Search PubMed⌕ Search

Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 235 records · Page 13Linked to original sources
PubMed1998

Signalling into the T-cell nucleus: NFAT regulation.

The nuclear factor of activated T cells (NFAT) plays an important role in T-cell biology. Activation of T cells results in the rapid calcineurin-dependent translocation of NFAT transcription factors from the cytoplasm to the nucleus. This translocation process coupled to the subsequent active maintenance of NFAT in the nucleus compartment is critical for the induction of expression of several genes encoding cytokines and membrane proteins that modulate immune responses. The molecular cloning of the NFAT family of transcription factors has facilitated rapid progress in the understanding of the signalling mechanisms that control the activity of NFAT.

Amino Acid Sequence↗
PubMed1998

Progression from myelodysplastic syndrome with monosomy 7 to acute monoblastic leukemia with MLL gene rearrangement.

We report a case of myelodysplastic syndrome (MDS) with the 11q23 translocation at its leukemic transformation. Southern blot analysis demonstrated that the MLL gene on chromosome 11 was rearranged during the progression from MDS to acute leukemia. The clinical observation in this case supports the notion that leukemic transformation involves multiple cytogenetic evolutionary progresses, and that MLL gene rearrangement corresponds to the final step of leukemogenesis.

Child↗
PubMed1998

Increase of CD57+ T cells in knee joints and adjacent bone marrow of rheumatoid arthritis (RA) patients: implication for an anti-inflammatory role.

The distribution of CD57+ T and CD56+ T cells in patients with RA was examined. In control osteoarthritis patients, these cells exist as a minor population in the peripheral blood. Our data show that in patients with RA, CD57+ T cell levels are elevated in peripheral blood, knee joint fluid, knee synovial membrane and bone marrow (BM), compared with peripheral blood of controls. CD57+ T cells are especially high in knee joint fluid and joint-adjacent BM, while CD56+ T cells show no such increase. CD57+ T cells contain a major population of CD8+ cells and higher proportions of CD4-8- cells and gammadelta T cells than do CD57- T cells. CD57+ T cells in peripheral blood and joint fluid increase with the duration of disease. Erythrocyte sedimentation rate (ESR) is inversely correlated with the proportion of CD57+ T cells in the joint fluid. Although RA frequently occurs in patients with CD3+57+ cell leukaemia, and some CD57+ T cells are likely to be involved in the onset of RA, we suggest that CD57+ T cells may rather suppress inflammation of RA, and other cellular components (e.g. granulocytes) may govern the severity of the inflammation of RA. These CD57+ T cells are probably generated extrathymically in the adjacent BM or joint space.

Adult↗
PubMed1998

Endoscopic ligation for non-esophageal variceal upper gastrointestinal hemorrhage.

BACKGROUND: Endoscopic ligation can be used for bleeding lesions in non-fibrotic tissue; however, only small numbers of patients with non-esophageal variceal upper gastrointestinal hemorrhage have been treated in this way. To evaluate the utility of the technique, we performed the procedure to treat hemorrhage not from esophageal varices during emergency endoscopy. PATIENTS AND METHODS: Bleeding was identified from gastric Dieulafoy's ulcers (n=4), duodenal ulcers (n=3), gastric angiodysplasia (n=2) and Mallory-Weiss tears (n=3). The bleeding points were aspirated and controlled by endoscopic ligation and complete hemostasis was achieved in all cases. RESULTS: Although these lesions were located in difficult areas where endoscopic injection therapy and clipping sometimes fail, endoscopic ligation was performed easily and effectively without complications. Six of the patients had severe underlying disease, including acute and chronic myelogenous leukemia, liver cirrhosis and chronic renal failure; none suffered deterioration in their general condition after endoscopic ligation. CONCLUSIONS: Our findings suggest that endoscopic ligation is an easy and effective method of treatment for patients with gastrointestinal hemorrhage not from esophageal varices, and is safe even in patients with poor general health.

Adult↗
PubMed1998

Gene expression and roles of angiotensin II type 1 and type 2 receptors in human adrenals.

Although stimulation of aldosterone secretion is one of the functions of angiotensin II, the gene expression and biological significance of the angiotensin II receptor subtypes, AT1 and AT2, in the human adrenal have not been characterized. We therefore investigated the transcription levels of the receptor subtype genes and their roles in regulation of steroid secretion by human adrenals. The expression of AT1 and AT2 receptor mRNA was assessed by reverse transcription-polymerase chain reaction followed by Southern blot analysis in normal adrenocortical tissues (n = 6) and a series of adrenal tumour tissues: aldosterone-producing adrenocortical adenoma (n=6), Cushing's syndrome (n = 6) and pheochromocytoma (n = 6). The role of the two receptor subtypes in steroid secretion in vitro was examined by incubating the tissue with angiotensin II(1 microM) with or without the selective AT1 antagonist CV-11974 (1 microM). Both AT1 and AT2 receptor mRNA transcripts were demonstrated in all of the human adrenal tissues tested. Angiotensin II-induced aldosterone secretion was suppressed 50% upon the addition of CV-11974. The selective AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control, which was not suppressed by CV-11974. Angiotensin II and CGP-42112 did not affect cortisol secretion. These results suggest that both AT2 and AT1 receptors may be involved in the regulation of aldosterone secretion and tumorigenesis of the human adrenals.

Adenoma↗
PubMed1998

Differential effects of immunosuppressants and antibiotics on human monoclonal antibody production in SCID mouse ascites by five heterohybridomas.

SCID mice were inoculated with five human-mouse heterohybridomas derived by fusion of human lymph node lymphocytes from lung cancer patients with murine myeloma cells or human-mouse heteromyeloma cells, and the production of their human monoclonal antibodies (MAb) in the mouse ascites was investigated. In a comparison of the effects of pretreatment by i.p. (intraperitoneal) injection of pristane and anti-asialo GM1 serum on the antibody production of three of the hybridomas, pristane pretreatment resulted in substantial antibody production by all three, and pretreatment with anti-asialo GM1 serum resulted in similar or slightly lower levels of antibody production by two of the hybridomas but none by the third. In a second series of experiments using four of the hybridomas with pristane pretreatment, the co-injection of either penicillin G and streptomycin or kanamycin together with the hybridoma at the time of i.p. inoculation resulted in enhanced MAb production by the two heterohybridomas that had been propagated in medium containing hypoxanthine-aminopterin-thymidine (HAT) but not by the two that had been propagated in HAT-free medium.

Animals↗
PubMed1998

Th2-specific DNase I-hypersensitive sites in the murine IL-13 and IL-4 intergenic region.

IL-4 and IL-13 are cytokines preferentially produced by Th2 cells, and their genes are located in close proximity on human chromosome 5 and mouse chromosome 11. To identify potential regulatory elements that confer Th2-specific expression of IL-4 and IL-13 genes, we constructed a physical map of the IL-13/IL-4 locus and conducted DNase I-hypersensitive (DH) site analysis using Th clones and in vitro-differentiated effector Th cells obtained from TCR transgenic mice. Three DH sites, HSS1, HSS2 and HSS3, were identified within the intergenic region between IL-13 and IL-4 genes. HSS3 was observed both in Th1 and Th2 cells as well as CD4+ naive T cells, while HSS1 and HSS2 were detected exclusively in Th2 cells. The correlation between differentiation into Th2 subtype and the appearance of HSS1 and HSS2 suggests that these regions may play a role in subtype-specific expression of the IL-13/IL-4 locus.

3' Untranslated Regions↗
PubMed1998

Role of the kringle domain in plasminogen activation with staphylokinase.

We have evaluated the effect of lysine binding sites in kringle structures on the activation of plasminogen with plasmin and staphylokinase (SAK) complex and on the binding of plasminogen to SAK. Activation of native plasminogen (Glu-plasminogen) by a catalytic amount of plasmin-SAK complex increased in the presence of epsilon-amino-n-caproic acid (EACA) and then decreased with higher concentrations of EACA. By contrast, activation of modified plasminogen (Lys-plasminogen) decreased in an EACA-concentration-dependent manner. This decrease was explained by a more than 10-fold higher Km for activation of Lys-plasminogen with a catalytic amount of plasmin-SAK complex in the presence of EACA. EACA was a competitive inhibitor with Ki 0.23 mM. In addition, the Km for activation of mini-plasminogen, which lacks first four kringle structures (K1+2+3+4), was at least 3.5-fold higher than that for the activation of Lys-plasminogen. Furthermore, EACA showed a negligible inhibitory effect on the activation of mini-plasminogen by the plasmin-SAK complex. We observed a similar biphasic effect of EACA on the binding of Glu-plasminogen to SAK and a dose-dependent effect on the Lys-plasminogen binding to SAK by gel filtration methods. Since EACA binds to plasminogen via lysine binding sites in the kringle structure, we propose that the lysine binding site in K1+2+3+4 domain plays a role in the activation of plasminogen by plasmin SAK complex, and in the binding of plasminogen to SAK.

Aminocaproic Acid↗
PubMed1998

Disintegration of lysosomes mediated by GTPgammaS-treated cytosol: possible involvement of phospholipases.

We showed previously that cytosol treated with guanosine 5'-O-(3-thiotriphosphate) (GTP-gammaS) disintegrated lysosomes in vitro [Sai, Y. et al. (1994) Biochem. Biophys. Res. Commun. 198, 869-877] in time-, temperature-, and dose-dependent manners. This also requires ATP, however, the latter can be substituted with deoxy-ATP, ADP, or ATPgammaS, suggesting no requirement of ATP hydrolysis. The lysis was inhibited by several chemical modifiers, including N-ethylmaleimide, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, and by various phospholipase inhibitors (trifluoperazine, p-bromophenacyl bromide, nordihydroguaiaretic acid, W-7, primaquine, compound 48/80, neomycin, and gentamicin), but not by ONO-RS-082, an inhibitor of phospholipase A2. The reaction was also inhibited by phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidic acid, and phosphatidylcholine) and diacylglycerol. Among the phospholipase A2 hydrolysis products of phospholipids, unsaturated fatty acids (oleate, linoleate, and arachidonate) and lysophospholipid (lysophosphatidylcholine) by themselves broke lysosomes down directly, whereas saturated fatty acids (palmitate and stearate) had little effect. We found that GTPgammaS-stimulated cytosolic phospholipase A2 activity was highly sensitive to ONO-RS-082. These results suggest the participation of phospholipase(s), though not cytosolic phospholipase A2, in the GTPgammaS-dependent lysis of lysosomes.

Animals↗
PubMed1998

ARF-induced lysosomal lysis in vitro.

Cytosol treated with guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) disintegrated lysosomes in a dose-dependent manner, as detected as the release of preloaded fluorescein isothiocyanate-dextran. The effect of GTPgammaS was suppressed by GTP or GDP, indicating a role of a GTP binding protein (G-protein) in the lysis [Sai, Y. et al. (1994) Biochem. Biophys. Res. Commun. 198, 869-877]. Gel filtration of cytosol and GTP-ligand blotting showed that a small GTP-binding protein participated in the lysosomal lysis. We partially purified the G-protein from rat liver cytosol and identified it as ARF1. GTPgammaS-stimulated lysis was reconstituted with ARF1 purified from bovine brain cytosol or recombinant ARF1. ARF bound to lysosomal membranes depending upon GTPgammaS in a dose-dependent manner. These results suggest that the transfer of ARF from the cytosol to the lysosomal membrane is necessary for GTPgammaS-stimulated lysis of lysosomes.

ADP-Ribosylation Factor 1↗
PubMed1998

Gastric small-cell carcinoma in Japan: a case report and review of the literature.

The authors encountered a patient with primary gastric small-cell carcinoma (primary gastric SCC). Histologic examination revealed combined carcinoma containing non-small-cell elements such as adenocarcinoma and squamous cell differentiation. On preoperative biopsy, only well-differentiated adenocarcinoma was collected. Since gastric SCC was first reported in 1976, this type of carcinoma has been detected in 54 patients in Japan. Concerning these cases, the authors reviewed the light and/or electron microscopic findings of neuroendocrine granules, positive reaction for neuron-specific enolase staining, and the histologic type of resected specimens. There were only three patients positive for neuron-specific enolase in which light and electron microscopy demonstrated neuroendocrine granules. However, 50 patients (approximately 93%) overall satisfied at least one of these findings. Concerning the histologic characteristics of the resected specimens, multidirectional differentiation was more markedly observed compared with that in SCC of the lung. Adenocarcinomatous and/or squamous differentiation was observed in more than half the cases, and preoperative biopsy suggested carcinoma other than SCC or undifferentiated carcinoma in several cases.

Aged↗
PubMed1998

Molecular basis for tissue expansion: clinical implications for the surgeon.

A wide variety of tissue expansion techniques have been used for breast reconstruction, craniofacial surgery, and burn care in plastic reconstructive surgery. However, the basic mechanism by which skin and surrounding tissue respond to mechanical expansion remains unclear. Recent studies have revealed the biomechanical aspects of cells subjected to strain and various factors involved in the stretch-induced signal transduction pathway. In this regard, we have reported previously that mechanical force increases keratinocyte growth and protein synthesis and alters cell morphology. The mechanism by which strain causes an enhancement of cellular growth appears to be a network of several integrated cascades, implicating growth factors, cytoskeleton, and the protein kinase family. Recently, additional evidence has accumulated that mechanical strain stimulates signal transduction pathways that could trigger a series of cascades eventually leading to a new skin production. For example, we have evidence suggesting a key role for protein kinase C (PKC) in mechanosignaling as PKC is activated and translocated in keratinocytes subjected to strain in an isoform-specific manner. In this report, molecular mechanisms leading to enhancement of skin surface area are reviewed, and possible future applications are discussed.

Burns↗
PubMed1998

Establishment and characterization of a human Epstein-Barr virus-associated gastric carcinoma in SCID mice.

A transplantable human Epstein-Barr virus-associated gastric carcinoma (EBVaGC), designated KT, was propagated in severe combined immunodeficiency (SCID) mice for 12 passages. Mucin and cytokeratin expression and the Alu sequence in tumor DNA confirmed that the KT tumor was derived from human epithelial tissue. The identity of clonal EBV in the original and KT tumors was demonstrated by terminal repeat analysis of EBV DNA. The pattern of latency gene expression of EBV was the same in both tumors. EBER1 was presented similarly in tumor cell nuclei by in situ hybridization. Reverse transcription-PCR analysis also demonstrated Q-promoter-driven EBNA1 expression but not BZLF1, EBNA2, or LMP1 expression. Thus, the transplantable human EBVaGC KT retains the original EBV with the same latency gene expression and can serve as a model for this unique type of gastric carcinoma.

Adenocarcinoma↗
PubMed1998

Stress induced urinary incontinence in patients with spinocerebellar degeneration.

OBJECTIVES: To examine the pathophysiology of "stress induced urinary incontinence" (urinary incontinence evoked by abdominal straining) in patients with spinocerebellar degeneration. METHODS: Micturitional symptoms of 184 patients with spinocerebellar degeneration who were admitted to hospital were studied repeatedly. Urodynamic studies were made in symptomatic patients, and consisted of uroflowmetry, measurement of residual urine, urethral pressure profilometry, medium fill water cystometry, and external sphincter EMG. RESULTS: Twenty nine (15.8%) patients with spinocerebellar degeneration showed stress induced urinary incontinence. Twenty of the 29 patients had detrusor overactivity, low compliance detrusor, or residual urine, resembling urgency and overflow types of incontinence (complicated form). The other nine had none of these findings (pure form), but showed decreased maximum urethral closure pressure in four, absence of bulbocavernosus reflex in two, absence of voluntary sphincter contraction in one, incompetent urinary storage even at the first sensation in two, and high amplitude and polyphasic neurogenic changes in three of five patients studied, indicative of neurogenic sphincter dysfunction. CONCLUSIONS: Stress induced urinary incontinence in spinocerebellar degeneration had various underlying mechanisms. Some of the patients only showed evidence of pudendal denervation, which can cause external sphincter weakness and may reflect lesions of the sacral Onuf's nucleus and the pudendal nerve. Urodynamic studies are necessary to evaluate stress induced urinary incontinence in patients with spinocerebellar degeneration, to prescribe appropriate therapies.

Adolescent↗
PubMed1998

Inhibition of ovarian follicular development associated with a decrease in luteinizing hormone levels during the estrous cycle of the rat.

To examine the importance of tonic LH secretion in ovarian follicular development, plasma concentrations of LH were lowered by administering antiserum to GnRH (GnRH AS). At 1100 h on metestrus or diestrus of the 4-day estrous cycle, rats were injected with GnRH AS, and blood samples were collected at 6 h intervals until 1100 h on the next metestrus. Separately, rats were injected with hCG after the administration of GnRH AS to examine the effect of lowered LH on the number of ovulatory follicles. Treatment with GnRH AS on either metestrus or diestrus lowered plasma concentrations of LH, inhibin, and estradiol. In contrast, the plasma concentrations of FSH increased after the GnRH AS treatment, probably due to a decrease in plasma levels of inhibin associated with suppression of ovarian follicular development. Administration of GnRH AS on metestrus noticeably reduced the number of ovulatory follicles in spite of the high FSH secretion. Such a reduction in the number of ovulatory follicles was blocked by replacing rat LH with ovine LH. These data indicate that tonic secretion of LH plays an important role in the regulation of follicular development during the estrous cycle of the rat.

Animals↗
PubMed1998

Effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy.

OBJECTIVE: Although some studies have suggested a direct action of troglitazone on vascular cells, its effects on diabetic vascular diseases have not been reported. We therefore investigated the effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 30 patients with type 2 diabetes associated with microalbuminuria (urinary albumin-to-creatinine ratio [ACR] [milligrams per gram creatinine] ranging from 30 to 300 mg/g creatinine) were studied. They were randomly divided into two groups: patients treated with metformin (500 mg/day, n = 13) or with troglitazone (400 mg/day, n = 17) for 12 weeks. ACR, lipid profile, blood pressure, glycated hemoglobin, and plasma glucose during meal-load tests were measured every 4 weeks. RESULTS: Anthropometric indices (BMI and percent fat), lipid profile, and blood pressure did not change with either treatment. Fasting and postmeal glucose levels decreased similarly in the two groups. Decrements in glycated hemoglobin were greater in the metformin group at 4 and 8 weeks after the initiation of treatment (P < 0.05). Troglitazone reduced ACR (median [25-75th percentiles]) from 70 (49-195) to 40 (31-90) mg/g creatinine at 4 weeks (P = 0.021) and maintained these reduced levels throughout the treatment period (8 weeks: 35 [26-68], P = 0.007; 12 weeks: 43 [26-103], P = 0.047). Metformin did not change ACR throughout the 12 weeks. CONCLUSIONS: Troglitazone ameliorated microalbuminuria in diabetic nephropathy. Furthermore, our findings suggest that troglitazone has some effects on vascular cells other than lowering plasma glucose levels. Troglitazone might be useful for diabetic angiopathy, including nephropathy and coronary artery disease.

Aged↗
PubMed1998

Transcriptional control of cytokine genes.

With antigen stimulation, cytokine genes are coordinately expressed in T cells. However, the optimal signals or helper T cell subset specificity for each cytokine gene expression differ. Mechanisms probably exist that transmit extracellular signals into the nucleus, thereby coordinately turning on and off transcriptional machinery in a signal-specific or cell type-specific manner. We compare here the regulation of cytokine genes and discuss possible mechanisms of coordinated and differential regulation of cytokine genes.

Animals↗