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Biomedical subjects

M Takahama

Publications and source records attributed to M Takahama.

At least 55 records · Page 3Linked to original sources
PubMed1997

p53 mutation and absence of mdm2 amplification and Ki-ras mutation in 4-hydroxyamino quinoline 1-oxide induced transplantable osteosarcomas in rats.

Previously, we reported the establishment of two transplantable osteosarcomas, one induced by local application of a carcinogen, 4-hydroxyamino quinoline 1-oxide(4-HAQO), and another which developed spontaneously in rats, and their subdivision into four lines with high and low metastatic potential to the lung. In the present study, mutations of p53 and Ki-ras genes were investigated by PCR and SSCP followed by direct sequencing, and the amplification of the mdm2 gene was assessed by Southern blot analysis. Mutations of p53 in exon 7 were detected in 4-HAQO-induced transplantable osteosarcomas, but not their spontaneous counterparts, irrespective of the metastatic potentials. Direct sequencing revealed a CGC to CAC transition with an amino acid change of Arg to His, at codon 246. Neither Ki-ras mutations nor mdm2 amplification were detected in any of the transplantable tumors. The results suggest that while p53 mutations occurred during osteosarcoma development by 4-HAQO without mdm2 amplification and Ki-ras mutation does not contribute to osteosarcoma development in rats.

4-Hydroxyaminoquinoline-1-oxide↗
PubMed1997

Detection of c-Ki-ras oncogene mutation in gastric adenomas with formalin-fixed, paraffin-embedded biopsy materials.

Point mutations at codon 12 of the c-Ki-ras gene were investigated in 103 biopsy tissues from 38 patients with gastric adenoma. DNA from minute specimens of formalin-fixed paraffin-embedded tissue was amplified by nested polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) method was used to detect mutations of the c-Ki-ras gene. Mutations were detected in 4 of the 38 gastric adenomas (10.5%), but were not detected in intestinal metaplasias and gastric adenocarcinomas. Of the 4 mutation-positive gastric adenomas, the GGT sequence in codon 12 changed to GAT in 2 cases, to GTT in 1 case and to TGT in 1 case. We classified gastric adenomas into three degrees of atypia; mutations were detected only in biopsy tissues with moderate and severe atypia but were not detected in biopsy tissues with mild atypia. When different biopsy tissues from a mutation-positive gastric adenoma were examined, the mutation was not always detected in every tissue sample examined. This suggests that mutations are not homogeneously distributed, even in the same adenoma. It is possible to follow up the mutation of biopsy materials of gastric adenoma by this method.

Adenoma↗
PubMed1997

Thoracoscopic wedge resection of blebs under local anesthesia with sedation for treatment of a spontaneous pneumothorax.

We performed thoracoscopic wedge resections of blebs with a stapling device under local anesthesia with sedation in 34 consecutive patients who presented with spontaneous pneumothoraces. The indications for surgery included the absence of parietal pleural adhesions and knowledge of the precise bleb location prior to the procedure. Prior to surgery, 0.5% lidocaine was administered into the pleural space, and IV butorphanol tartrate and diazepam were administered to reduce pain and anxiety during the procedure. In our series, the thoracoscopic procedure resulted in favorable outcomes in all but two patients. There was no evidence of hemodynamic instability or arterial blood gas abnormalities encountered during the procedure. Minor postoperative complications were seen in only three patients (two with air leakage and one with transient atelectasis). One patient had a recurrence of his spontaneous pneumothorax 3 months following the procedure. Therefore, the overall success rate was 91%. We compared the results of this therapeutic modality (group 1) with those of 38 patients who underwent the procedure under general anesthesia (group 2) during the same period. The length of hospital stay was shorter in group 1 than in group 2 (4.5 +/- 1.3 vs 5.8 +/- 1.1 days; p < 0.01). Thoracoscopic wedge resections under local anesthesia are safe and offer the benefit of shorter hospital stays. We believe that this thoracoscopic technique will further simplify the surgical treatment of pneumothoraces without incremental risks.

Adolescent↗
PubMed1997

Immunohistochemical localization of integrins and basement membrane components in colorectal epithelial tumors correlates with their histologic architecture.

We studied the immunohistochemical localization of integrins (alpha2, alpha6) and basement membrane components (type IV collagen, laminin) in colorectal epithelial tumors (adenomas and adenocarcinomas) with respect to their intramucosal and invasive growth. The integrins showed two patterns of localization: basal polarization and diffuse expression. In intramucosal tumors, the basement membrane components were well preserved, and the staining intensity for the basal polarization of alpha6 increased with increasing size and grade of dysplasia of the tumors. In invasive adenocarcinomas, the basement membrane components were preserved, and the basal polarization of alpha6 was apparent in well-differentiated areas, while the tumor cells showed disorganization or loss of the basement membrane components and the diffuse expression of alpha6 with a reduction or loss of the basal polarization in moderately and poorly differentiated areas. The expression of alpha2 did not correlate with the grade of dysplasia of intramucosal tumors or the pattern of differentiation of invasive adenocarcinomas. These results suggest that the basal polarization of alpha6 and the preservation of the basement membrane components contribute to the glandular architecture of colorectal epithelial tumors, and that the diffuse expression of alpha6 with a reduction or loss of the basal polarization, and the disorganization and loss of the basement membrane components to the dispolarized affinity of tumor cells to the extracellular matrix.

Adenocarcinoma↗
PubMed1997

[Clipping of the thoracic duct with video-assisted thoracic surgery in the treatment of chylothorax after pulmonary resection].

We describe a procedure for video-assisted thoracoscopic clipping of the thoracic duct to treat postoperative chylothorax. This technique was successfully performed on a 62-year-old man who developed chylothorax following right lower lobectomy and partial resection of the 11th and 12th vertebral bodies for squamous cell lung cancer. Because conservative therapy for 7 days failed to reduce the amount of pleural effusion, we performed thoracoscopic examination of the thoracic duct and found a site leaking chylous fluid. The thoracic duct was successfully and easily clipped resulting in complete elimination of the effusion in 2 days. Generally, chylothorax complicating pulmonary resection has been managed by medical treatment first, followed by surgical intervention in case that fail to respond to initial therapy. The newly designed video-assisted thoracic surgery procedure reduces the trauma, shortens the drainage period and hospital stay, and provides better exposure of the thoracic duct. We believe that this procedure can be carried out shortly after the occurrence of chylothorax.

Chylothorax↗
PubMed1996

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats.

Mutations of Ki-ras and p53 genes in hepatocellular carcinomas (HCCs) induced by the choline deficient L-amino acid defined (CDAA) diet in rats were investigated by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis followed by direct sequencing. Male Fischer 344 rats, 6 weeks old, were continuously given a CDAA diet for 70 weeks and then sacrificed. Macroscopically detectable nodules which were histologically confirmed to be well-differentiated HCCs were dissected free from the surrounding tissue and subjected to gene mutation analysis along with samples of non-tumor areas. Conformational change in the Ki-ras gene was detected in 1 out of 7 HCCs, involving a GGC to GTC transversion at codon 13. No p53 mutations were detected in 7 HCCs and also neither Ki-ras nor p53 mutations were found in non-tumor areas. The results suggest that neither Ki-ras nor p53 genes play an important role in hepatocarcinogenesis caused by long term expose to a CDAA diet in rats.

Amino Acids↗
PubMed1996

Frequent mutations of Ki-ras but no mutations of Ha-ras and p53 in lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine in rats.

Point mutations of the Ki-ras and p53 genes in rat lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) were investigated by polymerase chain reaction-single strand conformation polymorphism analysis followed by direct sequencing using paraffin-embedded tissues. Male Wistar rats 6 wk old were given 2000 ppm BHP in drinking water for 15 wk. Another group was given drinking water without BHP. The rats were killed 20-27 wk after the beginning of the experiment. Lung adenomatous and squamous lesions, including carcinomas, were induced. The frequencies of Ki-ras mutations were 40% (six of 15) in alveolar hyperplasias, 36% (five of 14) in adenomas, 72% (18 of 25) in adenocarcinomas, 20% (three of 15) in squamous metaplasias, 50% (three of six) in squamous cell carcinomas, and 50% (five of 10) in adenosquamous carcinomas. The mutations were all G-->A transitions at the second position of codon 12; no other mutations were detected. However, Ha-ras mutations in exons 1 and 2 and p53 mutations in exons 5, 6, and 7 were not detected in adenocarcinomas and squamous cell carcinomas. These results indicate that Ki-ras mutation is an early genetic event in some adenomatous and squamous lung carcinogeneses and that Ki-ras mutations can cause benign lesions to convert to malignant lesions. The results also show that Ha-ras and p53 mutations are not involved in rat lung carcinogenesis induced by BHP.

Adenocarcinoma↗
PubMed1996

Increased telomerase activity in hyperplastic nodules and hepatocellular carcinomas induced by a choline-deficient L-amino acid-defined diet in rats.

Activation of telomerase has been reported in several human cancers, including hepatocellular carcinomas (HCCs). We investigated telomerase activity during hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet in rats. Male F344 rats were given a CDAA diet or a choline-supplemented L-amino acid-defined (CSAA) diet from 6 weeks of age for 75 weeks, and subgroups were killed 10 weeks, 50 weeks and 75 weeks after the beginning of the experiment. Hyperplastic nodules and HCCs were noted in rats fed a CDAA diet for 50 weeks and 75 weeks, respectively. Normal control liver specimens were obtained from 6-week-old rats. Telomerase activity was assessed by using a telomeric repeat amplification protocol (TRAP). Normal liver and background parenchyma of rats fed either of the diets for 10 weeks or 50 weeks showed weak telomerase activity. In contrast, markedly increased levels were demonstrated in hyperplastic nodules and HCCs. These results suggest that increased telomerase activity may be a biological feature of preneoplastic lesions that evolve to HCCs in rat liver.

Amino Acids↗
PubMed1996

[Retroperitoneal malignant mesothelioma. A case report].

A case of primary malignant mesothelioma grew from retroperitoneal space is reported. A 39-year-old man was admitted to our hospital with the right non-functioning kidney on April, 1993. He had felt the right lumbal dull pain and scrotal pain about 6 month ago, the pain became stronger gradually. He consulted the other clinic, and there, he was pointed out of the loss of function of his right Kidney by the IVP. Examination of cystoscopy, retrograde pyelography, percutaneous antegrade pyelography, CT scan and ultrasonography suggested retroperitoneal tumor with unknown origin. His right ureter was totally obstructed by this tumor, and the right kidney had lost the function. The right nephrectomy and partial ureterectomy were done but this tumor was hard to be resected because of its sever invasion to the surrounding muscles and bones. The pathology of this tumor resulted in a Malignant Mesothelioma. After the operation several chemotherapy was done but any effectiveness was not gained. The tumor made rapid progress and he died of multiple organ failure in 8 months after the first operation. Malignant Mesothelioma generally arises from serous membrane, so almost of this tumor are found in the peritoneum and pleura. But in this case, the tumor developed in the retroperitoneum. I have given this case a great deal of consideration and due to its unusual nature I make this report.

Adult↗
PubMed1996

[Spinal intramedullary cavernous angioma associated with hematomyelia: case report with sequential MRI follow-up and histological verification of hematoidin deposits].

A 61-year-old woman first experienced sudden lower back and right leg pain 3 years prior to surgery. At this time, MRI showed an intramedullary cavernous angioma at Th10-11 with central T2 high and peripheral T2 low signal intensity. However, she completely recovered in two weeks. Four days prior to the present admission (day of the second hemorrhage), she again experienced severe lower back and right leg pain, followed by complete paralysis of the right leg. Despite vigorous medical treatment including administration of steroid, hemostatics and glycerol, her condition became aggravated with complete paraplegia and loss of sphincter control by the 4th hospital day. MRI taken two days after the second hemorrhage showed an increase of peritumoral T2 hypointensity and another area of T2 hypointensity in the lumbar spinal cord at L1-Th12 with cord swelling. MRI 13 days after the second hemorrhage showed that these areas of T2 hypointensity had changed to T1 and T2 hyperintensity suggesting conversion of deoxyhemoglobin to methemoglobin. Subsequent MRI showed longitudinal punctuate propagation of methemoglobin from the angioma down to the lumbar enlargement and into the conus medullaris, where a 30 x 6 mm spindle-shaped area of T1 and T2 hyperintensity indicating hematomyelia had formed. Total removal of the angioma was followed by gradual recovery and decrease in the size and signal intensity of the hematomyelia. Histopathological examination demonstrated the typical features of cavernous angioma with deposition of hematoidin. Propagation of extravasated blood from the ruptured thoracic cavernoma to the conus medullaris, with splitting of spinal cord nerve fibers, was demonstrated by MRI.

Bilirubin↗
PubMed1995

[Surgical repair of bilateral atrioventricular valves in corrected transposition of the great arteries].

The patient was a 50-year-old man who had an SLL-type corrected transposition of the great arteries (C-TGA) accompanied by significant regurgitation of the bilateral atrioventricular valves, atrial septal defect (ASD), persistent left superior vena cava, atrial fibrillation, and ventricular extrasystoles. The systemic tricuspid valve was repaired with a 28 mm Carpentier-Edwards ring (C-E ring) for the mitral valve, while the systemic mitral valve was repaired with a 32 mm C-E ring for the tricuspid valve. Simultaneously, the associated ASD was closed. Although mild tricuspid valve regurgitation persisted postoperatively, his general condition greatly improved. The report of valve repair for both atrioventricular valves in C-TGA is rare, and only 6 such cases have been reported in the Japanese literature.

Heart Valve Prosthesis↗
PubMed1994

Detection of c-Ki-ras gene mutation in paraffin sections of adenocarcinoma and atypical bronchioloalveolar cell hyperplasia of human lung.

DNA of minute specimens taken from formalin-fixed and paraffin-embedded tissue was used as a template for the polymerase chain reaction (PCR) to examine whether the c-Ki-ras gene is activated in atypical bronchioloalveolar cell hyperplasia (ABH) of human lung. The c-Ki-ras gene was successfully amplified on 131 samples from 29 cases of lung adenocarcinoma (87.3% of all samples used as templates) by the nested PCR method. Point mutations at codon 12 of the c-Ki-ras gene could be detected in carcinoma tissue of 6 cases (20.7% of all cases), also detected in ABHs showing moderate to severe atypia of 2 cases. PCR amplification is a useful technique for studying pin-point pathological lesions in a routine paraffin section at the molecular level.

Adenocarcinoma↗
PubMed1994

[A case of liposarcoma originating from the chest wall].

A 76-year-old woman with a growing tumor of the anterior chest wall was admitted to our hospital. This patient was diagnosed as having the malignant pleomorphic tumor using the needle biopsy and operated on. The operative procedure included wide resection of the tumor, associated excision of the major and minor pectoris muscle. The tumor size measured 10.5 x 5.8 x 5.5 cm and weighed 580 g. Histopathologically the tumor was confirmed to be poorly differentiated liposarcoma. While there was no invasion to the surrounding tissue, the local recurrence and metastasis wasn't confirmed for the past 7 months after the surgery. The major anatomic distribution of liposarcomas were retroperitoneum and lower extremities, and liposarcomas originating from the chest wall having been reported are only 7 cases of in Japan.

Aged↗
PubMed1993

Osteosarcoma of the patella. A case report.

A 34-year-old woman complained of pain and swelling in the left patella. Because of roentgenogram showed hardly any destruction of the patella, she was not initially treated for a bone tumor. The clinical course followed the initial symptoms of a respiratory disorder with pulmonary metastatic foci. A bone tumor was first suspected after aspiration cytology of a lung tumor mass. A left patellectomy was performed to relieve the pain and confirm the diagnosis. The pain was relieved by the operation, but respiratory failure set in and progressed rapidly. The patient died three days later. Histologic examination showed that the tumor tissue consisted of atypical cells, spindle to polygonal in shape. The marrow space of the patella was predominantly occupied by neoplastic cartilaginous tissue. The pathologic diagnosis was primary chondroblastic osteosarcoma of the patella.

Adult↗
PubMed1992

Catabolism of hemoglobin-haptoglobin complex in microsome subfractions.

After internalization of hemoglobin-haptoglobin complex (Hb-Hp) via receptor-mediated endocytosis (RME) into liver parenchymal cells, organelles containing the complex distribute in the microsome fraction (Ms). Prior to the catabolism, Hb-Hp dissociates symmetrically into two 82,000-dalton (82 kDa) subunits. In the present investigation, the first event of Hb-Hp metabolism in Ms were further examined after [3H-heme, 14C-glogin]Hb-Ho or [125I-Hb]Hp injection to rats. Shortly after the internalization of Hb-Hp, this complex in Ms was intact. At 60 min after injection, radioactive materials of Ms extracted by freezing and thawing (F&T) with yield of 15% were composed of Hb-Hp, 82 kilodaltons (kDa) subunits and Hb metabolites with a ratio of 1:6:13. The heme metabolites were identified as [3H]bilirubin by high performance liquid chromatography (HPLC). The ratio of Hb-Hp/82 kDa subunits/Hb metabolites in microsome residue of the F&T was 40:8:1. The radioactivity in Ms at 60 min localized microsomes subfraction except Golgi light fraction. In electron microscope radioautography of microsome subfraction using [125I]Hb-Hp, silver grains were observed over or within morphologically heterogenous vesicles, e.g. vesicles containing very low density lipoprotein (VLDL) particles with appendage like multi-vesicular body (MVB) or compartment of uncoupling of receptor and ligand (CURL) in Goligi light and intermediate fractions. These studies suggest that Hb-Hp internalized by RME is dissociated symmetrically into two 82 kDa subunits in organelles of Ms, and that organelles with MVB or CURL-like structures are associated with Hb-Hp metabolism.

Animals↗
PubMed1992

Papillary cystoadenocarcinoma of the prostate.

We report a papillary cystadenocarcinoma of the prostate found in a 66-year-old man presenting with gross hematuria. The tumor was identified as prostatic in origin because of positive immunohistochemical staining of prostate specific antigen.

Aged↗
PubMed1991

Metal concentrations in lung tissue of subjects suffering from lung cancer.

Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗