Biomedical subjects

K Takano

Publications and source records attributed to K Takano.

At least 55 records · Page 3Linked to original sources

PubMed2001

Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).

Amiodarone↗

PubMed2001

Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma: a case report and review of the literature.

A 50-year-old woman who had undergone lung lobectomy because of lung adenocarcinoma presented with thyrotoxicosis, neck swelling, and cervical lymphadenopathy one month after the operation. The total serum triiodothyronine (T3) and thyroxine (T4) levels were markedly elevated to 514 ng/dL and 26.4 microg/dL, respectively, and serum thyrotropin (TSH) was suppressed to less than 0.005 microU/mL. Although the thyroid gland had been normal before surgery, chest computed tomography (CT) scan revealed a markedly enlarged thyroid gland only 1 month after surgery. 123I uptake for 24 hours was suppressed to 4% in the thyroid gland with no uptake elsewhere including the lung. Fine-needle aspiration cytology (FNAC) of the thyroid showed invasion of poorly differentiated adenocarcinoma cells, cytologically identical to the cells obtained from sputum and those infiltrating the resected sections of the lung adenocarcinoma. Immunohistochemical studies of resected lung tissues did not show positive staining for thyroglobulin, carcinoembryonic antigen (CEA), or surfactant protein A. Clinically, the thyrotoxicosis had spontaneously improved, followed by a hypothyroid state with shrinkage of the thyroid gland after chemotherapy. Despite repeated chemotherapy and the administration of thyroxine for hypothyroidism, the patient died of respiratory failure 9 months after the onset of thyrotoxicosis. From these findings and the clinical course, thyroid metastasis, developing subacutely from lung adenocarcinoma, was diagnosed. We speculate that aggressive invasion of tumor cells into the thyroid gland resulted in highly destructive thyrotoxicosis.

Adenocarcinoma↗

PubMed2001

Uterine inversion caused by uterine sarcoma: a case report.

Uterine inversion caused by uterine sarcoma is a rare condition with 12 reported cases to date according to a MEDLINE search. We report two cases of this rare condition. A 71- and a 72-year-old woman presented with uterine sarcomas rapidly extruded into the vagina. In both cases, magnetic resonance imaging (MRI) scans showed U-shaped uterine cavities and the pedicles of these tumors were attached to the uterine fundi. Pathological examination confirmed a leiomyosarcoma and a heterologous carcinosarcoma. Uterine inversion can occur when uterine sarcoma rapidly increases in size and extrudes into the vagina. MRI should be performed in the diagnosis of this rare combination.

Aged↗

PubMed2001

Are the parameters of various stabilization factors estimated from mutant human lysozymes compatible with other proteins?

The various factors which contribute to protein stability have been extensively examined using mutant proteins, but the same kinds of substitutions have given different results depending on the substitution sites. Recently, the contributions of some stabilization factors have been quantitatively derived as parameters by a unique equation, considering the conformational changes due to the mutations using mutant human lysozymes [Funahashi et al. (1999) Protein ENG: 12, 841-850]. To evaluate these parameters estimated from the mutant human lysozymes, stability-structure datasets for the mutant T4 lysozymes were selected. The stabilities for the mutant T4 lysozymes could be roughly estimated using these parameters. Notable differences between the estimated and experimental stabilities were caused by the uncertainty in part of the structures due to some Arg and Lys residues fluctuating on the surface of the T4 lysozyme. Excluding these atoms from the estimation gave a good correlation between the estimated and experimental stabilities. These results suggest that the parameters of the various stabilization factors derived from the mutant human lysozymes are compatible with the mutant T4 lysozymes, although they should be improved with respect to some points using more information.

Amino Acid Substitution↗

PubMed2001

A new scale for side-chain contribution to protein stability based on the empirical stability analysis of mutant proteins.

The hydrophobicity scales for amino acid side chains based on the transfer Gibbs energy (DeltaG(trans)) of amino acids from non-aqueous phases to water have been widely used to estimate the contribution of buried side chains to the conformational stability of proteins. In this paper, we propose a new scale for the side-chain contribution to protein stability, which is derived from data on protein denaturation experiments using systematic and comprehensive mutant proteins. In the experiments, the contribution of some physical properties were quantitatively determined as parameters in a unique equation representing the stability change (DeltaDeltaG) of mutant proteins as a function of the structural changes due to the mutations. These parameters are able conveniently to provide a scale for the side-chain contribution to protein stability. This new scale also has the advantage over the previously reported hydrophobicity scales of residues with the contributions of hydrogen bonds or secondary structural propensity. It may find practical application in algorithms for the prediction of protein structures.

Amino Acids↗

PubMed2001

Correction of the bilateral complete cleft lip: transformation to a unilateral incomplete cleft lip closure.

The complete lip alveolus and cleft palate is the most difficult of all bilateral clefts to treat because of the deformity of and tissue insufficiency in the prolabium. A bilateral concomitant procedure is impractical for treatment of this condition because of the problems that have to be resolved postoperatively, including a short columella, a lack of philtrum, labial horizontal and vertical insufficiency, and vermilion and alveolar vestibulum insufficiency. A two-stage procedure called the transformation method has been developed to circumvent these problems, and the authors present it here. With this method one side is closed completely using the maximum amount of tissue available. Concomitantly, incomplete closure is performed on the other side. The result at the end of the first stage of the procedure is a condition approximating unilateral incomplete closure. The results were obtained from 6 patients who underwent complete bilateral closure and were followed for at least 2 years with satisfactory results.

Child, Preschool↗

PubMed2001

Somatic mutations of the MEN1 gene and microsatellite instability in a case of tertiary hyperparathyroidism occurring during high phosphate therapy for acquired, hypophosphatemic osteomalacia.

Somatic mutations of the MEN type 1 (MEN1) gene were recently shown to be responsible for tumorigenesis in 13-26% of sporadic, nonfamilial primary hyperparathyroidism. However, it is unknown whether these mutations are also involved in tumorigenesis of parathyroid glands occurring during high phosphate therapy for hypophosphatemic rickets or osteomalacia. A male patient with adult-onset, hypophosphatemic osteomalacia had been treated with 1alpha-OHD3 and oral phosphate for 13 yr when tertiary hyperparathyroidism developed. After total resection of four enlarged parathyroid glands and autotransplantation of a hyperplastic gland, the patient has continued to do well for the last 2 yr. Sequence analysis of the coding exons of MEN1 gene revealed a 36-bp deletion with a 2-bp insertion (exon 2) in the right upper parathyroid gland accompanied with loss of heterozygosity at 11q13 locus and a heterozygous mutation of 2-bp deletion (AG) in exon 10 in the right lower gland, in which microsatellite instability was also found. No MEN1 gene mutation was detected in the other two hyperplastic parathyroid glands or in the peripheral blood. These findings indicate that MEN1 gene mutations contributed to tumorigenesis of the right upper parathyroid gland in this case of phosphate-induced tertiary hyperparathyroidism. Very recently a bone tumor was found in the right femoral neck, and the tumor (chondroblastoma) was resected.

Adult↗

PubMed2001

Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives.

An aldosterone-producing adenoma causes surgically correctable hypertension. Screening tests should be assessed for their accuracy and ability to detect aldosterone-producing adenoma in an appropriate population. This study aims to validate the accuracy and efficacy of the basal plasma aldosterone concentration (picomoles per liter) to PRA (nanograms per liter/sec) ratio and of combined stimulation of PRA by the furosemide and upright posture test in screening for aldosterone-producing adenoma in hypertensives with PRA less than 0.28 ng/liter.sec (1 ng/ml.h). Thirty-five aldosterone-producing adenoma and 79 nonaldosterone-producing adenoma patients were retrospectively selected from among 159 patients examined with the furosemide and upright posture test between 1989 and 1999. Selection criteria were based on blood pressure, PRA, and plasma aldosterone concentration. Diagnosis was based on surgical outcome, computed tomography scans with adrenal scintigraphy, or venous sampling. The accuracy and efficacy of basal (aldosterone/PRA ratio) and dynamic (postfurosemide and upright posture PRA) screening tests were assessed based on test sensitivity, specificity, likelihood ratio, and receiver operating characteristics. At a cut-off value of 3,200, the aldosterone/PRA ratio had a high sensitivity of 1.0 and a low specificity of 0.61. The importance was strengthened by using a multilevel likelihood ratio, i.e. positive (aldosterone/PRA ratio >10,000), negative (aldosterone/PRA ratio <3,200), and neutral (intermediate aldosterone/PRA ratio) levels. Patients with a positive level had a likelihood ratio of 7.1 and were likely to have an aldosterone-producing adenoma. The aldosterone/PRA ratio enclosed a larger area under the receiver operating characteristics curve (0.905) than did postfurosemide and upright posture PRA (0.826). In conclusion, the plasma aldosterone concentration to PRA ratio is an effective screening and diagnostic test when a triple level likelihood ratio is applied. The furosemide and upright posture test did not raise the posttest probability over that obtained using the aldosterone/PRA ratio.

Adenoma↗

PubMed2001

A 10-kda fragment of fibronectin type III domain is a neutrophil chemoattractant purified from conditioned medium of rat granulation tissue.

A neutrophil chemoattractant has been purified from the conditioned medium of granulation tissue obtained from carrageenan-induced inflammation in rats. The purified chemoattractant was a basic protein with a molecular mass of 10 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing and non-reducing conditions. NH2-terminal amino acid sequence of the purified 10-kDa protein was identical with the sequence of rat fibronectin starting from the residue Thr585, indicating that the purified 10-kDa chemoattractant is a fragment derived from the NH2-terminal type III domain of rat fibronectin.

Amino Acid Sequence↗

PubMed2001

Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma.

We compared dynamic computer tomographic CT images of 3 cases of juxtaglomerular (JG) cell tumor with those of 8 cases of renal cell carcinoma (RCC). The JG cell tumor was visualized as a low- to high-density area in case 1, a low-density area in case 2, and a low- to iso-density area in case 3 before contrast enhancement. None of the JG cell tumors were stained during the early phase (1 min), but all were stained moderately during the late phase (5 min) after contrast enhancement. Although all cases of RCC were visualized as a low- to iso-density area before contrast enhancement, they were intensely stained during the early phase with significant washout during the late phase. The present results suggest that the dynamic CT scan is useful in the differential diagnosis of the JG cell tumor and RCC.

Adenocarcinoma↗

PubMed2001

Ectopic adrenocorticotropin syndrome exhibiting paradoxical adrenocorticotropin responsiveness to gonadotropin-releasing hormone.

In a 37-year-old man who had Cushing's syndrome, investigations, including overnight dexamethasone suppression test, corticotropin-releasing hormone (CRH) test, pituitary MRI and inferior petrosal sinus sampling suggested the presence of ectopic adrenocorticotropin (ACTH) production. Interestingly, gonadotropin-releasing hormone (GnRH) increased plasma ACTH from 73 pg/ml to 708 pg/ml at 15 min. Furthermore, desmopressin also increased plasma ACTH whereas CRH and thyrotropin-releasing hormone (TRH) had no effect. Such paradoxical responses of plasma ACTH were observed repeatedly. A thoracic CT scan revealed a right anterior mediastinal mass, which was surgically resected. Histological and immunohistochemical examination confirmed that the tumor was an ACTH-producing carcinoid. ACTH and cortisol decreased immediately following surgery. Neither desmopressin nor GnRH administration resulted in elevation of plasma ACTH while ACTH-responsiveness to dexamethasone and CRH was restored. To our knowledge, this is the first report documenting GnRH responsiveness in ectopic ACTH syndrome.

ACTH Syndrome, Ectopic↗

PubMed2001

Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's syndrome.

Transsphenoidal adenomectomy is currently the first choice for treatment of patients with pituitary ACTH-dependent Cushing's syndrome. However, pharmacotherapy is prescribed for some patients, e.g., unsuccessful surgery. We treated a woman in whom pituitary Cushing's syndrome was improved while she was on antimuscarinic cholinergic agents, atropine sulphate and pirenzepine hydrochloride. The diminished effect of anticholinergics on ACTH and cortisol was incidentally identified in an inferior petrosal sinus sampling procedure. A single intramuscular injection of atropine significantly decreased both ACTH (43.9 pg/ml to less than 12.0; normal, 12.0-40.0 pg/ml) and cortisol (29.9 microg/dl to 13.6; normal, 7.6-23.6 microg/dl). An M1-muscarinic receptor specific antagonist, pirenzepine hydrochloride, also had a diminishing effect on these hormones and this inhibiting effect was partially blocked by the simultaneous administration of an anticholinesterase agent, pyridostigmine bromide. Chronic oral ingestion of these agents led to improvement in clinical symptoms, and urinary 17-hydroxycorticosteroid and 17-ketosteroid levels were at normal to upper-normal levels. This is the first documentation of involvement of the cholinergic system in the pathogenesis of pituitary Cushing's syndrome.

17-Hydroxycorticosteroids↗

PubMed2001

Spontaneous recovery from hypopituitarism in a man with lymphocytic hypophysitis: a case report.

A 50-year-old man presented with hypopituitarism and a pituitary lesion on magnetic resonance imaging scan. He was diagnosed as having lymphocytic hypophysitis, and replacement therapy with hydrocortisone and thyroxine was started. He regained normal pituitary function after 10 months. Reports of spontaneous recovery from lymphocytic hypophysitis in men are rare. While the natural history of lymphocytic hypophysitis remains elusive and its management is not well established, our report shows that spontaneous resolution may occur with steroid supplementation even in men.

Adrenocorticotropic Hormone↗

PubMed2001

Postoperative plasma cortisol levels predict long-term outcome in patients with Cushing's disease and determine which patients should be treated with pituitary irradiation after surgery.

Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 microg/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 microg/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 microg/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 microg/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that 1) additional therapy should be avoided in patients with a postoperative plasma cortisol less than 2 microg/dl because relapse is very rare and radiotherapy will frequently induce hypopituitarism, 2) patients with a subnormal cortisol level following surgery should be treated with pituitary irradiation, because the relapse rate is reportedly high and radiotherapy is effective in preventing relapse, 3) radiotherapy in patients with persistent disease after surgery is effective only in 50% (5/10) of the patients.

Adenoma↗

PubMed2001

Rational, effective metyrapone treatment of ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH).

Standard therapy for ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH), a rare form of Cushing's syndrome, is bilateral adrenalectomy. Patients with AIMAH are usually elderly, with a variety of complications, and at risk for surgery. Postoperatively, they must receive lifelong corticosteroids and spend the remainder of their lives avoiding adrenal crisis. Therapy using metyrapone, a potent inhibitor of steroidogenesis, provides the advantages of avoiding the surgery. Its effectiveness is further anticipated because adrenal steroidogenic enzymes are reportedly weak in AIMAH. Treatment with metyrapone thus appears a good therapy for AIMAH, but its effectiveness has not, to our knowledge, been studied. We treated a 59-year-old man with AIMAH with metyrapone. At a low dose of metyrapone (500 to 750 mg/day), his plasma cortisol levels decreased to the normal range, and hypertension and diabetes mellitus were ameliorated. Therapy using metyrapone thus appears effective in treating AIMAH, and can be recommended for high risk AIMAH patients as an alternative therapy.

Adrenal Glands↗

PubMed2001

Thallium-201 scintigraphy was useful in diagnosing ectopic ACTH syndrome due to bronchial carcinoid.

Abstract. Initial investigations of a 70-year-old woman with clinical Cushing's syndrome, including overnight dexamethasone suppression test, CRH test, and pituitary MRI, suggested the presence of ectopic ACTH production. Thoracic computed tomography (CT) scan revealed a mass measuring 7 mm in the right lung, but it was thought to be an incidental opacity, leaving the source of ectopic ACTH undetermined for several years. During this period, although the size of the lung opacity did not change remarkably, serum cortisol levels became elevated to 43 microg/dl, and the patient's symptoms worsened. Tl-201 SPECT demonstrated intense accumulation in the right lung. The mass was surgically resected using thoracoscopy to investigate it as the focus of ACTH production. Histological and immunohistochemical examination confirmed that the area of intense Tl-201 uptake was an ACTH-producing bronchial carcinoid. Plasma ACTH and cortisol levels decreased immediately after the surgery. In conclusion, this case demonstrated Tl-201 scintigraphy as a useful tool in identifying the location of an ACTH-producing bronchial carcinoid.

ACTH Syndrome, Ectopic↗

PubMed2001

Seromucous cells in human sublingual glands: examination by immunocytochemistry of lysozyme.

This study examined the occurrence and morphological features of serous-type cells in human sublingual gland, using immunocytochemistry for lysozyme. Lysozyme-positive cells usually formed demilunes and occasionally their own acini. They were also found among cells of an intercalated duct and in its immature acinus consisting of a small number of secretory cells. All these serous cells could be classified as seromucous cells because they simultaneously revealed reactivity for mucus, i.e., a periodic acid-Schiff (PAS) and a periodic acid-thiocarbohydrazide-silver proteinate (PA-TCHSP) reaction under the light- and electron-microscope, respectively. Immunogold labeling of lysozyme in the seromucous cells was distributed on variously sized secretory granules. These usually possessed a single electron-dense spherule in an electron-lucent matrix, while granules of a homogenous structure were also present. Lysozyme-positive cells filled with large, lucent secretory granules could hardly be morphologically distinguished from the lysozyme-negative mucous cells; they corresponded to "intermediate" cells designated under the light microscope. All "immature" secretory cells with only a few secretory granules were also lysozyme-positive seromucous cells. The present study demonstrated that the seromucous cells in the human sublingual glands conform closely with those in the human labial glands (MIYAZAKI et. al., 1998).

Adolescent↗

PubMed2001

Clinical features and therapeutic outcomes of 65 patients with acromegaly at Tokyo Women's Medical University.

OBJECTIVE: The purpose of this study was to survey the clinical characteristics, complications, and therapeutic outcome in patients with acromegaly. PATIENTS AND METHODS: The clinical features of 65 patients with acromegaly (31 males, 34 females; mean age: 50+/-2 yr.) who were admitted to Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. RESULTS: The retrospective analysis revealed that the diagnosis of acromegaly was preceded by approximately 8.1+/-1.1 years of signs and symptoms of the disease. Forty-six of the 65 patients (71%) had macroadenomas, 16 (25%) had microadenomas, and the remaining three had empty sella. The rate of biochemical cure or remission was 81% for microadenoma (13/16), 64% for macroadenoma without extrasellar extension (9/14), and 13% for macroadenoma with cavernous sinus extension (2/15). Eighteen (28%) patients had impaired glucose tolerance (IGT) and 32 (49%) had diabetes mellitus (DM). After treatment for acromegaly, glucose metabolism was analyzed again in 38 patients, and it improved in 26 patients with IGT or DM. Twenty-five of 65 patients (38%) had hypertension. Of 26 patients who underwent barium enema or colonoscopy, 10 had colonic polyps and 4 had colon cancer. CONCLUSION: This study suggests that long-term excessive growth hormone (GH) secretion causes many complications. Therefore, awareness of the early symptoms and signs of acromegaly and long-term careful management of complications, along with therapy to reduce serum GH/insulin-like growth factor (IGF)-I levels, are important for patients with acromegaly.

Acromegaly↗