Biomedical subjects
Publications and source records attributed to T Obara.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In vivo transcriptional activity of the Bombyx mori fibroin and sericin genes was estimated by nuclear run-on assay. Tissue-specific and developmental stage-specific expression of the fibroin and sericin genes through larval development was shown to be primarily regulated at the level of transcription. The expression patterns of these two genes are quite different in their developmental profile, suggesting that they are probably regulated by different underlying mechanisms. A finer spatial control of transcription could be found. The sericin gene transcription is mostly restricted to the posterior region of the middle silk gland throughout the fifth larval instar. Interestingly, the fibroin gene transcription is observed only in the anterior region of the posterior silk gland on the first day of the fifth instar, and spreads toward the posterior region as the fifth instar stage proceeds.
In a previous paper, we demonstrated that a gene coding for a protein homologous to the alpha subunit of mammalian guanine nucleotide-binding regulatory (G) proteins occurs in Saccharomyces cerevisiae. The gene, designated GPA1, encodes a protein (GP1 alpha) of 472 amino acids with a calculated Mr of 54,075. Here we report the isolation of another G-protein-homologous gene, GPA2, which encodes an amino acid sequence of 449 amino acid residues with a Mr of 50,516. The predicted primary structure of the GPA2-encoded protein (GP2 alpha) is homologous to mammalian G proteins [inhibitory and stimulatory G proteins (Gi and Gs, respectively), a G protein of unknown function (Go), and transducins (Gt)] as well as yeast GP1 alpha. When aligned with the alpha subunit of Gi (Gi alpha) to obtain maximal homology, GP2 alpha was found to contain a stretch of 83 additional amino acid residues near the NH2 terminus. The gene was mapped in chromosome V, close to the centromere. Haploid cells carrying a disrupted GPA2 gene are viable. Cells carrying a high copy number of plasmid GPA2 (YEpGPA2) had markedly elevated levels of cAMP and could suppress a temperature-sensitive mutation of RAS2. These results suggest that GPA2 may be involved in the regulation of cAMP levels in S. cerevisiae.
Explore the source record for details and available documents.
Normal human tracheobronchial epithelial cells (NHTBECs) from nine donors were used to repopulate de-epithelialized rat tracheas. After transplantation into nude mice and treatment with 7,12-dimethylbenz[a]anthracene (DMBA), the transplants were removed at 3, 4, 5 and 6 months. Epithelial cells from DMBA-treated tracheas were subculturable. Epithelial cells from most untreated tracheas were not subculturable. After treatment with 0.5, 1, 2, 4, 6 and 8% serum, cells exhibited increased subculturability after in vivo treatment with DMBA, did not terminally differentiate and were still proliferating even in medium containing 8% serum. Karyotypes from these cells showed considerable aneuploidy. Although these cells did not survive for more than 10 subcultures (42 weeks), this was considerably longer than the survival of control cells. Because of their longer survival, resistance to serum-induced terminal differentiation and chromosome alterations, they were considered to be phenotypically altered or partially transformed cells produced by in vivo treatment of human cells with a chemical carcinogen.
A case of primary plasmacytoma of the thyroid gland which occurred in a 63-year-old woman is reported. Histologic and ultramicroscopic examination revealed that the excised thyroid tumor was plasmacytoma superimposed on lymphocytic thyroiditis. Immunohistological study showed that the tumor cells produced intracytoplasmic immunoglobulin (IgG-kappa). Electrophoretic and immunoelectrophoretic studies disclosed the presence of monoclonal immunoglobulin (IgG-kappa) in samples of the patient's serum which had been obtained preoperatively. After completion of irradiation therapy to the neck following tumor removal, the serum monoclonal immunoglobulin disappeared. The patient is currently alive and well without any evidence of the tumor three years after surgery.
Three cases of pseudogout associated with primary hyperparathyroidism are reported. Preoperative radiological studies revealed association of pseudogout. Considering the frequent development of acute pseudogout attack following parathyroidectomy, prevention of a sudden decrease in the serum calcium concentration was attempted using calcium supplement therapy starting on the first postoperative day in all three cases. Serum calcium slowly decreased to the normal range, and the postoperative courses were uneventful. From these experiences, we advocate that calcium supplement therapy is worth trying for the prevention of acute pseudogout attack following parathyroidectomy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
An in situ hybridization technique was applied to detect expression of keratin mRNAs in xenotransplanted human tracheobronchial epithelium and lung carcinomas. Tissues from eight tracheas repopulated with cells from five different noncancerous donors and 15 squamous cell carcinomas were used. Using a K6 (56 kd) human keratin cDNA (KA-1) and a K14 (50 kd) cDNA (KB-2) as probes, radiolabeled by nick-translation with 3H-dATP/TTP, the specificity and significant differences in the levels of silver grains on various epithelial lesions in formalin-fixed, paraffin-embedded tissue sections were demonstrated. In situ hybridization with either KA-1 or KB-2 probe showed similar localization of silver grains in all histologic types in consecutive tissue sections. In xenotransplanted tracheobronchial epithelia, very few grains were seen over cells of simple, pseudostratified, or stratified epithelia two to three cell layers thick. Nonkeratinizing stratified hyperplastic epithelia of more than three cell layers showed uniform localization of numerous grains throughout the lesions. In contrast, epidermoid metaplasias exhibited a dense and localized pattern of grains on the basal and parabasal cell layers with a decrease in grain density toward the surface layers. Carcinoma cells from bronchogenic squamous cell carcinomas showed a higher density and more uniform localization of grains. Well-differentiated carcinoma cells contained more keratin mRNAs than moderately to poorly differentiated carcinoma cells. This evidence obtained with the KA-1 and KB-2 probes demonstrates the different localization patterns of keratin mRNAs in different epithelial lesions. In addition, the levels of mRNA expressed show a positive correlation with the degree of squamous differentiation. It was of particular interest that an ordered program of keratin mRNA expression proportional to the level of cellular differentiation was observed in epidermoid metaplasias. Both of these probes serve as keratinization markers of human tracheobronchial epithelial lesions.
We have experienced 10 cases of insulinoma during the last 10 years from 1977 to 1986. All cases had strong hypoglycemic symptoms such as disturbance of consciousness, and insulinoma still tended to be misdiagnosed as epilepsy. The diagnosis of insulinoma was easily available from serum IRI (immunoreactive insulin)/plasma glucose ratio in all of the ten cases. As preoperative procedures for the diagnosis of localization, arteriography, computed tomography and portal blood sampling were positive in 6 of 8, 4 of 6 and 2 of 2 patients, respectively. At operation, all insulinomas could be identified by digital palpation. We performed simple excision of the tumor in 6 patients and distal pancreatectomy in 4 patients. The tumors were solitary and benign in all patients, ranging in size from 1.0 cm to 4.5 cm. Three cases were presented as case reports. In these cases, portal blood sampling and/or intraoperative monitoring of plasma glucose and serum IRI were performed. Portal blood sampling was effective even for a case which was negative in image diagnostic procedures. Furthermore, simultaneous monitoring of plasma glucose and serum IRI by quick radioimmunoassay seemed to be a good guide to the completeness of resection of insulin producing tumors.
Although the benign counterpart of medullary carcinoma of the thyroid has never been indicated in textbooks, we propose that C cell adenoma is a rare but distinct clinical entity. Two patients, a 43-year-old man and a 53-year-old woman, had similar thyroid tumors, both about 4 cm in diameter. The cut surfaces of the resected tumors were indistinguishable from a common microfollicular adenoma of the thyroid. Microscopically, the tumors were uniformly composed of fusiform cells without any follicle formation. Neither amyloid deposition nor calcification was found. Although some kind of C cell tumors were suggested, the exact nature was debatable. However, extremely high levels of calcitonin (1330 and 2065 pg/ml, respectively; normal level, less than 170 pg/ml) were found in the stored sera taken preoperatively. Serum levels of carcinoembryonic antigen (CEA) were normal in both patients. Immunohistochemically, the tumor tissues were positive for calcitonin and neuron-specific enolase but negative for CEA with a monoclonal anti-CEA antibody. No somatostatin, glucagon, or adrenocorticotropic hormone activity was found. It is highly probable that such tumors have not been closely studied and have been regarded as eccentric adenomas of the thyroid or simply as the so-called medullary carcinomas of the thyroid.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The human lung tumor-derived cell lines A549, Calu-1, Calu-3, HuT292, and SW900 and the transformed human bronchial epithelial cell line TBE-1, that was transfected with the v-Harvey-ras oncogene, were inoculated into deepithelialized Fisher 344 rat tracheas (5 X 10(5) cells/trachea). After the ends of the tracheas were sealed, the tracheas were transplanted into s.c. tissues of nude mice. In a parallel experiment, 1 X 10(6) cells from each of these cell lines were injected s.c. Histological examination of the tracheal transplants 2, 4, 8, 12, and 16 weeks after cell inoculation proved to be of greater usefulness than either clinical or histological observation of the s.c. injection sites. A549, Calu-1, and TBE-1 produced intratracheal neoplastic nodules as early as 2 weeks after cell inoculation. Calu-3, HuT292, and SW900 grew relatively slowly in the tracheas, and simple or stratified epithelia with slight or moderate atypia (preneoplastic lesions) were seen at 2 weeks. After the 4th week, they produced tumor nodules in the tracheal transplants, whereas no tumor cells could be seen at the s.c. injection sites. The human derivation of the cells was confirmed by in situ hybridization using human-specific DNA probes. The intratracheal inoculation and xenotransplantation of human-derived cell lines offers a time-saving alternative to the s.c. inoculation assay for tumorigenicity and is at the same time a potentially valuable approach to studying preneoplastic and neoplastic progression with human cell subpopulations.
Parathyroid carcinoma is a rare tumor and its clinical course is variable. Differentiation of patients with parathyroid carcinoma from those with parathyroid adenoma is often difficult both preoperatively and at operation. For good results, the surgeon must recognize this disorder and perform an en bloc resection at the initial surgery. A neck dissection is necessary only when there is evidence of regional node metastases. After surgery, periodic follow-up of the serum calcium and iPTH levels is essential. When hypercalcemia recurs or the serum iPTH increases, localization studies with the use of thallium-201 scanning help detect local recurrence and regional lymph node metastases, but unfortunately, this method often fails to localize pulmonary metastases. Chest radiographs and CT scanning are useful for delineating pulmonary metastases. A wide excision of locally recurrent tumor, an en bloc radical neck dissection and mediastinum dissection for lymphatic metastases, and an aggressive surgical resection of lung metastases are recommended. Although these operations are rarely curative, they usually offer definite palliation of the marked hypercalcemia, often for a considerable period. Drugs to lower the serum calcium level and systemic chemotherapy are currently of only limited benefit, and radiation therapy is generally ineffective.
The utility of gamma-glutamyltranspeptidase (gamma-GTP) as an enzyme marker during pancreatic acinar cell carcinogenesis in rats was assessed by measuring its enzyme-histochemical performance in pancreatic acinar cell lesions induced by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) and/or azaserine in partially-pancreatectomized Fischer 344 and Wistar rats. Rats were given a single intravenous injection of 4-HAQO (10 or 7 mg/kg body weight) 3 days after partial pancreatectomy followed by intraperitoneal injections of azaserine (30 mg/kg) once a week for 10 weeks, or the same treatment without azaserine. The animals were sacrificed at 3, 6, 10, 12 and 18 months. 4-HAQO predominantly induced basophilic foci in Fischer rats, while in Wistar rats acidophilic foci and acidophilic hyperplastic nodules were predominant. A preferential enhancement of the induction of acidophilic foci and hyperplastic nodules was exhibited in Fischer rats following co-administration with azaserine. Normal acinar cells were positive for gamma-GTP. 90 to 100% of basophilic foci were either negative or slightly positive for gamma-GTP, whilst 68 to 98% of acidophilic foci were positive. The gamma-GTP activities of acidophilic hyperplastic nodules were more variable between nodules than within nodules, and either co-administration of azaserine or extension of experimental duration time appeared to increase the gamma-GTP positive nodules. Between the gamma-GTP positive and decreased nodules, no histological but some morphometrical differences were observed. As far as the nodules induced by 4-HAQO in Fischer rats were concerned, all of the gamma-GTP decreased nodules had thin fibrous capsules and exhibited ultrastructurally more atypia than the positive ones. Present study thus revealed that gamma-GTP is neither a useful nor invariable enzyme marker during pancreatic acinar cell carcinogenesis in rats.