3-dimensional fast spin-echo in determining the indication for cochlear implantation.
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Biomedical subjects
Publications and source records attributed to Y Kanda.
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Computer analysis of the human placental lactogen-B (hPL-B) enhancer reveals two putative binding sites for the transcription factor NF-IL6, but the role of NF-IL6 in the regulation of the enhancer is unknown. Using gel mobility shift and supershift assays, we demonstrated that NF-IL6 binds to both enhancer sites. Transient transfection studies indicated that the transcription factor NF-IL6 stimulates hPL-B enhancer activity by 4.4-fold in primary cultures of human trophoblast cells and by 32.0- and 8.4-fold in JAR and BeWo choriocarcinoma cells, respectively. Overexpression of MEK (mitogen-activated protein [MAP] kinase kinase), which is known to stimulate phosphorylation of NF-IL6, induced a 3.6-fold increase in hPL-B enhancer activity. The induction by MEK was completely inhibited by an expression plasmid for a dominant/negative mutant of NF-IL6 or by mutation of the NF-IL6 binding sites on the enhancer. PD98059, an inhibitor of MEK, inhibited hPL release from cultured trophoblast cells by about 50%. Taken together, these results indicate that MAP kinase stimulates the hPL-B enhancer by an NF-IL-6-dependent pathway.
Oscillation of insulin release by the pancreatic islets was evaluated under stringent Ca(2+)-free conditions for the first time. Isolated single rat islets were exposed to 16.7 mM glucose in the presence of 1.9 mM Ca(2+), or under the stringent Ca(2+)-free conditions (Ca(2+) omission with 1 mM EGTA, 6 microM forskolin and 100 nM phorbol 12-myristate 13-acetate). Fifteen minutes after the initiation of glucose stimulation, effluent was collected at a 6-s interval, insulin was determined in duplicate by a highly sensitive insulin radioimmunoassay, and oscillation and pulsatility of release statistically analyzed. Significant oscillation of insulin release was observed in all islets irrespective of presence and absence of Ca(2+). Significant pulsatility of release was detected in 7 of 11 islets in the presence of Ca(2+) and three of six isl! ets in the absence of Ca(2+). In conclusion, high glucose elicits oscillatory insulin release both in the presence and absence of extracellular Ca(2+).
Adult T-cell leukemia/lymphoma (ATL) is a neoplastic disorder of T lymphocytes associated with human T lymphotropic virus type I (HTLV-I). The prognosis of ATL is generally poor. We present here a 79-year-old woman with spontaneous remission of acute type ATL. Spontaneous remission was preceded by surgical biopsy and pneumonia and lasted for two years until she died with pancreas cancer. Monoclonal integration of HTLV-I provirus DNA became undetectable after remission.
Interleukin 2 receptor is expressed not only on the surface of activated T or B lymphocytes, but also on certain lymphoid malignancies. The receptor is released from the cell membrane as soluble form (sIL-2R). Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation or specific tumor cell growth including non-Hodgkin's lymphoma (NHL). However, the relevance of serum sIL-2R levels relating to clinical outcome in adult patients with NHL remains uncertain. Therefore, we investigated the serial serum sIL-2R levels in 28 untreated patients with NHL to evaluate its correlation with clinical characteristics. High serum sIL-2R level (>1000 U/ml) at diagnosis was associated with a high incidence of treatment failure (p=0.03) and poor overall survival (p=0.057). The serum sIL-2R levels decreased significantly after achieving complete remission (p=0.003). Further larger studies are required to evaluate whether serum sIL-2R level is an independent prognostic factor or not. However, adding this parameter to those already employed in the International Prognostic Index would perhaps provide a better prognostic index for adult patients with NHL.
To examine whether serum levels of soluble interleukin-2 receptor (sIL-2R) may be a good marker of acute graft-versus-host disease (aGVHD), they were determined weekly in 56 patients receiving bone marrow transplantation (BMT). Because of wide variation in the pre-transplant sIL-2R levels (from 135 to 1918 IU/ml), we used a sIL-2R index in this study by comparing the peak levels with the pre-transplant levels. In agreement with previous reports, there was a significant correlation between the grade of aGVHD and the maximal sIL-2R index. The maximal sIL-2R index was 4.66 in patients with grade I to IV aGVHD, whereas it was 2.68 in patients without GVHD. This marker may be useful for monitoring the status of aGVHD. However, it was interesting that sIL-2R levels were elevated from the time of transplantation until the third week even in patients without GVHD or those who received autologous transplantation. Until the third week, no significant differences were observed in sIL-2R index between these patients and those who developed aGVHD during their clinical courses. After the fourth week, a higher sIL-2R index was observed in patients with aGVHD than in the other patients. Some factors other than GVHD contribute to the elevation of serum sIL-2R levels, and we should recognize the limitations of the measurement of this cytokine.
Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.
Oral complications occur frequently after bone marrow transplantation (BMT). Some of them are caused by regimen-related toxicity of the preparative regimen, and others by infections. In addition, oral tissues are targets of graft-versus-host disease (GVHD). Oral granulomatous lesions are not a common complication after BMT, and are especially rare on the tongue. Such rare lesions reported in the literature, developed late after BMT with oral chronic GVHD. We present here a patient who developed pyogenic granuloma of the tongue early after allogeneic BMT done for multiple myeloma. Regimen-related mucositis, oral acute GVHD, the administration of cyclosporine A, and the preexisting macroglossia might be responsible for the formation of granuloma.
BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.
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Recent studies have revealed that activated extracellular signal-regulated kinases (ERKs) 1 and 2 by the stimulation of beta(3)-adrenoceptors played a critical role in cell survival in brown adipocytes. On the other hand, phosphorylation of ERK1/2 via beta(3)-adrenoceptors and its physiological and pathological significance in white adipocyte has remained uncertain despite the increasing significance of functioning white adipocytes. Accordingly, we here studied phosphorylation of ERK1/2 caused by the stimulation of beta(3)-adrenoceptors in 3T3-L1 adipocytes, and the roles of phosphorylated ERK1/2 in lipolysis. Phosphorylation of ERK1/2 was induced by a selective beta(3)-adrenoceptor agonist, DL-4-[2'-¿2-hydroxy-2-(3-chlorophenyl)ethylamino¿propyl] phenoxyacetic acid sodium salt sesquihydrate (BRL37344), in 3T3-L1 adipocytes in a time- and dose-dependent manner. The phosphorylation of ERK1/2 by BRL37344 was sensitive to the cyclic AMP (cAMP)-dependent protein kinase inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H89). To elucidate the roles of phosphorylated ERK1/2 in lipolysis, the effect of a selective inhibitor of ERK1/2 phosphorylation, 2'-amino-3'-methoxyflavone (PD98059), was examined. This inhibitor did not alter the lipolytic action caused by BRL37344, even at concentrations sufficient to block phosphorylation of ERK1/2, suggesting that ERK1/2 play no role in the lipolysis caused by BRL37344 in 3T3-L1 adipocytes.
The Delta/Serrate/LAG-2 (DSL) domain containing proteins are considered to be ligands for Notch receptors. However, the physical interaction between DSL proteins and Notch receptors is poorly understood. In this study, we cloned a cDNA for mouse Jagged1 (mJagged1). To identify the receptor interacting with mJagged1 and to gain insight into its binding characteristics, we established two experimental systems using fusion proteins comprising various extracellular parts of mJagged1, a "cell" binding assay and a "solid-phase" binding assay. mJagged1 physically bound to mouse Notch2 (mNotch2) on the cell surface and to a purified extracellular portion of mNotch2, respectively, in a Ca(2+)-dependent manner. Scatchard analysis of mJagged1 binding to BaF3 cells and to the soluble Notch2 protein demonstrated dissociation constants of 0.4 and 0.7 nM, respectively, and that the number of mJagged1-binding sites on BaF3 is 5,548 per cell. Furthermore, deletion mutant analyses showed that the DSL domain of mJagged1 is a minimal binding unit and is indispensable for binding to mNotch2. The epidermal growth factor-like repeats of mJagged1 modulate the affinity of the interaction, with the first and second repeats playing a major role. Finally, solid-phase binding assay showed that Jagged1 binds to Notch1 and Notch3 in addition to Notch2, suggesting that mJagged1 is a ligand for multiple Notch receptors.
Although gonadotropin-releasing hormone agonists (GnRHa) have been used in the therapy of the endocrine-dependent cancers, their biological mechanism remained obscure. We have studied the roles of mitogen-activated protein kinase family in the antiproliferative effect of GnRHa on the Caov-3 human ovarian cancer cell line. Reverse transcription-PCR assays confirmed mRNA for GnRH receptor in Caov-3 cells. In the presence of 1 microM GnRHa, the proliferation of cells was significantly reduced to 76% of controls after 24 h, and the effect was sustained up to 4 days. Although GnRHa had no effect on the activation of the Jun N-terminal kinase (JNK), treatment of Caov-3 cells with GnRHa activated extracellular signal-regulated protein kinase (ERK), and its effect was more than that induced by GnRH. Activation of ERK by GnRHa occurred within 5 min, with the maximum occurring at 3 h and sustained until 24 h. GnRHa also activated ERK kinase (mitogen-activated protein/ERK kinase) and resulted in an increase in phosphorylation of son of sevenless (Sos), and Shc. Furthermore, we examined the mechanism by which GnRHa induced ERK activation. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase I, which specifically blocks signaling mediated by the betagamma subunits of G proteins, blocked the GnRHa-induced ERK activation. Phorbol 12-myristate 13-acetate (PMA) also induced the ERK activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of ERK by GnRHa. Elimination of extracellular Ca2+ by EGTA also did not abolish the activation of ERK by GnRHa. To examine the role of ERK cascade in the antiproliferative effect of GnRHa, PD98059, an inhibitor of mitogen-activated protein/ERK kinase, was used. This inhibitor canceled the antiproliferative effect of GnRHa and apparently reversed the GnRH-induced dephosphorylation of the retinoblastoma protein, the hyperphosphorylation of which is a hallmark of G1-S transition in the cell cycle. These results provide evidence that GnRHa stimulation of ERK activity may be mediated by Gbetagamma protein, not by PMA-sensitive protein kinase C nor extracellular Ca2+ in the Caov-3 human ovarian cancer cell line, suggesting that this cascade may play an important role in the antiproliferative effect of GnRHa.
The interaction and adhesive forces between a mica plate and SiO(2) surfaces in water-alcohol (ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol) mixtures were investigated on the molecular scale, using an atomic force microscope. The following results were obtained: (i) alcohols higher than 1-propanol adsorb standing on the hydrophilic surface vertically to form a structured monolayer, when the alcohol concentration is high enough; (ii) the adhesive force between surfaces depends on how closely two surfaces can be brought by breaking the adsorbed layers; (iii) the adhesive force between surfaces is maximized at w(w)/w(ws) approximately 0.25, independent of the kind of alcohol, where w(w) and w(ws) are the weight fractions of water and saturated water, respectively; and (iv) the adhesive force for a particle of rough surface is much smaller than the adhesive force predicted for a particle of smooth surface. It is hypothesized that this adhesive force much greater than the van der Waals attractive force originates from the water bridging between surfaces, and this hypothesis is confirmed by the predictions given by the Laplace equation and the Kelvin relation. Copyright 1999 Academic Press.
In this study, we identified a novel splice variant of 70-kDa heat shock cognate protein (HSC70), while screening differentially expressed molecules in rat brain after chronic antidepressant treatment. This clone, named HSC49, lacked 470 bp of nucleotides of rat HSC70. HSC49 encoded 442 amino acid residues with a calculated molecular mass of 48.6 kDa. DNA sequence analysis revealed that HSC49 lacked the entire Exon 7 and Exon 8 of the HSC70 gene. Chronic treatment with antidepressant, imipramine or sertraline, induced a 38.5 or 22.5% increase in mRNA levels in rat frontal cortex, respectively, when compared to controls. Western blot analysis also revealed that the protein expression of HSC49 was increased after antidepressant treatment. Our data suggest that HSC49 may be one of the common molecules induced after chronic antidepressant treatment.
[formula: see text] This report describes a new method to prepare optically active methylphenidate starting from piperidine. The method consists of a transformation of N-methoxycarbonylpiperidine to the corresponding alpha-methoxylated carbamate I by utilizing electrochemical oxidation followed by the coupling reaction with optically active Evans imides II to produce optically active methylphenidate derivatives III with high stereoselectivities, threo-(2R,2'R)-Methylphenidate (IV; Ar = Ph; Ritalin) was easily prepared from III in three steps.
BACKGROUND: Two serologic assays, Aspergillus latex agglutination testing (LA) and plasma (1-->3)-beta-D-glucan (BDG) measurement, are used when invasive pulmonary aspergillosis (IPA) is suspected. Despite the high specificity of these assays, false-positive results are frequent for neutropenic patients. This study was conducted to evaluate the efficacy of LA and BDG and to investigate the cause of the false-positive results. METHODS: Eighty-eight consecutive patients with hematologic malignancies who underwent intensive chemotherapy were tested weekly with LA and BDG. RESULTS: Sixteen of 88 patients were diagnosed as having IPA. The sensitivity, specificity, and positive predictive values were 23%, 98%, and 64% for LA and 27%, 88%, and 52% for BDG, respectively. Of 11 patients who became positive for LA only during neutropenic periods, 2 patients developed IPA. In contrast, six of eight patients who became positive for LA during nonneutropenic periods developed IPA. Transient Aspergillus antigenemia was more frequently encountered during neutropenia (2.9%) than during nonneutropenic periods (0.2%). The plasma BDG concentration increased at the nadir of neutropenia in 36 of 45 patients who had no signs of IPA, and it exceeded the level of 20 pg/mL in 2 patients. CONCLUSIONS: Both BDG and LA have a low sensitivity and a high specificity for IPA. However, the false-positive rate of LA increases during neutropenic periods. Caution should be exercised in interpreting the results of these blood tests, especially when patients are neutropenic.
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