until now, and the characteristics of these are not clear yet. Additional study is needed.
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http://dx.doi.org/10.1111/j.1440-1827.2011.02747.xDOI Listing
January 2012

Pyloric gland metaplasia/differentiation in multiple organ systems in a patient with Peutz-Jegher's syndrome.

Pathol Int 2011 Jun 27;61(6):369-72. Epub 2011 Apr 27.

Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.

Peutz-Jegher's syndrome (PJS) involves multiple organ systems and the development of hamartomatous, metaplastic, or neoplastic lesions of different cell lineages. Among them, glandular lesions are the most common, but their properties are obscure. We report here a 53-year-old woman with PJS who developed multiple hamartomatous polyps in the jejunum and mucinous glandular lesions in multiple organ systems: glandular metaplasia in the urinary bladder; lobular endocervical glandular hyperplasia in the uterine cervix; mucinous metaplasia in the right fallopian tube; mucinous adenoma in the left ovary. Histological and immunohistochemical analyses disclosed that all of the intestinal and extra-intestinal lesions were associated with pyloric gland metaplasia/differentiation across the organ systems. In the general population, the organs described above rarely or infrequently show pyloric gland phenotype, to say nothing of trans-organ involvement. It is strongly suggested that commitment to pyloric gland metaplasia/differentiation is closely associated with PJS.
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http://dx.doi.org/10.1111/j.1440-1827.2011.02670.xDOI Listing
June 2011

A case of serous cystic tumor, which recurred with severe acute pancreatitis.

Nihon Shokakibyo Gakkai Zasshi 2010 Jun;107(6):923-9

Department of Gastroenterology, Yamagata City Hospital Saiseikan, Japan.

A 76-year-old woman with serous cystic tumor (SCT) was admitted to our hospital with abdominal pain and was given a diagnosis of severe acute pancreatitis. Infusion of intravenous protein inhibitor and continuous hemodiafiltration (CHDF) were started and she was placed on a respirator, but she died on the 6th day after diagnosis. On autopsy, each SCT cyst showed evidence of hemorrhage. We supposed that the growth of the SCT after hemorrhage compressed the main pancreatic duct and caused severe acute pancreatitis. SCT is benign, and there are no standard treatments. During follow-up of patients with SCT, we should consider the risk of severe acute pancreatitis.
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June 2010

Differential immunophenotypic analysis of dendritic cell tumours.

J Clin Pathol 2010 Jun 3;63(6):497-503. Epub 2010 May 3.

Department of Pathological Diagnostics, Faculty of Medicine, Yamagata University, Yamagata, Japan.

Aims: The phenotypic and biological characteristics of dendritic cell (DC) tumours have not been fully elucidated. The aim of this study was to compare the immunophenotypic characteristics of DC-related markers and cell-cycle-associated markers among DC tumours and finally to utilise them for differential diagnosis of DC tumours.

Methods: Tissue sections from 28 patients with DC tumours were immunohistochemically examined using DC-related and cell-cycle-associated markers.

Results: The Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) samples were positive for S-100 protein, CD1a, Langerin, fascin, DEC-205 and DC-SIGN. Interdigitating dendritic cell sarcoma (IDCS) was positive for S-100 protein and fascin and negative for Langerin. In addition, two IDCS samples were positive for CD1a, DEC-205 and DC-SIGN. The labelling indices of Ki-67, cyclin A, cyclin B1 and acetylated histone H3 on the LCS and IDCS specimens were significantly higher than those on the LCH specimens. The expression of p53 was also significantly higher in the LCS specimens than in the LCH specimens. The numbers of infiltrating CD123(+) and FOXP3(+) cells were also significantly higher in the LCS samples than in the LCH and IDCS samples. Follicular dendritic cell sarcoma was distinguished from other DC tumours by the lack of DC-SIGN, Langerin and DCE-205.

Conclusions: These results suggest that Langerin can be used to distinguish LCS from IDCS, and DC-SIGN and DEC-205 can be used to identify DC tumour cells. The frequency of cell-cycle-associated markers can be used for the differential diagnosis of malignant and benign DC tumours.
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http://dx.doi.org/10.1136/jcp.2009.067819DOI Listing
June 2010

Clinicopathological significance of cell cycle regulatory factors and differentiation-related factors in pancreatic neoplasms.

Pancreas 2010 Apr;39(3):345-52

Department of Gastroenterological and General Surgery, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan.

Objectives: The aim of the present study was to compare the expression levels of the cyclins and the differentiation-related factors in pancreatic neoplasms.

Methods: The expression levels of cyclins A and B1, E1A-like inhibitor of differentiation 1 (EID-1), p300, 3'-5'-cyclic sdenosine monophosphate response element binding protein (CREB) binding protein (CBP), and acetylated histone H3 (AcH3) in ordinary ductal carcinoma (ODC) and intraductal papillary mucinous neoplasms (IPMNs) of the pancreas were investigated.

Results: More cells positive for cyclin A and EID-1 were present in the ODC than in the IPMNs. Cells positive for both cyclins and EID-1 were observed more frequently in invasive carcinoma derived from the IPMN than from the IP mucinous carcinoma. Multivariate regression analysis revealed that EID-1 and cyclin A overexpressions were independent factors associated with poor prognosis. Overall survival was significantly lower in ODC patients with overexpressions of cyclin A, EID-1, and AcH3 than in those without such overexpressions. There were significant differences in the survival curves between patients with ODC and invasive carcinoma derived from IPMN, regarding high frequency for cyclin A or B1.

Conclusions: These results indicated that the expressions of cyclins A and B1, EID-1, and AcH3 may be correlated with a malignant potential in IPMNs. Invasive carcinoma derived from IPMN may be slow growing as compared with ODC.
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http://dx.doi.org/10.1097/MPA.0b013e3181bb9204DOI Listing
April 2010

Expression of BAFF-R and TACI in reactive lymphoid tissues and B-cell lymphomas.

Histopathology 2009 Jan;54(2):221-32

Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.

Aims: The receptor for B-cell-activating factor belonging to the tumour necrosis factor family (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been established as binding molecules to BAFF. The aim of this study was to determine the pathological diagnostic roles and clinical significance of these BAFF-binding receptors in B-cell neoplasms.

Methods And Results: Expression of BAFF-R and TACI was examined immunohistochemically in reactive lymphoid tissues and B-cell lymphomas including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (MZBCL) and plasma cell myeloma (PCM). In reactive tissues BAFF-R was expressed exclusively in the cells of the mantle zone and within the germinal centres (GCs), whereas TACI appeared positive in the scattered cells in extrafollicular areas. There were variable patterns of expression of BAFF-R and TACI amongst the different types of B-cell lymphomas (MCL and FL: BAFF-R+TACI-; PCM: BAFF-R-TACI+; DLBCL and MZBCL: variable expression). Reverse transcriptase-polymerase chain reaction studies supported these results. The overall survival of the BAFF-R+ DLBCL group was significantly better than that of the BAFF-R- group.

Conclusions: These results indicate that the assessment of expression of BAFF-binding receptors aids subclassification and prognostication of DLBCL.
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http://dx.doi.org/10.1111/j.1365-2559.2008.03203.xDOI Listing
January 2009

Distribution of myeloid dendritic cells and plasmacytoid dendritic cells in the synovial tissues of rheumatoid arthritis.

J Rheumatol 2008 Oct 1;35(10):1919-31. Epub 2008 Sep 1.

Department of Orthopaedic Surgery, Yamagata University School of Medicine, and Yamagata Saisei Hospital, Yamagata, Japan.

Objective: To examine the precise tissue distribution of dendritic cells (DC) and indoleamine 2,3-dioxygenase (IDO)-expressing cells in synovial tissue and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods: Synovial tissues from 30 patients with RA and 7 with OA were immunohistochemically stained for DC markers. The examined areas were classified into 5 categories based on pathobiological staging and histopathological grading systems. Myeloid DC (mDC) and plasmacytoid DC (pDC) were isolated using positive and negative magnetic sorting systems, respectively, from SF samples (7 patients with RA and 4 with OA) and synovial tissues (3 RA, 4 OA).

Results: mDC were mainly observed in lymphoid aggregations. pDC were scattered around perivenular infiltration areas, and small and large lymphoid aggregations in RA. The mDC/pDC ratio increased significantly, with higher grading in RA SF tissues compared to OA synovial tissues (p<0.05). IDO-immunoreactivity was detected in pDC by serial sectioning and staining of RA synovial tissues.

Conclusion: Our results indicate that mature mDC play a central role in the RA inflammatory process. Although there were fewer pDC than mDC, the presence of IDO-positive pDC suggests a possible tolerance mechanism in RA synovial tissues. However, it is probably modest due to the marked inflammation in RA, in which mDC are dominant.
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October 2008

Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.

Int J Hematol 2008 May;87(4):405-409

Department of Internal Medicine, Suzuka Kaisei Hospital, 112-1 Koh-chou, Suzuka, Mie, 513-0836, Japan.

We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.
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http://dx.doi.org/10.1007/s12185-008-0059-6DOI Listing
May 2008

Clinical and histological responses of renal amyloidosis to high-dose melphalan supported by autologous stem cell transplantation.

Nephrol Dial Transplant 2008 Feb 7;23(2):747-50. Epub 2007 Nov 7.

Division of Molecular Medicine, Center for Translational and Advanced Animal Research, Tohoku University School of Medicine, Seiryouchou 2-1, Aoba-ku, Sendai 980-0875 Japan.

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http://dx.doi.org/10.1093/ndt/gfm488DOI Listing
February 2008

Maternal vitamin B12 deficiency affects spermatogenesis at the embryonic and immature stages in rats.

Congenit Anom (Kyoto) 2007 Mar;47(1):9-15

Department of Environment for Life and Living, School of Human Science and Environment, Himeji Institute of Technology, University of Hyogo, Shinzaike Honcho 1-1-12, Himeji, Japan.

To evaluate the role of cobalamin (Cbl) on spermatogenesis, the effect of dietary vitamin B(12) deficiency on early spermatogenesis was histologically investigated in male fetuses and newborns in the first filial generation (F(1) males) of rats. There was no difference in the number of gonocytes and supporting cells of Sertoli in the gonad in male fetuses on day 16 of gestation and in the testes in F(1) males at 0 days of age between vitamin B(12)-deficient (VB12-D) and vitamin B(12)-supplemented (VB12-S) groups. However, at 21 days of age, a decreased number of spermatogonia and no spermatocytes were observed in the VB12-D group. Numerous TUNEL positive cells were located among spermatocytes of the spermatogenic epithelium. The ultrastructural features examined using transmission electron microscopy were considered to be indicative of apoptosis. The incidence of seminiferous tubules having apoptotic cells was 51.5% in the VB12-D group. At 60 days of age, aplasia of the spermatids and spermatozoa was detected in the VB12-D group. In the connective tissue between the seminiferous tubules, many interstitial Leydig cells and blood vessels were observed in the VB12-D group, as compared with the VB12-S group. These changes produced by vitamin B(12) deficiency can be reversed by providing a VB12-S diet after weaning at 21 days of age. From these findings, such a vitamin B(12) deficiency during gestation and lactation could affect the germ cells and especially damage spermatocytes in F(1) male rats, which indicates that Cbl may be an essential constituent in the meiosis of spermatogenesis.
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http://dx.doi.org/10.1111/j.1741-4520.2006.00135.xDOI Listing
March 2007

In situ observation of germinal center cell apoptosis during a secondary immune response.

J Clin Exp Hematop 2006 Nov;46(2):73-82

Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.

Germinal centers are highly organized anatomic structures essential for the clonal expansion of germinal center (GC) B-cells and associated somatic hypermutation, isotype switching, selection of the high-affinity B-cells (affinity maturation), and elimination of irrelevant or autoreactive clones. The identification of cellular interactions and regulatory mechanisms controlling apoptosis within GCs is essential for a complete understanding of the cellular and molecular dynamics of the GC reaction. We performed a kinetic analysis of the apoptotic activity occurring within GCs of draining lymph nodes of mice immunized with sheep red blood cells (SRBC) after secondary stimulation. The apoptotic activity of GC cells can be divided into three distinct phases : 1) initial phase (within the first days after immunization), 2) reactive phase (from the 5th day to 15th day after secondary immunization), and 3) late phase (after the 15th day). Apoptosis decreased shortly after secondary immunization followed by an increase to peak after an additional 10 days. Finally, apoptosis of GC cells decreased to basal levels. Administration of apoptosis inhibitors decreased the amount of apoptosis during the reactive phase. These results suggest that the reactive phase may be the critical period in which clonal selection and cellular differentiation to antibody forming cells take place.
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http://dx.doi.org/10.3960/jslrt.46.73DOI Listing
November 2006

Development, maturation and subsequent activation of follicular dendritic cells (FDC): immunohistochemical observation of human fetal and adult lymph nodes.

Histochem Cell Biol 2006 Aug 10;126(2):261-73. Epub 2006 Feb 10.

Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

To elucidate the processes involved in development and activation of human follicular dendritic cells (FDC), immunohistochemistry was performed on paraffin sections of fetal lymph nodes (FLN) obtained from archived autopsy material, and of adult reactive lymph nodes (ARLNs) excised for diagnostic purpose, using a panel of antibodies. Our study showed that tiny clusters of CNA.42(+ )KiM4p(+) cells, surrounded by some B-lymphocytes, initially arose in the cortical area of underdeveloped FLN around the 20th gestational week. No co-expression of CD21 and CD35 was found. In the relatively developed FLN of the same gestational age, small eddies of immature FDC, which expressed CD21, CD35, and nerve growth factor receptor (NGFR), as well as CNA.42 and KiM4p, were observed within ill-defined aggregations of B-lymphocytes. As gestation progressed, more B-lymphocytes assembled in a compact manner and formed primary lymphoid follicles containing an extending web of mature FDC, which expressed CNA.42, KiM4p, CD21, CD35, NGFR, and sometimes CD23 and X-11. In well-developed secondary follicles of ARLNs, activated FDC expressed additional molecules such as CD55, CD106, and S100alpha. Our observations identified the processes of phenotypic alteration of human FDC and established practical indicators determining their developmental stage and functional phase.
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http://dx.doi.org/10.1007/s00418-006-0157-6DOI Listing
August 2006

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

Int J Gastrointest Cancer 2005 ;35(2):111-9

First Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.

Background: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail.

Aims: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two.

Methodology: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2.

Results: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015).

Conclusions: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.
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http://dx.doi.org/10.1385/IJGC:35:2:111DOI Listing
September 2005

Characterization of dendritic cells in differentiated thyroid cancer.

J Pathol 2005 Apr;205(5):565-76

Department of Pathology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.

In this study, the types and localization pattern of dendritic cells (DCs), the expression of chemokines on carcinoma cells and of the relevant receptors on DCs, and the adhesion molecules expressed on vascular endothelial cells and DCs were examined in thyroid carcinomas. Papillary carcinoma had a higher frequency of CD1a(+) immature DCs than other thyroid tumours. Macrophage inflammatory protein (MIP)-3 alpha was expressed strongly on the majority of papillary carcinoma cells and weakly on a minority of follicular carcinoma cells. DCs positive for chemokine receptor-6 (CCR-6) were densely accumulated in papillary carcinoma. DC-SIGN(+) DCs were accumulated in papillary carcinoma but rarely in follicular carcinoma. A binding assay for DC-SIGN-mediated adhesion of isolated DCs revealed significant inhibition of DC adhesion to papillary carcinoma tissues by neutralizing antibodies against intercellular adhesion molecule-2 or DC-SIGN. These results clearly indicated marked differences between papillary carcinoma and follicular carcinoma in the accumulation of immature DCs, in MIP-3 alpha expression on carcinoma cells, and in the frequency of CCR-6(+) DCs and DC-SIGN(+) DCs.
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http://dx.doi.org/10.1002/path.1731DOI Listing
April 2005

Immunohistochemical diagnosis of a rare case of epithelioid malignant peripheral nerve sheath tumor with multiple metastases.

Jpn J Ophthalmol 2004 Nov-Dec;48(6):565-9

Department of Ophthalmology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.

Background: The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST) is a rare tumor with poor prognosis that sometimes involves the head and neck. The diagnosis is based principally on the histological examination, and it is generally very difficult to reach the correct diagnosis.

Case: An 84-year-old Japanese woman presented with a tumor mass of 2 week's duration in the right medial canthal region.

Observations: Although the tumor was excised surgically, metastases occurred three times on her face and head, and the patient died of distant systemic multiple metastases. In the histopathological analysis, the tumor showed a composite pattern comprising spindle or polygonal cells arranged in irregular bands, and a population of larger epithelioid cells in solid sheets and nests. In the immunohistochemical analysis, the tumor cells were positive for S-100 protein, vimentin, and nerve growth factor receptor (NGFR), and negative for cytokeratin and HMB 45 (melanoma-associated antigen). These findings confirmed the diagnosis of MPNST.

Conclusions: Epithelioid MPNST has complex histopathological findings and histopathological features similar to other epithelioid tumors, especially malignant melanoma. Immunohistochemical examination using NGFR and HMB-45 is important in the differential diagnosis.
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http://dx.doi.org/10.1007/s10384-004-0121-8DOI Listing
February 2005

Characteristics of invasive cells found in between zona pellucida and oocyte during follicular atresia in mice.

Zygote 2004 Aug;12(3):269-76

Yamagata University School of Medicine, Yamagata City and Juntendo University Graduate School of Medicine, Urayasu City, Japan.

During the process of follicular atresia, cells are observed to invade the zona pellucida (invasive cells) where they presumably play an important role in eliminating degraded oocytes. Although our preliminary studies have suggested that these cells may originate from granulosa cells and not from macrophages, a detailed morphological analysis of the cells has not been conducted. The objective of this study was to characterize the cells more precisely by electron microscopy and immunohistochemistry, using sexually immature mice. The results show that the invasive cells were first observed within advanced primary (non-antral) atretic follicles. The cells frequently contained cytoplasmic lysosome-like granules after passing through the zona pellucida. F4/80 and Mac-1, reported as macrophage-specific antibodies, were reactive with the cells in most cases, but some immunonegative invasive cells were also observed. The ultrastructural features of the invasive cells were quite similar to those of granulosa cells, not macrophages. Gap junctions, which are typical cytoplasmic structures of epithelial cells, were frequently identified between neighbouring cells. Although direct evidence indicating a contribution by the cells to the elimination of degenerated oocytes was not obtained, our results strongly suggest that the invasive cells originated from granulosa cells surrounding the zona pellucida, and that they may have a macrophage-like cell function for the elimination of oocytes from atretic follicles in mice.
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http://dx.doi.org/10.1017/s0967199404002825DOI Listing
August 2004

Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction.

Circulation 2003 Dec 1;108(23):2905-10. Epub 2003 Dec 1.

First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.

Background: Toll-like receptors (TLRs) are members of the interleukin-1 receptor family and transduce similar signals as interleukin-1 receptor in response to exogenous pathogens. Recent studies have demonstrated that TLRs are activated by endogenous signals, such as heat shock proteins and oxidative stress, that may contribute to ventricular remodeling after myocardial infarction. In this study, we determined whether TLR-2 was involved in cardiac remodeling after myocardial infarction.

Methods And Results: Myocardial infarction was induced by surgical left anterior descending coronary artery ligation on wild-type (WT) mice and TLR-2-knockout (KO) mice. The survival rate was significantly higher in KO mice than in WT mice 4 weeks after myocardial infarction (65% versus 43%, P<0.03). Infarct size and degree of inflammatory cell infiltration in infarct area were similar between WT and KO mice. However, myocardial fibrosis in the noninfarct area of KO mice was much less than in WT mice (P<0.01) and was accompanied by reduced transforming growth factor-beta1 and collagen type 1 mRNA expressions (P<0.01 and P<0.05, respectively). Left ventricular dimensions at end diastole were smaller in KO mice than in WT mice at 1 week (P<0.05) and 4 weeks (P<0.01) after surgery. Furthermore, fractional shortening was higher (27.7+/-2.5% versus 21.2+/-2.6%, P<0.05, at 1 week, and 24.3+/-2.0% versus 16.6+/-2.5%, P<0.01, at 4 weeks) in KO mice compared with WT mice.

Conclusions: These data suggest that TLR-2 plays an important role in ventricular remodeling after myocardial infarction.
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http://dx.doi.org/10.1161/01.CIR.0000101921.93016.1CDOI Listing
December 2003

Immunohistochemical recognition of human follicular dendritic cells (FDCs) in routinely processed paraffin sections.

J Histochem Cytochem 2002 Nov;50(11):1475-86

Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan.

A number of monoclonal antibodies (MAbs) that recognize human follicular dendritic cells (FDCs) have been identified. Although some of them have already been applied individually in routine immunolabeling using formalin-fixed paraffin sections for diagnostic and experimental purposes, many antibodies are still employed only for immunolabeling using cryostat sections or particularly processed sections because they have been thought unsuitable for routine sections. A comprehensive examination re-evaluating their suitability in paraffin sections has not been reported. Accordingly, there is limited ability to examine the immunopathological contribution or diagnostic value of FDCs using routinely processed specimens or archived materials. In this study a broad panel of antibodies was systematically applied to the immunolabeling of paraffin sections of reactive tonsils or lymph nodes, in combination with advanced antigen retrieval (AR) techniques. Several antibodies, including Ki-M4p, X-11, 12B1, CNA.42, 1F8/BU32 (anti-CD21), BU38/1B12 (anti-CD23), Ber-MAC-DRC/To5 (anti-CD35), 1.4C3 (anti-CD106), NGFR5 (anti-nerve growth factor receptor p75), IIH6 (anti-CD55), 55K-2 (anti-fascin), and anti-S100 protein alpha-chain, were found to label FDCs in routine sections when combined with suitable AR techniques. Our results are easily adaptable for routine practice and provided useful suggestions concerning the immunopathological behavior and diversity of the particular cells.
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http://dx.doi.org/10.1177/002215540205001107DOI Listing
November 2002
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