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H Uchiyama

Publications and source records attributed to H Uchiyama.

At least 91 records · Page 5Linked to original sources
PubMed1996

Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B.

Adhesion of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) not only localizes MM cells in the marrow microenvironment, but also triggers interleukin-6 (IL-6) secretion by BMSCs and related MM cell proliferation. In the present study, we characterized the regulation of IL-6 gene expression in BMSCs during MM cell adhesion. Adhesion of ARH-77, HS-Sultan, IM-9, and U266 MM cell lines to BMSCs and BMSC lines (LP 101 and AA 101) triggered 5-through 15-fold and 2-through 4-fold increases in IL-6 secretion, respectively. IL-6 mRNA transcripts were undetectable by Northern blotting in IM-9 MM cells or LP 101 BMSCs cultured alone; however, adherence of IM-9 cells to LP 101 cells induced a transient increase in IL-6 transcripts at 6 hours, followed by peak IL-6 secretion at 24 hours. To confirm increased IL-6 transcription and characterize its regulation, LP101 BMSCs were transiently transfected with full length and deletion fragments of the IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Transient transfection of LP101 BMSCs with plasmid containing an intact NF-kappa B site showed a 6.8 +/- 0.4-fold increase in CAT activity triggered by IM-9 MM cell adhesion (n = 3, P < .05). Transfection of LP 101 cells with plasmid containing a single base pair deletion from the NF-kapp B binding motif abolished the MM adhesion-induced increase in CAT activity, whereas transfection with plasmid containing three copies of synthetic NF-kappa B sequence resulted in an 8.1 +/- 0.7-fold increase in CAT activity related to MM adhesion (n = 3, P < .05). These data suggest that the NF-kappa B site is one of the essential regulatory elements for MM cell adhesion-induced IL-6 transcription in BMSCs. Electrophoretic mobility shift assays confirmed the involvement of NF-kappa B activation in regulating MM adhesion-induced IL-6 transcription in BMSCs. Further characterization of the upstream events in the signalling cascade regulating IL-6 may not only delineate mechanisms of IL-6 regulation during paracrine MM cell growth, but also provide new therapeutic strategies based on interruption of IL-6 mediated tumor cell growth.

Base Sequence↗
PubMed1996

Detection of undegraded oligonucleotides in vivo by fluorescence resonance energy transfer. Nuclease activities in living sea urchin eggs.

A method was investigated for monitoring the integrity of oligonucleotides in solution and in cells using fluorescence resonance energy transfer between two different fluorochromes attached to a single oligonucleotide. Ten-mer oligodeoxyribonucleotides labeled with fluorescein at one end and with rhodamine X at the other end were used. The oligomer had a specific absorption spectrum with peaks at 497 and 586 nm, which corresponded to fluorescein and rhodamine X, respectively. When excited at 494 nm, the oligomer had a specific fluorescence spectrum with peaks at 523 and 610 nm. The fluorescence intensity at 610 nm was 6-8 times higher than that at 523 nm. After digestion of the oligomer with an endonuclease, the fluorescence at 523 nm increased more than 12-15-fold but its fluorescence peak at 610 nm almost completely disappeared. To examine effects in vivo, sea urchin eggs were injected with a solution of the oligomer and excited with blue light at 470-490 nm. Two fluorescent images, a green image at 520-560 nm and a red image at above 580 nm, were obtained when a single egg was viewed under a fluorescence microscope. The ratio of the intensities of red to green fluorescence decreased in dependence on time after injection of the oligomer. These changes were not observed in eggs that had been injected with a solution of similarly double-labeled, phosphorothioate oligomer. These results indicated that unfertilized sea urchin eggs had nucleolytic activity. Analysis in vitro on supernatant of the egg homogenate indeed demonstrated the existence of nucleases. All together, our results indicate that the integrity of oligonucleotides can be estimated in living cells by monitoring the fluorescence resonance energy transfer of the double-labeled oligonucleotide.

Animals↗
PubMed1996

Occurrence of immunoreactive activin/inhibin beta(B) in gonadotrophs, thyrotrophs, and somatotrophs of the Xenopus pituitary.

An antibody against the Xenopus activin/inhibin beta(B) subunit (94-107) was raised in a rabbit. Using this antibody, the distribution of activin/inhibin beta(B) immunoreactivity in the pituitary of adult X. laevis was studied. Beta(B) immunoreactivity was detected in gonadotrophs, thyrotrophs, and somatotrophs under light microscopy. Electron microscopy revealed that a beta(B)-immunoreactive substance exists in LH, TSH, and GH granules, in contrast to findings in the rat and goldfish. These results indicate that the expression of activin/inhibin beta(B) in pituitary cells is not consistent among vertebrate species.

Activins↗
PubMed1996

Tuberculosis following liver transplantation: report of a case and review of the literature.

We report on a 44-year-old man who developed tuberculosis 4 months after liver transplantation. The diagnosis was confirmed using a polymerase chain reaction (PCR) technique in bronchial alveolar lavage (BAL) fluid, and the patient was successfully treated by reducing his immunosuppression and administering antituberculous drugs. The patient became afebrile 20 days after starting antituberculous therapy and remains well at home. A review of the literature revealed that tuberculosis after liver transplantation is a rare complication with a reported mortality rate of as high as 40%. The mortality is highest for patients who become symptomatic within 3 months after transplantation (83% vs 0%, P < 0.01; Fisher's exact test) and for those with an interval between the initial symptom and diagnosis of more than 2 weeks (71% vs 0%, P < 0.05). Early diagnosis is, therefore, essential for successful resolution of tuberculosis after liver transplantation.

Adult↗
PubMed1996

Testicular morphological changes in children with acute lymphoblastic leukemia following chemotherapy.

Morphological changes in the testis induced by chemotherapy given according to the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children with acute lymphoblastic leukemia (ALL). After informed consent, testicular biopsies were performed 14 times in 12 patients at the end of treatment. The testicular morphology in all cases had sustained a degree of damage. The tubular fertility index (TFI), calculated as the percentage of seminiferous tubules containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the normal value. Infiltration of leukemic cells was the most significant factor contributing to the decrease in TFI. There were no differences in the TFI among the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was performed twice. In the second biopsy, TFI was elevated and sperm formation with the maturation of Leydig cells was observed. A number of other pathological changes were observed: modification of spermatogonia, Sertoli cells and inclusion bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of interstitial fibrosis and thickening of the basement membrane. These results suggest that recent strong chemotherapy for the treatment of ALL might cause severe but not fatal damage to children's testicular tissue. As chemotherapy escalates, more investigation of testicular function will be necessary.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Two cases of ventricular parasystole associated with ventricular tachycardia.

In two patients, ventricular parasystole (VP) was associated with ventricular tachycardia (VT), and in one patient, catheter ablation was successful. In patient 1, with dilated cardiomyopathy, VP led to VT, which converted to ventricular fibrillation. In patient 2, VP led to symptomatic nonsustained polymorphic VT. The origin of parasystolic focus was determined by endocardial mapping, and a radiofrequency current was delivered to patient 2. Both VP and VT disappeared immediately, and no recurrence has been observed during a follow-up of 8 months. Catheter ablation to the parasystolic focus was effective and a relationship between VP and VT was strongly suggested.

Cardiomyopathy, Dilated↗
PubMed1996

Electrophysiological findings in idiopathic recurrent ventricular fibrillation: special reference to mode of induction, drug testing, and long-term outcomes.

Electrophysiological studies can be useful in the presence of idiopathic ventricular fibrillation (VF) and may be used when selecting antiarrhythmic drugs. However, the yield, the mode, and the long-term reproducibility of the induction of VF have not yet been fully elucidated. Eight patients with idiopathic VF underwent electrophysiological study. The mean age (+/- SD) was 45 +/- 17 years. Six were males and two were females. Diagnosis was done by exclusion. VF was induced in 6 (75%) of 8 patients using double extra stimuli at coupling intervals of 233 +/- 39 and 191 +/- 20 ms for the first and second extra stimuli, respectively. Of note, VF was induced by stimulation exclusively at the origin of the premature ventricular beat, which was the first complex of VF in two patients. In another patient, VF was initiated by two premature stimuli and also by a pause produced by rapid pacing. The inducibility of VF was reproduced 9-18 months after the first induction in all of the four patients studied. When the ability of antiarrhythmic drugs to suppress VF inducibility was confirmed, no recurrence was observed during the follow-up period of 40-160 months, but a recurrence of VF was observed in one of two nonresponders. In one patient, amiodarone administration failed in preventing VF induction 9 months after initiation of therapy, and reassessment of long-term drug-efficacy might be indicated in some patients. In conclusion, idiopathic VF was highly inducible (75%) with double extra stimuli. In this study, it was induced from a specific site (2/8) or by a pause (1/8). Induction of VF seemed to be reproduced 9-18 months after the first study. The outcome was considered favorable when the inducibility of VF was suppressed by antiarrhythmic drugs.

Adolescent↗
PubMed1996

Cellular distribution of bronchus-associated lymphoid tissue in rheumatoid arthritis.

Bronchus-associated Lymphoid tissue (BALT) has been reported to be present in the lungs of patients with rheumatoid arthritis (RA). However, little is known about the structure and cellular distribution of BALT in this disease, so we investigated these points using immunohistochemical methods. The subjects were eight RA patients with BALT in biopsy specimens and a histologic diagnosis of follicular bronchiolitis. Seven patients had cough and purulent sputum, and four patients had positive sputum cultures. BALT was histologically composed of four distinct regions, which were the lymphoepithelium, the dome area, the follicular area, and the parafollicular area. Surface IgM+ B cells were predominant in the follicular area, whereas IgA+ cells were scattered in the dome and parafollicular areas. T cells were mainly found in the parafollicular area (CD4+ > CD8+), and most of them expressed the T Cell receptor alpha beta (alpha beta TCR). These findings were similar to those described previously for BALT in diffuse panbronchiolitis, which manifests as a chronic respiratory infection. The present study indicated that extrinsic stimulation as well as alterations of the immune response are involved in the development of BALT in RA, although the exact mechanism requires further clarification.

Adult↗
PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A fertility study in rats by subcutaneous administration].

Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks prior to pairing in males and 2 weeks prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (day 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. 1. In the male 25 micrograms/kg group, opacity of the eyeball surface was observed, and depression of body weight gain, and decreases of body weight and food consumption, and increases in the weight of the kidney were statistically significant in comparison with vehicle controls. 2. In the female 25 micrograms/kg group, depression of body weight gain and food consumption were statistically significant in comparison with vehicle controls. 3. No changes in parameters of reproductive performance were seen in any dosed groups. 4. No changes in parameters of implantation performance were seen. There were no treated-related abnormalities in fetal mortality, weights of fetuses, and external, visceral and skeletal examinations. Based on there results, it is considered that in the present study the no-toxic dose levels of MC903 were 5 micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance and fetal development.

Animals↗
PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (2)--A teratogenicity study in rats by subcutaneous administration].

Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied. MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were subcutaneously administered to pregnant Slc:SD rats from day 7 to 17 of gestation. 1. In animals administered 25 micrograms/kg/day MC903, food consumption decreased significantly and body weight gains lowered marginally. MC903 administered at any doses did not adversely affect female animals in regard to pregnancy, delivery and maternal behavior. 2. In fetuses, suppression of growth were noted at 25 micrograms/kg group. However, fetotoxicity and teratogenicity were not noted at all groups administered MC903. 3. In F1 pups, the postnatal growth, development, responses, behaviors, learning ability and reproductive ability were not influenced. Additionally, no embryonic or fetal abnormalities of their fetuses (F2) were detected. 4. On the basis of results obtained in the present study, it is considered that the no-toxic doses level of MC903 are 12.5 micrograms/kg/day for pregnant animals and fetuses, 25 micrograms/kg/day for pups.

Abnormalities, Drug-Induced↗
PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (3)--A teratogenicity study in rabbits by subcutaneous administration].

Teratogenicity of calcipotriol (MC903), an anti-psoriasic agent, was studied. MC903 at doses of 0.1, 0.5, 1, 2.5 and 5 micrograms/kg/day was subcutaneously administered to pregnant Std:NZW rabbits from day 6 to 18 of gestation. 1. A decrease in locomotor activity was observed in the group administered MC903 5 micrograms/kg/day. Food consumption and body weight gain decreased dose-dependently in groups administered MC903 1 microgram/kg/day or more. Granular whitish kidneys were observed in groups administered MC903 2.5 and 5 micrograms/kg/day. Rough and whitish aorta were noted in groups administered MC903 1 microgram/kg/day or more. 2. Significant fetotoxicity was not induced by administration of MC903 up to 0.5 microgram/kg/day. 3. On the basis of results obtained in the present study, it is considered that no-toxic dose level of MC903 is 0.5 microgram/kg/day for pregnant animals and fetuses.

Abnormalities, Drug-Induced↗
PubMed1996

[Reproductive and developmental toxicity studies of calcipotriol (MC903): (4)--A perinatal and postnatal study in rats by subcutaneous administration].

Perinatal and postnatal toxicity of calcipotriol (MC903), an antipsoriasic agent, was studied. MC903 at doses of 6.25, 12.5 and 25 micrograms/kg/day were subcutaneously administered to pregnant Slc:SD rats from day 17 of gestation to day 21 after delivery. 1. Administration of MC903 at any doses did not adversely affect pregnant animals in regard to gestation, delivery and maternal behavior. In dams administered MC903 25 micrograms/kg/day, food consumption and body weight gain were marginally lower than those of control animals during lactation period. 2. In group administered MC903 25 micrograms/kg/day, body weight gain in F1 offsprings was significantly lower as compared with those of control group. The drug did not have any adverse effects on the postnatal development of the offspring such as differentiation, functional development, emotionality, motor ability, learning ability or reproductive performance. 3. On the basis of results obtained in the present study, it is considered that the no-toxic dose level for general toxicity and reproduction in the dams was estimated to be 12.5 and 25 micrograms/kg/day, respectively, the no-toxic dose levels in the offspring was also estimated to be 12.5 micrograms/kg/day.

Animals↗
PubMed1996

Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody.

We have established a new method capable of measuring the very low concentrations of oxidized low density lipoprotein (OxLDL). In our previous study, we obtained a novel murine monoclonal antibody against oxidized lipoproteins (Itabe, H. et al. 1994. J. Biol. Chem. 269: 15274-15279). The epitope of this antibody resides in oxidized products of phosphatidylcholine that can form complexes with polypeptides, including apolipoprotein B. When the monoclonal antibody was precoated onto microtiter wells prior to carrying out a sandwich ELISA using an anti-human apolipoprotein B antibody, it was possible to detect 0.5 ng protein of copper-induced OxLDL. The detection of OxLDL was dependent on the presence of monoclonal antibody and was blocked by oxidized phosphatidylcholine (OxPC). Under the same sandwich ELISA condition, native LDL showed a dose-dependent increase of absorbance that was inhibited by complex of OxPC with BSA. These results suggest the possible occurrence of oxidative modification of human plasma LDL, which is recognized by the antibody against OxPC. The level of LDL oxidation of normal human subjects was found to be 0.52 +/- 0.35 units per 5 mu g protein of LDL, where one unit was defined as the reactivity corresponding to 1 ng of copper-induced OxLDL by this assay. Furthermore, we found that the LDL oxidation level in patients who had been receiving hemodialysis treatment was increased more than eightfold over that of normal subjects. We suggest that LDL in human plasma is oxidatively modified under certain conditions and this method for measurement of OxLDL could be used to study the relationship between in vivo oxidation reaction and various pathological conditions.

Antibodies, Monoclonal↗
PubMed1995

Is cyclic AMP involved in the defibrillating effect of sotalol?

Ventricular fibrillation induced in animals pretreated with sotalol, a class III antiarrhythmic agent, would spontaneously terminate and revert into a sinus rhythm. This phenomenon has been attributed to the class III action of this drug, i.e., prolongation of myocardial action potential duration and effective refractory period. Since various observations suggested that these alone cannot explain the defibrillating phenomenon, we hypothesised that sotalol affected ventricular intercellular synchronization by increasing intercellular coupling. Our recent experimental studies have shown that sotalol antagonized the cellular decoupling to guinea pig ventricular muscle strip caused by perfusion with either a hypoxic normal Tyrode's solution or an oxygenated high Ca2+ Tyrode's solution. We assumed that the most likely mechanism for the restoration of intercellular coupling would be increasing intracellular cAMP concentration. In order to test this hypothesis, we studied the modification of this sotalol-induced recoupling by a cAMP dependent protein kinase inhibitor. The results clearly supported our assumption since the addition of Arg-Gly-Tyr-Ala-Leu- Gly (pure A- kinase inhibitor) prevented the aforementioned cellular recoupling action of sotalol in a dose-dependent manner. It can thus be concluded that changes in intracellular cAMP level are involved in the synchronizing / defibrillating effect of sotalol.

Amino Acid Sequence↗
PubMed1995

Catheter ablation of ventricular tachycardia with radiofrequency currents, with special reference to the termination and minor morphologic change of reinduced ventricular tachycardia.

During catheter ablation with radiofrequency (RF) currents, the incidence of the termination of reentrant ventricular tachycardia (VT) during application of RF energy and the morphologic change of the reinduced VT were analyzed. Twenty-five patients (20 men and 5 women, aged 44 +/- 17 years) were studied. After induction of monomorphic sustained VT, the ablation site was determined by endocardial activation mapping, identification of isolated mid-diastolic potential, and pacing during tachycardia. Thirty-six monomorphic VTs were induced in 25 patients and terminated with programmed stimulation. The cycle length was 323 +/- 55 ms and all VTs were entrained with rapid ventricular pacing. The target site was the earliest site of activation of VT in 26 VTs in 16 patients, and the area of slow conduction in 10 VTs in 9 patients. VT was terminated soon after the application of RF currents in 33 VTs in 22 patients at 6.0 +/- 3.1 seconds, and VT was induced immediately after the cessation of RF currents in 11 patients. Of these, 4 patients with idiopathic left ventricular VT had an alternation in the QRS configuration before catheter ablation and required repeat ablation of the other VT morphology. In the other 7 patients, such morphology was not observed before ablation, but was observed in VT induced when the original VT was terminated. Repeated attempts of catheter ablation 2 to 9 times at the remapped site was, however, successful in 7 of 8 VTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Superoxide generation by alveolar macrophages from aged rats: improvement by in vitro treatment with IFN-gamma.

Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but it is unclear whether or not this is due to the inability of these cells to be activated. To elucidate this, we investigated the capacity of AM from young (16-week-old) and aged (100-week-old) rats to become primed with recombinant rat interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)-elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma production by the spleen cells of young and aged animals. The data indicated that AM freshly harvested from non-sensitized aged rats produced less O2- than those from young animals. A similar result was obtained in BCG-sensitized rats. However, AM from aged rats were primed with in vitro treatment with IFN-gamma for increased rate of O2- production to an equivalent level of that by AM from young animals. In addition, the ability of spleen cells to produce IFN-gamma was well maintained in aged rats. These results suggest that AM function is suppressed in the lungs of aged animals. Our observation that the decreased AM function in aged rats can be reversed is important because it suggests that appropriate treatment may reduce the incidence and mortality of respiratory infections in the elderly.

Aging↗
PubMed1995

Retinal neurones specific for centrifugal modulation of vision.

The avian retina receives centrifugal projections from a midbrain nucleus, the isthmo-optic nucleus. We labelled target cells for the isthmo-optic fibres by intracellular injections of Lucifer Yellow in fixed retinal slices. The isthmo-optic recipient (IOR) cells had no major dendrites extending into the inner plexiform layer, but had a thin axon-like process running horizontally in the junction between the inner nuclear layer and the inner plexiform layer. The IOR cells were morphologically similar to the association amacrine cells of Cajal. Immunohistochemical localization of aspartate and glutamate in the IOR cells suggested that they may use these excitatory amino acids as neurotransmitters.

Animals↗