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Biomedical subjects

Takashi Nakajima

Publications and source records attributed to Takashi Nakajima.

At least 19 recordsLinked to original sources
PubMed2007

Up-regulation of a BCL9-related beta-catenin-binding protein, B9L, in different stages of sporadic colorectal adenoma.

Aberrant activation of Wnt signaling is a critical event in the development of human colorectal tumors. The aim of this study was to elucidate the role of B9L and its association with beta-catenin in each stage of the adenoma-carcinoma sequence of human colorectal tumorigenesis. We investigated the expression levels of B9L in sporadic colorectal adenomas and carcinomas, categorized according to the Vienna classification, using real-time quantitative polymerase chain reaction (RTQ-PCR) and immunohistochemical analysis. B9L was expressed in the nuclei of non-neoplastic colonic mucosa cells and was overexpressed in the nuclei of neoplasias and invasive carcinoma cells. Immunoreactivity to B9L protein was correlated with the progressive grades of colorectal neoplasias, as was the expression of B9L mRNA. A high level of immunoreactivity to nuclear B9L was present in 27% of low-grade neoplasias and in more than 50% of high-grade neoplasias and invasive carcinomas, whereas a high level of nuclear B9L immunoreactivity was not observed in any of the non-neoplastic mucosa samples. The expression of B9L was dramatically increased in low-grade neoplasias compared with that in non-neoplastic mucosa. B9L may play an important role in tumorigenesis induced by aberrant activation of Wnt signaling and may act as a key protein in the progressive dysplasia of adenoma.

Adenocarcinoma↗
PubMed2006

Prognostic model of stage II non-small cell lung cancer by a discriminant analysis of the immunohistochemical protein expression.

PURPOSE: We aimed to identify the key proteins that influence the prognosis of non-small cell lung cancer (NSCLC) using protein expression profiles of previously known prognostic markers. METHODS: Thirty-one cases of Stage II NSCLC with 5-year follow-up data were selected. Tissue microarrays (TMA) and immunohistochemistry were used to make protein expression profiles of 18 previously reported immunohistochemical prognostic markers and their value in NSCLC was statistically re-evaluated by a discriminant analysis. RESULTS: For the discriminant analysis using marker protein expression profiles, we selected three significant markers, TTF-1, RCAS1 and c-MET, to evaluate each patient's 5-year survival. The requested discriminant function was V = -1.08754 x (RCAS1 score) - 0.83174 x (TTF1 score) + 0.55204 x (cMET score) + 5.46972, and V = 0 served as a cut-off point. The correctness for evaluating a patient's 5-year survival by a discriminant analysis was 87.1%. CONCLUSIONS: A discriminant analysis is thus considered to be a useful statistical method for analyzing the protein expression profiles obtained by combined TMA and immunohistochemical techniques using archival NSCLC tissues. However, the sample size and selection of the marker protein depending on the histology greatly influence the results of a NSCLC study.

Antigens, Neoplasm↗
PubMed2006

High incidence of microscopic gastrointestinal stromal tumors in the stomach.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms with an annual incidence of approximately 10 to 20 per 1 million cases. Although pathologists have often observed incidental small GISTs in the stomach resected from patients with gastric cancer, no report on the real incidence of gastric GISTs is available. In this study, 100 whole stomachs resected from patients with gastric cancer were sectioned at 5-mm intervals and hematoxylin and eosin-stained slides (a mean of 130 slides for each case) were examined for microscopic GISTs. KIT (CD117), CD34, and desmin expression of the incidental tumors was evaluated by immunohistochemistry, and genomic DNA extracted from formalin-fixed and paraffin-embedded tumor tissues was analyzed for c-kit gene mutations in exon 11. In 35 of the 100 whole stomachs, we found 50 microscopic GISTs, all of which were positive for KIT and/or CD34 and negative for desmin. Most microscopic GISTs (45/50, 90%) were located in the upper stomach. Two of the 25 (8%) microscopic GISTs had c-kit gene mutations. Fifty-one leiomyomas with positive expression for desmin were observed in 28 of the 100 stomachs. Both leiomyomas and GISTs were found in 12 stomachs. These results indicate that microscopic GISTs are common in the upper portion of the stomach. Considering the annual incidence of clinical GISTs, only few microscopic GISTs may grow into a clinical size with malignant potential. Further studies are required to clarify the genetic events responsible for the transformation of microscopic GISTs to clinical GISTs.

Aged↗
PubMed2006

Phase-dependent excitation and ionization in the multiphoton ionization regime.

We theoretically study the dependence of atomic excitation and ionization on the carrier envelope phase of few-cycle laser pulses in the multiphoton ionization regime. Our theoretical results for the hydrogen atom based on the solution of the 3D time-dependent Schrödinger equation show that the strong phase dependence can be seen in not only total ionization, but also bound-state population under the weak laser intensity regime.

Journal Article↗
PubMed2006

Effects of the carrier-envelope phase in the multiphoton ionization regime.

We theoretically investigate the effects of the carrier-envelope phase of few-cycle laser pulses in the multiphoton ionization regime. For atoms with low ionization potential, total ionization yield barely exhibits phase dependence, as expected. However, population of some bound states clearly shows phase dependence. This implies that the measurement of the carrier-envelope phase would be possible through the photoemission between bound states without energy-and-angle-resolved photoelectron detection. The considered scheme could be particularly useful to measure the carrier-envelope phase for a light source without an amplifier, such as a laser oscillator, which cannot provide sufficient pulse energy to induce tunneling ionization.

Journal Article↗
PubMed2006

Interlaminar bony fusion after cervical laminoplasty: its characteristics and relationship with clinical results.

STUDY DESIGN: A radiographic study in 32 patients with cervical myelopathy. OBJECTIVE: To investigate postoperative interlaminar bony fusion, and its characteristics and relationship to clinical results in patients undergoing laminoplasty. SUMMARY OF BACKGROUND DATA: Laminoplasty is being increasingly performed for multi-segmental cervical myelopathy, and its superior long-term results have been reported in some articles. We often see cases that develop postoperative interlaminar bony fusion after laminoplasty. METHODS: In 32 patients, lateral cervical radiographs were obtained every year after surgery, and postoperative interlaminar bony fusion was evaluated. Range of motion (ROM) of the cervical spine at last follow-up was compared with the respective preoperative values. Furthermore, the neurologic recovery rates at last follow-up were compared to preoperative values. RESULTS: Postoperative interlaminar bony fusion was shown in 17 patients (53%, group 1), and in most, fusion appeared within 3 years after surgery. Average age at surgery in group 1 and the remaining 15 patients (group 2) was 64.6 years and 57.0 years, respectively (P < 0.04). Preoperative and postoperative ranges of motion in group 1 were 45.6 degrees and 28.1 degrees on average, respectively. However, those of group 2 were 50.3 degrees and 39.8 degrees on average, respectively. Postoperative ROM in group 2 was significantly better maintained than that in group 1(P < 0.04). In group 1, the average preoperative Japanese Orthopedic Association score was 9.56 points, which improved to 13.6 points at the final follow-up, providing a 55.6% average recovery. In group 2, it was 10.9 points, which improved to 14.1 points at the final follow-up, providing a 56.5% average recovery. There was no significant difference in the average percentage of recovery between the 2 groups (P > 0.93). CONCLUSIONS: Postoperative interlaminar bony fusion occurred in 53% of patients, with marked frequency at C2/3 after laminoplasty. It did not influence neurologic recovery, but it did reduce the postoperative sagittal ROM of the cervical spine.

Aged↗
PubMed2006

Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers.

Allelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall-cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer.

Base Sequence↗
PubMed2006

Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens.

A diagnosis of low-grade fibromyxoid sarcoma (LGFMS) remains problematic because of its bland-looking histologic features that can be potentially confused with other benign or low-grade fibromyxoid lesions. Recent cytogenetic and molecular analyses have shown that most LGFMSs have a characteristic chromosomal abnormality, t(7;16)(q33;p11), resulting in the FUS-CREB3L2 fusion gene. However, such assays have only rarely been used to analyze formalin-fixed, paraffin-embedded tumor samples. In the present study, we conducted a reverse transcription-polymerase chain reaction assay to detect the FUS-CREB3L2 fusion transcripts using formalin-fixed, paraffin-embedded tumor tissue specimens from 16 LGFMSs including 3 cases with giant collagen rosettes. The primers were newly designed to specifically amplify most of the junctional regions of the FUS-CREB3L2 fusion gene transcripts previously reported. The FUS-CREB3L2 fusion gene transcripts were detected in 14/16 (88%) cases of LGFMS. A nucleotide sequence analysis of the PCR products revealed that different portions of the FUS exon 6 or 7 were fused with various sites of the CREB3L2 exon 5, resulting in 12 different nucleotide sequences. We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case. The FUS-CREB3L2 fusion transcripts were not detected in any of the 123 other soft-tissue tumors, including desmoid-type fibromatoses, myxofibrosarcomas, soft-tissue perineuriomas, and congenital or adult fibrosarcomas. These data suggest that our reverse transcription-polymerase chain reaction assay is a reliable method to detect FUS-CREB3L2, which can thus help in accurately diagnosing LGFMS.

Adolescent↗
PubMed2006

Unique case of pulmonary bronchial gland type tumor with broad spectrum of cell differentiation from the terminal duct-acinar unit to excretory duct.

In the lung, acinic cell carcinoma (ACC) is a rare form of tumor. Reported herein is a unique bronchial gland-type tumor diagnosed as well-differentiated ACC that developed in the B9 bronchus of the left lung. Various immunohistochemical and histochemical staining partly satisfied the diagnosis of ACC. Moreover, this tumor contained various sizes of mucous cysts lined by columnar mucous cells, which produced abundant mucin positive for Alcian blue, which is usually present in mucoepidermoid carcinoma. Therefore, the present case is a unique tumor having a broad spectrum of cell differentiation from the terminal duct--acinar unit to the striated duct and excretory duct. This is the first case of unique bronchial gland-type tumor with mixed histological features of ACC and mucoepidermoid carcinoma.

Carcinoma, Acinar Cell↗
PubMed2006

Immunohistochemical expression of aminopeptidase N (CD13) in human lung squamous cell carcinomas, with special reference to Bestatin adjuvant therapy.

Bestatin, a specific inhibitor of aminopeptidase N (CD13), has been reported to prolong survival time in patients with completely resected stage I lung squamous cell carcinoma. Considering the antitumor mechanism of Bestatin, it is interesting to know whether CD13 is expressed in human lung squamous cell carcinoma. The immunohistochemical expression of CD13 was examined in human lung carcinoma and the question of whether CD13 was immunohistochemically expressed in the interstitial tissue was investigated, mainly in the fibroblasts and blood vessels, surrounding the tumor nests of various kinds of non-small cell lung cancers, especially of squamous cell carcinomas. In Japanese squamous cell carcinoma of the lung, 38 (61.3%) out of 62 cancers were positively stained in the same manner on immunohistochemistry for CD13. The area of interstitial tissue positively stained for CD13 varied depending on the case. To confirm the cell nature of the interstitial tissue with CD13 positivity, double immunohistochemistry using CD34 and alpha-smooth muscle actin was performed. Double immunohistochemistry showed that the majority of CD13-positive cells were slender fibroblastic cells around the blood vessels and some endothelial cells.

Adjuvants, Immunologic↗
PubMed2006

Epigenetic inactivation of the RUNX3 gene in lung cancer.

The silencing of tumor suppressor genes (TSGs) by aberrant hypermethylation occurs frequently in human cancer. Recently the RUNX3 gene was identified as a TSG inactivated by hypermethylation. We examined RUNX3 expression by reverse transcription-PCR and the methylation status of this gene by methylation specific-PCR in 43 lung cancer cell lines and 120 primary non-small cell lung cancer (NSCLC) tumor samples. RUNX3 expression was absent in 10 (50%) of 20 small cell lung cancer (SCLC) cell lines, 8 (50%) of 16 adenocarcinoma (AdC) cell lines, and 1 (33.3%) of 3 squamous cell carcinoma (SqC) cell lines. The frequency of RUNX3 methylation was significantly higher in AdC (7/16, 43.8%) than SCLC cell lines (1/20, 5%; p=0.032). RUNX3 expression was restored by treatment with 5-aza-2'-deoxycytidine and/or trichostatin-A in AdC cell lines. These results indicated that RUNX3 expression was regulated by aberrant hypermethylation in AdC cell lines. RUNX3 methylation was detected in 30 (25%) of 120 primary NSCLC tumors. RUNX3 methylation was significantly more frequent in non-smokers (16/43, 37.2%) than smokers (12/71, 16.9%; p=0.014), and in patients with AdC (26/72, 36.1%) than in patients with SqC (3/45, 6.7%; p<0.001). These results indicated that silencing of the RUNX3 gene plays an important role in the pathogenesis of lung cancer, and aberrant methylation is an important mechanism of inactivation of the RUNX3 gene in lung AdC.

Cell Line, Tumor↗
PubMed2006

[A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints].

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.

Alcoholism↗
PubMed2006

[Transient elevation of the number of microembolic signal in a patient with primary antiphospholipid antibody syndrome].

We report a 55-year-old man complaining of monoparesis of the right arm and dementia. Brain magnetic resonance imaging (MRI) demonstrated multiple foci of fresh cerebral embolism. The serum lupus anticoagulant was positive, however, the serum anticardiolipin antibody and other autoantibodies indicating connective tissue diseases were negative. This patient received a diagnosis of primary antiphospholipid antibody syndrome. Transcranial Doppler(TCD) monitoring of the middle cerebral artery showed the presence of microembolic signal (MES). We initiated anticoagulant therapy with intravenous heparin administration, and three days later we added oral warfarin administration. We used both warfarin and heparin together for only three days. The number of MES increased transiently after initiating of warfarin administration, then decreased by warfarin therapy with production of an international normalized ratio (INR) of prothrombin time over 2. His neurological symptoms normalized except for monoparesis of the right arm. There were no foci of fresh cerebral infarct disclosed on brain MRI performed two months after admission. The treatment strategy for antiphospholipid antibody (APS) patients has not yet been established. Some reports and guideline recommended that the stroke patients with APS should be treated with long-term oral anticoagulant therapy, target INR 2.5 (optimal range 2.0 to 3.0). In this patient, we confirmed a decrease in the number of MES by warfarin therapy with production of INR over 2. In APS patients, detection of MES by TCD is a useful device for adjustment of the warfarin dose. Concerning the course of MES and warfarin therapy, transient elevation of the number of MES after initiation of warfarin therapy would suggest the hypercoagulability due to an acute decrease in serum protein C level. Using the TCD technique, we detected such hypercoagulability for the first time.

Anticoagulants↗
PubMed2005

Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro.

Experimental evidence supports a role for E-cadherin in suppressing invasion, metastasis, and proliferation. Germline mutations of the E-cadherin represent the genetic cause of hereditary diffuse gastric cancer (HDGC). In this type of tumor, isolated cancer cells permeate the basal membrane and paradoxically survive in the gastric wall in the absence of contact with neighbor epithelial cells or with the extracellular matrix. This suggests that upon E-cadherin deregulation, cells acquired resistance to apoptosis. To test this hypothesis, CHO cells stably expressing either wild-type E-cadherin or the HDGC-related germline mutations T340A and V832M were seeded either on a thin layer of collagen type I or on plastic and then subjected to the apoptotic agent taxol. We found that in vitro functional E-cadherin renders cells more sensitive to the effect of taxol. Our results also indicate that this effect is associated to decreased level of the anti-apoptotic bcl-2 protein.

Animals↗
PubMed2005

Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer.

PURPOSE: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. RESULTS: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). CONCLUSIONS: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Correlation between laminin-5 gamma2 chain and epidermal growth factor receptor expression in esophageal squamous cell carcinomas.

OBJECTIVES: Laminin-5 gamma2 chain (LN-5 gamma2) is an extracellular matrix protein that plays an important role in cell migration and tumor invasion. We evaluated the association of LN-5 gamma2 and epidermal growth factor receptor (EGFR) expression in esophageal squamous cell carcinoma (SCC). METHODS: LN-5 gamma2 and EGFR expression was evaluated in 110 esophageal SCC patients by immunohistochemistry, and was confirmed using esophageal SCC cell lines by Western blot analysis. RESULTS: LN-5 gamma2 expression in the invasive front of the tumor was correlated with the depth of invasion (p = 0.0001), lymph node metastasis (p = 0.0011) and pathological stage (p = 0.0001). The strong expression of EGFR was also correlated with lymph node metastasis (p = 0.0456) and the pathological stage (p = 0.0055). In patient survival, LN-5 gamma2 positivity and/or strong EGFR expression showed a significantly low survival rate as compared with those with lesser expression of LN-5 gamma2 and EGFR. Immunohistochemically, LN-5 gamma2 expression was significantly correlated with EGFR expression (p < 0.0001). Western blot analysis also confirmed the correlated expression of LN-5 gamma2 and EGFR in SCC cell lines except 2 of the 5 cell lines. CONCLUSIONS: This study suggests that coexpression of LN-5 gamma2 and EGFR is closely related to the progression and poor prognosis of esophageal SCC.

Aged↗
PubMed2005

Detection of human papillomavirus infection of the cervix in very elderly women using PCR.

PURPOSE: To determine the incidence of human papillomavirus (HPV) infection and the morphologic lesions induced by HPV infection of the uterine cervix in elderly Japanese women (including very elderly women) and to clarify the natural history and outcome of HPV infection. EXPERIMENTAL DESIGN: We detected squamous intraepithelial lesions (SIL) by cytology and the presence of HPV infection by PCR on cervical smears obtained at autopsy from 335 women ages 60 to 105 years (mean, 82.7 years). Two primers were used for PCR, one for low-risk HPV subtypes and one for high-risk HPV subtypes. RESULTS: SILs were observed in 20 (6.0%) of the women autopsied; 18 (5.4%) had low-grade SIL and 2 (0.6%) had high-grade SIL. HPV-DNA was not detected in any of the women with normal cervical cytology but was found in 9 (45.0%) of the 20 with SIL (2.7% of all subjects). Of these 9 women, 2 (22%) were positive for low-risk types of HPV and 7 (78%) were positive for high-risk types. All 9 had spent their last days in hospitals or nursing homes, the duration of institutional care ranging from 17 days to 10 years 2 months. CONCLUSIONS: Our results suggest that HPV infection of the cervix may occasionally persist for long periods of time (the maximum duration noted in this study being 10 years 2 months). It is also possible that HPV infection in young women with normal cervical cytology will not persist into advanced age.

Aged↗