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Biomedical subjects

T Sano

Publications and source records attributed to T Sano.

At least 361 records · Page 20Linked to original sources
PubMed1996

Molecular analysis of females manifesting thyroxine-binding globulin (TBG) deficiency: selective X-chromosome inactivation responsible for the difference between phenotype and genotype in TBG-deficient females.

T4-binding globulin (TBG) is the major transport protein of thyroid hormone in man. Inherited TBG abnormalities were manifested fully in hemizygous males and partially in heterozygous females and transmitted in an X-chromosome-linked fashion, compatible with its location on Xq21-22. We have previously reported that complete deficiency (CD) and partial deficiency (PD) in Japanese subjects resulted from two distinct mutations of the TBG gene, TBG-CDJ and TBG-PDJ, respectively. Recently, we encountered a female manifesting TBG-CD and herein investigated the molecular mechanisms. She was found to possess TBG-CDJ and common-type TBG (TBG-C) alleles by characterizing the TBG gene. Then, X-chromosome inactivation status was evaluated in her family members using a phosphoglycerate kinase (PGK) gene, located on Xq13. Three TBG-CDJ heterozygotes and one unaffected female, confirmed to be PGK heterozygotes for a polymorphic BstXI site, were analyzed. Only the CD female was shown to undergo selective inactivation by examining the BstXI site in amplified products after digestion with a methylation-sensitive enzyme, HpaII. Among an additional eight informative females with TBG deficiency, one heterozygous female for TBG-PDJ shared this selective inactivation pattern. Moreover, the X-chromosome with TBG-C was suggested to be inactivated selectively from the linkage of PGK and TBG alleles recognized in eight of nine family members. Selective X-chromosome inactivation was considered to be the cause of a female heterozygous for TBG-CDJ or -PDJ manifesting the same phenotype as a hemizygote.

Base Sequence↗
PubMed1996

Immunohistochemical localization of activin A and follistatin in human tissues.

We immunohistochemically investigated the localization of activin A and follistatin in various human tissues with specific antibodies to recombinant human (rh-) activin A and rh-follistatin. Specific immunostaining of activin A was detected in Leydig and Sertoli cells of the testis. In the ovary, granulosa cells of mature follicle and luteal cells of the corpus luteum stained for activin A. Immunoreactive activin A was present in somatotrophs of the pituitary gland and insulin-positive B cells of the pancreatic islets. Immunoreactivity for activin A was also found in thyroid follicular cells, adrenocortical cells, neuronal cells of the cerebrum and monocytoid cells in the bone marrow. Follistatin, an activin-binding protein, was immunostained in the same tissues as activin A. These findings indicated that activin A and follistatin are widely distributed in human tissues, suggesting that activin plays important roles as a common regulator in various tissues under the control of co-existing follistatin.

Activins↗
PubMed1996

Obvious mRNA and protein expression but absence of mutations of the RET proto-oncogene in parathyroid tumors.

The study on the expression of the RET proto-oncogene in parathyroid tumors disclosed obvious mRNA expression by the reverse transcription (RT)-polymerase chain reaction (PCR) method and protein expression by Western blotting. To find out whether mutations in the cysteine-rich regions or tyrosine kinase domain of the RET proto-oncogene are etiological for parathyroid tumorigenesis, sporadic parathyroid adenomas and carcinomas, parathyroid tumors from multiple endocrine neoplasia 1, familial isolated hyperparathyroidism or hereditary hyperparathyroidism-jaw tumor syndrome were screened by PCR-single strand conformation polymorphism and PCR restriction fragment length polymorphism. Missense mutations in the cysteine-rich region, or codons 768 or 918 in the tyrosine kinase domain of the RET proto-oncogene, were not detected in any of the examined cases of parathyroid tumors. These results suggest that mutations of the RET proto-oncogene do not represent a frequent mechanism of tumorigenesis for parathyroid tumors.

Adult↗
PubMed1996

Double pituitary adenoma--two case reports.

A 43-year-old male and a 39-year-old male presented with multiple pituitary adenomas with two distinct histological types. The first patient who had multiple endocrine neoplasia type 1 had developed acromegaly due to a growth hormone-releasing hormone (GHRH)-producing pancreatic tumor. Both plasma GHRH and growth hormone (GH) levels decreased to normal after resection of the pancreatic tumor. However, the plasma GH level gradually increased again and magnetic resonance imaging revealed pituitary adenoma formation. Histological examination revealed two different histological types of pituitary adenoma: GH cell adenoma and null cell adenoma. The second patient, with no such genetic condition, had a non-functioning pituitary adenoma. Histological examination revealed two different histological types of silent GH cell adenoma and silent gonadotroph adenoma. Careful histological examination is required to exclude the possibility of multiple pituitary adenomas.

Adenoma↗
PubMed1996

Poor capacity for proliferation of pancreatic beta-cells in Otsuka-Long-Evans-Tokushima Fatty rat: a model of spontaneous NIDDM.

Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the beta-cell proliferation per se is the primary pathogenetic event in OLETF rat. To determine whether it is, we used partially pancreatectomized rats as a model, with administration of phlorizin to control blood glucose level, to examine whether the capacity for proliferation of beta-cells during hyperglycemia or normoglycemia differs between OLETF and their diabetes-resistant counterparts, Long-Evans-Tokushima-Otsuka (LETO) rats. We also examined whether such a defect, if present, could be improved by nicotinamide. Male rats, 6 weeks of age, were allocated at random to two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into four subgroups by date of killing after surgery: 3-day, 7-day, 28-day (treated with phlorizin, nicotinamide, or saline), and 91-day. A sustained hyperglycemia was evident in the Px OLETF rats after surgery, which was associated with insufficient proliferation of beta-cells, characterized by decrease in beta-cell labeling index in proportion to decrease in beta-cell mass and reduction in insulin content in the remnant pancreas. This defect was unaffected by restoration of normoglycemia induced by phlorizin injection. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing beta-cell proliferation. These findings suggest that OLETF rats have poor capacity for proliferation of pancreatic beta-cells and that this change may be the critical pathogenetic event before the onset of overt diabetes.

Animals↗
PubMed1996

Comparative properties of a technetium-99m-labeled single-stranded natural DNA and a phosphorothioate derivative in vitro and in mice.

Oligonucleotides, particularly single stranded, may ultimately be of considerable use as radiopharmaceuticals. We have compared a synthetic 22-base single-stranded phosphodiester DNA with its phosphorothioate analog after both were radiolabeled with 99mTc via the hydrazino nicotinamide chelator. Whole body clearance of the label in mice was much slower when introduced on the phosphorothioate (30% vs. 75% clearance at 6 hr) because of immediate and persistent accumulation in liver (47% vs. 2% injected dose/g at 4 hr). The label in both cases was present in urine primarily on low molecular weight catabolites. High-performance liquid chromatography analysis of 37 degrees C serum incubates showed serum protein binding of 99mTc in both cases (about 100% bound at 24 hr) but to different proteins. Different behavior with respect to protein binding was also observed in the analysis of liver and kidney homogenates: the phosphodiester label was almost quantitatively converted to lower molecular weight catabolites after only 15 min, whereas the phosphorothioate label was primarily on proteins. The rapid digestion of the phosphodiester by nucleases was not observed, probably because protein binding of the labeled oligonucleotides stabilized against degradation. Thus the phosphodiester DNA may be the preferred 99mTc-labeled oligonucleotide in certain circumstances to avoid the high and persistent liver uptake observed with the phosphorothioate DNA.

Animals↗
PubMed1996

Surgical treatment for gastric cancer: the Japanese approach.

Present status of gastric cancer surgery in Japan and several new procedures are reviewed in this article. Japanese treatment results of this disease were significantly better than Western results even when stages were adjusted. Generally speaking, Japanese surgical procedures are more aggressive and meticulous compared with the Western approach, and these attitudes have produced the difference in survival. Particularly, systematic lymph node (LN) dissection is included as a standard procedure, and the adjacent organs are frequently resected when tumor invades them. The latest topics in surgery are the transdiaphragmatic approach for procedures in the mediastinum, para-aortic LN dissection, computer-assisted rational lymphadenectomy, LN imaging for complete dissection, removal of the peritoneum, and hyperthermo-chemotherapy for peritoneal carcinomatosis. Consideration of postoperative quality of life (QOL) is a new trend, and many interesting procedures have been proposed to maintain QOL, such as endoscopic mucosal resection and laparoscopic wedge resection for early cancer, pylorus-preserving gastric resection to reduce dumping syndrome, pancreas-preserving total gastrectomy to reduce fistula and postoperative diabetes.

Endoscopy↗
PubMed1996

[A case of small cell carcinoma (oat-cell type) of the esophagus].

We experienced a case of small cell carcinoma of the esophagus treated by operation. A 57-year-old female was examined for a complaint of dysphagia. The radiologic and endoscopic examination revealed Borrmann III like tumor (8 cm long) at lower esophagus (EiEa). Endoscopic biopsy led to a diagnosis of poorly differentiated squamous cell carcinoma. Chest X-ray and chest CT showed no lung tumor, no swelling of lymph node and no invasion of esophageal tumor. Lower esophagectomy, proximal gastrectomy and esophago-gastrostomy through intrathoracic route was performed. Histopathologically, resected tumor was diagnosed as small cell carcinoma (Oat-cell type) with rosette formation. Grimerius stain revealed negative reaction and immunohistochemical stain by NSE monoclonal antibody revealed positive reaction in tumor cells. Histological staging was a0, n1(+), M0, P1(zero), stage II. Recurrence at paraaortic lymph node occurred in 2 months after the surgery. Chemotherapy (CDDP, 5-FU and Leucovorin) was performed, but not effective. She died from multiple metastases in 5 months after the surgery (6 months after the diagnosis).

Adult↗
PubMed1996

[Benign infantile mitochondrial myopathy caused by reversible cytochrome c oxidase deficiency].

A 2-month-old girl had generalized weakness, profound muscular hypotonia, hepatomegaly and severe lactic acidosis. She needed ventilatory support. Muscle specimen taken at 2 months showed ragged-red fibers, abnormal mitochondria, and reduced cytochrome c oxidase (CCO) staining Biochemical analysis showed CCO activity to be reduced to about 16% of the normal mean. She received carnitine and coenzyme Q10 supplementation from the age of 3 months and abnormal blood lactate values declined to near normal values during the first three weeks. Gradually her condition started to improved: she held her head at 9 months, and walked alone at 15 months. The second biopsy specimen at 3 years and 8 months showed almost normal CCO staining and she was free of clinical signs. This case is an example of a rare benign infantile mitochondrial myopathy caused by CCO deficiency. Early diagnosis is crucial to provide intensive treatment until spontaneous clinical improvement appears. We concluded that carnitine and coenzyme Q10 supplementation was a useful treatment for clinical improvement in patients with a benign infantile mitochondrial myopathy caused by CCO deficiency.

Carnitine↗
PubMed1996

[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↗
PubMed1996

Structural and calcification patterns of the neonatal line in the enamel of human deciduous teeth.

The neonatal line of the enamel in human deciduous teeth was observed by scanning electron microscopy using secondary and backscattered electron signals. The neonatal line containing irregular structures of enamel prisms with disordered crystal arrangements was basically formed by the abrupt bending of the prisms towards the root. Usually, the prisms gradually bent back again to regain their previous orientation, but the prisms in the inner and the surface layer sometimes ran straight ahead after bending. The prism sheath regions showing hypocalcification contained a relatively large amount of organic material as shown by treatment with chromium sulfate. When etched with ethylenediaminetetraacetic acid (EDTA), such prism sheath regions were extensively eroded due to the lower density of crystals caused by the abrupt bending of the prisms. Abnormally shaped prisms and small prismless areas were occasionally present. The neonatal line formed by the double bending of the prisms is likely to represent a particular type of rhythmic Retzius line rather than a pathologic Retzius line, whereas the hypocalcified sheath regions may be similar to those of some pathologic lines of Retzius.

Child↗
PubMed1995

Recombinant core streptavidins. A minimum-sized core streptavidin has enhanced structural stability and higher accessibility to biotinylated macromolecules.

Two recombinant core streptavidins were designed and characterized to understand the role of the terminal sequences, present in naturally truncated core streptavidins, in the properties of streptavidin. One recombinant core streptavidin, Stv-25, has an amino acid sequence very similar to natural core streptavidins. The other recombinant molecule, Stv-13, has further truncation of the terminal residues and consists essentially of only the beta-barrel structure characteristic of streptavidin. These recombinant core streptavidins are tetrameric and bind four biotins/molecule, as does natural streptavidin. The solubility characteristics of Stv-13, determined by varying the concentration of ammonium sulfate or ethanol, were almost the same as those of Stv-25 and natural core streptavidin. However, Stv-13 showed an enhanced structural stability compared with Stv-25 and natural core streptavidin. For example, Stv-13 retained greater than 80% of its biotin binding ability after incubation in 6 M guanidine hydrochloride at pH 1.5, under which conditions, Stv-25 and natural core streptavidin retained only about 20% of their biotin binding ability. In addition, Stv-13 showed higher accessibility to biotinylated DNA than natural core streptavidin. Apparently, the terminal regions, present on the surface of natural core streptavidin, spatially hinder biotinylated macromolecules from approaching the biotin binding sites.

Amino Acid Sequence↗
PubMed1995

Molecular evidence for the direct involvement of a protein kinase C in developmental and behavioural susceptibility to tumour-promoting phorbol esters in Caenorhabditis elegans.

The nematode Caenorhabditis elegans displays developmental and behavioural sensitivity to tumour-promoting phorbol esters. This sensitivity involves the gene tpa-1, which encodes two protein kinase C isoforms, TPA-1A and TPA-1B. Here we report the molecular nature of the sensitivity in this animal. Characterization of transposon Tc1-induced phorbol ester-resistant mutants has revealed that Tc1 was inserted in a region encoding the kinase domain, resulting in the loss of tpa-1 products. Introduction of a genomic DNA containing the entire wild-type tpa-1 locus into a Tc1-inserted mutant restored the sensitivity to tumour promoters, and tpa-1 products were also produced. These results suggest that the function of wild-type TPA-1 is necessary and sufficient for tumour promoters to cause developmental and behavioural sensitivity in C. elegans.

Amino Acid Sequence↗
PubMed1995

Intermediate-term outcome after intracardiac repair of associated cardiac defects in patients with atrioventricular and ventriculoarterial discordance.

BACKGROUND: Limited information is available concerning long-term results, especially systemic right ventricular (RV) or tricuspid valvular function, after intracardiac repair of anomalies associated with discordant atrioventricular (AV) and ventriculoarterial (VA) connections ("congenitally corrected transposition of the great arteries"). METHODS AND RESULTS: We retrospectively reviewed the intermediate-term follow-up of 28 patients, totaling 158 patient-years (median, 60 months), after intracardiac repair involving closure of a ventricular septal defect (VSD) with or without additional surgery. Seven patients had VSD closure alone, 5 had VSD repair with pulmonary stenosis relief, and 16 had VSD closure with conduit insertion between left ventricle and main pulmonary artery. Hospital mortality was 4% (1 of 28 patients; 70% confidence limits, 0.07% to 12%) and the 1-, 5-, and 10-year actuarial survival probabilities were 89%, 83%, and 83%, respectively. Twenty-one of 24 long-term survivors were in New York Heart Association functional class I and 3 were in class II. Sixteen of 24 patients showed increasing tricuspid regurgitation (TR) of more than moderate degree, which occurred within 3 years after surgery in 7 patients. Twelve of 22 patients showed deterioration of RV pump function, mainly (9 of 12 patients) within 3 years postoperatively. The pulmonary to systemic flow ratio at the preoperative cardiac catheter study was significantly (P < .05) higher in patients who developed RV dysfunction (2.3 +/- 1.0, mean +/- SD) than in those with well-maintained RV function (1.4 +/- 0.6). CONCLUSION: Intermediate-term results of intracardiac repair for AV and VA discordance were satisfactory in terms of survival and clinical functional status; however, there is concern about systemic RV dysfunction with development of TR relatively early after the operation. Alternative surgical approaches such as anatomic correction or Fontan repair for cases unsuitable for biventricular repair may improve the long-term results, including ventricular and valvular function.

Adolescent↗
PubMed1995

The tpa-1 gene of Caenorhabditis elegans encodes two proteins similar to Ca(2+)-independent protein kinase Cs: evidence by complete genomic and complementary DNA sequences of the tpa-1 gene.

The gene tpa-1 on chromosome IV of the nematode Caenorhabditis elegans plays a major and definitive role in the adversary action of tumour-promoting phorbol esters, which induce growth arrest and locomotory distress in the animal. The gene was deduced to code for a protein kinase C (PKC) homologue by molecular cloning. We have now sequenced the complete genomic and complementary DNAs for tpa-1 and have analysed their structural features in detail: (1) tpa-1 spans over 20 kb consisting of eleven exons and ten introns; (2) two different-sized mRNAs are generated from the tpa-1 locus; (3) both mRNAs are trans-spliced to the trans-spliced leader SL1; (4) both mRNAs encode PKC isoforms, which are most similar to Ca(2+)-independent novel PKC0; (5) the two PKC isoforms differ from each other in that the smaller lacks the amino-terminal region of the larger corresponding to the first four exons and a portion of the fifth exon; and (6) three introns are located at; identical positions in the polypeptide sequences aligned between the C. elegans tpa-1 product and a PKC of the fruit fly Drosophila melanogaster.

Amino Acid Sequence↗
PubMed1995

Prognostic implication of the p53 protein and Ki-67 antigen immunohistochemistry in malignant fibrous histiocytoma.

BACKGROUND: Mounting evidence indicates that p53 regulates cell growth and abnormal p53 immunophenotypic expression is associated with an unfavorable prognosis for patients with some types of carcinoma. The prognostic significance of p53 overexpression in malignant fibrous histiocytomas (MFHs) of soft tissue has not yet been elucidated. METHODS: Expressions of p53 protein and Ki-67 antigen in 54 primary MFHs of soft tissue were investigated immunohistochemically and indexed quantitatively by counting the number of immunoreactive nuclei versus the total neoplastic nuclei in the representative fields of each tumor to evaluate their prognostic implications and interrelations with other clinicopathologic parameters. RESULTS: The percentages (labeling indices [LIs]) of p53 and Ki-67-immunoreactive nuclei versus the total neoplastic nuclei were 0.1-93.2% (mean +/- standard deviation [SD], 40.6% +/- 21.8%) and 5.3-90.8% (mean +/- SD, 42.7% +/- 29.4%), respectively. The Ki-67 LI correlated with histologic grade (P = 0.01498), primary tumor size (P = 0.04985), disease free interval (reverse correlation, P = 0.00776), and recurrence and metastasis (P = 0.00360). The p53 LI correlated with primary tumor size (P = 0.00431) but did not show any significant correlation with histologic grade, Ki-67 LI, primary tumor size, disease free interval, or recurrence and metastasis. Other significant correlations included histologic grade and disease free interval (P = 0.00010), primary tumor size and disease free interval (reverse correlation, P = 0.00869), histologic grade and recurrence (P = 0.02714), and primary tumor size and primary tumor location (P = 0.00028). In the grouped survival analysis, patients with recurrence or metastasis or with tumors of larger size (> or = 7 cm), high histologic grade, or higher Ki-67 LI (> or = 25%) had a significantly reduced survival (P < 0.05). The different p53 immunohistochemical expression and the different histologic types did not reflect different cumulative survival (P > 0.05). Regression analysis revealed that the primary tumor size and histologic grade, but not Ki-67 or p53 LIs, were independent statistical variables for prognostication. CONCLUSIONS: These results indicate that (1) primary tumor size and histologic grade are two important prognostic factors, (2) Ki-67 LI should be used in adjunct with other main prognostic factors for patients with MFHs, and (3) nuclear p53 overexpression in MFHs of soft tissue is a comparatively common event that has no prognostic implication.

Adult↗