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Biomedical subjects

T Sekine

Publications and source records attributed to T Sekine.

At least 109 records · Page 6Linked to original sources
PubMed1998

[A case of squamous cell carcinoma of the lung associated with exophthalmos and hypercalcemia].

A 69-year-old man visited in the department of ophthalmology of this university, complained with exophthalmos. He was pointed out hypercalcemia and transferred to the department of endocrinology. The chest X-ray and thoracic CT showed a large mass in lower lobe of the left lung. Cytological diagnosis of this tumor was squamous cell carcinoma. In clinical examination, serum CA was 12.2 mg/dl in spite of normal level of PTH, calcitonin, 1 alpha, -25 (OH) 2D3 and uric cAMP. On the other hand, PTHrP-intact in serum was 9.8 pmol/l. His thyroid gland had no abnormality in palpation or roentogenological examination. The thyroid functions, thyroglobulin, thyrotropin receptor antibody, thyroid test and microsome test were all in normal limit. From these results, he was diagnosed of lung cancer with humoral hypercalcemia of malignancy and euthyroid "isolated" Graves' ophthalmopathy. Left lower lobectomy with mediastinal lymph node dissection (R 2 a) was done and p-stage was IIIA. After operation, serum Ca decreased in normal level and the exophthalmos was also improved gradually. He was in well until 10 months after operation, and died with multiple lung metastases and hypercalcemia. Exophthalmos was also recurred in his terminal stage. Similar case could not find in literature and some discussion of the literatures was mentioned.

Aged↗
PubMed1998

[A case of pulmonary sequestration with atypical mycobacterial infection].

A 30-year-old woman complaining of cough, bloody sputum and left chest pain was admitted to our hospital. She had a history of recurrent pneumonia in the left lower lobe. On admission an abnormal shadow was recognized in the left lower lobe on chest radiograph. An enhanced CT scan showed an abnormal blood vessel extending from the descending aorta to the left lower lung. Aortography also indicated one aberrant artery, 15 mm in diameter, extending from the thoracic aorta to the left lower lobe. Pulmonary sequestration was subsequently diagnosed, and left lower lobectomy was later performed. Pathological examination after surgery revealed epithelioid cell granulomas and atypical Mycobacteria avium were detected on sputum culture. Cases of pulmonary sequestration complicated by atypical mycobacterial infection are rare.

Adult↗
PubMed1997

T cell clonality in synovial fluid of a patient with rheumatoid arthritis: persistent but fluctuant oligoclonal T cell expansions.

Recently, oligoclonal T cell accumulation has been reported in affected joints of patients with rheumatoid arthritis. To characterize such clonally accumulating T cells, we quantitatively monitored their frequency by analyzing TCR B chains. As a result, despite a similar TCR BV usage between synovial fluid (SF) and PBL, obviously skewed TCR BJ usage was detected in SF. Subsequent DNA sequencing demonstrated that the skewed BJ gene usage in SF resulted from clonal T cell accumulation. The complementarity-determining region 3 of TCR B chains of the detected clones appeared to have homologous amino acid sequences. Further, one of the predominant TCR B chains of the clones was identical with that reported previously. In the follow-up study, most of the accumulated clones persisted; however, in some, proportions were drastically decreased or increased during the time course. In particular, one of the clones expanded sixfold, from 11 to 67%, in the BV8-BJ2S3 TCR population of SF, even though the clone was not detected in PBL. In summary, oligoclonal T cell accumulation in SF was persistent, but it appeared to fluctuate independently of the clonality in PBL. The expansion of the clones in SF may occur by antigenic stimuli within the joint.

Amino Acid Sequence↗
PubMed1997

Expression cloning and characterization of a novel multispecific organic anion transporter.

Numerous drugs and endogenous compounds are efficiently excreted from the renal proximal tubule via carrier-mediated pathways. Transepithelial excretion of organic anions occurs via their accumulative transport from the blood into the proximal tubule cells across the basolateral membrane and subsequent secretion into the urine through the apical membrane. Here we report on the isolation of a novel complementary DNA from rat kidney that encodes a 551-amino acid residue protein (OAT1) with 12 putative membrane-spanning domains. When expressed in Xenopus laevis oocytes, OAT1 mediated sodium-independent para-aminohippurate (PAH) uptake (Km = 14.3 +/- 2.9 microM). The uptake rate of PAH was increased by the outwardly directed dicarboxylate gradient, consisting with the idea that OAT1 is an organic anion/dicarboxylate exchanger. OAT1 displayed remarkably wide substrate selectivity, covering endogenous substrates such as cyclic nucleotides, a prostaglandin and uric acid, and a variety of drugs with different structures (e.g. antibiotics, a nonsteroidal anti-inflammatory drug, diuretics, an antineoplastic drug, and a uricosuric drug). The Northern blot analysis and in situ hybridization revealed that OAT1 is exclusively expressed in the particular segment of the proximal tubule in the kidney. These data suggest that OAT1 is a multispecific organic anion transporter at the basolateral membrane of the proximal tubule. Isolation of OAT1 will facilitate elucidation of the molecular basis of drug kinetics and the development of new drugs lacking unwanted side effects.

Amino Acid Sequence↗
PubMed1997

Two-dimensional millisecond analysis of intracellular Ca2+ sparks in cardiac myocytes by rapid scanning confocal microscopy: increase in amplitude by isoproterenol.

Two dimensional images of myocardial Ca2+ sparks, non-propagating local rises in cytoplasmic Ca2+ concentration, were obtained at 4 msec intervals with a rapid-scanning confocal laser microscope, Nikon RCM 8000, and fluo-3. Spontaneous Ca2+ sparks were observed at apparently random sites throughout the cytoplasm of rat ventricular cells. The duration of sparks was 30 to 40 msec and the time to peak intensity about 10 msec. Ryanodine (1 microM) completely inhibited Ca2+ sparks while nicardipine (3 microM) had no effect. Isoproterenol (1 microM) had no effect on the frequency and distribution of Ca2+ sparks but significantly increased their amplitude. These results suggest that myocardial Ca2+ sparks are the result of spontaneous release of Ca2+ from the sarcoplasmic reticulum and that beta-adrenergic stimulation may result in functional modification of the ryanodine receptor channel.

Adrenergic beta-Antagonists↗
PubMed1997

Cardioprotective effect against ischemia-reperfusion injury of AHC-52, a dihydropyridine compound with inhibitory effect on Cl- but not Ca2+ current.

We examined the effects of a dihydropyridine compound, AHC-52, on guinea pig myocardium. In ventricular cardiomyocytes, AHC-52 (1 microM) had no effect on the basal peak inward and steady state currents, but inhibited the isoprenaline-induced time independent Cl- current. In coronary perfused right ventricular preparations, no-flow ischemia induced decreases in developed tension which recovered only to about 50% of initial values after reperfusion. AHC-52 (0.1 microM) had no effect on developed tension under normal conditions and during ischemia, but significantly improved the recovery of developed tension after reperfusion to about 80% of preischemic values. Thus, AHC-52 inhibits Cl- channels in cardiac muscle and may have protective effects against ischemia-reperfusion injury.

Animals↗
PubMed1997

A unique downregulation of h2-calponin gene expression in Down syndrome: a possible attenuation mechanism for fetal survival by methylation at the CpG island in the trisomic chromosome 21.

To understand the effect of trisomic chromosome 21 on the cause of Down syndrome (DS), DNA methylation in the CpG island, which regulates the expression of adjacent genes, was investigated with the DNAs of chromosome 21 isolated from DS patients and their parents. A methylation-sensitive enzyme, BssHII, was used to digest DNAs of chromosome 21, and the resulting DNA fragments were subjected to RLGS (restriction landmark genomic scanning). Surprisingly, the CpG island of the h2-calponin gene was shown to be specifically methylated by comparative studies with RLGS and Southern blot analysis. In association with this methylation, h2-calponin gene expression was attenuated to the normal level, although other genes in the DS region of chromosome 21 were expressed dose dependently at 1.5 times the normal level. These results and the high miscarriage rate associated with trisomy 21 embryos imply that the altered in vivo methylation that attenuates downstream gene expression, which is otherwise lethal, permits the generation of DS neonates. The h2-calponin gene detected by the RLGS procedure may be one such gene that is attenuated.

Base Sequence↗
PubMed1997

Long-term persistent accumulation of CD8+ T cells in synovial fluid of rheumatoid arthritis.

OBJECTIVE: To characterise the type and kinetics of T cell clones in synovial lesions of patients with rheumatoid arthritis (RA). METHODS: Mononuclear cells from serial samples of synovial fluid (SF) and peripheral blood from nine RA patients were separated phenotypically using antibody coated magnetic beads. After mRNA preparation, reverse transcription-polymerase chain reaction (RT-PCR) was performed to amplify V-D(N)-J (that is, the third complementarity determining, CDR3) regions of their T cell receptor beta chain genes. This was followed by single strand conformation polymorphism (SSCP) analysis to detect the clonotypes of accumulating T cells. Amino acid sequences of the dominant clones were also determined. RESULTS: Although peripheral T cells were heterogeneous, accumulation of oligoclonal T cells was detected in SF. The predominant accumulating clone was the CD8 subset, which was persistently present in serial samples obtained over almost one year of follow up. A proportion of these cells expressed CD25 or CD45RO, or both, suggesting they are 'memory' clones. CONCLUSION: The persistent presence of CD8+ T cell clones in RA joints indicates that they may be involved in the perpetuation of the chronic inflammatory process in RA joints.

Adult↗
PubMed1997

Chemical modification of L-asparaginase with comb-shaped copolymer of poly(ethylene glycol) derivative and maleic anhydride.

L-asparaginase from Escherichia coli, an antitumor enzyme, was chemically modified with a comb-shaped copolymer of poly(ethylene glycol) derivative and maleic anhydride (activated PM). The PM-modified asparaginase lost the immunoreactivity with retaining high enzymic activity and also prolonged the clearance time in blood. Intraperitoneal administration of PM-asparaginase markedly increased the mean survival-time of lymphoma L5178Y-bearing mice in comparison with that of unmodified asparaginase. Pretreatment of mice with PM-asparaginase before immunizing with unmodified asparaginase extremely suppressed the anti-asparaginase antibody production.

Animals↗
PubMed1997

A new T-lymphocyte cloning assay for detection of in vivo mutations in the human hypoxanthine-guanine phosphoribosyltransferase gene.

The X-linked hypoxanthine-guanine phosphoribosyl transferase (hprt) gene is a target of analyses of in vivo mutation frequencies in circulating T-lymphocytes. We established a novel, accessory cell-free cloning method of T-lymphocytes with a hprt mutation by a combined use of recombinant interleukin-2, conditioned medium from activating T-lymphocytes and culture plates coated with anti-CD3 monoclonal antibody. Using the method, we examined mutation frequencies of the hprt gene in T-lymphocytes from six healthy individuals, nine patients with colon cancer including two patients from different families with hereditary nonpolyposis colon cancer and six cancer-free relatives of the patients. In six healthy individuals, the mean cloning efficiency and mutation frequency (MF) of the hprt gene in T-lymphocytes were 0.51 +/- 0.28 and 9.4 +/- 7.5 x 10(-6), respectively. These data were similar to the reported values. The mean MFs in the nine colon cancer patients (10.6 +/- 7.3 x 10(-6)) were not significantly different from those of the 12 cancer-free individuals (11.6 +/- 9.4 x 10(6)). The correlation between mutation frequencies and age of the individuals was significant regardless of the presence or absence of cancers. The single-strand conformation polymorphism analyses of nested RT-PCR products of hprt mRNA were done in 33 mutant clones from five members of a family of which MF values were high. All the analyzed mutant clones show a genetic aberration in the coding region of the hprt gene. At least 28 of 33 mutants were independent. Our method provides a new versatile tool for in vivo analysis for mutations of the hprt gene.

Adult↗
PubMed1996

Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer.

In the human pancreatic cancer cell line PANC1, we detected several DNA fragments with abnormally intensified signals by restriction landmark genomic scanning. Major five of these fragments were cloned. All of the cloned fragments were mapped at the 19q13.1-13.2 region where the AKT2 oncogene was located. Southern blotting using the cloned DNA fragments and a fragment of AKT2 cDNA as probes revealed that the AKT2 gene was amplified in 3 of 12 pancreatic cancer cell lines analyzed including PANC1 and in 3 of 20 primary pancreatic cancers. The AKT2 gene was overexpressed in the 3 cell lines with the amplified gene. The results suggest that the AKT2 gene is a candidate oncogene activated by amplification in some human pancreatic cancers.

Base Sequence↗
PubMed1996

Myocardial and vascular effects of efonidipine in vitro as compared with nifedipine, verapamil and diltiazem.

1. Effects of efonidipine on isolated myocardial and aortic preparations were compared with those of nifedipine, verapamil and diltiazem. 2. All drugs produced concentration-dependent negative chronotropic effects on isolated guinea-pig atrial preparations. The potency order was efonidipine > or = nifedipine > diltiazem > or = verapamil, EC30 values being 3.08 x 10(-8)M, 3.48 x 10(-8)M, 1.27 x 10(-7)M and 1.47 x 10(-7)M, respectively. 3. Nifedipine, verapamil and diltiazem produced concentration-dependent negative inotropic effects on isolated guinea-pig left atrial preparations. The potency order was nifedipine > verapamil > diltiazem, EC30 values being 4.94 x 10(-8)M, 1.49 x 10(-7)M and 8.03 x 10(-7)M, respectively. Efonidipine, even at 1 microM produced no inotropic effect: 10 microM efonidipine decreased the contractile force by about 20%. 4. All drugs concentration-dependently attenuated the KCl-induced contraction of isolated rat aortic ring preparation. The potency order was nifedipine > efonidipine > verapamil > diltiazem, EC30 values being 2.98 x 10(-9)M, 1.24 x 10(-8)M, 3.96 x 10(-8)M and 2.13 x 10(-7)M, respectively. 5. Thus, efonidipine was demonstrated to be a potent vasodilator with negative chronotropic but minimal negative inotropic activity, which may be of benefit in the treatment of cardiovascular disorders.

Animals↗
PubMed1996

Gene expression of insulin signal-transduction pathway intermediates is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet.

To elucidate the effects of dietary fatty acid composition on the insulin signaling pathway, we measured the gene expression of the earliest steps in the insulin action pathway in skeletal muscle of rats fed a safflower oil diet or a beef tallow diet. Rats were meal-fed an isoenergetic diet based on either safflower oil or beef tallow for 8 weeks. Both diets provided 45%, 35%, and 20% of energy as fat, carbohydrate, and protein, respectively. Insulin resistance, assessed from the diurnal rhythm of plasma glucose and insulin and the oral glucose tolerance test (OGTT), developed in rats fed a beef tallow diet. Body fat content was greater in rats fed a beef tallow diet versus a safflower oil diet. The level of insulin receptor mRNA, relative expression of the insulin receptor mRNA isoforms, and receptor protein were not affected by the composition of dietary fatty acids. The abundance of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol (PI) 3-kinase mRNA and protein was significantly lower in rats fed a beef tallow diet versus a safflower oil diet. We conclude that long-term feeding of a high-fat diet with saturated fatty acids induces decrease in IRS-1 and PI 3-kinase mRNA and protein levels, causing insulin resistance in skeletal muscle.

Actins↗
PubMed1996

Tolerogenic capacity of poly(ethylene glycol) (PEG)--modified ovalbumins in relation to their immunoreactivity towards anti-ovalbumin antibody.

Ovalbumin (OVA) was chemically modified with poly(ethylene glycol) (PEG) derivatives: activated PEG2, 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine and activated PM13, copolymer of poly(oxyethylene) allyl methyl diether and maleic anhydride. Pretreatment of BALB/c mice with PEG2- or PM13-OVA suppressed the production of both IgG- and IgE-class anti-OVA antibodies induced by subsequent immunizations with unmodified OVA. PEG2-OVA had higher potency to suppress OVA-specific immune response than PM13-OVA. Although extensive modification (62%) of amino groups in the OVA molecule with activated PEG2 was required to diminish most of its immunoreactivity towards anti-OVA antibodies, only a low degree of modification (27%) was sufficient to induce tolerogenicity to OVA. Thus, the loss of immunoreactivity of PEG2-OVA was not prerequisite for its tolerogenic capacity. Moreover, the use of completely denatured PEG2-OVA immunogen lead to the loss of its ability to induce immune tolerance to native OVA. These observations are discussed in relation to the regulatory mechanism of immune response.

Animals↗
PubMed1996

[A case report of surgical resection of renal cell carcinoma with intrathoracic metastasis].

Reported herein is a surgical resection of rare intrathoracic metastasis of renal cell carcinoma. A 50-year-old man was admitted because of dispnea. Chest roentgenogram and computed tomogram (CT) revealed massive left pleural effusion, diffuse pleural thickening and multiple pleural tumors. Pleural biopsy with video assisted thoracoscopic surgery was performed and the pathological diagnosis of the pleural tumor was adenocarcinoma or malignant mesothelioma. Furthermore, abdominal CT showed a left renal tumor of 5 cm in diameter. For these information, the patient was diagnosed with pleural metastasis of renal cell carcinoma or renal metastasis of diffuse malignant pleural mesothelioma. Because there is no effective medical treatment for these two diseases, and the functions of patient's other organs were good, a left pleuropneumonectomy and left nephrectomy was performed at once. The final pathological diagnosis was renal cell carcinoma. Most of the metastatic lesions were localized in the pleura, though minute subpleural metastasis was seen.

Carcinoma, Renal Cell↗
PubMed1996

[The mechanisms of urate transport in the kidney and the intestine].

Most urate is secreted from the kidney, but the intestine can also secrete urate. In the kidney, urate is transported in the proximal tubule which shows marked species differences. In human and rat, net urate reabsorption is seen, whereas rabbit and pig show net secretion. The transport of urate in the proximal tubule is bidirectional, reabsorption in S1, secretion in S2, and postsecretory reabsorption in S3. Although the mechanisms of transcellular urate transport are not fully understood, the influx of urate into the proximal tubule cell should be carried out by urate/anion exchanger, and the efflux by potential driven pathway. In the intestine, purine compounds are strongly metabolized to urate, that is transported. When the kidney function is normal, urate is reabsorbed, but in renal insufficiency urate can be excreted from the intestine.

Aged↗
PubMed1995

Reproducible alterations of DNA methylation at a specific population of CpG islands during blast formation of peripheral blood lymphocytes.

We investigated the changes in the methylation patterns of CpG islands associated with blast formation of human peripheral blood lymphocytes activated by anti-CD3 and interleukin-2 (IL-2), using restriction landmark genomic scanning with a methylation-sensitive restriction enzyme (RLGS-M) system. Of about 2,100 NotI spot/loci which were analyzed, only 10 showed changes, whereas drastic changes have been observed in cases of malignant and SV40 transformation. These changes were highly reproducible for samples from both the same and different individuals. Even the timing of the changes after cultivation was the same. Thus, we concluded that at least the genomic DNA methylation state in vivo was essentially retained in T blast cells activated in vitro by induction with IL-2 and anti-CD3, which are commonly used in biological experiments as well as clinical diagnosis and therapy.

CD3 Complex↗