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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 181 records · Page 10Linked to original sources
PubMed1998

Vasoconstriction induced by zooxanthellatoxin-B, a polyoxygenated long-chain product from a marine alga.

We found that zooxanthellatoxin-B from a symbiotic marine alga, Symbiodinium sp., caused a concentration-dependent contraction of the rabbit isolated aorta at concentrations of 10(-7)-10(-5) M. Verapamil (10(-6) M) and mefenamic acid (10(-5) M) significantly attenuated the contractile response to zooxanthellatoxin-B at lower concentrations (10(-7)-10(-6) M) but not at higher concentrations (3 X 10(-6)-10(-5) M). The response to zooxanthellatoxin-B was partly inhibited by phentolamine (10(-6) M), whereas it was potentiated by ouabain (10(-5) M). Tetrodotoxin (10(-6) M), methysergide (10(-6) M), chlorpheniramine (10(-6) M) or indomethacin (3 X 10(-6) M), however, did not affect it. The zooxanthellatoxin-B-induced contraction was abolished by incubation in Ca2+-free solution. The contractile response increased in a concentration-dependent fashion with Ca2+ (0.03 and 10 mM) or Sr2 + (0.10 and 10 mM). After treatment with verapamil (10(-6) or 5 X 10(-6) M), the concentration-contractile response curves for Ca2+ and Sr2+ in the presence of zooxanthellatoxin-B were shifted to the right in parallel. MgCl2 (10 mM) shifted the concentration-response curve for Ca2+ more markedly than did verapamil. Zooxanthellatoxin-B increased tissue Na+ and reduced tissue K+ contents in the aorta, suggesting that zooxanthellatoxin-B increases Na+ and K+ permeability across the plasma membrane. These results suggest that the zooxanthellatoxin-B-induced contraction of the aorta is caused mainly by a direct action on smooth muscle, i.e., an increase in Ca2+ permeability that occurs at least partly through voltage-sensitive Ca2+ channels as well as through nonselective cation channels in the cell membrane of smooth muscle.

Animals↗
PubMed1998

Abdominal vagotomy attenuates interleukin-1 beta-induced nitric oxide release in the paraventricular nucleus region in conscious rats.

Nitric oxide (NO) has recently been shown to modulate the hypothalamic-pituitary-adrenal axis response to interleukin-1 beta (IL-1 beta). We measured levels of nitrite (NO2-) and nitrate (NO3-) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1 beta produced a significant increase in both NO2- and NO3- levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1 beta-induced NO release in the PVN region.

Abdomen↗
PubMed1998

Serotonergic activity in the rat striatum after intrastriatal transplantation of fetal nigra as measured by microdialysis.

In vivo microdialysis was used to examine the effects of dopaminergic transplants on extracellular concentrations of dopamine (DA), serotonin (5-HT), and their precursors and major metabolites in the denervated rat striatum. Dialysis perfusates were collected from intact 6-hydroxydopamine (6-OHDA) lesion plus sham grafted, and lesion plus fetal substantia nigra (SN) grafted striata. The SN transplants ameliorated the reduction of striatal DA and dihydroxyphenylacetic acid (DOPAC) levels in rats with unilateral 6-OHDA lesions of the mesostriatal pathway. The transplants also increased extracellular levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the denervated striatum. In response to NSD-1015 (an inhibitor of aromatic L-amino acid decarboxylase, AADC), 5-hydroxytryptophan (5-HTP) levels were substantially elevated in the SN grafted striata as compared with those in the sham grafted controls, which continued even after subsequent administration of L-3,4-dihydroxyphenylalanine (L-DOPA, 100 mg/kg i.p.). Immunohistochemical analysis showed hyperinnervation of 5-HT fibers in the grafted striatum, which was consistent with the results of microdialysis experiments. These results indicated that implantation of SN grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of 5-HT synthesis, release and metabolism.

5-Hydroxytryptophan↗
PubMed1998

Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2.

BACKGROUND: Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here and compared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics. METHODS: Formalin fixed, paraffin embedded sections of 11 cases of BCAC and 9 cases of BCA, selected from the authors' files of 1851 primary tumors of the major salivary gland, were examined using immunostaining for Ki-67 (MIB-1), p53, bcl-2, and EGFR. In addition, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling. RESULTS: The incidence of BCAC was 0.6% among patients with major salivary gland tumors in the current series. Nine cases of BCAC arose in the parotid gland and two were of submandibular gland origin. Approximately 50% of the patients had recurrences, but no patient developed metastases or died of disease. Vascular involvement (75%), perineural invasion (36%), and necrosis (45%) were common features. Cell proliferative activity, including mitotic count, Ki-67 labeling index (LI), and apoptotic index were significantly higher in BCAC than BCA. More than four mitotic figures per ten high-power fields or a Ki-67 LI > 5% appeared to be limited to cases of BCAC. Considering those cases expressing p53 or EGFR in > 10% of tumor cells as positive, 6 of the 11 BCAC cases were positive for p53 and 3 were positive for EGFR. In contrast, all BCA cases were negative for p53 and EGFR. Although all cases of BCA were strongly positive for bcl-2 (> 50% of tumor cells), 3 of 11 cases of BCAC were completely negative. CONCLUSIONS: BCAC is a rare salivary gland tumor with a relatively high recurrence rate. Examination of cell proliferation, apoptosis, and expression of p53, bcl-2, and EGFR were found to be useful in distinguishing malignant basal cell tumors from their benign counterparts arising in the salivary gland.

Adenocarcinoma↗
PubMed1998

Simultaneous assessment of the hemodynamic, cardiomechanical, and electrophysiological effects of terfenadine on the in vivo canine model.

Prolongation of the QT interval, sometimes leading to torsades de pointes, has been clinically reported during terfenadine treatment. However, information regarding the cardiovascular profile of terfenadine is still limited, particularly in in vivo animal models. In the current study, we examined the cardiovascular effects of terfenadine using halothane-anesthetized, closed-chest in vivo canine models (n = 6) to better simulate the clinical situation. Intravenous infusion of 0.3 mg/kg of terfenadine over 10 min, which would attain the antihistaminic plasma concentration, reduced the heart rate and left ventricular contractility and prolonged the repolarization period as well as the ventricular effective refractory period. An additional infusion of a ten times higher dose of terfenadine over 10 min caused hypotension and increased left ventricular preload and atrioventricular conduction time, in addition to potentiating the changes observed by the lower dose. A reverse use-dependent prolongation of the repolarization period was observed after the higher dose infusion. Moreover, early afterdepolarization-like potential was detected in four out of six experiments. Since each suppressive effect can become deleterious during terfenadine overdose, caution must be taken for those patients with potential cardiac dysfunction and with the risk of elevated plasma drug concentrations.

Analysis of Variance↗
PubMed1998

Increased bone mineral turnover without increased glucose utilization in sclerotic and hyperplastic change in fibrous dysplasia.

Fibrous dysplasia is a benign bone disorder. It is diagnosed by distinctive X-ray radiography, CT, and MRI findings. Although bone scintigraphy helps to identify the tumor origin according to accelerated bone turnover, the glucose metabolism in fibrous dysplasia has not yet been investigated. We reported a case of fibrous dysplasia in craniofacial bone which showed signs of the acceleration of bone mineral turnover without elevated glucose utilization by Technetium-99m-HMDP SPECT and Fluorine-18-FDG PET. We concluded that the growth of fibrous dysplasia needed the acceleration of bone mineral turnover without an increase in glucose metabolism.

Bone Density↗
PubMed1998

Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy: assessment by F-18-FDG PET study.

In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75 +/- 0.34%, 0.65 +/- 0.25%, and 0.43 +/- 0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17 +/- 0.49%, 0.80 +/- 0.44% and 0.99 +/- 0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38 +/- 0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy.

Blood Glucose↗
PubMed1998

Maintained function of primary human hepatocytes by cellular interactions in coculture: implications for liver support systems.

The application of primary hepatocytes in hybrid artificial liver systems has been hampered by the gradual loss of differentiated morphology and function in vitro. Therefore, we have established a coculture model of autologous human hepatocytes and biliary epithelial cells (BEC) in collagen gel in the presence of hepatotrophic growth factors. Furthermore, we examined the effect of hepatocyte cell perfusion in a women multicompartment capillary membrane system. Normal hepatocytes isolated from human liver produced albumin for more than 2 weeks in serum-free media, and were further stimulated by conditioned medium. When cocultured with BEC, albumin secretion was greatly enhanced, suggesting that cellular interactions promote tissue-specific differentiation. When perfused in bioreactors, albumin levels were maintained at steady state for longer than 2 weeks. These data indicate that differentiation of primary hum hepatocytes can be maintained by coculture interactions and three-dimensional hybrid organ devices, providing appropriate growth factors and matrix for tissue regeneration.

Cell Communication↗
PubMed1998

The decrease in bone mass associated with aging and menopause.

The human skeleton accumulates bone up to approximately age 30, after which bone is gradually lost. Although estrogen replacement therapy prevents postmenopausal bone loss, it is not certain that estrogen deficiency alone is responsible for the decrease in bone mass. Progesterone deficiency could also be a factor, and progesterone replacement therapy has been shown to prevent postmenopausal bone loss associated with ovarian dysfunction. This article reviews what is known about bone remodeling and bone loss as a function of age and gender, discusses evidence from studies in rats that progesterone plays an important role in regulating bone formation, and suggests directions for future studies in predicting the success or failure of implant therapy based on the number and kinds of osteoprogenitor cells present.

Adult↗
PubMed1998

Methamphetamine-induced Fos expression in the substantia nigra pars reticulata in rats with a unilateral 6-OHDA lesion of the nigrostriatal fibers.

In rats with a unilateral 6-hydroxydopamine (6-OHDA)-induced lesion in the nigrostriatal fibers, methamphetamine (3 mg/kg, i.p.) induced Fos-like immunoreactivity (FLI), which was inhibited by pretreatment with N-methyl-D-aspartate antagonist MK-801 (1 mg/kg, i.p.), not only in the medial striatum contralateral to the lesion but also in the substantia nigra pars reticulata (SNr) ipsilateral to the lesion. Thus, hemispheric asymmetries in FLI were induced by methamphetamine in the medial striatum and the SNr in the 6-OHDA model of turning which may be related to the altered function of glutamatergic transmission.

Animals↗
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

The death domain kinase RIP mediates the TNF-induced NF-kappaB signal.

The death domain serine/threonine kinase RIP interacts with the death receptors Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis, SAPK/JNK, and NF-kappaB activation. To define the physiologic role(s) that RIP plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice through homologous recombination. RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1-3 days of age. In contrast to a normal thymic anti-Fas response, rip-/- cells are highly sensitive to TNFalpha-induced cell death. Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a failure to activate the transcription factor NF-kappaB.

Adipose Tissue↗
PubMed1998

Advances in cereal gene transfer.

Over the past five years, transgenic strains of various major cereals have been produced, with transformation of rice and maize being most common. A majority of the cereal transformants obtained to date has been generated by the particle bombardment technique, but Agrobacterium-mediated transformation is rapidly becoming the method of choice. Rice, the plant in which transformation-related technology is most advanced, appears to be the model monocotyledon for basic and applied studies.

Edible Grain↗
PubMed1998

Fatal obstructive lung disease after haploidentical sibling cord blood transplantation.

We report the case of a patient with fatal obstructive lung disease after an HLA-haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2-year-old girl developed expiratory air trapping gradually with acute and chronic GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy were ineffective, and the patient died of progressive respiratory acidosis. Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic inclusion cells in the granulation tissues of the bronchiolitis. Thus, immunologic and GVHD problems can occur even in CBT.

Bronchiolitis Obliterans↗
PubMed1998

Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies.

AIMS: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland. METHODS AND RESULTS: Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT. CONCLUSIONS: Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.

Adenolymphoma↗
PubMed1998

Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.

Active vitamin D3 is extensively used for the treatment of secondary hyperparathyroidism in hemodialysis patients. But it is often impossible to administer enough dose to suppress parathyroid hormone (PTH) level, because of hypercalcemia and hyperphosphatemia. New modalities with higher specificity for PTH suppression are desirable. We conducted a crossover comparative study of falecalcitriol, an active vitamin D3 analog, and alfacalcidol (1alpha[OH]D3). In this study, 25 hemodialysis patients with moderate to severe secondary hyperparathyroidism who had normal serum calcium levels were enrolled. They received daily oral doses of alfacalcidol during an 8-week observation period. Based on serum calcium levels and intact PTH, the subjects were allocated into two groups, and a comparative study was conducted using unmasked crossover design of two drugs x two periods. The dosage of both drugs was adjusted to maintain the initial serum calcium levels, and the relative change (%change) of serum biochemical parameters were compared. Comparison of two drugs in period 1 was taken as primary efficacy evaluation. Reproducibility of drug action was confirmed by comparing the effect of falecalcitriol between period 1 and 2. The percent change of PTH of falecalcitriol was lower than that of alfacalcidol: Those were, respectively, -7.89% and +30.42% for c-terminal PTH (P = 0.022), -4.39% and +38.88% for i-PTH (P = 0.077), and +3.68% and +30.52% for midregion PTH (P = 0.099). The similar changes were observed in the falecalcitriol group during period 2, confirming the reproducibility. Falecalcitriol was found to be superior to alfacalcidol in suppression of PTH levels in patients with moderate to severe secondary hyperparathyroidism when it is administered in equivalent doses that might maintain similar serum calcium levels.

Adult↗
PubMed1998

Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder.

Fas is an apoptosis-signaling receptor important for homeostasis of the immune system. In this study, Fas-mediated apoptosis and Fas mutations were analyzed in three Japanese children from two families with a lymphoproliferative disorder characterized by lymphadenopathy, hepatosplenomegaly, pancytopenia, hypergammaglobulinemia and an increase in TCR alphabeta+ CD4- CD8- T cells. Apoptosis induced by anti-Fas mAb was defective in both activated T cells and B cells, and granulocytes from these patients. Truncated Fas receptor lacking the cytoplasmic death domain caused by a point mutation in the splice region of intron 7 were demonstrated in two siblings. A homozygous point mutation in the splice acceptor of intron 3 was found in the Fas gene of the third patient, which resulted in the skipping of exon 4 and complete loss of Fas expression. Corresponding to these mutations, soluble Fas concentrations were decreased and reciprocally soluble Fas ligands were increased in patients' sera. Interestingly, co-stimulation by immobilized anti-Fas mAb in T cells from the two siblings was comparable to that seen in normal T cells. These results suggest that Fas-mediated apoptosis plays a pivotal role in immunological homeostasis in vivo, especially regarding clonal deletion of immune cells in humans.

Apoptosis↗