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Biomedical subjects

S Nakamura

Publications and source records attributed to S Nakamura.

At least 181 records · Page 10Linked to original sources

Evaluation of the expression of NADPH oxidase components during maturation of HL-60 clone 15 cells to eosinophilic lineage.

OBJECTIVE: Superoxide-generating NADPH oxidase consists of the membrane-bound cytochrome b558 (gp91phox and p22Phox) and the cytosolic components (p67phox, p47phox, p40phox and rac). In this study, we evaluated the superoxide-generating activity and the expression of NADPH oxidase components during eosinophilic maturation using HL-60 clone 15 cell line. MATERIALS AND METHODS: HL-60 clone 15 cells were matured to eosinophils by incubation with 0.5 mM butyrate for 7 days, and NADPH oxidase components were detected by Northern blot, Western blot analyses and immunocytochemical staining. Moreover, superoxide-generating activity was examined by nitro blue tetrazolium (NBT) assay. RESULTS: Northern blot and Western blot analyses revealed that mRNAs and proteins for gp91phox, p67phox and p47phox were expressed after eosinophilic myelocyte stages, whereas mRNAs and proteins for p40phox and rac-2 were expressed from the promyelocyte stage. Interestingly, p22phox mRNA was expressed from the promyelocyte stage, but its protein was expressed after eosinophilic myelocyte stages. Consistent with the results of Western blotting, immunocytochemical staining of butyrate-induced HL-60 clone 15 cells indicated that gp91phox, p22phox, p67phox and p47phox were detected after eosinophilic myelocyte stages (eosinophilic myelocytes, eosinophilic metamyelocytes, eosinophilic band cells and eosinophilic-segmented cells), whereas p40phox and rac-2 were expressed from the promyelocyte stage. Moreover, almost the same results as those with butyrate-treated HL-60 clone 15 cells were obtained using human bone marrow cells by immunocytochemical staining. Furthermore, nitro blue tetrazolium (NBT) assay indicated that superoxide could be produced after eosinophilic myelocyte stages but not produced before the promyelocyte stage. CONCLUSIONS: Together these observations indicate that all the components for NADPH oxidase are expressed, and the superoxide-producing activity is obtained after myelocyte stages during eosinophilic maturation.

Amino Acid Sequence↗

Ceramic endoprosthesis for aggressive giant cell tumors near the knee: eight cases followed for more than 10 years.

Eight patients with locally aggressive giant cell tumor were treated with marginal resection and implantation of a ceramic endoprosthesis with a non-hinged knee joint. The patients have been followed-up for between 10 to 16 years. Newly formed bone appeared at the junction between implant and cortex and in 2 cases subsidence of the implant was seen. All the patients had good function of the knee and no revision was needed.

Adult↗

Comparative study between daily and 5-days-a-week administration of oral 5-fluorouracil chemotherapy in mice: determining the superior regimen.

BACKGROUND: Oral administration of derivatives of 5-fluorouracil (5-FU) is currently used to treat colorectal cancer in the United States. Oral chemotherapy possesses certain advantages: it is simple, easy to administer, and has few side effects. We compared conventional daily oral administration of 5-FU (daily schedule) with administration on 5 consecutive days followed by 2 drug-free days (5-days-a-week schedule) in a mouse tumor model. METHODS: The maximal tolerated dose (MTD) in the 5-days-a-week schedule and in the daily schedule were determined in 6-week-old non-tumor-bearing CDF1 male mice. In antitumor experiments, CDF1 mice were inoculated subcutaneously with Colon26 cells (1x10(6) per mouse). Antitumor efficacy was evaluated in terms of the ratio of tumor size in treated to control mice (T/C ratio). RESULTS: The MTD of 5-FU in the 5-days-a-week schedule was 42 mg/kg, and in the daily schedule was 29 mg/kg. In the 5-days-a-week schedule dose escalation nearly 1.4 times that in the daily schedule was possible, although the total dose over 7 days was similar between the two schedules (203 mg/kg and 210 mg/kg, respectively). When the doses of 5-FU were compared under the condition of no body weight loss, the 5-days-a-week schedule produced a comparative dose escalation of 2.1 times per day (from 20 to 42 mg/kg), and 1.5 times per total weekly amount (from 140 to 210 mg/kg) compared to the daily schedule. With regard to the antitumor effect as indicated by the T/C ratio, the 5-days-a-week schedule produced over 70% tumor suppression, whereas the daily schedule produced only 50% suppression at the MTD. Therapeutic efficacy was calculated in terms of the ratio of body weight change to antitumor effect (T/C ratio), and revealed that the MTD of 42 mg/kg 5-FU in the 5-days-a-week schedule produced a therapeutic efficacy almost three times that of the MTD of 29 mg/kg 5-FU in the daily schedule (P<0.001). CONCLUSIONS: Using oral administration of 5-FU, we confirmed that the 5-days-a-week schedule allowed dose intensity escalation and was superior to the daily schedule in both enhancement of antitumor effect and protection against adverse effects.

Animals↗

P39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple system atrophy.

Glial cytoplasmic inclusions (GCIs) characteristically occur in the oligodendrocytes of patients with multiple system atrophy (MSA). Cyclin-dependent kinase 5 (Cdk5) regulates cytoskeletal dynamism through phosphorylation of cytoskeletal proteins such as neurofilament proteins, tau and microtubule-associated protein 2. We examined the immunohistochemical localization of p39, a Cdk5 activator, in human brain specimens obtained post mortem from controls and patients with MSA. Among control specimens, p39 immunoreactivity was found in some neuronal somata and axons. Similar immunoreactivity was detected in MSA neuronal cell bodies and axons, but a number of inclusions were heavily labeled. These results suggest that p39 and Cdk5 are up-regulated in oligodendrocytes and may be involved in the formation of GCIs through phosphorylation of cytoskeletal proteins in oligodendrocytes in MSA.

Aged↗

Three-dimensional structures of canine senile plaques.

In this study, the three-dimensional structures of two types of canine senile plaques (SP), diffuse plaques (DP) and mature plaques (MP), were compared using a confocal laser scanning microscope. The three-dimensional observation revealed that canine DP were uneven nebula-like assemblies of amyloid-beta (Abeta), while MP were comparatively uniform assemblies of membrane-like or fibrous Abeta materials with some differences among subtypes (primitive, classic and compact). We also noticed the presence of areas with low-density Abeta deposition inside DP and MP, indicating degradation of Abeta. Double staining for Abeta and other SP constituents was also conducted. Amyloid precursor protein (APP) was mainly deposited as rough granules around Abeta assemblies in DP and both inside and around Abeta assemblies in MP. The patten of ubiquitin deposition was quite similar to that of APP. Glial fibrillary acidic protein-positive astroglial projections were found around and inside Abeta assemblies in both types of SP, but were more prominent in MP than DP. DP were often invaded by neurofilament-positive neuronal processes (neurites), while no such neurites were observed inside MP. Dystrophic neurites were, however, frequently detected around MP. These results clearly showed that canine DP and MP have completely different three-dimensional structures, consistent with different processes of DP and MP formation.

Aging↗

Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed-type intestinal metaplasia of the human stomach.

We have proposed that intestinal metaplasia (IM) of the human stomach be divided into two types on the basis of cell differentiation status: a gastric and intestinal (GI) mixed type and a solely intestinal (I) type. In the GI mixed type, gastric (foveolar epithelial and pyloric gland cells) and intestinal (goblet, intestinal absorptive, and Paneth cells) phenotype cells coexist in the same intestinalized gastric glands in various combinations and degrees. Consequently, intestinalized gastric glands are hybrids. Although we have described the rare appearance of Paneth-like cells in pyloric glands of GI mixed-type IM, the absence of an appropriate Paneth cell marker leaves room for doubt as to their true character. The purpose of this study was to clearly identify Paneth cells in pyloric glands in IM lesions using a new Paneth cell marker, a polyclonal antibody human defensin (HD)-5, raised against HD-5, which is included in granules of Paneth cells. A total of 105 gastric samples (4 biopsy and 101 surgical resected specimens) were examined. In only nine cases (8.6%), the antibody allowed demonstration of Paneth cells in pyloric glands in GI mixed-type IM, confirming our previous finding. Analysis of the proliferative cell (P) zone indicated that a common stem cell might generate both GI phenotype cells by upward and downward migration. No Paneth cells were found above the P zone. The results suggest that the stem cells show abnormal cell differentiation in IM lesions but preserve their normal direction of migration.

Adenocarcinoma↗

Sebaceous gland metaplasia in intraductal papilloma of the breast.

We report here the first case of sebaceous gland metaplasia arising within an intraductal papilloma of the breast of a 70-year-old female. Several lobules and nests composed of clear cells closely resembling sebaceous glands of the skin were discovered within an intraductal papilloma of the breast. Squamous metaplasia was also noted in certain areas of the tumor. Immunohistochemically, the cells of the lobules and nests stained positively for monoclonal antibodies anti-cytokeratin 14 and epithelial membrane antigen. This study confirms a novel type of metaplasia of the breast.

Aged↗

The formation of capsule and septum in human hepatocellular carcinoma.

The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC.

Actins↗

Keratoameloblastoma with unique histological architecture: an undescribed variation of ameloblastoma.

Keratoameloblastoma is an extremely rare variant of ameloblastoma, and a review of the English language literature yields only several documented cases of ketatoameloblastoma. This paper reports a keratoameloblastoma showing unique histological architecture. The patient was a 76-year-old Japanese man with a multilocular radiolucent lesion of the mandible extending from the left canine to the second molar area. Microscopically, the lesion was characterized by multicystic spaces lined by papillary projections of proliferating odontogenic epithelium with extensive surface parakeratinization in a lamellar accumulation of keratin. In addition, "hair-like" extensions of keratin were frequently found. There was no ghost cell type keratinization. Histological features of the odontogenic epithelium were similar to those of conventinal ameloblastoma. An additional prominent feature of the present ameloblastoma was formation of hard tissue in continuation, in part, of the accumulated keratin in the fibrous tissue. These hard tissues showed a woven bone- or cellular cementum-like appearance and were not in contact with odontogenic epithelium. The present case was finally diagnosed as "keratoa meloblastoma," although such a type of keratoameloblastoma has not been documented previously in the spectrum of ameloblastoma.

Aged↗

Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice.

We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/- 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2-25 months). With respect to tumor location, the median survival time was 4 months (range, 2-25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection.

Bile Duct Neoplasms↗

Huge cystic lymphangioma of the pancreas: report of a case.

We report herein the case of a 33-year-old woman who presented with palpable abdominal swelling found to be caused by a huge lymphangioma of the pancreas. An abdominal computed tomographic (CT) scan showed a large multilocular cystic mass with water-dense contents, which was derived from the pancreatic head. A pancreaticoduodenectomy (PD) was performed because the tumor had invaded the duodenum. The resected tumor, which was 23 x 12 x 23 cm in size with 21 of serous fluid, was pathologically diagnosed as a cystic lymphangioma. The endothelial cells lining the internal surface of the cystic spaces were immunohistochemically positive for factor VIII-R antigen and CD31. Our review of the literature revealed 45 reports of lymphangioma of the pancreas, including this one, but to the best of our knowledge this is only the fifth case that required a PD. Nevertheless, we recommend that a complete resection be performed to reduce the risk of recurrence.

Adult↗

Antimetastatic effect of hepatotropic liposomal adriamycin on human metastatic liver tumors.

Adriamycin (ADM) was encapsulated in a galactose-conjugated hepatotropic liposome (hLip-ADM) and its ability to enhance the antitumor effect while reducing toxicity was compared with that of free ADM and a control Lip-ADM (cLip-ADM), in two in vitro animal models. Liver metastases were induced in rats by an intravenous injection of 8 x 10(6) AH-130 rat hepatoma tumor cells. All forms of the ADM completely inhibited liver metastasis when given at a dose of 5 mg/kg on day 14 after tumor implantation, whereas liver metastatic foci were observed in six of ten rats in the control group. The reduction in ADM toxicity by liposomalization was remarkable, as significant body weight loss was observed only in the free ADM group, in which four of ten rats died. Additional experiments utilized a human colon cancer xenograft (TK-4) to induce the growth of the liver metastases in mice by orthotopic implantation. The hLip-ADM completely inhibited liver metastasis in rats (0/11), whereas liver metastases developed in 10 of 12 mice in the control group and in 5 of 12 mice given cLip-ADM. Interestingly, liposomal ADM did not have a significant inhibitory effect on transplanted tumor growth assessed 6 weeks after transplantation. These findings indicate that hLip-ADM may be an effective strategy for inhibiting liver metastases from human colon cancer.

Animals↗

Transabdominal approach for intrapelvic migration of a total hip prosthesis component.

We report a patient with severe intrapelvic migration of the acetabular component after total hip arthroplasty. Preoperative drip infusion pyelography showed a medial shift in the ureter caused by the migrated acetabular component. Preoperative angiography showed that the right external iliac artery was compressed and shifted medially by the migrated acetabular component. At revision surgery, the migrated acetabular component was successfully removed through a transabdominal (transperitoneal) approach, with the assistance of a general surgeon, and reconstruction was performed through a transtrochanteric approach. We concluded that the transabdominal approach was a useful approach for removing a severely migrated acetabular component.

Female↗

Long-term results of rotational acetabular osteotomy in patients with slight narrowing of the joint space on preoperative radiographic findings.

Between 1975 and 1984, we performed rotational acetabular osteotomy in 22 female patients with painful hip dysplasia. At the time of surgery, the patients were in their twenties, and radiographs showed slight narrowing of the joint space. Of these patients, 15 were followed-up for 15 to 22 years (average, 19.8 years) after surgery. The preoperative severity of coxarthrosis in all 15 hips was graded as stage II, according to the classification of coxarthrosis advocated by the Japanese Orthopaedic Association. All 15 patients available for follow-up had had no additional operations on the operated side during the follow-up period. At the time of follow-up, the patients were aged 41 to 48 years (average, 44.3 years). Of the 15 patients, 12 had little or no pain and 14 could walk for more than 30 min without a cane; the severity of coxarthrosis was graded stage I in 3 hips, stage II in 4 hips, stage III in 5 hips, and stage IV in 3 hips. We conclude that rotational acetabular osteotomy is efficacious for patients who have preoperative radiographic findings of slight narrowing of the joint space.

Acetabulum↗

Evaluation of metastatic potential of gastric tumors by staining for proliferating cell nuclear antigen and chromosome 17 numerical aberrations.

BACKGROUND: Aberrations in chromosome 17 are important in carcinogenesis. We recently reported that numerical aberrations in chromosome 17 were associated with tumor progression in gastric cancer. The aim of this study was to determine the biological characteristics of gastric tumor cells with chromosome 17 numerical aberrations. METHODS: Gastric tumor sections (n = 105) and metastatic lymph nodes (n = 16) were stained simultaneously for PCNA (proliferating cell nuclear antigen) and chromosome 17 centromere. Cancers were classified as follows: Group 1: PCNA(+) and numerical chromosomal aberration(+); Group 2: PCNA(-) and numerical chromosomal aberration(+); Group 3: PCNA(+) and numerical chromosomal aberration(-); and Group 4: PCNA(-) and numerical chromosomal aberration(-). RESULTS: The frequency of Group 1 cells correlated with lymphatic invasion (P < .0001), lymph node metastasis (P < .0001), and venous invasion (P < .01). The frequency of these cells in gastric lesions was lower than in metastatic lymph nodes (P < .01). Logistic regression analysis identified the depth of invasion followed by the frequency of Group 1 cells were two of the most significant independent factors that could predict lymph node metastasis and lymphatic invasion. CONCLUSIONS: The frequency of gastric tumor cells positive for PCNA and chromosome 17 numerical aberrations may be an indicator of the metastatic potential of gastric cancers.

Adult↗

Treatment of retinal detachment resulting from myopic macular hole with internal limiting membrane removal.

PURPOSE: To examine the efficacy of vitrectomy with internal limiting membrane removal for retinal detachment resulting from a macular hole in highly myopic eyes. METHODS: Eleven consecutive highly myopic eyes (11 patients) with retinal detachment resulting from a macular hole were treated by vitrectomy with removal of the internal limiting membrane, which was stained with indocyanine green and sulfur hexafluoride gas injection. Postoperatively, the patients were instructed to remain prone for 2 weeks. The excised specimens were evaluated with transmission electron microscopy. RESULTS: The mean postoperative follow-up was 9.2 +/- 2.3 months (range, 7 to 13 months). In 10 of the 11 eyes (91%) the retina was reattached during the initial surgery. Redetachment occurred in one eye, which was successfully treated during the second surgery. Best-corrected visual acuity improved in all eyes and ranged from 20/400 to 20/50. Pathologic examination showed that the internal limiting membrane and epiretinal tissues were present in all specimens. CONCLUSIONS: The use of indocyanine green staining can facilitate removal of a macular internal limiting membrane and overlying epiretinal membrane, resulting in complete relief of the macular traction. Primary removal of the internal limiting membrane may contribute to a high initial success rate for retinal reattachment and be an important adjuvant to the treatment of retinal detachment resulting from a macular hole in highly myopic eyes.

Aged↗

Detection of cyclin D1 overexpression by real-time reverse-transcriptase-mediated quantitative polymerase chain reaction for the diagnosis of mantle cell lymphoma.

The diagnosis of mantle cell lymphoma (MCL) is particularly important for clinical management because of a remarkable prognostic difference between MCL and other types of B-cell lymphoma. In addition to immunohistochemical analysis, we have established a 5' exonuclease-based real-time reverse transcriptase-mediated quantitative polymerase chain reaction (RQ-PCR) method to detect cyclin D1 overexpression for the diagnosis of MCL. The RQ-PCR could detect cyclin D1 overexpression in all nine examined MCL cases, in contrast genomic PCR detected t(11;14) in only two of nine cases. By RQ-PCR the expression of G6PDH was significantly higher in myeloid leukemias than those in B-cell lymphomas (P = 0.018). As a result, cyclin D1/G6PDH ratio ranged from 0.78 to 12.4 (mean, 1.83) in MCL, exclusively higher than those in other B-cell lymphoma (0.00009 approximately 0.16) and myeloid leukemia (0.00011 approximately 0.085). The high expression of cyclin D1 in certain myeloid leukemias was identified to reflect their proliferative activity and not to represent the oncogenic overexpression. The 95% confidence interval of the cyclin D1/G6PDH ratio was 0.29 approximately 11.1 for MCL, 0.014 approximately 0.25 for other B-cell lymphomas and 0.000014 approximately 0.083 for myeloid leukemia, suggesting that a cutoff value can be set at 0.25. The RQ-PCR of cyclin D1 is convenient and especially useful for the diagnosis of MCL.

Biomarkers, Tumor↗