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Biomedical subjects

M Tokunaga

Publications and source records attributed to M Tokunaga.

At least 127 records · Page 7Linked to original sources

Malignant eccrine spiradenoma with smooth muscle cell differentiation: histological and immunohistochemical study.

Malignant transformation in a benign eccrine spiradenoma is rare. Since it was first reported in 1972, 31 cases have been reported. Of these, six cases had sarcomatous components, mainly osteosarcomatous, and one had rhabdomyoblastic differentiation. A case is presented in which there were some small nodules of benign eccrine spiradenomas adjacent to a large nodule of malignant eccrine spiradenoma with leiomyosarcomatous components, determined by histologic and immunohistochemical studies.

Adenoma, Sweat Gland↗

A case of Kabuki make-up syndrome with EBV+Burkitt's lymphoma.

Kabuki make-up syndrome was first reported in 1981 and is characterized by peculiar facies with post natal growth deficiency and mental retardation. Since the first report, approximately 100 cases have been reported, but there have been no reports of tumor development. A case is reported of a patient with Kabuki make-up syndrome who developed malignant lymphoma in his abdomen at the age of 3 years. The tumor was histologically diagnosed as Burkitt's lymphoma and Epstein-Barr virus was detected by in situ hybridization.

Abdominal Neoplasms↗

Oculopharyngeal muscular dystrophy in two unrelated Japanese families.

The occurrence of oculopharyngeal muscular dystrophy (OPMD) in Orientals is uncertain. We identified two unrelated Japanese families, including 30 affected individuals (14 men, 16 women, mean age 58 years) of OPMD through four generations, with complete penetrance. Their major clinical manifestations were late-onset bilateral ptosis and dysphagia. Histologic studies of slightly affected muscles reveal mild myogenic changes, occasional rimmed vacuoles, and small angulated fibers. By contrast, the severely involved cricopharyngeal muscle showed marked loss of fibers and massive proliferation of connective tissue. Ultrastructural studies of four different biopsied muscles disclosed subsarcolemmal intranuclear tubulofilamentous inclusions, identical to those of non-Japanese OPMD patients.

Aged↗

Isolation and genetic characterization of pGKL killer-insensitive mutants (iki) from Saccharomyces cerevisiae.

The linear double stranded DNA plasmid pGKL1 encodes the yeast killer toxin complex (Gunge et al., 1981) of which the killing mechanism is not understood. We isolated and characterized eight mutants in Saccharomyces cerevisiae that were insensitive to both the intracellularly expressed 28-kDa killer subunit and the native killer toxin complex. These mutations (iki1 through iki5) were all recessive, and classified into five complementation groups. The iki2 mutation was mapped to a position near the centromere on chromosome XIII. We developed a novel screening system to isolate the DNA fragments complementing the iki mutations from a Saccharomyces gene library, and isolated three DNA fragments that complement the iki1, iki3, and iki4 mutations, respectively.

Cloning, Molecular↗

Distribution of dystrophin and dystrophin-associated protein 43DAG (beta-dystroglycan) in the central nervous system of normal controls and patients with Duchenne muscular dystrophy.

In skeletal muscles of patients with Duchenne muscular dystrophy (DMD), the absence of dystrophin was thought to lead to the large reduction in all of the dystrophin-associated proteins (DAPs). Of the seven types of DAPs identified in skeletal muscle, only the 43-kDa glycoprotein (beta-dystroglycan) has recently been found in the monkey brain. To clarify the distribution and characterization of dystrophin and beta-dystroglycan in the brain of humans, we carried out immunostaining and immunoblotting studies on tissues from three DMD patients with intellectual disturbances (ages 17,22, and 26 years) and in five controls (age range, 42-74 years). An antidystrophin antibody revealed dystrophin to be localized in neuronal cells and in the vascular wall in control brains, but it was absent from these tissues in DMD patients. In contrast, beta-dystroglycan was distributed throughout neuronal cells and in the vascular wall of control brains, and was well preserved in the brain of patients with DMD.

Adolescent↗

Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk.

A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR1Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR1Sv = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR1Sv = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR1Sv = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR1Sv = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study.

Dose-Response Relationship, Radiation↗

Independent thallium-201 accumulation and fluorine-18-fluorodeoxyglucose metabolism in glioma.

UNLABELLED: SPECT with 201TI is an effective procedure for evaluating the malignancy of glioma. Our goal was to investigate the diagnostic relevance of both 201TI SPECT and [18F]fluorodeoxyglucose (FDG) PET and the relation between 201TI uptake and glucose metabolism in glioma using comparative SPECT and PET studies. METHODS: Thallium-201 SPECT and FDG dynamic PET studies were performed in 20 patients with untreated glioma (5 with glioblastoma, 5 with anaplastic glioma, 10 with low-grade glioma). Thallium-201 uptake in the tumor was estimated using the 201TI index, defined as the ratio of 201TI uptake in the tumor to that in the contralateral normal brain on SPECT images obtained 15 min after intravenous injection. We measured regional glucose metabolic parameters, including rate constants and regional cerebral metabolic rate of glucose utilization (rCMRgl), in the tumor. We then compared the regional 201TI index and glucose metabolic parameters with the histologic characteristics, malignancy and computed tomographic/ magnetic resonance imaging findings. In addition, we investigated the correlation between the 201TI index and glucose metabolic parameters. RESULTS: Thallium-201 SPECT showed abnormal 201TI uptake in all patients with glioblastoma and anaplastic glioma. Thallium-201 indices of glioblastoma (202.6 +/- 22.1%) and anaplastic glioma (176.6% +/- 26.6%) were significantly higher than that for low-grade glioma (106.7% +/- 13.8%). The rCMRgl value of glioblastoma (17.6 +/- 3.5 mumole/100 g/min) was also significantly higher than that for low-grade glioma (10.8 +/- 4.5 mumole/100 g/min), although rCMRgl showed a large variability in both high- and low-grade glioma. Rate constants of FDG kinetics had no correlation with histological grade of glioma. Some patients with high-grade glioma, however, showed false-negative results with FDG-PET because of high normal brain uptake of FDG. Conversely, most low-grade glioma could not be localized by 201TI SPECT. There was no correlation between the 201TI index and glucose metabolic parameters. CONCLUSION: Thallium-201 indices and rCMRgl values for glioblastoma were higher than those for low-grade glioma. Thallium-201 uptake in the tumor may be independent of increased glucose transport or metabolism. Thallium-201 SPECT and FDG-PET are complementary in the diagnosis of glioma, although 201TI SPECT is more significantly correlated with the malignancy of glioma.

Brain Neoplasms↗

[Preoperative management of the aged patients with cancer of the esophagus].

The peak incidence of esophageal cancer is in the sixth decade, but the number of resections in patients older than 70 is increasing. 184 patients who underwent esophageal resections (C > or = 1) were divided into five groups according to age; Group A: under 50, B: 50s, C: 60s, D: 70s E: over 80. Five-year survival for Group D (20.5%) was much lower than other groups. Group E had better 1- and 2-year survival than Group D. Preoperative condition, stage and postoperative course were investigated in 145 patients who underwent subtotal esophagectomy with two-field lymphadenectomy and reconstruction with the stomach. In Group D, more respiratory dysfunction and abnormality of electrocardiogram were seen than Group C (p < 0.05) preoperatively. There was no difference in stage. Group D had higher incidence of postoperative pneumonia, abnormal ECG (p < 0.01) and delirium (p < 0.05). Group D had less cancer deaths and more deaths from other diseases. These results indicate that patients older than 70 should be called aged and it is safe to reduce the lymph node dissection in the upper mediastinum for these patients.

Age Factors↗

[Intra-arterial infusion chemotherapy for liver metastases from breast cancer].

Twelve patients with liver metastases of breast cancer were treated with hepatic arterial infusion chemotherapy using 20-30 mg/body of epi-adriamycin (epi-ADM) every 2 weeks and continuous infusion of 250 mg/body/day of 5-fluorouracil (5-FU). All patients were followed by systemic chemo-endocrine therapy with oral administration of 600-1,200 mg/day of me droxyprogesterone acetate (MPA) alone or with 600-800 mg/day of 5'-deoxy-5-flurouridine (5'-DFUR). The response rate was 41.7% (5/12 cases). Duration of response was 2-28 months (mean 10 months). At one year, the survival rate was 46.8% (Kaplan-Meier method). As for side effects, gastrointestinal disturbance, bone marrow depression and alopecia were mild. These results suggest that hepatic arterial infusion therapy in combination with MPA is safe and effective for controlling liver metastases of breast cancer.

Adult↗

Three histologically different tiny gastric cancers developing adjacent to each other, resected endoscopically in a single mucosal piece.

In this report, we describe a case with triple tiny cancers of the stomach developing adjacent to each other and resected endoscopically in a single mucosal piece. The three cancers differed from each other histologically. The surrounding mucosa was atrophic pyloric gland mucosa with moderate to severe intestinal metaplasia. Both histological and serological examinations were negative for Helicobacter pylori. Each of the three cancer lesions was positive for mutant p53 product immunohistochemically. None of the cancers were positive for Epstein-Barr virus sequence in an in situ hybridization analysis. These lesions suggest that certain local conditions in the gastric mucosa can result in carcinogenesis of different histological types of gastric cancers.

Adenocarcinoma↗

[A case of so-called carcinosarcoma of the lung].

A 69-year-old male was followed at our institute for the purpose of hemo-dialization. During follow-up, a tumor shadow (phi 6.5 x 7.0 cm) was found in rt. S5 by chest X-ray. This tumor was diagnosed as squamous cell carcinoma by TBLB. Right middle lobectomy (R 2 a) was performed. Histological staging was pT 2 N 2 M 0, stage IIIa. This tumor was cystic, filled with keratin like substance. Histologically, the cyst wall was composed of well differentiated squamous cell carcinoma and sarcomatous stroma which didn't differentiate into bone, cartilage, muscle, and etc. Immunohistologically, sarcomatous stroma was positively stained by vimentin, negatively by keratin and EMA. This patient survived 7 months with recurrence.

Aged↗

Imaging of single fluorescent molecules and individual ATP turnovers by single myosin molecules in aqueous solution.

Visualization of single actin filaments by fluorescence microscopy led to the development of new in vitro assays for analysing actomyosin-based motility at the molecular level. The ability to manipulate actin filaments with a microneedle or an optical trap combined with position-sensitive detectors has enabled direct measurements of nanometre displacements and piconewton forces exerted by individual myosin molecules. To elucidate how myosin generates movement, it is necessary to understand how ATP hydrolysis is coupled to mechanical work at the level of the single molecule. But the most sensitive microscopic ATPase assay available still requires over 1,000 myosins. To enhance the sensitivity of such assays, we have refined epifluorescence and total internal reflection microscopies to visualize single fluorescent dye molecules. We report here that this approach can be used directly to image single fluorescently labelled myosin molecules and detect individual ATP turnover reactions. In contrast to previously reported single fluorescent molecule imaging methods, which used specimens immobilized on an air-dried surface, our method allows video-rate imaging of single molecules in aqueous solution, and hence can be applied to the study of many types of enzymes and biomolecules.

Adenosine Triphosphate↗

Mitochondrial DNA mutation and muscle pathology in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.

We sought a relationship between abnormalities of mitochondrial DNA (mtDNA) and muscle pathology in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS) at the single fiber level, using histochemistry, in situ hybridization, and single fiber PCR. Most type 1 ragged-red fibers (RRF) showed positive cytochrome c oxidase (COX) activity at the subsarcolemmal region, while type 2 RRF showed little COX activity. However, there was no difference in the amount of total (mutant and wild-type) mtDNAs and the proportion of mutant mtDNA between type 1 RRF and type 2 RRF. These observations suggest that mitochondrial proliferation and nuclear factors affect muscle pathology, including COX activity, in MELAS. Total mtDNAs were greatly increased in RRF. The proportion of mutant mtDNA was significantly higher in RRF than in non-RRF. The amount of both wild-type and mutant mtDNAs was increased in RRF in MELAS, which fact does not support the contention of a replicative advantage of mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the strongly succinate dehydrogenase-reactive blood vessels (SSV) than in non-SSV. The similar morphological behavior in these vessels and fibers suggests that increased mutant mtDNA is responsible for mitochondrial proliferation and dysfunction in both tissues. It seems likely that systemic vascular abnormalities involving cerebral vessels lead to the evolution of strokelike episodes in MELAS.

Arteries↗

Polymerase chain reaction fiber analysis and somatic mosaicism in autopsied tissue from a man with Duchenne muscular dystrophy.

Single muscle fibers, obtained at autopsy from a 22-year-old man with Duchenne muscular dystrophy were examined immunocytochemically and also using polymerase chain reaction (PCR). Dystrophin-positive cells were widespread in skeletal, cardiac, smooth muscle, and in brain cells. PCR and Southern blot analyses of DNA from peripheral blood lymphocytes revealed a deletion of exon 45 in the dystrophin gene. With PCR of single fibers, three bands corresponding to exons 44, 45, and 47 were present in the normal control muscle fibers and dystrophin-positive fibers from the patient, while only two bands, exons 44 and 47, were observed in dystrophin-negative fibers. Therefore, in this patient, the genotype of dystrophin-positive fibers differed from that of the dystrophin-negative fibers, possibly because of a somatic mosaicism for deletion in the dystrophin gene. A mutation of the dystrophin gene may have occurred in one cell at an early stage of ontogenesis.

Adult↗

Surgically resected adrenal leiomyoma: report of a case.

This report describes the case of a 48-year-old woman found to have a leiomyoma of the left adrenal gland after presenting with anemia and hypertension. An upper gastrointestinal series revealed a mass in the posterior region of the body that distorted the stomach. A computed tomography (CT) scan showed a well-circumscribed mass with a high-density outline in the left adrenal gland, and magnetic resonance imaging (MRI) revealed a homogeneous mass. Multiple catheter samplings of vena cava blood revealed a slight elevation of epinephrine and norepinephrine in the left adrenal vein and the left renal vein. Thus, asymptomatic pheochromocytoma of the left adrenal gland was highly suspected as a preoperative diagnosis and a left adrenalectomy was performed. However, histologic examination subsequently revealed findings suggestive of leiomyoma of the adrenal gland, which was confirmed by electron microscopy. The patient's postoperative course was uneventful and she has remained free from any further symptoms.

Adrenal Gland Neoplasms↗

DNA aneuploidy in a case of rectosigmoid adenocarcinoma complicated by ulcerative colitis.

A case of Borrmann type IV colorectal adenocarcinoma detected as a complication of long-standing ulcerative colitis is reported. Barium enema and colonoscopy disclosed a stenotic area associated with a tumoral mass and a flat elevated lesion in the rectosigmoid region and a submucosal tumor-like lesion in the rectum. Total colectomy was performed and histological studies demonstrated a moderately differentiated adenocarcinoma accompanied by high- and low-grade dysplasia. DNA ploidy pattern analysis showed aneuploidy in the adenocarcinoma and high-grade dysplasia, but diploidy in the normal and atrophic mucosa and in low-grade dysplasia. DNA aneuploid content was associated with the presence of colorectal carcinoma complicating ulcerative colitis, indicating that DNA content studies should be included in screening programs to detect early colorectal carcinoma following this disease, as a complementary study to histological assessment.

Adenocarcinoma↗