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Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 109 records · Page 6Linked to original sources

Renal arteriovenous malformation with thrombus in the inferior vena cava.

BACKGROUND: Thrombus formation in the inferior vena cava (IVC) is usually seen in cases with malignancy. In contrast, vascular anomalies hardly ever accompany this disorder. Herein, a case of thrombus formation in the IVC associated with renal arteriovenous malformation (AVM) is reported. METHODS/RESULTS: A 50-year-old woman who received transarterial embolization (TAE) for AVM in the right kidney noticed right flank pain with macrohematuria 12 months later. Because radiographic evaluation could not rule out malignancy in the kidney, nephrectomy was performed. During nephrectomy, a palpable thrombus was found in the IVC, so thrombectomy was performed simultaneously. Histopathologic examination revealed an old infarction due to the TAE, circumferential arteriovenous thrombi and a large organized thrombus up to the IVC, but neither renal cell carcinoma nor transitional carcinoma in the kidney. CONCLUSIONS: Careful observation may be required, even after treatment for renal AVM, such as TAE, to avoid the formation of an IVC thrombus.

Angiography↗

Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5.

The mature form of Alzheimer's beta-amyloid precursor protein (APP) is phosphorylated specifically at Thr(668) in neurons. In mature neurons, phosphorylated APP is detected in neurites, with dephosphorylated APP being found mostly in the cell body. In vitro, active cyclin-dependent kinase 5 (Cdk5) phosphorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature neurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and significantly diminished the level of phosphorylated APP. The expression of APP was unaffected in antisense-treated neurons. These results indicate that in neurons APP is phosphorylated by Cdk5, and that this may play a role in its localization.

Amyloid beta-Protein Precursor↗

Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function.

Omega-hydroxyceramides (omega-OHCer) are the predominant lipid species of the corneocyte lipid envelope in the epidermis. Moreover, their omega-esterified-derivatives (acylCer) are major components of the stratum corneum extracellular lamellae, which regulate cutaneous permeability barrier function. Because epidermal omega-OHCer appear to be generated by a cytochrome P450-dependent process, we determined the effects of a mechanism-based inhibitor of omega-hydroxylation, aminobenzotriazole (ABT), on epidermal omega-OH Cer formation and barrier function. We first ascertained that ABT, but not hydroxybenzotriazole (OHBT), a chemical relative with no P450 inhibitory activity, inhibited the incorporation of [14C]-acetate into the omega-OH-containing Cer species in cultured human keratinocytes (68.1% +/- 6.9% inhibition versus vehicle-treated controls; p < 0.001), without altering the synthesis of other Cer and fatty acid species. In addition, ABT significantly inhibited the omega-hydroxylation of very long-chain fatty acids in cultured human keratinocytes. Topical application of ABT, but not OHBT, when applied to the skin of hairless mice following acute barrier disruption by tape-stripping, resulted in a significant delay in barrier recovery (e.g., 38.3% delay at 6 h versus vehicle-treated animals), assessed as increased transepidermal water loss. The ABT-induced barrier abnormality was associated with: (i) a significant decrease in the quantities of omega-OHCer in both the unbound and the covalently bound Cer pools; (ii) marked alterations of lamellar body structure and contents; and (iii) abnormal stratum corneum extracellular lamellar membrane structures, with no signs of cellular toxicity. Furthermore, pyridine-extraction of ABT- versus vehicle-treated skin, which removes all of the extracellular lamellae, leaving the covalently attached lipids, showed numerous foci with absent corneocyte lipid envelope in ABT- versus vehicle-treated stratum corneum. These results provide the first direct evidence for the importance of omega-OHCer for epidermal permeability function, and suggest further that acylCer and/or corneocyte lipid envelope are required elements in permeability barrier homeostasis.

Administration, Topical↗

Regulatory mechanisms for transforming growth factor beta as an autocrine inhibitor in human hepatocellular carcinoma: implications for roles of smads in its growth.

Transforming growth factor beta (TGF-beta) initiates signaling through heteromeric complexes of transmembrane type I and type II serine/threonine kinase receptors. Activated TGF-beta type I receptor phosphorylates receptor-regulated Smads (2 and 3). Antagonistic Smad 7 forms stable association with the activated TGF-beta type I receptor, blocking phosphorylation of receptor-regulated Smads. On the other hand, elevated serum concentration of TGF-beta along with resistance to its growth-inhibitory effect is commonly observed in human hepatocellular carcinoma (HCC) patients. In this study, we investigated the mechanisms of resistance to tumor-derived TGF-beta in human HCC and hepatoblastoma-derived cell lines, focusing on the roles of receptor-regulated Smads and antagonistic Smad 7. HuH-7 and HepG2 cells showed poor response to TGF-beta-mediated growth inhibition. Because neutralization of TGF-beta in the medium or blockage of signal transduction pathway by inductions of dominant negative Smad 2/3 resulted in a stimulation of cell growth, tumor-derived TGF-beta signal acts on cell growth negatively. However, Smad 7 induced by TGF-beta negatively regulated Smad 2 action and rendered most Smad 2 proteins in the cytoplasm. Taken together, these results indicate that endogenous TGF-beta-mediated induction of Smad 7 results in a higher "threshold" for the antiproliferative signals mediated by receptor-regulated Smads, and can be involved in reduced responsiveness to the cytokine in some human HCC cells.

Carcinoma, Hepatocellular↗

Cerebrospinal fluid somatostatin levels in febrile seizures and epilepsy in children.

We analysed the level of cerebrospinal fluid (CSF) somatostatin in children with febrile seizures and epilepsy. In the febrile seizure group (n = 23), the somatostatin level was 83.9 +/- 11.2 pg/ml, which was significantly higher than that of age-matched controls. CSF samples obtained within 3 h of the last seizure had higher somatostatin levels (106.1 +/- 12.4 pg/ml;n = 14) than did the CSF obtained after 3 h (49.4 +/- 15.6 pg/ml;n = 9). The mean somatostatin level in the epilepsy group was 35.3 +/- 4.3 pg/ml (n = 34), and was distributed as follows: 27.6 +/- 3.6 pg/ml in the idiopathic generalized epilepsy group (n = 16), 44.0 +/- 9.4 pg/ml in the symptomatic generalized epilepsy group (n = 13), and 37.2 +/- 10.1 pg/ml in the partial epilepsy group (n = 5). The levels in each group were significantly higher than those in age-matched controls. Somatostatin is a hypothalamic tetradecapeptide with excitatory effects on neurons in children with febrile seizures and epilepsy. The finding that patients with convulsive disease had elevated levels of CSF somatostatin suggests that somatostatin release is somehow related to seizure activity. It remains to be determined whether this is due to increased release from over-active excitatory neurons or leakage from damaged or anoxic neurons, secondary to seizure activity.

Adolescent↗

Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis.

Galloyl glucoses and galloyl proanthocyanidins obtained from rhubarb (Rhei Rhizoma, Rheum palmatum L., Polygonaceae); e.g. 1,2,6-tri-O-galloyl-beta-D-glucose (IC50 = 0.63 microM), 1,6-di-O-galloyl-2-O-cinnamoyl-beta-D-glucose (IC50 = 0.58 microM), procyanidin B-2 3,3'-di-O-gallate (IC50 = 0.54 microM), and procyanidin B-5 3,3'-di-O-gallate (IC50 = 0.55 microM), were found to be potent inhibitors of rat squalene epoxidase (SE). The inhibition at submicromolar level was far more potent than that of chemically synthesized substrate analogs. It was demonstrated for the first time that the cholesterol-lowering effect of rhubarb may be attributed to the potent inhibition activities of SE, a rate-limiting enzyme of cholesterol biogenesis.

Animals↗

Effect of application volume of ethanol-isopropyl myristate mixed solvent system on permeation of zidovudine and probenecid through rat skin.

Permeation of zidovudine (AZT) and probenecid from an ethanol-isopropyl myristate (IPM) mixed system through rat skin was studied in a finite system. Several volume sizes of the ethanol-IPM mixed systems containing AZT and probenecid, both as suspensions, were applied on the skin of the hairless rat using a vertical glass cell, and the fractions of the drugs permeated in 8 hr Q%,8 hr were determined. For the systems containing 40% ethanol, the Q%,8 hr value decreased with the reduction of volume of the system applied, and the decreasing profile was similar to that calculated on the assumption that the permeability of the drug does not change with the volume of the sample applied. On the other hand, in the systems containing 10% or 20% ethanol, the Q%,8 hr value showed a maximum when a specific volume of the sample was applied. Therefore, the effect of sample volume on the Q%,8 hr value was different between the 40% ethanol-IPM system and the 10% or 20% ethanol-IPM system. Following pretreatment of the skin with 0.105 ml/cm2 of drug-free 40% ethanol-IPM for 2 hr, several volume sizes of 10% ethanol-IPM systems containing the drugs were applied on the skin to explain why the different profiles were observed in the system containing 10% or 20% ethanol. The results for pretreated skin suggest that the amount of ethanol in the systems with low ethanol concentration and small application volume is too small to exert an effect that enhances permeation of the drugs. In those systems, the integrated effect of ethanol on the skin would be important for the enhancing effect. Total volume, as well as concentration, of an enhancer should be set precisely in designing an efficient transdermal delivery system.

Administration, Cutaneous↗

Differential expression of mouse alpha5(IV) and alpha6(IV) collagen genes in epithelial basement membranes.

We first completed the primary structure of the mouse alpha5(IV) and alpha6(IV) chains, from which synthetic peptides were produced and a chain-specific monoclonal antibodies were raised. Expression of collagen IV genes in various basement membranes underlying specific organ epithelia was analyzed by immunohistochemical staining using these monoclonal antibodies and other antibodies from human and bovine sequences. It was possible to predict the presence of the three collagen IV molecules: [alpha1(IV)](2) alpha2(IV), alpha3(IV)alpha4(IV)alpha5(IV), and [alpha5(IV)](2)alpha6(IV). In skin basement membrane two of the three forms, [alpha1(IV)](2)alpha2(IV) and [alpha5(IV)](2)alpha6(IV), were detected. The alpha3(IV)alpha4(IV)alpha5(IV) molecule was observed as the major form in glomerulus, alveolus, and choroid plexus, where basement membranes function as filtering units. The molecular form [alpha5(IV)](2)alpha6(IV) was present in basement membranes in tubular organs such as the epididymis, where the tubes need to expand in diameter. Thus, the distribution of the basement membranes with different molecular composition is consistent with tissue-specific function.

Amino Acid Sequence↗

A case of hemangioma accompanied by inflammatory pseudotumor of the spleen.

Both hemangioma and inflammatory pseudotumor (IPT) of the spleen are rare benign mass lesions. Moreover, a splenic hemangioma accompanied by IPT is extremely rare. A 61-year-old woman who suffered from liver cirrhosis had a splenic cavernous hemangioma surrounded by granuloma. The literature on IPT of the spleen has described several possibilities of its causes; however, it is still unknown. This case was accompanied by portal hypertension due to liver cirrhosis, which may cause microrupture of hemangioma resulting in an IPT.

Female↗

Hydralazine decreases blood pressure and endothelin-1 mRNA expression in tissues but not cardiac weight in SHR-SP/Izm rats.

Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac hypertrophy and ET-1 gene expression in various tissues of spontaneously hypertensive rats (SHR-SP/Izm). Hydralazine (20 mg/kg/day) was administered orally from the age of 4 weeks for 8 weeks. Tissues of the kidney, heart, aorta and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Administration of hydralazine resulted in a significant decrease in the blood pressure (156 +/- 1 mmHg vs 212 +/- 4 mmHg in controls) and an increase in the heart rate (470 +/- 20 bpm vs 402 +/- 23 bpm in controls). ET-1 mRNA expression was significantly decreased in the heart (x 1/2), kidney (x 1/4) and brain (x 1/2). There was no significant change of the cardiac weight (309 +/- 4 mg/100 g body weight vs 307 +/- 5 mg/100 g body weight in controls). The dissociation between ET-1 mRNA expression and cardiac hypertrophy in hydralazine-treated rats may suggest that the increased tissue ET-1 is not an indispensable factor of cardiac hypertrophy in hypertension. Sympathetic activation, as shown by the reactive tachycardia, may overcome the effects on the blood pressure and ET-1 expression.

Animals↗

Augmented expression of tissue endothelin-1 messenger RNA is a common feature in hypertensive rats.

Recent studies revealed important roles for endothelin-1 (ET-1) in the pathogenesis of hypertension. Whether ET-1 could be a primary cause of hypertension or a secondary factor associated with hypertension, however, remains unknown. In this study, we determined plasma ET-1 levels and the expression of ET-1 mRNA in tissues of rats rendered hypertensive using distinct mechanisms: deoxycorticosterone acetate (DOCA)-salt hypertension: N(G)-nitro-L-arginine-methyl ester- (L-NAME) induced hypertension; and spontaneously hypertensive rats (SHR-SP). ET-1 mRNA expression level was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blotting. There was no significant difference in plasma ET-1 levels between the hypertensive rats and normotensive rats. By contrast, ET-1 mRNA level was significantly increased in various tissues including the adrenal, lung, kidney and brain of these hypertensive rats compared with control rats. Thus, ET-1 gene expression was ubiquitously augmented in tissues of hypertensive rats irrespective of the cause of the hypertension. The results suggest that the increase in ET-1 expression is not the primary cause of hypertension but a secondary outcome which may further exacerbate the hypertension.

Animals↗

Hemodynamic and biochemical effects of endothelin-A- and -B-receptor antagonist TAK-044 in stroke-prone spontaneously hypertensive rats.

We have demonstrated previously that endothelin-1 (ET-1) mRNA expression is increased in hypertensive rats. The aim of the study reported here was to elucidate the effects of the endothelin (ET) receptor antagonist on the hemodynamic and biochemical parameters in stroke-prone spontaneously hypertensive rats (SHRSPs/Izm). The endothelin-A- and -B- (ETA/ETB) receptor antagonist (TAK-044, Takeda Chemical Industries, Osaka, Japan) was administered subcutaneously at a dose of 10 mg/kg/day from the age of 8 weeks for 4 weeks. Blood samples and tissues of the kidney, heart and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Treatment with TAK-044 resulted in a significant decrease in systolic blood pressure (SBP), blood urea nitrogen (BUN), serum creatinine concentration, plasma aldosterone level, heart weight, and kidney weight. In addition, ET-1 contents and mRNA expression level in the kidney, heart and brain were significantly decreased by the treatment with TAK-044. These results suggest that the ET receptor antagonist TAK-044 is able to attenuate ET-1 gene expression in addition to its specific antagonism of the biological actions of ET via the receptors.

Animals↗

Different amounts of K-ras mutant epithelial cells in pancreatic carcinoma and mass-forming pancreatitis.

Clinically, differential diagnosis of pancreatic carcinoma (PC) and so-called "mass-forming pancreatitis (MFP)" is difficult. We analyzed the amount, ductal level, and K-ras mutation of ductal hyperplasia and intraductal carcinoma in surgically resected cases of MFP (n = 18) and PC (n = 16). DNAs extracted from microdissected epithelial foci were analyzed for K-ras codon 12 mutation by nested polymerase chain reaction and restriction fragment length polymorphism. The histology of MFP showed severe destruction of exocrine tissue and pancreatic stones and/or protein plugs (72%, 13 of 18 cases) in mostly peripheral ducts. The average basal membrane lengths of nonpapillary and papillary hyperplasia in cases of carcinoma were about 4 and 15 times more than those of MFP, respectively. The frequency of K-ras mutation in hyperplastic foci increased from nonpapillary [six (27%) of 22] to papillary foci [16 (64%) of 25] in K-ras mutant PCs, but there was no difference between nonpapillary [one (6%) of 18] and papillary foci (none of 19) in K-ras wild-type PCs, and also between nonpapillary (none of 24) and papillary foci [one (7%) of 14] in MFPs.

Adenocarcinoma↗

Asaia bogorensis gen. nov., sp. nov., an unusual acetic acid bacterium in the alpha-Proteobacteria.

Eight Gram-negative, aerobic, rod-shaped and peritrichously flagellated strains were isolated from flowers of the orchid tree (Bauhinia purpurea) and of plumbago (Plumbago auriculata), and from fermented glutinous rice, all collected in Indonesia. The enrichment culture approach for acetic acid bacteria was employed, involving use of sorbitol medium at pH 3.5. All isolates grew well at pH 3.0 and 30 degrees C. They did not oxidize ethanol to acetic acid except for one strain that oxidized ethanol weakly, and 0.35% acetic acid inhibited their growth completely. However, they oxidized acetate and lactate to carbon dioxide and water. The isolates grew well on mannitol agar and on glutamate agar, and assimilated ammonium sulfate for growth on vitamin-free glucose medium. The isolates produced acid from D-glucose, D-fructose, L-sorbose, dulcitol and glycerol. The quinone system was Q-10. DNA base composition ranged from 59.3 to 61.0 mol% G + C. Studies of DNA relatedness showed that the isolates constitute a single species. Phylogenetic analysis based on their 16S rRNA gene sequences indicated that the isolates are located in the acetic acid bacteria lineage, but distant from the genera Acetobacter, Gluconobacter, Acidomonas and Gluconacetobacter. On the basis of the above characteristics, the name Asaia bogorensis gen. nov., sp. nov. is proposed for these isolates. The type strain is isolate 71T (= NRIC 0311T = JCM 10569T).

Acetic Acid↗

Mutations in zinc-binding domains of p53 as a prognostic marker of esophageal-cancer patients.

Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 (P=0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others (P=0.0105). Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.

Adult↗

Normal kinematics of the interosseous membrane during forearm pronation-supination--a three-dimensional MRI study.

We studied in vivo dynamic shape changes of the interosseous membrane (IOM) during forearm rotation using three-dimensional magnetic resonance imaging (3D-MRI), and simultaneously analysed 3D-motion of the forearm rotation. Wavy deformities were seen in the IOM in the pronated position, and similar small changes were also seen at maximum supination (average 82 degrees ) and in the neutral position. These dynamic changes mainly occurred in the membranous part of the IOM, whereas the tendinous part demonstrated minimal dynamic changes during rotation in all subjects. On the dorsal aspect, deformity around the dorsal oblique cord was seen at maximum pronation. From this 3D-MRI observation, the tendinous part is considered to be taut during rotation to provide stability between the radius and ulna, because of its straightness and less dynamic changes. The more deformable membranous part is important to allow for smooth rotation, since it lies at a distance from the rotation axis. Inelasticity developing in the membranous part from trauma may pre-dispose to pronation-supination contracture. The radius rotated around the ulna from maximum supination to 45 degrees pronation. At maximum pronation (average 75 degrees ), the radius translated average 1.8 mm palmarly and rotated average 4.0 degrees ulnarward on the ulna. Incongruity of the distal radioulnar joint, contraction of the pronator quadratus and torsion between the radius and ulna at maximum pronation may produce this irregular motion of the radius and cause the dynamic changes of the IOM.

Adult↗