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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 469 records · Page 26Linked to original sources

[Effectiveness of etoposide on reactive histiocytosis and refractory state to platelet transfusion during therapy of leukemia: case report].

The patient is 11-year-old girl who was diagnosed as having hybrid acute leukemia (myeloid and lymphoid) from morphological (cytochemistry) findings, immunophenotype and genotype. During reinduction therapy after a second relapse, she presented hepatosplenomegaly and the remittent fever unresponsive to the intensified antibiotics. The diagnosis of reactive histiocytosis was made because of the remarkable elevation of serum ferritin value and proliferation of mature histiocytes in the bone marrow. Treatment with etoposide resulted in the disappearance of her fever and other symptoms. The subsequent refractoriness to platelet transfusion was also overcome by etoposide (p.o.) therapy. The results suggested that the treatment with etoposide might be effective for reactive histiocytosis and the related refractory state to platelet transfusion during therapy for leukemia.

Blood Component Transfusion↗

[Clinical significance of I-123 MIBG myocardial scintigraphy for evaluating the severity of congestive heart failure].

We studied the significance of I-123 MIBG (metaiodobenzylguanidine) myocardial scintigraphy for evaluating the severity of congestive heart failure. I-123 MIBG scintigraphy was performed in 7 patients with congestive heart failure (CHF) of NYHA class I-III (6 with dilated cardiomyopathy and 1 with Adriamycine cardiomyopathy) and in 2 normals. The SPECT and anterior planar myocardial images were obtained 15 minutes after (initial images) and 4 hours after (delayed images) an injection of I-123 MIBG (111 MBq). Compared with normals, patients with CHF demonstrated (1) low myocardial uptake and (2) rapid myocardial washout of I-123 MIBG, indicating myocardial sympathetic disarrangement. Then, quantitating these abnormalities with the heart to upper mediastinum uptake ratio (H/B) and the percent washout rate (%WR) during 4 hours, respectively, we compared these two indices with LV ejection fraction (EF) at rest measured by echocardiography and exercise capacity (max VO2 and VO2 at anaerobic threshold (AT] determined with respiratory gas exchange analysis during maximal bicycle exercise. H/B was lower and %WR was greater in patients with CHF than in normals. H/B correlated with EF (r = 0.77, p less than 0.05) and AT (r = 0.74, p less than 0.05). On the other hand, %WR significantly correlated with EF (r = 0.79, p less than 0.05), max VO2 (r = -0.74, p less than 0.05) and AT (r = -0.81, p less than 0.05). Thus, H/B and %WR were closely related to the severity of CHF. These results suggest that I-123 MIBG myocardial scintigraphy and the quantitative analysis of I-123 MIBG myocardial uptake provide useful information about the severity of CHF.

3-Iodobenzylguanidine↗

Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat.

A mutant strain (LEC) of rats was found to have a novel defect in T cell maturation, that is, arrest of differentiation from CD4+8+ to CD4+8- but not to CD4-8+ thymocytes. FACS analyses demonstrated a deficiency in the CD4+8- T cell subset in the thymus and a marked decrease in CD4+ T cells in peripheral lymphoid organs. Expression of the T cell receptor (TCR)/CD3 complex in CD4+8+ and CD4-8+ thymocytes of LEC rats was normal. Expression of class II major histocompatibility complex (MHC) in the thymus of LEC rats was also the same as that of normal rats. These results indicate that maturational arrest occurs only in the transition pathway from CD4+8+ to CD4+8- thymocytes, and that this mutation can not be attributed to the default of expression of either TCR/CD3, CD4, or class II MHC antigen. Consequently, dysfunction of helper T cells was observed in LEC rats, while killer T cells and B cells functioned normally. Although the complete identification of the origin of this mutation requires further studies, it is hoped that such investigations will throw light on the mechanism of positive selection.

Animals↗

[Differential diagnosis between nonhyperfunctioning adenoma and adrenal metastasis on adrenocortical scintigraphy].

Adrenocortical scintigraphy using I-131-adosterol was performed in six cases of nonhyperfunctioning adenoma incidentally discovered on CT scans and four cases of adrenal metastasis. In all six cases of nonhyperfunctioning adenoma, there was increased uptake of of the I-131-adosterol on the side of the adrenal mass discovered at CT. In three of four cases of adrenal metastasis, there was no uptake of the I-131-adosterol on the side of the mass detected at CT. Uptake was symmetrical in one case of adrenal metastasis. Adrenocortical scintigraphy is able to differentiate nonhyperfunctioning adenoma from adrenal metastasis in recognition of increased uptake of I-131-adosterol on the side of the adrenal mass discovered on CT scans.

Adenoma↗

Expression of murine IL-2 receptor beta-chain on thymic and splenic lymphocyte subpopulations as revealed by the IL-2-induced proliferative response in human IL-2 receptor alpha-chain transgenic mice.

Lymphocytes from the human (h) IL-2R alpha chain transgenic mice (TGM) constitutively express high affinity binding sites for hIL-2, consisting of transgenic h-IL-2R alpha and endogenous murine IL-2R beta, and therefore easily proliferate in vitro in response to hIL-2. Our study was undertaken to clarify the hIL-2-responsive lymphocyte subsets in the TGM, which should most likely reflect the normal distribution of m IL-2R beta expression. In both thymus and spleen, the majority of expanded cells by hIL-2 was CD3+CD4-CD8+ TCR alpha beta+ cells. The proliferation of CD4+ cells was not observed at all from either organ despite the expression of transgenic hIL-2R alpha. Potent cellular proliferation was also observed from the thymocytes that had been depleted of CD8+ cells, the expanded cells consisting of CD3- (15-40%) and CD3+ populations (60-85%). Among CD3+ cells, approximately the half portion expressed TCR alpha beta, whereas the other half was suggested to express TCR gamma delta. A variable portion (5-20%) of the CD3+ cells expressed CD8 (Lyt-2) in the absence of Lyt-3, and the CD3+CD8+ cells were confined preferentially to the TCR alpha beta- (TCR gamma delta+) population. In the culture of splenocytes depleted of CD8+ cells, however, the proliferated cells were mostly CD3-CD4-CD8-TCR-Mac1-, whereas a minor portion (10-30%) was CD3+CD4-CD8-TCR alpha beta- (TCR gamma delta+. Analysis of TCR genes at both DNA and mRNA levels confirmed the phenotypical observations. These results strongly suggested that IL-2R beta was constitutively and selectively expressed on the primary murine thymocytes and splenic T and NK cells, except for CD4+ cells in both organs.

Animals↗

Calcified ligamenta flava in a patient with Coffin-Lowry syndrome: biochemical analysis of glycosaminoglycans.

Glycosaminoglycans in calcified cervical ligamenta flava from a male patient with Coffin-Lowry syndrome were analyzed biochemically. Hexuronate content based on the tissue dry weight was 8-fold and 5-fold concentrated in the calcified center as compared with the peripheral area and with age-matched, normal ligamenta flava, respectively. Two-dimensional electrophoresis of glycosaminoglycan preparations on cellulose acetate film revealed that, although dermatan sulfate was the major glycosaminoglycan in the normal ligamenta flava, chondroitin sulfate was the predominant glycosaminoglycan in the pathological tissue. Relative amounts of chondroitin sulfate disaccharide units were determined after digestion of glycosaminoglycans with chondroitinase, and the ratio of chondroitin 6-sulfate to chondroitin 4-sulfate tended to decrease with the distance from the calcified center to the peripheral area. These observations suggest that an alteration in glycosaminoglycan metabolism may be a contributing factor in calcification of ligamenta flava in Coffin-Lowry syndrome.

Abnormalities, Multiple↗

Ventilatory and heart rate chemosensitivity in track-and-field athletes.

Fifty-four male track-and-field athletes and 18 male non-athletes were examined by isocapnic progressive hypoxia and CO2 rebreathing tests. Ventilatory and heart rate (HR) responses to hypoxia were analysed by a hyperbolic relationship and the ventilatory response to hypercapnia by a linear regression. The results showed that ventilatory sensitivity during hypoxia was significantly attenuated in the long-distance runners and sprinters compared to the non-athletes. Although heart rate sensitivity during hypoxia in none of the athletes showed a significant difference compared to that of the non-athletes, baseline HR in the long-distance runners was significantly lower than that of the non-athletes. None of the athletes showed significant differences in ventilatory sensitivity during hypercapnia compared to the non-athletes.

Adolescent↗

Lack of favorable effect of immunomodulators on outbred syngeneic rodent islet transplantation.

We studied the effect of two immunomodulators, lobenzarit disodium and OK-432, on outbred syngeneic islet transplantation. Six hundred fresh islets taken from two male Wistar rats were transplanted intraportally into other male Wistar rats that had been made diabetic with streptozotocin. Lobenzarit was given to 12 recipients and OK-432 to seven recipients intraperitoneally for 1 month, while nine controls received only intraperitoneal saline. Both drug-treated groups could not maintain lower fasting plasma glucose levels or higher fasting body weights at each time as compared with controls. The islet survival time in lobenzarit-treated (23.5 +/- 8.0 days) and OK-432-treated (25.3 +/- 13.4 days) groups was not longer than that (21.6 +/- 9.4 days) of the control group. All the pancreatic insulin contents of the seven surviving controls, ten surviving lobenzarit and five surviving OK-432 recipients were less than 0.8% of the mean insulin content obtained from 12 normal male rats. The hepatic insulin content of both drug-treated groups was not higher than that of the control group. These results suggest that lobenzarit disodium and OK-432 cannot protect outbred syngeneic islet grafts.

Adjuvants, Immunologic↗

Effects of cadmium ions, D-600 and KCN on calcium-45 uptake in smooth muscle of guinea-pig taenia coli.

1. The effects of Cd2+ on Ca2+ uptake was compared with that of D-600 and KCN in guinea-pig taenia coli. Cd2+ inhibited both the phasic and tonic K+ responses, however, D-600 and KCN preferentially inhibited the tonic response. 2. Cd2+ (2 x 10(-6) M) which had no effect on the tissue ATP concentration, inhibited La3+ resistant residual Ca2+ binding at the high and low affinity site. Cd2+ (10(-5) M) which decreased the tissues ATP concentration, markedly inhibited Ca2+ binding at the low affinity site. 3. Both D-600 and KCN showed a greater inhibitory effect on Ca2+ binding at the low affinity site than at the high affinity site. 4. These findings suggest that Cd2+ at low concentration may inhibit Ca2+ influx through Ca2+ channel at surface membrane while at high concentrations (greater than 10(-5) M), Cd2+ would inhibit the accumulation of Ca2+ into low affinity sites relating to energy metabolism at mitochondria.

Adenosine Triphosphate↗

Behavioral and biochemical effects of intra-accumbens dopaminergic grafts.

6-Hydroxydopamine (6-OHDA) lesions in the ventral tegmental area (VTA) in rats prevented the hyperactivity response to methamphetamine in an open field. Transplantation of mesencephalic dopaminergic cells, obtained from rat embryos, into the nucleus accumbens (NAC) of 6-OHDA-lesioned animals restored the hyperactivity 4 weeks after grafting. By microdialysis of the NAC in freely moving rats no significant differences in baseline concentration of dopamine (DA) among the 3 groups (control, lesioned, grafted) were observed. However, after methamphetamine administration, DA increased significantly during the first 80 min in control animals, during the first 40 min in grafted animals, but did not increase in lesioned animals. On the other hand baseline concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased to one sixth to one third of those of controls in 6-OHDA-lesioned animals, and they did not respond to methamphetamine. After grafting, however, DOPAC and HVA restored to control levels and responded to methamphetamine with decreases as was observed in control animals. Data suggest that grafts not only restore the ability to release DA but also improve DA metabolism in the NAC. This might be a reason for recovery of locomotor activity.

3,4-Dihydroxyphenylacetic Acid↗

Resolution, absolute stereochemistry, and enantioselectivity of 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol.

Racemic 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1) was found to be an effective potentiator of the contractile response of norepinephrine (NE) on rat anococcygeus muscle. This paper describes the resolution of racemic PI-OH by an HPLC method to give the optically pure enantiomers (+)-1 and (-)-1. The absolute configuration of (+)-1 was R as determined by CD analysis and by single-crystal X-ray diffractometric analysis of the methiodide 6 derived from (+)-1. Examination of the effects of the enantiomers to potentiate the contraction of the rat anococcygeus muscle by NE showed a high degree of enantioselectivity. The NE potentiation was found to reside exclusively in (R)-(+)-1; the activity ratio being 21 at 3 x 10(-6) M, whereas (S)-(-)-1 did not show any potentiating and inhibiting activity.

Animals↗

Swollen cortical neurons in Creutzfeldt-Jakob disease contain a phosphorylated neurofilament epitope.

The distribution of swollen neurons and the presence of a phosphorylated neurofilament protein (NFP) epitope in these cells were studied in six cases of Creutzfeldt-Jakob disease (CJD). Swollen neurons are widely distributed in the cerebral cortex and are most abundant in the cingulate and parahippocampal gyri. They are more numerous in the panencephalopathic type of CJD than in the subacute spongiform encephalopathic type. A phosphorylated epitope of NFP was detected in the perikarya of swollen neurons by an immunocytochemical method using a series of monoclonal antibodies that distinguish phosphorylated and nonphosphorylated epitopes of NFP. This abnormal distribution of phosphorylated NFP epitopes indicates that the process of NFP phosphorylation is altered in neurons affected by CJD. This investigation, in accordance with previous studies, suggests that the abnormal post-translational modification of the neurofilament may play an important role in the pathogenesis of several neurodegenerative disorders.

Antibodies, Monoclonal↗

Oligodendroglial microtubular tangles in olivopontocerebellar atrophy.

Oligodendroglial microtubular tangles (OMT), a distinctive oligodendroglial change, was observed in seven of eight cases of olivopontocerebellar atrophy (OPCA). This change was a well-defined glassy cytoplasmic structure showing intense argyrophilia. OMT were distributed in the brain stem, cerebellum, and basal ganglia where severe neurodegenerative changes were consistently observed. In 45 control cases, no OMT were found regardless of the presence or absence of neurological disorders. The OMT were immunostained by anti-tubulin antibodies, but no other antibodies reacted with them. Each OMT consisted of a meshwork of randomly oriented fibrils studded with granular and fuzzy material. The fibrillary elements were between 20 and 30 nm in diameter. It is suggested that OMT are primarily composed of altered microtubules, and are related to the neurodegenerative process of OPCA.

Humans↗

Synergistic effect of cyclosporin A and verapamil in overcoming vincristine resistance of multidrug-resistant cultured human leukemia cells.

Reversal of vincristine (VCR) resistance by cyclosporin A (CyA) or the combination of CyA and verapamil (VER) was investigated by using four P-glycoprotein (P-gp)-associated human multidrug-resistant (MDR) cell lines (K562/ADM, KYO-1, HEL and CMK). Drug sensitivity was expressed as 50% inhibitory concentration (IC50). The degree of reversal of resistance was expressed as x-fold decrease by dividing the IC50 value without modifier(s) by that with modifier(s). CyA overcame P-gp-associated MDR significantly in all four MDR cell lines. Reversal of VCR resistance by CyA appeared to be dose-dependent. In the case of low-grade MDR cell lines (KYO-1, HEL and CMK), CyA at the low concentration of 0.5 microgram/ml was still effective. The degree of reversal of VCR resistance in this condition was greater (6.3- to 16-fold decrease) in the low-grade MDR cell lines than in a high-grade MDR cell line (K562/ADM) (2.9-fold decrease). At a high concentration (5 micrograms/ml) of CyA, however, it was greater (240-fold decrease) in the high-grade MDR cell lines than in the low-grade MDR cell line (20- to 100-fold decrease). This indicates that concentration of CyA required for overcoming drug resistance in MDR cells was dependent on the degree of drug resistance. CyA overcame VCR resistance more efficiently than VER. The combination of CyA and VER enhanced reversal of VCR resistance in a supra-additive or at least an additive manner and overcame VCR resistance at low concentrations of both modifiers that are clinically achievable with safety.

Cyclosporins↗

Alterations in histamine receptors of guinea-pig ileal smooth muscle produced during agonist-induced desensitization.

1. The effects of prolonged treatment with histamine (10(-4) M, 30 min) on desensitization at histamine H1-receptors of guinea-pig ileal longitudinal muscle were investigated. 2. This treatment did not change either the maximum amount or dissociation constant (Kd) of [3H]-mepyramine binding to membranes of guinea-pig ileal muscle. 3. In contrast, this treatment shifted the histamine inhibition curves of [3H]-mepyramine binding to the right both in the presence and absence of 0.5 mM guanosine-5'-triphosphate (GTP). This rightward shift of the curves occurred rapidly in the first 10 min of exposure to histamine. 4. The histamine inhibition curves were analyzed with a two binding sites model. It was shown that the histamine-induced affinity change of the receptor for the agonist occurred with the high affinity binding component (which comprise about 80% of the total), whereas no significant change occurred with the low affinity component. The GTP-dependent decrease in the affinity of the receptor for the agonist also occurred with the high affinity component both in control and histamine-treated preparations. 5. These studies suggest that histamine-induced desensitization was caused by alteration in the affinity of the receptor for the agonist rather than reduction in the number of the receptors and that the interaction of the receptor with a guanine nucleotide regulatory protein was retained in the desensitized state.

Animals↗

Temperature-dependence of desensitization induced by acetylcholine and histamine in guinea-pig ileal longitudinal muscle.

1. The effects of temperature on the time course of desensitization induced by acetylcholine and histamine, and on the recovery from desensitization were studied in the longitudinal muscle of the guinea-pig ileum. 2. Self- and cross-desensitization produced by acetylcholine (10(-5) M) occurred rapidly in the first 10 min of exposure to the agonist, with the same time course and the same degree of desensitization over the temperature range of 11 degrees C to 31 degrees C. 3. Self-desensitization produced by histamine (10(-5) M) also occurred rapidly in the first 10 min of exposure to the agonist, and showed great temperature-dependence, especially at 11 degrees C and 21 degrees C, but scarcely occurred at 6 degrees C. 4. Cross-desensitization produced by histamine developed gradually with time and showed a moderate temperature-dependence between 11 degrees C and 31 degrees C, but scarcely occurred at 6 degrees C. 5. The recovery processes from desensitization showed marked temperature-dependence. Recovery was halted completely at 11 degrees C. 6. These studies suggest that acetylcholine-induced desensitization may be attributed to a single non-specific mechanism. Histamine-induced desensitization may be due to at least two mechanisms: it occurs in both a specific and non-specific manner. Each of these desensitizations can be characterized by its unique temperature-dependence.

Acetylcholine↗