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Biomedical subjects

M Fujimori

Publications and source records attributed to M Fujimori.

At least 37 records · Page 2Linked to original sources
PubMed2000

Allelic loss of the region of chromosome 1p35-pter is associated with progression of human gastric carcinoma.

In order to identify the region on distal chromosome 1p that is thought to include one or more tumor suppressor genes for gastric carcinoma, 39 gastric carcinomas were examined for allelic loss using 11 polymorphic microsatellite markers and 1 marker of single strand conformation polymorphism. Loss of heterozygosity (LOH) was found in 18 (46%) of 39 informative patients. The regions with high frequency of loss of heterozygosity were the loci at D1S548 (6 / 17; 35.3%) and D1S2843 (7 / 20; 35%), and we found three commonly deleted regions on chromosome 1p35-pter. The frequency of allelic loss in the region of chromosome 1p35-pter was significantly associated with advanced-stage gastric carcinoma, but not with early-stage tumor or with the histology. These results suggest that allelic loss at chromosome 1p35-pter may play a role in the progression of gastric carcinoma.

Adenocarcinoma↗
PubMed2000

The processing of global and local visual information in Alzheimer's disease.

We examined the quantitative and qualitative difference of the pattern with visuo-cognitive processing impairment in patients with early onset AD (EOAD) and late onset AD (LOAD). We use a visual attention task introduced by Navon (1977) to examine the function to integrate local visual stimuli into global image. Although the ability to identify solid digits ether of large and small size presented at the same exposure duration, EOAD performance was poor in the global perception especially at the short duration (20~msec). We provide evidence that this dysfunction is attribute to the AD pathology specific to early onset type.

Journal Article↗
PubMed1999

Tumor Marker Levels Elevate False-Positively in Postsurgical Breast Cancer Patients with High sGPT Levels or with Receiving Oral 5-FU or Its Derivatives.

BACKGROUND: False elevation of tumor marker levels (TM) has been encountered in some postsurgical breast cancer patients. METHODS: We investigated 33 postsurgical breast cancer patients whose TM (CEA, CA15-3, NCC-ST-439, or BCA225) measured every 3 months, showed elevation 3 times in a row in a 6-month period, and in whom metastases were not detected at theend of the 6-month period. Nine patients developed recurrence within 36 months of the end of the 6-month period and 24 patients did not develop recurrence for more than 36 months after the end of the 6-month period. RESULTS: Seven patients who stopped treatment with oral 5-FU or its derivatives because of severe nausea and appetite loss did not develop recurrence. Normalization of TM (CEA, NCC-ST-439, or BCA225) manifested within 3 months of the interruption of the medication. Six patients who showed simultaneous increase in serum glutamic-pyruvic transaminase (sGPT) and TM (CEA or BCA225) in the initial 6months did not develop recurrence. Three of 6 patients did not take any anti-cancer drugs. Correlation coefficiencies of sGPT with CEA in 4 patients were 0.467, 0.569, 0.738, and 0.910 and those of sGPT with BCA225 in 3 patients were 0.663, 0.826, and 0.840. CONCLUSION: A false-positive increase in CEA, NCC-ST-439 or BCA225 might be caused by treatment with oral 5-FU or its derivatives. CEA or BCA225 elevates false-positively in patients with high sGPT levels.

Journal Article↗
PubMed1999

Fusion of a novel gene, ELKS, to RET due to translocation t(10;12)(q11;p13) in a papillary thyroid carcinoma.

In papillary thyroid carcinomas, the genes for receptor-type tyrosine kinase, RET or TRKA, are sometimes rearranged, resulting in fusion of its tyrosine kinase domain to 5' portions of several activating genes. In a papillary thyroid carcinoma, we identified a novel gene (ELKS), the 5' portion of which is fused to the RET gene by gene rearrangement due to the translocation t(10;12)(q11;p13). Subsequent cloning of the ELKS cDNA revealed that ELKS encodes a novel 948 amino acid peptide and is expressed ubiquitously in human tissues. The presence of multiple coiled-coil domains in the ELKS product suggests that the ELKS protein forms dimers. Since the tyrosine kinase of RET is activated by dimerization that occurs when its ligands bind to the receptor, fusion of RET with the 5' dimerization domains of ELKS would activate its cytoplasmic tyrosine kinase constitutively in papillary thyroid carcinomas.

Amino Acid Sequence↗
PubMed1999

Ret/PTC3 is the most frequent form of gene rearrangement in papillary thyroid carcinomas in Japan.

Rearrangements of the RET and TRK proto-oncogenes, which generate fusion oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations. To determine the spectrum of gene rearrangements in Japanese patients, we systematically examined 40 papillary thyroid carcinomas for all possible types of gene fusion events involving RET or TRK genes. RET rearrangements were found in ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3 in six, and a novel RET rearrangement in the remaining patient. In this last patient, the 5' novel sequence was fused in-frame to the RET amino acid sequence; thus, the fusion gene may encode a protein with a RET kinase domain at the carboxy terminus. The RET gene was fused to 5' donor sequences at the beginning of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found in this panel of carcinomas. Our results indicated that constitutive activation of the RET by gene rearrangement is a frequent mechanism of papillary thyroid carcinogenesis in Japanese adults.

Adult↗
PubMed1999

Utility of colorimetric end-tidal carbon dioxide detector for monitoring during prehospital cardiopulmonary resuscitation.

The purpose of this study was to evaluate a colorimetric end-tidal CO2 (ETCO2) detector (EASY CAP) as a monitor during prehospital cardiopulmonary resuscitation (CPR) without tracheal intubation. This detector was used for 121 patients during CPR with a laryngeal mask airway or face mask by authorized emergency lifesaving technicians. At 7 to 15 minutes after the initiation of CPR, ETCO was <0.5% in 30 cases (group A), 0.5% to 2.0% in 46 cases (group B) and >2.0% in 45 cases (group C). The rate of return of spontaneous circulation was 17% in group A, 24% in group B, and 48% in group C (groups A v C, P < .01). There was a significant difference in the rate of hospital admission between groups A and C. The ETCO2 value may be useful for monitoring during prehospital CPR with a laryngeal mask airway or face mask.

Adult↗
PubMed1999

Three-dimensional structure of the micro-blood vessels in thyroid tumors analyzed by immunohistochemistry coupled with image analysis.

The structure of micro-blood vessels, one of the most important factors influencing the tumor growth and tumor metastasis among histological types of thyroid malignancy, was analyzed immunochemically by staining tissues for platelet endothelial cell adhesion molecule-1 (PECAM-1). Human thyroid tumor tissue obtained at surgery, consisting of 18 cases of papillary carcinoma, 9 cases of follicular carcinoma, and 9 cases of anaplastic carcinoma were fixed in formalin solution, and paraffin sections were made. They were stained for PECAM-1 using the avidin-biotin complex (ABC) technique. The volume of the blood vessels and their three-dimensional (3D) structure were analyzed using an image analyzer. The volume ratios of blood vessels in thyroid tissues were: normal tissues, 1.10%; papillary carcinoma, 3.01%; follicular carcinoma, 8.13%; and anaplastic carcinoma, 0.91%. Ratios in malignant tumors were larger than in normal tissues, except for anaplastic carcinoma. The typical 3D structure of micro-blood vessels was histopathologically varied: branching tree-like blood vessels in papillary carcinomas; vessels of varied diameter surrounding follicle structure in follicular carcinomas; and simple and immature vessels in anaplastic carcinomas. The volume and 3D structure of micro-blood vessels in thyroid malignant tumors differed from those in normal tissues, and varied according to histological classification.

Adenocarcinoma, Follicular↗
PubMed1999

Concurrent administration of amrinone with nitric oxide most improves PaO2/FiO2 in acute respiratory and cardiac failure.

A 55-year-old man developed acute respiratory failure, pulmonary hypertension and left heart failure due to acute myocardial infarction. Nitric oxide (NO) inhalation improved arterial oxygenation, decreased pulmonary arterial pressure and increased cardiac output (CO), but combined use of dobutamine with NO produced increases in pulmonary arterial pressure and pulmonary capillary wedge pressure (PCWP). In this patient, amrinone decreased pulmonary arterial pressure and PCWP, and increased PaO2/FiO2 effectively while increasing CO. Combined use of inhaled NO and intravenous amrinone may have beneficial effects for a patient with acute respiratory and cardiac failure.

Acute Disease↗
PubMed1999

Identification of a 5-cM region of common allelic loss on 8p12-p21 in human breast cancer and genomic analysis of the hEXT1L/EXTR1/EXTL3 gene in this locus.

The short arm of chromosome 8 is frequently lost in many human carcinomas including breast cancer, suggesting the presence of a tumor suppressor gene(s) in this region. We identified a gene termed hEXT1L/EXTR1/EXTL3 (hEXT1L hereinafter) that was mapped to chromosome bands 8p12-p21 where frequent LOHs of this region was reported in breast cancer. The existence of the third breast cancer susceptibility gene was also suggested in this region by linkage analysis. We further performed LOH analysis in 8p12-p21 in 34 breast cancers and identified a 5-cM region of common allelic loss that overlapped with the locus for positive lod score in familial breast cancer. We further analyzed genomic alterations of hEXT1L in tumors in which frequent LOHs of 8p were reported. A total of 327 cancers (313 primary tumors and 14 cancer cell lines) including 22 primary breast cancers were analyzed, but none of the tumors had somatic mutations: only one thyroid cancer patient without any family history of cancer had a 9-bp insertion in the constitutional DNA. These results suggest that mutations of hEXT1L do not play a major role in the development of sporadic cancers including breast cancer, and that other tumor suppressor gene(s) exists in the 5-cM region identified in this study.

Alleles↗
PubMed1999

[Advances in endoscopic therapies for cancers of the digestive tract].

Endoscopic therapies for the treatment of cancers of the digestive tract have been improved. Today, some early cancers can be curatively treated by endoscopy (endoscopic polypectomy, endoscopic mucosal resection, heatprobe method, etc.). In addition, endoscopic local injection chemotherapy is performed for some advanced cancers as an adjuvant therapy. Recent progress in endoscopic therapies for cancer is reviewed in this paper, including their historical background. Improvements in these endoscopic treatment methods are expected to provide increased advantages for the treatment of patients with cancer in the near future.

Colonic Polyps↗
PubMed1998

Novel V184E MEN1 germline mutation in a Japanese kindred with familial hyperparathyroidism.

We studied the MEN1 gene in a kindred where three patients (the proposita and two of her sons) were affected with hyperparathyroidism. By polymerase chain reaction (PCR)-based direct sequencing of 10 exons of MEN1, a novel germline mutation was identified in the proposita. This mutation, a T-to-A transition at codon 184 in exon 3, predicts an amino acid change from valine to glutamine (V184E). PCR-single-strand conformational polymorphism (PCR-SSCP) analysis of exon 3 followed by sequencing showed the same mutation in the two sons, and in two clinically normal granddaughters of an affected son. Since the T-to-A substitution segregated with the disorder in the kindred except for the granddaughters and it was not detected in 100 alleles from 50 normal individuals, the change observed in MEN1 is not a polymorphism, but causes familial hyperparathyroidism. Thus the two grandchildren with the mutation were diagnosed as presymptomatic carriers.

Adolescent↗
PubMed1998

p73, a gene related to p53, is not mutated in esophageal carcinomas.

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the P1 genomic library to obtain a P1 clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9. Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single-strand conformation polymorphism (SSCP) and LOH studies, respectively. Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR. We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR-SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with p53.

Adenocarcinoma↗
PubMed1998

Bilateral Synchronous Spindle Cell, Apocrine and Scirrhous Carcinoma Breast Cancer in a Case of Malignant Lymphoma.

An unusual case of synchronous bilateral breast cancer occurring during combination chemotherapy and radiation to the outside of the breast for malignant lymphoma is reported. Two histologically rare carcinomas, spindle cell carcinoma and apocrine carcinoma, were observed in this case. A 77-year-old woman, who had been treated for stage IIIA non-Hodgkin's lymphoma, developed bilateral breast tumors. Aspiration biopsy cytology findings of the tumor in the left breast showed several clusters of adenocarcinoma cells and some large atypical spindle shaped cells, which suggested spindle cell carcinoma. The cytologic findings of the right breast tumor were highly suggestive of scirrhous carcinoma. A modified radical mastectomy was performed on both breasts. Pathological examination disclosed two separate cancer lesions in the left breast. The lesion which had been detected before the operation, was a spindle cell carcinoma. Another lesion, detected for the first time by pathological examination, was an apocrine carcinoma. The lesion in the right breast was a scirrhous carcinoma. Since non-invasive fociwere detected in these three cancer lesions, each lesion was thought to be a primary cancer. All dissected bilateral axillary lymph nodes showed malignant lymphoma. Immuno-histochemistry of the spindle cell carcinoma revealed positive immunoreactivity for cytokeratin, which suggested the epithelial as well as mesenchymal nature of this tumor. Synchronous existence of malignant lymphoma and three independent breast cancers including spindle cell carcinoma and apocrine carcinoma is very rare.

Journal Article↗
PubMed1998

Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers.

To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha), urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PA-R) and plasminogen activator inhibitor-1 (PAI-1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis-related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa (p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively (p < 0.05). On the other hand, u-PA-R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u-PA-R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u-PA-R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u-PA-R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels.

Adult↗
PubMed1998

A rare case of spontaneous esophageal rupture (Boerhaave's syndrome) associated with pulmonary rupture.

Spontaneous esophageal rupture (Boerhaave's Syndrome) is a life-threatening condition that requires early diagnosis and effective treatment. The authors describe a rare case of spontaneous rupture of the esophagus associated with pulmonary rupture in a 54-year-old man. The anatomical basis for the occurrence of a spontaneous esophageal rupture associated with pulmonary rupture is discussed.

Esophageal Diseases↗
PubMed1998

Novel MEN1 gene mutations in familial multiple endocrine neoplasia type 1.

The recent isolation of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1) has enabled direct genetic diagnosis for people with endocrine tumors and family members of affected patients. Although MEN 1 is rarely recognized in the Japanese population compared to its prevalence in Caucasians, we have previously reported a high prevalence of this disease in a limited area (Nagano Prefecture; population, 2.15 million). In this communication, we report mutations of the MEN1 gene in kindreds living in Nagano Prefecture. The absence of a common mutation among these kindreds indicates that the high prevalence of MEN 1 in this area is not due to a regional accumulation of patients descended from a common ancestor. This result implies that the prevalence of MEN 1 in other areas of Japan could also be higher than had been thought.

Frameshift Mutation↗