Biomedical subjects

A Takano

Publications and source records attributed to A Takano.

At least 19 recordsLinked to original sources

PubMed2004

Chain elongation suppression of cyclic block copolymers in lamellar microphase-separated bulk.

Chain elongation suppression of cyclic block copolymers in microphase-separated bulk was determined quantitatively. Solvent-cast and annealed films are confirmed to show alternating lamellar structure and their microdomain spacing D increases with increasing total molecular weight M according to the relationship D proportional, variant M0.59, which agrees quite consistently with the theoretically predicted power law, i.e., D proportional, variant M3/5. This result is in contrast to the well-established issue for linear block copolymers, where the relationship D proportional, variant M2/3 has been confirmed to hold both experimentally and theoretically. This means that chain elongation of each component block is suppressed considerably, owing to their looped conformation in strongly segregated bulk.

Journal Article↗

PubMed2001

Abnormal neuronal network in anorexia nervosa studied with I-123-IMP SPECT.

Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.

Adolescent↗

PubMed2001

Intracystic carcinoma of the male breast: report of a case.

We experienced a very rare case of male intracystic breast carcinoma. A 66-year-old man presented at our hospital because of a palpable mass in his right breast. The imaging diagnosis was an intracystic carcinoma with hemorrhagic fluid and two mural nodules. Modified radical mastectomy was performed under general anesthesia. The pathological examination revealed the intracystic papillary carcinoma with foci of microinvasion. The findings of power Doppler ultrasonography and dynamic magnetic resonance imaging were very useful for the differential diagnosis of our case.

Aged↗

PubMed2001

Triterpenoids from Adiantum caudatum.

Three triterpenoids, 8alpha-hydroxyfernan-25,7beta-olide, 3alpha-hydroxy-4alpha-methoxyfilicane and 19alpha-hydroxyferna-7,9(11)-diene were isolated from the fresh fronds of Adiantum caudatum. Their structures were elucidated by spectroscopic techniques. Thirteen known triterpenoids were also identified from this fern.

Ferns↗

PubMed2001

Interleukin-6 (IL-6) producing phaeochromocytoma: direct IL-6 suppression by non-steroidal anti-inflammatory drugs.

A 35-year-old Japanese woman presented with a phaeochromocytoma and demonstrated marked inflammatory reactions and pyrexia as a result of excessive production of interleukin-6 (IL-6) by the tumour. Serum IL-6 level was 262 ng/l (normal; < 4.0 ng/l). Fever and inflammatory markers were largely overcome by the administration of the nonsteroidal anti-inflammatory drug, naproxen, and all symptoms disappeared soon after the tumour was excised. Immunohistochemical study revealed positive staining using an antihuman IL-6 antibody and Northern analysis showed increased IL-6 mRNA levels in the tumour. Cultured tumour cells showed IL-6 protein synthesis, and nonsteroidal anti-inflammatory drugs such as naproxen and indomethacin directly inhibited IL-6 release. These results indicate that the effects of naproxen in vivo were due, at least in part, to direct suppression of IL-6 secretion from the tumour.

Adrenal Gland Neoplasms↗

PubMed2001

Two cell-counting factors regulate the aggregate size of the cellular slime mold Dictyostelium discoideum.

Countin, a cell-counting factor in Dictyostelium discoideum, is considered to limit the maximum size of the multicellular structure, because a countin null strain forms a huge fruiting body compared to that of the wild-type. A novel gene, countin2, that is highly homologous to countin (40% identity in amino acid sequence) was identified in the D. discoideum genome. The countin2 null strain formed a 1.7-fold higher number of the aggregates, resulting in smaller fruiting bodies compared with those of wild-type cells. Thus, the Countin2 protein is thought to limit the minimum size of the multicellular structure. The size and number of aggregates formed by a mixture of countin null and countin2 null strains were the same as those of the wild-type. These findings demonstrate that a combination of Countin and Countin2 proteins determines the appropriate size of the multicellular structure of D. discoideum.

Amino Acid Sequence↗

PubMed2001

Glomerulocystic kidney associated with subacute necrotizing-encephalomyelopathy.

A 22-year-old man with subacute necrotizing-encephalomyelopathy (SNE; Leigh's disease) was diagnosed as having progressive renal dysfunction. The clinical diagnosis of Leigh's disease was obtained by the typical central nervous lesions, abnormalities in other organs, and increased lactate concentrations in blood and cerebrospinal fluid. We performed an open biopsy of the right kidney. Light microscopic studies of the renal specimen showed diffuse glomerulocystic kidney (GCK) with tubulointerstitial damage. Electron microscopic examination showed marked swelling and increase in the number of mitochondria of the renal tubular epithelial cells. Therefore, it is suggested that mitochondrial disease seems to play an important role in developing GCK.

Adult↗

PubMed2001

Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes.

Osmotic shock induces GLUT4 translocation and glucose uptake through a mechanism independent of PI 3-kinase, but dependent on tyrosine phosphorylation of cellular proteins. To identify the tyrosine phosphorylated proteins required for osmotic shock-stimulated glucose uptake, we examined tyrosine phosphorylation of candidate proteins, and found that the 60-80kDa species including paxillin and the 120-130kDa species including p130Cas, PYK2, FAK and Gab1 were tyrosine-phosphorylated in response to osmotic shock. Inhibition of actin polymerization by cytochalasin D significantly decreased the tyrosine phosphorylation of paxillin, p130Cas, PYK2 and FAK but not Gab1, but had no effect on 2-deoxyglucose (DOG) uptake, suggesting a role for Gab1 in osmotic shock-induced glucose transport. Also, we found that osmotic shock increases the association of phospholipase C-gamma (PLC-gamma) with Gab1 and stimulates tyrosine phosphorylation of PLC-gamma itself. The PLC inhibitor, U73122, inhibited osmotic shock-induced 2-DOG uptake. These results suggest that tyrosine phosphorylation of Gab1 and subsequent recruitment and activation of PLC-gamma may play a role in osmotic shock-induced glucose transport.

3T3 Cells↗

PubMed2001

Clinical advantages of interictal SPECT coregistered to magnetic resonance imaging in patients with epilepsy.

PURPOSE: The aim of this study was to investigate the clinical value of coregistration of interictal SPECT and magnetic resonance imaging (MRI) in patients with partial epilepsy. MATERIALS AND METHODS: Seventeen patients with partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer SPECT during the interictal phase. The SPECT images were automatically coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated in both nonregistered images and coregistered images. RESULTS: SPECT images showed areas of decreased tracer uptake in 12 patients. In two patients, the relation between the tumor and the extent of decreased uptake became more accurate in the coregistered images. In five cases, the coregistered images clearly showed that the decreased uptake was located in the sulcus. The AIs were significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the images were coregistered in these cases. In five cases, the coregistered images indicated that the decreased areas were in agreement with the cortical findings. No significant differences in the AIs were observed in these cases (16.50 +/- 6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only to differentiate actual hypoperfusion from artificial hypoperfusion resulting from partial volume effects but also to improve the accuracy of AIs. CONCLUSION: The coregistration of interictal perfusion SPECT and MRI is useful not only to provide precise functional and anatomic mapping but also to improve the accuracy of calculations of the semiquantitative analysis of regional cerebral blood flow parameters during the interictal state of epilepsy.

Adolescent↗

PubMed2001

Thalamic asymmetry on interictal SPECT in patients with frontal lobe epilepsy.

BACKGROUND: Interictal brain single photon emission computed tomography (SPECT) is useful for the detection of seizure focus. Recent reports indicate a hypoperfusion in the ipsilateral thalamus as a seizure focus on interictal SPECT in temporal lobe epilepsy. In frontal lobe epilepsy (FLE), however, the alteration of perfusion in the thalamus has not been well documented. This study aimed to assess whether perfusion analysis on the thalamus may add useful information for the detection of epileptic foci in patients with FLE. METHODS: Interictal brain SPECT was performed in 11 patients with FLE. The asymmetry index for the thalamus and frontal area in the SPECT image was calculated in order to compare the laterality of the seizure foci. RESULTS: Thalamic asymmetry was seen in seven patients (64%), while cortial asymmetry was seen in six patients (55%). The concordance with the lateralization of the seizure foci was 6/7 (86%) in the thalamus, and 4/6 (67%) in the frontal area. Four patients showed only thalamic asymmetry. Concordance with the lateralization of the seizure focus was found in all of them. CONCLUSION: These preliminary results suggest that hypoperfusion in the thalamus may have a complementary role to lateralize the epileptic foci in patients with FLE.

Adolescent↗

PubMed2001

Mammalian target of rapamycin pathway regulates insulin signaling via subcellular redistribution of insulin receptor substrate 1 and integrates nutritional signals and metabolic signals of insulin.

A pathway sensitive to rapamycin, a selective inhibitor of mammalian target of rapamycin (mTOR), down-regulates effects of insulin such as activation of Akt (protein kinase B) via proteasomal degradation of insulin receptor substrate 1 (IRS-1). We report here that the pathway also plays an important role in insulin-induced subcellular redistribution of IRS-1 from the low-density microsomes (LDM) to the cytosol. After prolonged insulin stimulation, inhibition of the redistribution of IRS-1 by rapamycin resulted in increased levels of IRS-1 and the associated phosphatidylinositol (PI) 3-kinase in both the LDM and cytosol, whereas the proteasome inhibitor lactacystin increased the levels only in the cytosol. Since rapamycin but not lactacystin enhances insulin-stimulated 2-deoxyglucose (2-DOG) uptake, IRS-1-associated PI 3-kinase localized at the LDM was suggested to be important in the regulation of glucose transport. The amino acid deprivation attenuated and the amino acid excess enhanced insulin-induced Ser/Thr phosphorylation and subcellular redistribution and degradation of IRS-1 in parallel with the effects on phosphorylation of p70 S6 kinase and 4E-BP1. Accordingly, the amino acid deprivation increased and the amino acid excess decreased insulin-stimulated activation of Akt and 2-DOG uptake. Furthermore, 2-DOG uptake was affected by amino acid availability even when the degradation of IRS-1 was inhibited by lactacystin. We propose that subcellular redistribution of IRS-1, regulated by the mTOR-dependent pathway, facilitates proteasomal degradation of IRS-1, thereby down-regulating Akt, and that the pathway also negatively regulates insulin-stimulated glucose transport, probably through the redistribution of IRS-1. This work identifies a novel function of mTOR that integrates nutritional signals and metabolic signals of insulin.

Acetylcysteine↗

PubMed2001

A case of bilateral middle-ear squamous cell carcinoma.

Only eight cases of bilateral middle-ear squamous cell carcinoma (SCC) have been reported to date. We present the case of a 75-year-old male with bilateral middle-ear SCC and review the previously reported cases. The patient was diagnosed as having moderately-differentiated SCC in the left middle ear in February 1995 and well-differentiated SCC in the right middle ear in September 1997. He initially received radiation therapy with (60)Co pendulum (64 Gy) in the left ear and was subsequently treated by Liniac irradiation (50 Gy) in the right ear. He has now been followed up at our ENT clinic for 29 months without vertigo or facial nerve palsy since the second radiation therapy. Although he has a residual tumour in the right middle ear invading the middle cranial fossa dura, no sign of recurrence has been detected in the left ear.

Aged↗

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

Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator--activated receptor-gamma.

Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin resistance associated with obesity, a major risk factor for the development of type 2 diabetes. The insulin resistance induced by TNF-alpha is antagonized by thiazolidinediones (TZDs), a new class of insulin-sensitizing drugs. The aim of the current study was to dissect the mechanism whereby pioglitazone, one of the TZDs, ameliorates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Pioglitazone restored insulin-stimulated 2-deoxyglucose (DOG) uptake, which was reduced by TNF-alpha, with concomitant restorations in tyrosine phosphorylation and protein levels of insulin receptor (IR) and insulin receptor substrate (IRS)-1, as well as association of the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase with IRS-1 and PI 3-kinase activity. Adenovirus-mediated gene transfer of either wild-type human peroxisome proliferator-activated receptor (PPAR)-gamma2 or a mutant carrying a replacement at the consensus mitogen-activated protein kinase phosphorylation site (hPPAR-gamma2-S112A) promoted adipogenesis of 3T3-L1 fibroblasts and restored TNF-alpha-induced decrease of triglyceride in adipocytes as effectively as pioglitazone. Overexpression of the PPAR-gamma proteins in TNF-alpha-treated adipocytes restored protein levels of IR/IRS-1, but did not improve insulin-stimulated tyrosine phosphorylation of IR/IRS-1 or insulin-stimulated 2-DOG uptake. These results indicate that the ability of pioglitazone to restore insulin-stimulated tyrosine phosphorylation of IR/IRS-1, which is necessary for amelioration of TNF-alpha-induced insulin resistance, may be independent of the adipogenic activity of PPAR-gamma that regulates protein levels of IR/IRS-1.

3T3 Cells↗

PubMed2001

Growth hormone induces cellular insulin resistance by uncoupling phosphatidylinositol 3-kinase and its downstream signals in 3T3-L1 adipocytes.

Growth hormone (GH) is well known to induce in vivo insulin resistance. However, the molecular mechanism of GH-induced cellular insulin resistance is largely unknown. In this study, we demonstrated that chronic GH treatment of differentiated 3T3-L1 adipocytes reduces insulin-stimulated 2-deoxyglucose (DOG) uptake and activation of Akt (also known as protein kinase B), both of which are downstream effects of phosphatidylinositol (PI) 3-kinase, despite enhanced tyrosine phosphorylation of insulin receptor substrate (IRS)-1, association of IRS-1 with the p85 subunit of PI 3-kinase, and IRS-1-associated PI 3-kinase activity. In contrast, chronic GH treatment did not affect 2-DOG uptake and Akt activation induced by overexpression of a membrane-targeted form of the p110 subunit of PI 3-kinase (p110(CAAX)) or Akt activation stimulated by platelet-derived growth factor. Fractionation studies indicated that chronic GH treatment reduces insulin-stimulated translocation of Akt from the cytosol to the plasma membrane. Interestingly, chronic GH treatment increased insulin-stimulated association of IRS-1 with p85 and IRS-1-associated PI 3-kinase activity preferentially in the cytosol. These results indicate that cellular insulin resistance induced by chronic GH treatment in 3T3-L1 adipocytes is caused by uncoupling between activation of PI 3-kinase and its downstream signals, which is specific to the insulin-stimulated PI 3-kinase pathway. This effect of GH might result from the altered subcellular distribution of IRS-1-associated PI 3-kinase.

3T3 Cells↗

PubMed2000

Retinoblastoma protein phosphorylation via PI 3-kinase and mTOR pathway regulates adipocyte differentiation.

In the early phase of adipocyte differentiation, transient increase of DNA synthesis, called clonal expansion, and transient hyperphosphorylation of retinoblastoma protein (Rb) are observed. We investigated the role of these phenomena in insulin-induced adipocyte differentiation of 3T3-L1 cells. Insulin-induced clonal expansion, Rb phosphorylation and adipocyte differentiation were all inhibited by the PI 3-kinase inhibitors and rapamycin, but not the MEK inhibitor, whereas the MEK inhibitor, but not PI 3-kinase inhibitors or rapamycin, decreased c-fos induction. We conclude that insulin induces hyperphosphorylation of Rb via PI 3-kinase and mTOR dependent pathway, which promotes clonal expansion and adipocyte differentiation of 3T3-L1 cells.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Cloning and characterization of rat casein kinase 1epsilon.

Genes differentially expressed in the subjective day and night in the rat suprachiasmatic nucleus (SCN) were surveyed by differential display. A gene homologous to human casein kinase 1epsilon (CK1epsilon) was isolated, which initially appeared to be expressed in the suprachiasmatic nucleus (SCN) in a circadian manner. We here describe the cDNA cloning of the rat CK1epsilon and characterization of the protein products. The rCK1epsilon is predominantly expressed in the brain including the SCN, binds and phosphorylates mPer1, mPer2, and mPer3 in vitro, and translocates mPer1 and mPer3, but not mPer2, to the cell nucleus depending on its kinase activity when coexpressed with these Per proteins in COS-7 cells.

Alternative Splicing↗

PubMed2000

Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis.

Polymyositis (PM) is an autoimmune inflammatory muscle disease of unknown cause in which cellular immunity is thought to play an important pathogenic role. Class II major histocompatibility complex (class II MHC: human leukocyte antigen (HLA)-DR operates as a cofactor of antigen presentation in immunological responses. There has been a major debate over whether muscle fibers themselves synthesize and express HLA-DR molecules and play a role in antigen presentation in PM pathogenesis. In this study, we demonstrated that most muscle fibers from patients with PM synthesized and expressed HLA-DR molecules on their surface. Human leukocyte antigen-DR expression was highly specific to PM. In addition, class II transactivator (CIITA), human leukocyte antigen DM (HLA-DM), and invariant chain (Ii), which are indispensable for expression of mature HLA-DR molecules and for antigen processing and presentation, were co-expressed. One of the cytokines that could induce this expression is interferon-gamma (IFN-gamma), released by activated lymphocytes. Our results indicate that in PM muscle fibers synthesize and express HLA-DR molecules and may contribute to the inflammatory responses together with lymphocytes.

Adult↗