Biomedical subjects

Kiyoshi Mukai

Publications and source records attributed to Kiyoshi Mukai.

At least 37 records · Page 2Linked to original sources

PubMed2004

Sudden infant death syndrome due to parainfluenza virus 2 associated with hemophagocytic syndrome.

We report a child with Sudden Infant Death Syndrome (SIDS), aged 16 months. The histological findings of tonsils, spleen, and bone marrow revealed many hemophagocytic cells. Parainfluenza virus type 2 (PIV2) was cultured in the nasopharynx and detected by reverse-transcription (RT)-PCR in liver tissue and bone marrow. His laboratory data of elevated level of ferritin and IL-6 suggested hemophagocytic syndrome (HPS). It is suspected that PIV2 infection in infants is a risk factor for SIDS.

Histiocytosis, Non-Langerhans-Cell↗

PubMed2004

Involvement of Arp2/3 complex in the process of colorectal carcinogenesis.

Increased motility is one of the characteristics of cancer cells, and actin polymerization and disassembly are essential for cellular motility. Since actin-related protein (Arp) 2/3 complex acts as a nucleus for actin polymerization, in this study, we immunohistochemically investigated the expression of Arp2 and Arp3 in 175 colorectal tumors in various stages of neoplastic progression. Arp2 and Arp3 showed identical expression patterns, and both were expressed in the stromal cells around neoplastic tubules or glands and in the tumor cells themselves. The frequency of expression of Arp2 and Arp3 (Arp2 and 3) by the stromal cells increased with the atypia of the colorectal neoplasms, from 5.5% (3/55) in adenoma with mild or moderate atypia, to 11.8% (2/17) in adenoma with severe atypia, 53.3% (16/30) in intramucosal carcinoma, and 91.8% (67/73) in invasive carcinoma (P<0.0001). The frequency of expression of Arp2 and 3 in the tumor cells was similar and was 1.8% (1/55) in adenoma with mild or moderate atypia, 23.5% (4/17) in adenoma with severe atypia, 23.5% (7/30) in intramucosal carcinoma, and 32.9% (24/73) in invasive carcinoma. Expression of Arp2 and 3 by the stromal cells was significantly correlated with nuclear accumulation of p53 in the tumor cells and stromal expression of CD10. These results suggest that formation of Arp2/3 complex by both neoplastic and stromal cells contributes to the increased motility of both cell types and thus provides suitable conditions for invasion.

Actin-Related Protein 2↗

PubMed2004

Hemophagocytic syndrome associated with CD8 positive T-cell chronic lymphocytic leukemia.

We describe a case of hemophagocytic syndrome (HPS) associated with CD8-positive T-cell chronic lymphocytic leukemia (CD8 + T-CLL). A 68-year-old man with CD8 + T-CLL presented with fever, progressive pancytopenia, and lymphadenopathy. Laboratory findings showed a hyper-ferritinemia, abnormalities of coagulation tests, and liver and renal dysfunction with hypoproteinemia. He did not respond to any treatments and died of respiratory failure 10 days after the admission and 14 months after the onset of CD8 + T-CLL. Pathological findings of the autopsy demonstrated infiltration of CD8 + T-CLL cells in multiple organs along with the increase of histiocytes with prominent hemophagocytosis. Serum concentration levels of IL-6, soluble IL-2 receptor and VEGF were all elevated at admission. These findings revealed that he had a secondary HPS. It was suggested that HPS should be considered in patients with an unexplained cytopenia and a fever during the clinical course of CD8 + T-CLL.

Aged↗

PubMed2004

Human DNA damage checkpoints and their relevance to soft tissue sarcoma.

Soft tissue sarcoma (STS) is a malignant neoplasm, arising in mesenchymal tissues, that is difficult to treat clinically because it can be highly resistant to chemo-radiotherapy. At present, the mechanism of that resistance remains unclear. Cell cycle checkpoints engender strict control of cell proliferation, arresting the cell cycle to provide time for repair or apoptosis when DNA damage is induced by unprogrammed extrinsic events. These pathways involve at least two checkpoints: one at the G1/S transition and one at the G2/M transition. The p53 gene, which is mutated in several malignant tumors, plays an important role in DNA repair at the G1/S transition; however, there is little information on the G2/M checkpoint in STS. In the present study, several proteins (phospho-p53, -cdc25, -cdc2, -Chk1 and -Chk2) involved in checkpoint pathways were investigated using immunohistochemistry in STS specimens. Most STSs maintain a well-preserved G2/M checkpoint despite the loss of the G1/S checkpoint (phospho-p53: 4.9% (2/41); -cdc25: 41% (17/41); -cdc2: 61% (25/41); -Chk1: 29% (12/41); -Chk2: 46% (19/41)). Furthermore, in a postoperative chemotherapy case the number of cells positive for phospho-cdc25 and -Chk2 was higher in a recurrent tumor than in the primary tumor (n = 7, P = 0.046 < 0.05, Wilcoxon signed-ranks test). These findings indicate that the G2/M checkpoint pathway is well preserved and might contribute to the chemotherapeutic resistance associated with STS.

Adolescent↗

PubMed2004

[Primary diffuse large B-cell lymphoma of the esophagus].

A 64-year-old man with primary esophageal lymphoma suffered from dysphagia. An upper gastrointestinal examination revealed a partly ulcerated submucosal tumor in the upper portion of the esophagus. Histopathological and immunohistological examination of endoscopic biopsy specimens showed diffuse large B-cell lymphoma of the immunoblastic type. Improvement of the dysphagia and esophageal findings were noted after chemotherapy and radiotherapy. A review of the literature indicated that primary esophageal lymphomas account for less than 1% of all gastrointestinal lymphomas, and less than 0.1% of all malignant lymphomas. Because of the rarity of primary esophageal lymphoma, its clinical and biological characteristics are not currently well known. It is important to accumulate information on, and to further investigate patients with, primary esophageal lymphoma.

Esophageal Neoplasms↗

PubMed2004

[Relapse of diffuse large B cell lymphoma to CD20-negative multiple cutaneous tumors immediately after anti-CD20 monoclonal antibody (rituximab) therapy].

A 60-year-old male was referred to our hospital because of cervical lymphadenopathy and a left hilar abnormal shadow seen on chest X-ray in May 1999. The pathological findings of the cervical lymph nodes revealed that the patient had a malignant lymphoma, of the diffuse large B cell type, at clinical stage IIIB. Immunohistochemistry demonstrated that the lymphoma cells were positive for CD11a, CD19, CD20, CD23, CD25, CD45, IgM, IgD and lambda, but negative for CD5. Although a complete remission was obtained after 8 courses of CHOP therapy, the patient relapsed 32 months later. Two courses of a half dose of CHASE therapy consisting of CPM, ara-C, VP-16 and dexamethasone, followed by rituximab (600 mg/week x4) resulted in a transient re-induction of complete remission. However, multiple cutaneous tumors became apparent just 10 days after the last rituximab therapy. Immunohistochemistry of the cutaneous tumors revealed infiltration of CD20-negative lymphoma cells. A series of chemotherapy including high-dose MTX was ineffective, and the patient died in August 2003. Autopsy findings revealed the systemic intra-capillary infiltration of CD20 negative-lymphoma cells into multiple organs, including the lungs, liver, and kidneys. A CD20 negative-clone selected by rituximab therapy appeared to have expanded in this case.

Antibodies, Monoclonal↗

PubMed2003

Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors.

BACKGROUND: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma. METHODS: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively). CONCLUSIONS: MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma.

Adult↗

PubMed2003

Expression of cyclooxygenase-2 in chondroblastoma: immunohistochemical analysis with special emphasis on local inflammatory reaction.

To investigate the frequency and mechanism of the peritumoral inflammatory reaction in chondroblastoma, we evaluated the relationship between clinicoradiological findings and immunohistochemical expression of cyclooxygenase-2 (COX-2) in excised tumors. Twenty-one cases of chondroblastoma were studied. Imaging analysis was performed with radiographs and T1- and T2-weighted magnetic resonance images in all cases and with computed tomography scan and bone scintigraphy in some cases. Immunohistochemical study for COX-2 was carried out using formalin-fixed paraffin-embedded tissues. Periosteal reaction was observed in 6 cases (29%) and bone marrow edema in 15 cases (71%). Soft-tissue edema, joint effusion, and synovitis were found in 10 cases (48%), in 7 cases (33%), and in 9 cases (43%), respectively. Immunohistochemical expression of COX-2 in chondroblastoma cells was found in 15 of 21 cases (71%). The intensity of COX-2 immunoreactivity was correlated statistically with the presence of periosteal reaction, bone-marrow edema, soft-tissue edema, and synovitis. Our results indicate that activation of eicosanoid synthesis by COX-2 expression in the tumor itself is probably an important factor, inducing peritumoral inflammatory changes in chondroblastomas.

Adolescent↗

PubMed2003

Increased expression of IgE-dependent histamine-releasing factor in endometriotic implants.

A complex network of cytokines mediates the immunoregulatory responses leading to endometriosis. Recent intensive studies suggest that monocyte and T cell chemoattractants contribute to the inflammatory environment of endometriotic implants. The relationship between the inflammation present during endometriosis and the development of endometriotic implants in the peritoneal cavity remains unclear. On the other hand, the association between endometriosis and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) exposure has been discussed in recent years, and our previous results revealed that IgE-dependent histamine-releasing factor (HRF) is inducible by TCDD. The present study aimed to clarify the expression, localization, and function of HRF in endometriosis. Northern blot analysis demonstrated that HRF is overexpressed in endometriotic implants. RT-PCR with Southern blot analysis, however, showed that HRF overexpression was not always accompanied by CYP1A1 induction in endometriotic implants, suggesting that HRF is inducible in endometriosis without exposure to TCDD. HRF is also inducible by macrophage colony-stimulating factor (M-CSF). Immunohistochemistry showed CD68-positive macrophages in the stroma of endometriotic implants, adjacent to regions with prominent HRF accumulation. HRF-overexpressing cells exhibited high implantation efficiency in comparison to control cells when the cells were injected into the peritoneal cavities of nude mice. These results suggest that the accumulation of macrophages in endometriotic implants induces HRF; the overexpression of HRF accelerates the growth of endometriotic implants.

3T3 Cells↗

PubMed2003

Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis.

Beta-catenin is involved in cell motility in the extracellular matrix, and is expressed in normal and neoplastic mesenchymal cells. In order to clarify whether beta-catenin expression in the cytoplasm and/or nucleus is associated with a propensity for pulmonary metastasis in osteosarcoma, the LM8 murine osteosarcoma cell line with a high metastatic potential to the lung was compared with original Dunn cells in terms of the beta-catenin expression level. Both osteosarcoma cell lines lost membrane localization of beta-catenin. However, beta-catenin gene had no mutation in exon 3 by direct sequence analysis. A large number of LM8 cells showed diffuse cytoplasmic and/or nuclear staining of beta-catenin (30.8 per high power field (HPF)), while a much smaller number of Dunn cells showed expression of beta-catenin (7.7 per HPF). Cells with positive staining of beta-catenin were frequently seen at the invasive front and in intravenous tumor deposits within the metastatic lesions to the lung. Thus, LM8 cells express a larger amount of the beta-catenin protein than Dunn cells, as judged by immunoblot analysis. In five resected cases of pulmonary metastasis, translocation of beta-catenin to the cytoplasm and/or nucleus of osteosarcoma cells was detected, although seven primary osteosarcomas cells that did not metastasize for more than five years did not show beta-catenin expression. These data indicate that the cytoplasmic and/or nuclear staining of beta-catenin is a biological marker of metastatic potential of osteosarcoma to the lung.

Animals↗

PubMed2003

Subphrenic bronchopulmonary foregut malformation with pulmonary-sequestration-like features.

A retroperitoneal bronchopulmonary foregut malformation in a 62-year-old man is reported. The lesion was composed of mature lung tissue with randomly distributed bronchial structures and ciliated epithelium-lined cysts, some of which were lined with gastric mucosa. The histological features of this lesion were of both pulmonary sequestration and a bronchogenic, or foregut, cyst, and thus were a unique example of bronchopulmonary foregut malformation with pulmonary differentiation. This case is important in understanding the pathogenesis of foregut anomalies (i.e. bronchopulmonary foregut malformations), which range from pulmonary sequestrations to bronchogenic cysts and foregut duplication cysts.

Apoproteins↗

PubMed2003

Natural killer cell lymphoma in the duodenum.

We present a case of duodenal non-Hodgkin lymphoma in a 71-year-old woman. Immunohistochemistry characterized the lymphoma cells as CD2(+); surface CD3(-) but cytoplasmic CD3(+); CD7(+); and CD56(+) without a rearrangement of the T-cell receptor gene. Cells had a high N/C ratio and irregular nuclear outlines and lacked azurophilic granules and these features indicated that the lymphoma cells arose from natural killer (NK) cells. She was treated with intensive chemotherapy including pirarubicin, cyclophosphamide, vincristine, and prednisolone, but died three weeks after diagnosis. CD56(+) lymphomas originate from NK or cytotoxic T cells and are designated "extranodal NK/T-cell lymphoma, nasal type" in the WHO classification. Nasal NK cell lymphoma is most common in East Asians and CD56(+) lymphomas usually occur in the nasal area. Extranasal forms such as gastrointestinal lymphomas are very rare and usually carry a poor prognosis. Extranodal NK/T-cell lymphoma, nasal type, is characterized by a broad morphologic spectrum and have variable prognosis. These lymphomas constitute an heterogeneous group, and their subclassification has not yet been established.

Aged↗

PubMed2003

Multiple pulmonary nodules caused by B-cell post-transplant lymphoproliferative disorder after bone marrow transplantation: monitoring Epstein-Barr virus viral load.

We report a patient with myelodysplastic syndrome who underwent an allogeneic bone marrow transplantation during the first remission. On day 110 he had a low-grade fever and pulmonary nodules, without superficial lymphadenopathy, were observed. The pulmonary nodules gradually increased in size and in number despite administration of anti-fungal and anti-tuberculosis agents. Transbronchial lung biopsy was performed on day 204, yielding a diagnosis of polyclonal post-transplant lymphoproliferative disease (PTLD) positive for Epstein-Barr virus (EBV)-encoded RNA (EBER) and CD20. Subsequent measurement of herpesvirus viral load demonstrated a consistent elevation of EBV viral load from day 96 to day 221. After treatment with anti-CD20 monoclonal antibody (rituximab), regression of pulmonary nodules was confirmed and the number of EBV genome copies decreased to a normal range. This case suggests that monitoring the quantitative EBV viral load may be necessary in cases of EBV-associated PTLD, even in cases presenting pulmonary nodules. Solitary pulmonary nodules may be a rare symptom of PTLD, but in such cases, an aggressive approach may be necessary to obtain a correct diagnosis.

B-Lymphocytes↗

PubMed2003

Advanced pancreatic ductal cancer: fibrotic focus and beta-catenin expression correlate with outcome.

INTRODUCTION: Many investigators have examined prognostic factors for advanced pancreatic ductal cancer, but it is still difficult to accurately predict the outcome of the disease. AIM: To examine correlation between histopathologic factors and outcome of advanced ductal carcinoma of the pancreas. METHODOLOGY: The subjects were 23 patients who underwent resection of pancreatic ductal cancer classified as stage III according to pTNM classification. Fibrotic focus (which is evidence of intratumoral fibroblast proliferation), tumor size and differentiation, invasion to the portal vein, and immunohistologic expression of E-cadherin and alpha-, beta- andbgr;- and gamma-catenins were evaluated. Correlation between histologic and immunohistologic data and correlation between these data and liver metastasis-free survival and overall survival were assessed by means of the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards regression model (for multivariate analysis). RESULTS: The presence of fibrotic focus correlated with reduced membranous beta-catenin expression. The presence of fibrotic focus, reduced membranous beta-catenin expression, and reduced cytoplasmic alpha-catenin expression were significantly associated with shorter liver metastasis-free survival. The presence of fibrotic focus also significantly correlated with shorter survival and was the only factor significantly associated with survival in multivariate analysis. CONCLUSION: The presence of fibrotic focus and reduced beta-catenin expression closely correlated with poor survival of patients with advanced ductal carcinoma of the pancreas.

Adult↗

PubMed2003

Ubiquitin-immunoreactive degradation products of cytokeratin 8/18 correlate with aggressive breast cancer.

Decreased amounts of cytokeratin (CK) 8/18 in the cytoplasm of breast cancer cells correlate with a poor prognosis. Although such decreases have been attributed to suppressed gene expression, accelerated protein degradation may also be responsible. In order to investigate whether selective degradation via the ubiquitin (Ub)-dependent proteasome pathway occurs in breast cancer, one- and two-dimensional (1-D and 2-D) immunoblot analysis was performed on cancerous and normal breast tissue from 50 breast cancer patients using the anti-Ub monoclonal antibodies (mAbs) KM691 and KM690. On 1-D gel electrophoresis, one broad band or two bands were detected at about 43 kDa; these were detected only in cancer tissue. Immunoreactive bands at 43 kDa were significantly associated with aggressive morphology (P = 0.011), nuclear p53 accumulation (P = 0.015) and overexpression of Her2 / neu protein (P = 0.012). On 2-D gel electrophoresis, these bands were fractionated into a group of several spots that formed a staircase pattern at 40-45 kDa. Partial amino acid sequencing analysis demonstrated that these Ub-immunoreactive spots corresponded to CK8 and CK18; however, since they did not have an amino-terminal domain, and were located at lower molecular weight positions than intact CK8 and CK18 on the 2-D gel, they were regarded as degradation products. CK18 degradation was confirmed by confocal microscopy as loss of the frame-like network that forms the luminal structure. These results indicate that CK 8/18 degradation products are detected specifically in breast cancer and may determine its aggressiveness.

Adult↗

PubMed2003

Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells after myocardial infarction.

Tumor necrosis factor (TNF) family proteins including TNF-alpha and Fas (CD95)-ligand have been implicated in the development of acute myocardial infarction (AMI). We studied whether AMI patients displayed up-regulation of another TNF family member, TNF-related-apoptosis-inducing ligand (TRAIL), on peripheral blood mononuclear cells (PBMCs). We compared expression of TRAIL on PBMCs from 26 patients in the acute phase of AMI with that on PBMCs from 16 healthy control subjects using flow cytometry and RT-PCR. In addition, expression of TRAIL protein on PBMCs from patients in the acute phase of AMI was also compared with that from the same patients 7 days later. Furthermore, we compared the expression of TRAIL protein on CD4+, CD8+, CD14+, and CD19+ cells from patients in the acute phase of AMI with that from control subjects using flow cytometry. Finally, expression of the TRAIL receptors (TRAILR)-1 and TRAILR-2 in human cardiomyocytes was examined immunohistochemically. Expression of TRAIL protein was significantly higher in the acute phase of AMI than in control subjects. Expression of TRAIL protein was significantly higher in the acute phase of AMI than 7 days later. TRAIL mRNA expression in the acute phase of AMI was higher than in control subjects. Expression of TRAIL protein on CD4+ and CD14+ cells from AMI patients was significantly higher than that from control subjects. Expression of TRAILR-1 and TRAILR-2 in human cardiomyocytes was confirmed immunohistochemically. TRAIL on infiltrating CD4 and CD146 cells may be involved in the induction of cardiomyocyte apoptosis after AMI.

Apoptosis↗

PubMed2003

A case of myxoid adrenocortical carcinoma with extensive lipomatous metaplasia.

We report a combination of unusual myxoid change and extensive lipomatous metaplasia of an adrenocortical carcinoma. The patient was a 38-year-old man with hypertension and heart failure. Radiographic examination revealed the presence of a left adrenal tumor, and adrenalectomy was performed. The tumor weighed 380 g and appeared encapsulated. The cut surface was predominantly gelatinous. Histologically, the tumor was composed of atypical round cells with eosinophilic to vacuolated cytoplasm. The tumor was diagnosed as adrenocortical carcinoma. The stroma accumulated copious mucinous material. In addition, individual to nodular mature adipocytes were admixed throughout the tumor. The transition from carcinoma cells to mature adipocytes was recognized. Myxoid change is a very rare phenomenon in adrenocortical carcinoma, and only 10 similar cases have been reported to date. Lipomatous metaplasia is another peculiar feature of adrenocortical lesions that has been reported only in benign conditions. To our knowledge, this is the first reported case of adrenocortical carcinoma with lipomatous metaplasia.

Adipocytes↗

PubMed2003

[Spontaneous regression of MALT lymphoma of the hard palate accompanied by Sjögren syndrome].

A 46-year-old woman visited our hospital in January 1998 because of a painful palate mass. In the ten years previous to presenting, she noticed dryness of the mouth and occasionally had conjunctivitis. The pathological findings of the biopsy from the hard palate revealed that she had an extranodal marginal zone B cell type lymphoma (MALT type). Results of the Schirmer test, rose-bengal test and a gum test all supported the diagnosis that she had also Sjögren syndrome. However, complete self-remission of the hard palate lymphoma was observed 4 months after the diagnosis, and no relapse has been seen in a follow-up of over 2.5 years. Watch and wait should be emphasized for a patient having a palate MALToma at an early stage accompanied by Sjögren syndrome.

Female↗