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Biomedical subjects

K Kotani

Publications and source records attributed to K Kotani.

At least 37 records · Page 2Linked to original sources

Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL.

BACKGROUND: Hypertriglyceridemia is associated with decreased HDL-cholesterol (HDL-C) and increased small dense LDL. In addition, small dense LDL is known to be susceptible to oxidation. METHODS: We measured LDL particle size, using gradient gel electrophoresis, and malondialdehyde-modified LDL (MDA-LDL), using an ELISA, and investigated the association between triglyceride (TG) concentrations, LDL size, and MDA-LDL. RESULTS: TG concentrations correlated negatively with the predominant LDL size (r = -0.650) and HDL-C concentration (r = -0.556). The relationship between TG concentration and LDL size, evaluated by measuring MDA-LDL, distinguished subgroups derived from four subfractions of TG concentrations and four distribution ranges of LDL size. These experiments indicated that there is a threshold for oxidation susceptibility at an LDL size of 25.5 nm and a TG concentration of 1500 mg/L. To investigate the relationship between LDL size, MDA-LDL concentration, and other lipids (TGs, HDL-C, apolipoprotein B, and total cholesterol), we evaluated them in control subjects and patients with diabetes mellitus or hypertriglyceridemia. When the size range for normal LDL was postulated to be 25.5 < or = phi (LDL diameter) < 26.5 nm, the MDA-LDL concentration was significantly higher in the subgroups of patients with LDL in the size range 24.5 < or = phi < 25.5 nm compared with patients with normal LDL. This result also suggests that the threshold is at a LDL size of 25.5 nm. CONCLUSION: The threshold for oxidation susceptibility coincided with the point of LDL size separation between the LDL subclass patterns A and B as an atherosclerotic risk.

Adult↗

[A case of schwannoma arising in brachial plexus with intrathoracic extension].

A case of benign schwannoma arising in the brachial plexus with intrathoracic extension was presented. The patient was a 55-year-old man, who was pointed out an abnormal shadow in the left apical region on routine chest X-ray examination. MRI showed that the mass extended to the lowest trunk of the brachial plexus. He had no complaint. Therefore, a diagnostic operation was performed. The tumor was subcapsularly resected with thoracoscopic surgery. Histopathological examination revealed a schwannoma (Antoni type A and B). It should be kept in mind that tumors arising in the brachial plexus are a probable differential diagnosis for tumors at the pulmonary apex, even if no neurological symptoms are seen in the upper extremities.

Brachial Plexus↗

[Video-assisted thoracoscopical surgery for pericardial cyst: report of two cases].

Two cases of pericardial cyst are reported. Case 1: A 51-year-old man, was admitted to the hospital because of an abnormal shadow on a chest CT scan. We confirmed a cystic mediastinal tumor situated between the superior vena cava and azygos vein. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. Patient 2, a 34-year-old woman was admitted to the hospital because of an abnormal shadow on a chest radiographic film. Chest CT scan showed a cystic mediastinal tumor. The cystic tumor was excised with a video-assisted thoracoscopic surgical procedure. Histopathological examination revealed a mesothelial-lined structure. We would recommend video-assisted thoracoscopic surgery which is of great value in the treatment of pericardial cyst.

Adult↗

Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes.

Atypical protein kinase C (PKC) isotype-specific interacting protein (ASIP) specifically interacts with the atypical protein kinase C isozymes PKClambda and PKCzeta. ASIP and atypical PKC, as well as their Caenorhabditis elegans counterparts (PAR-3 and PKC-3, respectively), are thought to coordinately participate in intracellular signaling that contributes to the maintenance of cellular polarity and to the formation of junctional complexes. The potential role of ASIP in other cellular functions of atypical PKC was investigated by examining the effect of overexpression of ASIP on insulin-induced glucose uptake, previously shown to be mediated through PKClambda, in 3T3-L1 adipocytes. When overexpressed in these cells, which contain PKClambda but not PKCzeta, ASIP was co-immunoprecipitated with endogenous PKClambda but not with PKCepsilon or with Akt. The subcellular localization of PKClambda was also altered in cells overexpressing ASIP. Overexpression of ASIP inhibited insulin stimulation of both glucose uptake and translocation of the glucose transporter GLUT4 to the plasma membrane, but it did not inhibit glucose uptake induced by either growth hormone or hyperosmolarity both of which promote glucose uptake in a PKClambda-independent manner. Moreover, glucose uptake stimulated by a constitutively active mutant of PKClambda, but not that induced by an active form of Akt, was inhibited by ASIP. Insulin-induced activation of PKClambda, but not that of phosphoinositide 3-kinase or Akt, was also inhibited by overexpression of ASIP. These data suggest that overexpression of ASIP inhibits insulin-induced glucose uptake by specifically interfering with signals transmitted through PKClambda.

3T3 Cells↗

Developmentally and regionally regulated participation of epidermal cells in the formation of collagen lamella of anuran tadpole skin.

We investigated the cellular mechanism of formation of subepidermal thick bundles of collagen (collagen lamella) during larval development of the bullfrog, Rana catesbeiana, using cDNA of alpha1(I) collagen as a probe. The originally bilayered larval epidermis contains basal skein cells and apical cells, and the collagen lamella is directly attached to the basement membrane. The basal skein cells above the collagen lamella and fibroblasts beneath it intensively expressed the alpha1(I) gene. As the skin developed, suprabasal skein cells ceased expression of the gene. Concomitantly, the fibroblasts started to outwardly migrate, penetrated into the lamella and formed connective tissue between the epidermis and the lamella. These fibroblasts intensively expressed the gene. As the connective tissue developed, the basal skein cells ceased to express the gene and were replaced by larval basal cells that did not express the gene. These dynamic changes took place first in a lateral region of the body skin and proceeded to all other regions except the tail. Isolated cultured skein cells expressed the gene and extracellularly deposited its protein as the type I collagen fibrils. Thus, it is concluded that anuran larval epidermal cells can autonomously and intrinsically synthesize type I collagen.

Animals↗

Mutation in bombesin receptor subtype-3 gene is not a major cause of obesity in the Japanese.

Bombesin receptor subtype-3 (BRS-3) is one of the candidate genes of obesity. The mice lacking BRS-3 have been shown to develop mild obesity. These mice also showed hypertension and impaired glucose metabolism, supporting these mice as a good model for human obesity. We screened 104 Japanese obese men (BMI > 26.4, 26.5-44.1) to investigate whether there is any genetic defect in BRS-3 gene. The DNA fragments containing each exon of BRS-3 gene were amplified by polymerase chain reaction (PCR) and were directly sequenced. No mutation, nor polymorphism was found in the coding region of BRS-3, suggesting that mutation of this gene is not a major cause of obesity in humans.

DNA Primers↗

Allele frequency of human endothelial nitric oxide synthase gene polymorphism in abdominal aortic aneurysm.

OBJECTIVE: This study was performed to examine the role of the endothelial constitutive NO synthase (ecNOS) gene in patients with abdominal aortic aneurysm (AAA). METHODS: We determined the distributions of polymorphism in intron 4 of the ecNOS (ecNOS4) gene, amplified by polymerase chain reaction, and compared the allele frequencies between subjects with abdominal aortic aneurysms (AAAs) and healthy individuals. PATIENTS: Fifty-eight patients with AAAs and 410 race-matched healthy controls were studied. RESULTS: Two alleles of the ecNOS4 gene, containing 4 (a-allele) and 5 (b-allele) repeats, were identified. We found that the a-allele frequency of this gene was significantly higher in the surgical than in the non-surgical group. CONCLUSION: The results of this study suggest that the a-allele of the ecNOS4 gene is indicative of the need for surgery for AAA. Analysis of the alleles of the ecNOS4 gene polymorphism could provide useful information concerning the clinical course of AAA progression.

Aged↗

[A case report of a mediastinal bronchogenic cyst with back pain].

We performed thoracoscopic surgery for a mediastinal bronchogenic cyst with complaining of back pain. The patient, a 38-year-old male, was admitted with an abnormal shadow on chest X-ray. Chest CT showed a localized tumor on the mediastine. MRI showed a cyst. Under thoracoscopy the tumor was based on parietal pleura and movable in chest cavity. We concluded that back pain was caused by a stimulus of a nerve in parietal pleura. Pathological diagnosis was a bronchogenic cyst.

Adult↗

Analysis of respiratory sinus arrhythmia with respect to respiratory phase.

We evaluated the respiratory modulation of heart rate, i.e., respiratory sinus arrhythmia (RSA), with respect to respiratory phase derived from an analytic signal from the lung volume curve, during spontaneous breathing and paced breathing with different patterns. The magnitudes and waveforms of RSA in the phase domain were similar regardless of breathing pattern, even including spontaneous breathing. An examination of the occurrence of heart beats with respect to the respiratory phase revealed that synchronized patterns recently reported in the literature (Nature 392: 239, 1998) were observed during paced breathing with breath holding periods whereby the respiratory phase advanced more slowly. It was concluded that the phase domain approach might be useful in extracting RSA during spontaneous breathing and for elucidating detailed mechanisms for RSA. However, the use of this technique for studies investigating cardio-respiratory coupling should be approached cautiously, as the results may be influenced by breathing patterns.

Adult↗

APS, an adapter protein with a PH and SH2 domain, is a substrate for the insulin receptor kinase.

APS (adapter protein with a PH and SH2 domain) is the newest member of a family of tyrosine kinase adapter proteins including SH2-B and Lnk. We previously identified SH2-B as an insulin-receptor-binding protein and substrate [Kotani, Wilden and Pillay (1998) Biochem J. 335, 103-109]. Here we show that APS interacts with the insulin receptor kinase activation loop through its SH2 domain and insulin stimulates the tyrosine-phosphorylation of APS. Furthermore, the phosphorylation of activation-loop tyrosine residues 1158 and 1162 are required for this interaction.

Adaptor Proteins, Signal Transducing↗

Dominant negative forms of Akt (protein kinase B) and atypical protein kinase Clambda do not prevent insulin inhibition of phosphoenolpyruvate carboxykinase gene transcription.

Transcriptional regulation of phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in hepatic gluconeogenesis, by insulin was investigated with the use of adenovirus vectors encoding various mutant signaling proteins. Insulin inhibited transcription induced by dexamethasone and cAMP of a chloramphenicol acetyltransferase (CAT) reporter gene fused with the PEPCK promoter sequence in HL1C cells stably transfected with this construct. A dominant negative mutant of phosphoinositide (PI) 3-kinase blocked insulin inhibition of transcription of the PEPCK-CAT fusion gene, whereas a constitutively active mutant of PI 3-kinase mimicked the effect of insulin. Although a constitutively active mutant of Akt (protein kinase B) inhibited PEPCK-CAT gene transcription induced by dexamethasone and cAMP, a mutant Akt (Akt-AA) in which the phosphorylation sites targeted by insulin are replaced by alanine did not affect the ability of insulin to inhibit transcription of the fusion gene. Akt-AA almost completely inhibited insulin-induced activation of both endogenous and recombinant Akt in HL1C cells. Furthermore, neither a kinase-defective mutant protein kinase Clambda (PKClambda), which blocked insulin-induced activation of endogenous PKClambda, nor a dominant negative mutant of the small GTPase Rac prevented inhibition of PEPCK-CAT gene transcription by insulin. These data suggest that phosphoinositide 3-kinase is important for insulin-induced inhibition of PEPCK gene transcription and that a downstream effector of phosphoinositide 3-kinase distinct from Akt, PKClambda, and Rac may exist for mediating the effect of insulin.

Cell Line↗

Requirement for Akt (protein kinase B) in insulin-induced activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1).

The roles of Akt (protein kinase B) and the atypical lambda isoform of protein kinase C (PKClambda), both of which act downstream of phosphoinositide 3-kinase, in the activation of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1) in response to insulin were investigated. A mutant Akt (Akt-AA) in which the phosphorylation sites targeted by growth factors are replaced by alanine was shown to inhibit insulin-induced activation of both Akt and glycogen synthase in L6 myotubes. Expression of a mutant Akt in which Lys179 in the kinase domain was replaced by aspartate also inhibited insulin-induced activation of glycogen synthase but had no effect on insulin activation of endogenous Akt. A kinase-defective mutant of PKClambda (lambdaDeltaNKD), which prevents insulin-induced activation of PKClambda, did not affect the activation of glycogen synthase by insulin. Insulin-induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells. However, lambdaDeltaNKD had no effect on 4E-BP1 phosphorylation induced by insulin. These data suggest that Akt, but not PKClambda, is required for insulin activation of glycogen synthase and for insulin-induced phosphorylation of 4E-BP1.

Amino Acid Sequence↗

Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese.

We determined polymorphism in the serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the polymerase chain reaction of Lesch et al., with minor modifications. The distribution of allele frequencies was determined and found to differ from that in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR to anxiety traits, by having 189 of the 501 subjects complete a self-rating questionnaire for anxiety and depression. Subjects with the short/short (s/s) genotype had significantly higher anxiety scores than those with the long/long (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the 1 allele.

Adult↗

Platelet nitric oxide metabolites in migraine.

Nitric oxide (NO) is a candidate as a causative molecule in migraine. We determined nitrite, total nitrate/nitrite, and cyclic guanosine 3',5'-monophosphate (cGMP) concentrations in platelets from 30 migraine without aura (MwoA) patients and 17 migraine with aura (MwA) patients. All migraine patients were studied during their migraine attacks. The control group consisted of 28 healthy volunteers. Concentrations of platelet nitrite and total nitrate/nitrite were determined using simple and sensitive nitrate/nitrite fluorometric assay techniques. High concentrations of platelet nitrite and total nitrate/nitrite were found in patients with MwoA and MwA when compared with healthy controls. High concentrations of platelet cGMP were also found in patients with MwoA and MwA. The levels of platelet total nitrate/nitrite significantly decreased in headache-free periods after treatment with oral propranolol. These findings suggest that NO is produced in platelets during migraine attacks. It may also be related to the migrainous pain and the changes in cerebral blood flow experienced during migraine attacks. These data may provide new strategies for the treatment of migraine.

Adult↗

Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt.

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in adipocytes in a phosphoinositide 3-kinase-dependent manner; however, downstream effectors that mediate signaling to PDE3B remain unknown. Insulin-induced phosphorylation and activation of endogenous or recombinant PDE3B in 3T3-L1 adipocytes have now been shown to be inhibited by a dominant-negative mutant of the serine-threonine kinase Akt, suggesting that Akt is necessary for insulin-induced phosphorylation and activation of PDE3B. Serine-273 of mouse PDE3B is located within a motif (RXRXXS) that is preferentially phosphorylated by Akt. A mutant PDE3B in which serine-273 was replaced by alanine was not phosphorylated either in response to insulin in intact cells or by purified Akt in vitro. In contrast, PDE3B mutants in which alanine was substituted for either serine-296 or serine-421, each of which lies within a sequence (RRXS) preferentially phosphorylated by cAMP-dependent protein kinase, were phosphorylated by Akt in vitro or in response to insulin in intact cells. Moreover, the serine-273 mutant of PDE3B was not activated by insulin when expressed in adipocytes. These results suggest that PDE3B is a physiological substrate of Akt and that Akt-mediated phosphorylation of PDE3B on serine-273 is important for insulin-induced activation of PDE3B.

3',5'-Cyclic-AMP Phosphodiesterases↗

Abdominal fat: standardized technique for measurement at CT.

The authors estimated abdominal fat distribution on the basis of measurements at computed tomography (CT). The attenuation range for fat tissue was defined as the interval within the mean plus or minus 2 SDs considered to be individual variation. Fat areas found with this method were closely correlated with those obtained by means of the computed planimetric method or with a fixed attenuation range from -190 to -30 HU as the standard of reference. Although the average CT numbers obtained with different scanners were distributed widely, the calculated fat areas were almost identical. This method might be a practical and standardized method at CT.

Adipose Tissue↗

[An effective case of a new biological adhesive agent, gelatin-resorcinol formaldehyde-glutaralhyde glue (GRFG-glue) in treating refractory pulmonary fistula following lobectomy for pulmonary aspergilloma].

We report a successful case of thoracoscopic therapy using a new biological adhesive agent, Gelatin-Resorcinol Formaldehyde glue (GRFG glue) for refractory pulmonary fistula. A 69-year-old male underwent right upper lobectomy for lung aspergilloma. Air leakage began 11 days after lobectomy. Closing alveolar fistula was performed 28 days after first operation. Relapsing air leakage began 2 days after second operation. The insertion of fibrin glue through thoracoscope at two times was not effective for refractory pulmonary fistula. But the insertion of GRFG glue was effective to close the fistula completely.

Aged↗

[Use of an expandable metallic stent in 4 patients with superior vena syndrome].

Recently developed expandable metallic stents have been adopted to superior vena cava syndrome with good results. We inserted stents into the superior vena cava in 4 patients with superior vena cava syndrome. The results were comfortable and no complications. We should consider the stenting as the first choice for superior vena cava syndrome.

Adult↗