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Biomedical subjects

N Matsubara

Publications and source records attributed to N Matsubara.

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

Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene.

Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We constructed a recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the sensitivity to all six drugs regardless of the cellular p53 status, and a synergism was observed by the isobolic method in combination studies (D<1). We conclude that our strategy using adenoviral mediated p53 gene transfer to cancer cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an improvement of lung cancer chemotherapy.

Adenoviruses, Human↗
PubMed2000

Crohn's disease mimicking as bowel endometriosis. Are the symptoms reduced by nafarelin acetate?

We report a 27-year-old female with Crohn's disease clinically misdiagnosed with intestinal endometriosis. Her complaints were abdominal pain and fullness, which occurred monthly during her menstrual period. Although we had no histopathological evidence, we diagnosed her as bowel endometriosis on the basis of her clinical course. Since nafarelin acetate therapy started, the symptoms due to mechanical subileus have improved. The transverse colon, a 70 cm segment of the ileum, including the terminal ileum, were resected because of repeated symptoms of bowel obstruction despite prolonged nafarelin therapy. Histopathological findings of the resected specimen revealed Crohn's disease without endometrial tissue. In our patient, an increased cortisol and ACTH secretion, a side effect of nafarelin, was noted during the therapy. This case showed that nafarelin therapy could increase serum concentration of ACTH and cortisol, which was considered to suppress the pathology of Crohn's disease by its anti-inflammatory action. We emphasize that intestinal examination must be performed with Crohn's disease in mind, even if nafarelin acetate is effective.

Adrenocorticotropic Hormone↗
PubMed2000

Immunohistochemical studies of colorectal cancers that developed following pelvic irradiation.

Radiation therapy is believed to be a predisposing factor in the development of carcinoma. During the period from 1974 to 1997, we treated five colorectal cancers in four patients who had undergone pelvic irradiation for cervical cancer. Radiation-induced changes in the remaining bowel were recognized in all of these patients. Of the five tumors, two were histologically diagnosed as mucinous adenocarcinoma, demonstrating a higher distribution than usual: To clarify the characteristics of the tumors, we examined the frequency of mutation in K-ras and p53 genes, and the proliferating cell nuclear antigen (PCNA) proliferation activity. The K-ras and PCNA stains did not show any clear characteristics of radiation-induced colorectal cancers in comparison with ordinary colorectal cancers; however, it was of interest that strongly positive staining was observed in our mucinous adenocarcinomas, even though a low frequency of p53 gene mutation has been reported in ordinary mucinous adenocarcinomas.

Adenocarcinoma, Mucinous↗
PubMed2000

Multiple tumors and a novel E2F-4 mutation. A case report.

Defects in the DNA mismatch-repair are known to cause microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC) as well as sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at the trinucleotide coding region microsatellite (CAG)n in a subset of human sporadic CRC with MSI. We report a 65-year-old man with triple tumors in the abdomen, including colon cancer, stomach cancer, and lipoma of the retroperitoneum, with the analysis of E2F-4 mutation. We report the first case of colon cancer with a homozygous E2F-4 mutation along with a detailed analysis of other cancer related genes as well as a prognosis.

Adult↗
PubMed2000

[Genetic analysis for colorectal cancer: what can we learn from microsatellite research?].

Recent advances in molecular biology have unveiled the mechanisms of carcinogenesis, especially colorectal carcinogenesis. A large body of evidence supports the idea that accumulated genetic changes due to inherited as well as environmental factors underlie colorectal cancer development. Recently, several reports have suggested that aberrant methylation of the CpG island may also play an important role in colorectal carcinogenesis. This genetic information is not yet sufficient but some useful genetic information can be applied clinically. This paper presents the results of intensive study of microsatellite instability in colorectal cancers and some clinically applicable discoveries. Future problems are also discussed.

Colorectal Neoplasms↗
PubMed1999

Mapping of five subtype genes for muscarinic acetylcholine receptor to mouse chromosomes.

Muscarinic acetylcholine receptors in mammals consist of five subtypes (M1-M5) encoded by distinct genes. They are widely expressed throughout the body and play a variety of roles in the peripheral and central nervous systems. Although their pharmacological properties have been studied extensively in vitro, colocalization of the multiple subtypes in each tissue and lack of subtype-specific ligands have hampered characterization of the respective subtypes in vivo. We have mapped mouse genomic loci for all five genes (Chrm1-5) by restriction fragment length variant (RFLV) analyses in interspecific backcross mice. Chrm1, Chrm2, and Chrm3 were mapped to chromosome (Chr) 19, 6, and 13, respectively. Both Chrm4 and Chrm5 were mapped to Chr 2. Although a comparison of their map positions with other mutations in their vicinities suggested a possibility that the El2 (epilepsy 2) allele might be a mutation in Chrm5, sequencing analyses of the Chrm5 gene in the El2 mutant mice did not support such a hypothesis.

Animals↗
PubMed1999

[A case of adult neuronal ceroid lipofuscinosis type A].

A 20-year-old Japanese woman was diagnosed as suffering from adult type A neuronal ceroid lipofuscinosis (NCL) by rectal biopsy in the first year of manifestation. Her sister was in good health, and her parents were non-consanguineous. She had graduated from a public high school and then went to a typist school, when she developed action myoclonus and dystonia. On admission, she was of short stature and her clinical features included high arched palate, cataracta, and accentuated deep tendon reflexes. Her IQ was 50. Visual failure was not observed. Brain MRI showed no abnormalities. Together with myoclonus and the abnormalities in EEG which included poly spike and wave complex, progressive myoclonus epilepsy was considered as differential diagnoses. Ultrastructurally, lipopigments of granular matrix and curvilinear profile were found in Schwann cells in rectal biopsy. Adult NCL, known as Kufs' disease, is classified into two clinical types; progressive myoclonus epilepsy (type A) and dementia with motor disturbance (type B). Adult NCL is very rare in Japan, and this is the first report of adult NCL type A in Japan.

Adult↗
PubMed1998

Metabolic changes in hibernating myocardium after percutaneous transluminal coronary angioplasty and the relation between recovery in left ventricular function and free fatty acid metabolism.

To elucidate the changes in oxidative metabolism in hibernating myocardium after coronary revascularization, we performed myocardial single-photon emission computed tomography with a free fatty acid analog, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP), and thallium-201 before and 1 month after percutaneous transluminal coronary angioplasty (PTCA) in 11 patients with angina pectoris caused by single artery stenosis. All patients had improvement in wall motion after PTCA at the region with coronary stenosis; the wall motion abnormality score evaluated by left ventriculography decreased from 5.5+/-0.8 (mean +/- SE) to 2.1+/-0.9, p <0.01) after PTCA. The defect score of I-123 BMIPP images was significantly larger than that of thallium-201 images either before (14+/-1.3 vs 8.9+/-1.1, p <0.01) or 1 month after (7.4+/-1.5 vs 3.7+/-0.8, p <0.01) PTCA. The decrease in the defect score of both images was significant (p <0.01). Changes in the wall motion abnormality score showed a significant correlation with both the change in the defect score of thallium-201 images (r = 0.58, p < 0.01) and that of I-123 BMIPP images (r = 0.75, p <0.01). These results indicate that the metabolism of free fatty acid is impaired in hibernating myocardium, and that improvement in left ventricular function after successful PTCA is strongly associated with the recovery of oxidative metabolism.

Adult↗
PubMed1998

Local structure study of dilute Er in III-V semiconductors by fluorescence EXAFS.

For understanding the luminescence of Er atoms in III-V semiconductors, OMVPE-grown InP doped with Er has been investigated by fluorescence EXAFS (extended X-ray absorption fine structure) in order to study the local structure around Er atoms. The local structures around the Er atoms doped in InP, with doping as dilute as 3 x 10(12) Er atoms in a 1.5 mm x 1.0 mm spot, were successfully measured by fluorescence EXAFS. The EXAFS analysis revealed that the Er atoms doped in InP above 853 K (which showed low luminescence) formed the rock-salt-structure ErP, while the Er atoms doped in InP below 823 K (which showed high luminescence) substituted on the In site of InP. The dependence of the local structure on growth temperature was observed for the samples doped with 3 x 10(12) atoms and 1.2 x 10(13) atoms of Er.

Journal Article↗
PubMed1998

Close correlation between mutations of E2F4 and hMSH3 genes in colorectal cancers with microsatellite instability.

Defects in mismatch repair function can lead to the microsatellite instability (MI+; replication error) phenotype in certain human cancers. We previously reported that MI+ tumor-specific repeat number alteration at 13 consecutive trinucleotide (CAG) repeats within a coding exon of the E2F4 gene is a possible target of the defective repair pathway. Additional investigations revealed that E2F4 mutations are common (11 of 17 cases, 65%, mostly deletions) in a subset of human colorectal cancers with extensive MI+ phenotype, with respect to the proportion of loci affected and that most of these E2F4-mutated tumors (9 of 11, 82%) were accompanied by frameshift mutations in a polyadenine stretch within the seventh exon of the hMSH3 gene, a known mismatch repair gene that is responsible for repair of mismatch loops of two to four nucleotides. However, neither of these mutations was detected in 15 tumors with a lower incidence of MI+ loci. Similar repeat number alterations were less frequent in CAG repeats from other genes in all of the MI+ tumors we examined. These results indicate the presence of a novel cascade of mutational events that may be involved in acquisition of the malignant phenotype of human colorectal cancers with genetic instability.

Colorectal Neoplasms↗
PubMed1998

Simple synthesis of sialyllactose-carrying polystyrene and its binding with influenza virus.

Glycoconjugate polystyrenes bearing sialyllactose moieties were prepared via a simple method from a mixture of alpha2-6 and a2-3 linked sialyllactose isomers of bovine milk origin. The reducing end of sialyllactose was converted to an amino function with ammonium hydrogen carbonate and then coupled with p-vinylbenzoyl chloride. The resulting styrene derivative substituted with sialyllactose via an amide linkage was polymerized with ammonium peroxodisulfate and N,N,N',N-tetramethylethylenediamine in water at 30 degrees C. The interaction of the glycopolymer with influenza A and B viruses was investigated by three different methods. The glycopolymer inhibited the hemagglutination of influenza A virus (PR/8/34) and its activity was 10(3) times higher than that of the oligosaccharide itself. The cytopathic effect of virus-infected MDCK (Madine-Darby canine kidney) cells was inhibited by the glycopolymer. The homopolymer showed 10(2) times higher inhibitory activity than naturally-occurring fetuin. It was also found that various viruses could be trapped by the glycopolymer adsorbed on a polystyrene surface. The inhibitory and trapping activities of the glycopolymers were correlated with the sialyl linkage specificities of the virus strains.

Animals↗
PubMed1998

Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes.

Secretory leukoprotease inhibitor (SLPI) is a serine protease inhibitor involved in antineutrophil elastase protection at inflammatory sites. To elucidate both the function and regulation of SLPI in vivo, we isolated and characterized the mouse Slpi gene. An entire 3-kb mouse Slpi gene fragment was sequenced, including an 0. 8-kb 5'-flanking region, the 2.2-kb Slpi gene, and a 0.1-kb 3'-flanking region. The mouse Slpi gene spans 2,222 base pairs containing four exons and three introns. All splicing borders between exons and introns are conserved as predicted by GT-AG rules. Using primer extension analysis, the transcription start site was located 20 nucleotides upstream from the methionine (ATG) initiation codon. At the defined transcription start site, the sequence TCA+1GAGC is present. These results indicate that both mouse and human genomic structure are highly conserved. Using fluorescence in situ hybridization, we confirmed that, consistent with the genomic similarity, the human SLPI gene is localized on chromosome 20q12-13. 2 and the mouse homologue on chromosome 2H, which are syntenic with each other.

Animals↗
PubMed1998

Structures of novel acidic galactooligosaccharides synthesized by Bacillus circulans beta-galactosidase.

The structures of acidic oligosaccharides synthesized by a transglycosylation reaction by Bacillus circulans beta-galactosidase, using lactose as the galactosyl donor, and N-acetylneuraminic acid (NeuAc) and glucuronic acid (GlcUA) as the acceptors were investigated. Acidic oligosaccharides thus synthesized were purified by anion exchange chromatography and charcoal chromatography. The MS and NMR studies indicated that the acidic oligosaccharides from NeuAc were Gal beta-(1-->8)-NeuAc, Gal beta-(1-->9)-NeuAc, and Gal beta-(1-->3)-Gal beta-(1-->8)-NeuAc, and those from GlcUA were Gal beta-(1-->3)-GlcUA and Gal beta-(1-->4)-Gal beta-(1-->3)-GlcUA. These are novel acidic galactooligosaccharides.

Bacillus↗
PubMed1998

[A case of idiopathic intussusception of the stomach].

A 73-year-old man was admitted to our hospital because of vomiting. A fist-sized tumor with tenderness was palpated on his epigastric region. Fluoroscopic examination of the stomach showed narrow body and dilated antrum with intussusception. Endoscopic findings revealed fold convergence to the antrum. Intraoperatively, the body of the stomach was invaginated into the antrum with hepatoduodenal ligament. It was difficult to repair or resect, and a gastrojejunostomy was performed. On the 10th operative day, fluoroscopic examination of the stomach showed no intussusception of the stomach and no lesion in the upper gastrointestinal tract. To our knowledge, such cases of idiopathic intussusception of the stomach are rare.

Aged↗
PubMed1997

Extension injury of the thoracolumbar spine.

STUDY DESIGN: This is a report of a patient with a rare fracture in the thoracolumbar spine. OBJECTIVES: To illustrate the previously undescribed fracture in the thoracolumbar spine and to propose a new mechanism of this rare lesion with a literature review. SUMMARY OF BACKGROUND DATA: Extension injury of the thoracolumbar spine is uncommon. Although there have been several reports of hyperextension injuries in the thoracolumbar spine, the injury mechanism of the present case was different from those in the previously reported cases. METHODS: The clinical findings, roentgenographic appearance, treatment, and follow-up result were presented, and the mechanism of this lesion was analyzed. RESULTS: Physical examination revealed no neurologic deficit. Radiographs showed the oblique fracture line extended from the middle region of the L1-L2 disc to the posteroinferior edge of the L2 vertebral body, with the widening of bilateral L2-L3 facet joints. The patient was treated conservatively with a successful outcome. Two years after his injury, the patient had resumed his previous activity completely. CONCLUSIONS: The authors considered that the mechanism of this rare injury was a combination of hyperextension force and axial loading.

Adult↗
PubMed1997

Frequent mutation of the E2F-4 cell cycle gene in primary human gastrointestinal tumors.

The E2F group of transcription factors transactivates genes that promote progression through the G1-S transition of the cell cycle. Members of the retinoblastoma (Rb) family of proteins bind to E2Fs and inhibit this function. E2F-4, one example of the E2F group, functions as an oncogene when transfected into nontransformed cells in vitro. On the other hand, mice that are homozygously lacking a normal E2F-1 gene develop cancers, consistent with a tumor-suppressive role for this gene. The exact function of E2Fs has thus been unclear; moreover, direct involvement of this gene in primary human tumorigenesis has not been shown. We, therefore, investigated mutation within the E2F-4 coding region in 16 primary gastric adenocarcinomas, 12 ulcerative colitis-associated neoplasms, 46 sporadic colorectal carcinomas, 9 endometrial cancers, and 3 prostatic carcinomas. We limited our investigation to the serine repeat within E2F-4, reasoning that this tract might be altered in genetically unstable tumors (replication error-positive, or RER+). All tumors were RER+, with the exception of a control group of 15 RER- sporadic colorectal carcinomas. PCR with incorporation of [32P]dCTP was performed using primers flanking the serine trinucleotide (AGC) repeat. Twenty-two of 59 gastrointestinal tumors (37%) contained E2F-4 mutations; these comprised 5 of 16 gastric tumors (31%), 4 of 12 ulcerative colitis-associated neoplasms (33%, including 1 dysplastic lesion), and 13 of 31 sporadic colorectal cancers (42%). No mutation was present in any of the endometrial, prostate, or RER- colorectal tumors. Of note, homozygous mutations occurred in three cases, and two of seven informative patients showed loss of one E2F-4 allele in their tumors. Furthermore, the RER+ sporadic colorectal tumors were evaluated at trinucleotide repeats within the genes for N-cadherin and B-catenin; no tumors demonstrated mutation of these genes. These data suggest that E2F-4 is a target of defective DNA repair in these tumors.

Adenocarcinoma↗