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Biomedical subjects

R Katoh

Publications and source records attributed to R Katoh.

At least 37 records · Page 2Linked to original sources

Autoregulation of thyroid-specific gene transcription by thyroglobulin.

Thyroglobulin (TG), the primary synthetic product of the thyroid, is the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and degradation control thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases thyroid hormone levels by up-regulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of several thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneously. This helps maintain self-tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. In this report we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases class I expression. TG acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The inhibitory effect of TG on gene expression is not duplicated by thyroid hormones or iodide and may be mediated by a TG-binding protein on the apical membrane. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism that limits follicular function and contributes to follicular heterogeneity.

Animals↗

Increased expression of the sodium/iodide symporter in papillary thyroid carcinomas.

Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as compared with the normal gland. The Na+/I- symporter (NIS) is primarily responsible for the uptake of iodide into thyroid cells. Our objective was to compare NIS mRNA and protein expression in papillary carcinomas with those in specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold increase in the level of NIS mRNA in specimens with papillary carcinoma versus specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody that was produced with a glutathione S-transferase fusion protein containing NIS protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of 12 carcinomas, whereas NIS protein was barely detected in specimens with normal thyroid. Although considerable patient-to-patient variation was observed, our results indicate that NIS mRNA is elevated, and its protein tends to be more abundant, in a subset of papillary thyroid carcinomas than in normal thyroid tissue.

Carcinoma, Papillary↗

Solitary, multiple, and familial oxyphil tumours of the thyroid gland.

A study of 169 oxyphil tumours of the thyroid, correlating histological features with age, sex, thyroiditis, and available clinical history, has shown two significant findings relevant to pathogenesis, diagnosis, and treatment. Oxyphil tumours with a papillary architecture can be divided into papillary carcinomas with secondary oxyphilia and true oxyphil tumours. The tumours of the former group are typically unencapsulated, invasive, show nuclei characteristic of papillary carcinoma generally, are associated with thyroiditis, and frequently show psammoma bodies. The tumours of the latter group are typically encapsulated, with nuclei similar to those found in other oxyphil tumours; usually lack psammoma bodies; and some show capsular and vascular invasion. Papillary architecture alone is not thought to justify a diagnosis of malignancy in this group of tumours, and further study with follow-up is needed to determine the appropriate treatment. It is suggested that oxyphilia in the first group is secondary to the accompanying thyroiditis, comparable to the oxyphilia in follicular cells in Hashimoto's thyroiditis, while the oxyphilia in the latter group, as in other oxyphil tumours, is due to a somatic mutation leading to an increase in mitochondrial number. About 20 per cent of all cases showed multiple oxyphil tumours. These were more frequently female, more often associated with thyroiditis, younger, and less often malignant than solitary tumours. The occurrence of multiple tumours of the same uncommon histological type in these patients is compatible with a germline mutation conferring a liability to oxyphil follicular cell tumours. This is supported by the occurrence of oxyphil tumours in families; the present series of cases included two mother-daughter pairs and similar examples have been reported, including multiple oxyphil tumours in identical twins. Further studies are needed to identify the gene involved and any co-operating genes. Oxyphil carcinoma in patients with multiple oxyphil tumours occurred at a mean age 10 years greater than that for multiple adenomas, suggesting that the carcinomas arose by progression from adenomas. It is important to complete thyroidectomy in a case with multiple oxyphil tumours if there is evidence of the presence of lesions in both lobes. It is necessary to consider the differences between primary and secondary oxyphilia, and between sporadic and multiple or familial oxyphil tumours in future studies of these lesions.

Adenoma, Oxyphilic↗

Poorly differentiated desmin-negative and vimentin-positive leiomyosarcoma of the stomach examined by the immunohistochemical and quick-freezing and deep-etching methods.

A poorly differentiated leiomyosarcoma of the stomach in a 41-year-old woman is reported. The diagnosis was confirmed by the diffuse immunohistochemical reaction to HHF35, and the presence of focal density and caveolas in some of the tumour cells by conventional electron microscopy. Immunohistochemically, most tumour cells had an undifferentiated nature, in which negative immunostaining for desmin, alpha-smooth muscle actin, and type IV collagen, and positive immunostaining for vimentin were observed. By the quick-freezing and deep-etching (QF-DE) method, these tumour cells revealed the loss of bundled actin and myosin filaments, which constitute desmin associated structures (focal densities and dense patchy areas). Their cytoplasm had many mitochondria and other cell organelles. The intermediate filaments (IFs), which were determined to be vimentin by immunohistochemistry, were observed in the inter-organellar spaces, and connected with these cell organelles. Actin filaments formed a meshwork structure and were distributed mainly in subplasmalemmal regions. Although a basal lamina was not detected by conventional electron microscopy, basal lamina-like structures, an association between the extracellular matrices and the cell membrane, were observed. Using the QF-DE method, three dimensional ultrastructural alterations of the cytoskeleton and extracellular matrix of the leiomyosarcoma were observed.

Actins↗

Mitochondrial function in Babesia microti and Babesia rodhaini.

The role of mitochondria in the energy metabolism of Babesia microti and Babesia rodhaini was investigated. A variety of mitochondrial inhibitors showed greater sensitivity to B. microti than to B. rodhaini. Additionally, alpha-glycerophosphate- and succinate-cytochrome c reductase activities in the crude mitochondrial fraction from B. microti were substantially higher than those from B. rodhaini. Our results suggest that the mitochondria of these parasites possess a series of "classical" apparati for energy production and their relative functional role may be quantitatively greater in B. microti when compared with B. rodhaini.

ATP Synthetase Complexes↗

Sonochemical polymerization of benzene derivatives: the site of the reaction.

Sonochemical polymerization of benzene and halogen-substituted benzenes has been studied. The difference of absorption spectra of polymerization products can be explained qualitatively using bond energies of the primary products. The relative rate constant of the polymerization reaction is apparently proportional to the inverse of the vapour pressure of the liquids. Using this relation, we analysed the relative rate constant of the polymerization in benzene/chrolobenzene mixtures. From this, we conclude that sonochemical polymerization proceeds in the vapour phase of a bubble.

Journal Article↗

Thyroid transcription factor 1 is calcium modulated and coordinately regulates genes involved in calcium homeostasis in C cells.

Thyroid transcription factor 1 (TTF-1) was identified for its critical role in thyroid-specific gene expression; its level in the thyroid is regulated by thyrotropin-increased cyclic AMP levels. TTF-1 was subsequently found in lung tissue, where it regulates surfactant expression, and in certain neural tissues, where its function is unknown. Ligands or signals regulating TTF-1 levels in lung or neural tissue are unknown. We recently identified TTF-1 in rat parafollicular C cells and parathyroid cells. In this report, we show that TTF-1 is present in the parafollicular C cells of multiple species and that it interacts with specific elements on the 5'-flanking regions of the extracellular Ca2+-sensing receptor (CaSR), calmodulin, and calcitonin genes in C cells. When intracellular Ca2+ levels are increased or decreased in C cells, by the calcium ionophore A23187, by physiologic concentrations of the P2 purinergic receptor ligand ATP, or by changes in extracellular Ca2+ levels, the promoter activity, RNA levels, and binding of TTF-1 to these genes are, respectively, decreased or increased. The changes in TTF-1 inversely alter CaSR gene and calcitonin gene expression. We show, therefore, that TTF-1 is a Ca2+-modulated transcription factor that coordinately regulates the activity of genes critical for Ca2+ homeostasis by parafollicular C cells. We hypothesize that TTF-1 similarly coordinates Ca2+-dependent gene expression in all cells in which TTF-1 and the CaSR are expressed, i. e., parathyroid cells, neural cells in the anterior pituitary or hippocampus, and keratinocytes.

Animals↗

Identification of thyroid transcription factor-1 in C cells and parathyroid cells.

We have identified thyroid transcription factor-1 (TTF-1) mRNA in parafollicular C cells of the adult rat thyroid and in parathyroid cells; in each case the signal is stronger than in the thyrocytes themselves. We additionally identify TTF-1 RNA in other adult rat tissues not previously recognized to contain TTF-1 in developmental or knockout studies: basal layer cells of flattened squamous epithelium in skin and esophagus, three layers of the retina, i.e. pigmented epithelium, inner granular layer, and ganglion cell layer, and three areas of the brain, i.e. anterior pituitary, cerebellum, and hippocampus. Based on the array of cells that are shown to contain TTF-1 in this report, we speculate that TTF-1 may have a role in the regulation of genes important in calcium homeostasis in the intact organism as well as different tissues.

Animals↗

A new fine probe for electric cautery during endoscopic surgery.

The present paper introduces a new fine probe for electric cautery (1.65 mm in diameter, 22 cm long) that can be connected to a conventional cylindrical hand-controlled cautery holder, which is monopolar and widely used in general surgery. When cautery was required, a 14-gauge intravenous catheter was inserted at an appropriate site under the guidance of a videoscope. After removing the steel inner needle, the extra tube was used as the fine surgical port for the cautery probe. The position of insertion could be altered according to the operating field. Cautery was performed by conventional methods. There was no bleeding or air leakage at the site of puncture during or after surgery. The puncture wound was closed without any sutures. Based on these results, the new fine probe for cautery can reduce the number of surgical ports required for instruments during video-assisted surgery, thus improving the ease and safety of endoscopic surgery.

Electrocoagulation↗

[Metamorphopsia and transient increase in the cerebral blood flow of the left occipital pole on 123I-IMP SPECT: a case report].

A 55-year-old right-handed man suddenly developed unformed visual hallucination of rainbow-colored balls coming out from the lower quadrant of the right visual field. Visual field examination revealed a right lower quadrant homonymous hemianopia. Metamorphopsia of the hand or face appeared 6 days later when he looked at his hands or at the face in the mirror, and persisted for about 10 minutes. 123I-IMP SPECT demonstrated a marked increase in CBF of the left occipital pole while the patient realized the visual symptoms, and a marked decrease in CBF after the symptoms disappeared. T1 and T2-weighted MRIs of the brain were unremarkable, but the Gd-DTPA-enhanced T1-weighted MRI showed high signal in the subcortical white matter of the left occipital pole. The metamorphopsia was induced probably by the activation of the left occipital lesion by the epileptogenic mechanism although the nature of the lesion remained unclarified.

Amphetamines↗

A case of small cell carcinoma of the uterine cervix presenting Cushing's syndrome.

A proportion of small cell carcinoma of the uterine cervix is known to secrete a neuroendocrine substance. However, cases presenting Cushing's syndrome due to ACTH secreted from a cervical small cell carcinoma are extremely rare. Here, we report a case of small cell carcinoma of the uterine cervix that ectopically secreted ACTH and presented Cushing's syndrome. A 42-year-old woman was initially admitted to the endocrine unit for investigation of ectopic ACTH syndrome. Serum cortisol and plasma ACTH levels were elevated with no diurnal variation. After gynecologic examination, her original disease was found to be a stage IIb cervical small cell carcinoma. She underwent a radical hysterectomy and pelvic lymphadenectomy. The entire tumor was excised and post-TNM classification was T2bN1M0. Immunohistochemically, tumor cells stained strongly for ACTH and chromogranin. Electronmicroscopic pictures showed typical neurosecretory granules. Although plasma ACTH returned to normal after surgery, liver metastasis appeared during the course of postoperative irradiation. She died 9 months after operation in spite of vigorous systemic chemotherapy.

Adrenocorticotropic Hormone↗

Different organization of intermediate filaments in columnar cells of rat large intestinal mucosa as revealed by confocal laser scanning microscopy and quick-freezing and deep-etching method.

The relationship between cell differentiation and ultrastructural changes of intermediate filaments (IF) was studied in columnar cells of large intestinal mucosa of rats by confocal laser scanning microscopy and quick-freezing and deep-etching method. A feature of the IF in immature columnar cells was minibundle formation with prominent branching, which organized the meshwork structures. The minibundles, which appeared to be formed by the attachment of two or more IF in side-to-side fashion, were loosely distributed throughout the cytoplasm. In contrast, in mature columnar cells, the IF were densely distributed under the terminal web in the cytoplasm and beneath the upper part of the lateral membrane regions, whereas the other areas of the cytoplasm contained only a small number of IF. Minibundle formation was not observed, and the branching was rarely identified. The changes in the distribution and density of IF, which are expressed in specific areas of mature columnar cells, apparently represent a characteristic of intracellular differentiation. It is suggested that the dissociation of minibundled IF, which was often observed in the immature columnar cells, is an important step in the acquisition of functional polarity in cells of this type.

Animals↗

Growth activity in hyperplastic and neoplastic human thyroid determined by an immunohistochemical staining procedure using monoclonal antibody MIB-1.

To increase our understanding of the basic biological mechanisms of thyroid diseases, growth activity (GA) in 232 thyroid lesions was determined by immunohistochemistry using monoclonal antibody MIB-1. The GA tended to be higher in hyperplastic lesions, adenomatous goiter (MIB-1-positive cell rate, 0.73%), and Graves' disease (1.68%) than in normal tissue (0.19%). The GA for differentiated thyroid carcinomas (2.00%) was much lower than for adenocarcinomas of other organs, such as breast, lung, stomach and colon (44.67%). Of the thyroid carcinomas, the highest GA was observed in undifferentiated carcinomas (32.67%), and follicular carcinomas (3.18%) showed a higher GA than papillary carcinomas (1.83%). There was no significant difference between the GA of follicular carcinomas and solid/trabecular adenomas, although widely invasive follicular carcinomas showed a higher GA than minimally invasive carcinomas. No significant correlations between GA and patient age, sex, and tumor diameter, metastasis, or histological features were observed in papillary carcinomas. Familial medullary carcinomas showed a higher GA than sporadic tumors. All latent papillary carcinomas had a very low GA. Our findings suggest that immunohistochemical investigation using the antibody MIB-1 contributes to the understanding of growth characteristics and biological activities in thyroid diseases.

Adenoma↗

Primary cutaneous CD30(Ki-1)-positive lymphoma of non-T, non-B origin.

A 71-year-old Japanese woman had two dome-shaped tumors on her right buttock with several surrounding papules. Histological examination revealed that large anaplastic cells and atypical lymphoid cells densely infiltrated the entire dermis. On immunohistochemical examination, Ki-1, HLA-DR, CD25 (IL-2 receptor alpha), CD122 (IL-2 receptor beta), CD4, CD11c and CD68 were all positive in the tumor cells, whereas CD1a, CD3, CD5, CD8 and CD19 were negative. Neither rearrangement of the T-cell receptor beta, T-cell receptor gamma nor the immunoglobulin heavy-chain was seen. Ultrastructurally, most of the tumor cells contained thick bundles of intermediate filaments in the perinuclear cytoplasm. Thus, this patient was diagnosed as having Ki-1-positive lymphoma of non-T, non-B origin. No recurrence or metastasis of the tumor has been observed in the last 2 years, although surgical resection was required 3 times before control was achieved.

Aged↗

Racial variation in the O-acetylation phenotype of human colonic mucosa.

O-acetylated and non-O-acetylated sialoglycoproteins can be distinguished by the mPAS (mild periodic acid-Schiff) histochemical technique. Individual adults show one of three different patterns of staining of large intestinal mucosa: uniformly mPAS-positive, uniformly mPAS-negative, or mPAS-negative with scattered mPAS-positive crypts. To test our hypothesis that these variations are the result of a single autosomal gene (oat) polymorphism, we have studied the frequency of the three patterns of staining in a total of 435 adult colon specimens from six geographically separate populations: British, South African blacks, Icelanders, Japanese, Hong Kong Chinese, and Bahrainis. The distribution of the three types of staining fell into two groups. In Japanese and Chinese, uniformly mPAS-positive cases were much more frequent than uniformly mPAS-negative cases; this distribution differed significantly (chi 2, P < 0.001) from that in non-Sino-Japanese, where the uniformly mPAS-positive phenotype was much less frequently found than the uniformly mPAS-negative phenotype. In neither of the groups did the frequency of the three phenotypes differ significantly from that predicted for a single gene polymorphism by the Hardy-Weinberg law. The variation in staining patterns between populations is consistent with variation in frequency of a single polymorphic autosomal gene (oat) controlling O-acetylation of sialic acid, probably by an O-acetyl transferase enzyme. Loss of function mutation in the high acetylator gene (oata) in a colonic crypt stem cell in heterozygous individuals would account for the scattered discordant crypts. Gene frequencies for a variety of enzymes differ between the Sino-Japanese and non-Sino-Japanese races.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗