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Biomedical subjects

Y Ishida

Publications and source records attributed to Y Ishida.

At least 271 records · Page 15Linked to original sources

Epstein-Barr virus-associated undifferentiated carcinoma with lymphoid stroma of the salivary gland in Japanese patients. Comparison with benign lymphoepithelial lesion.

BACKGROUND: Undifferentiated carcinoma with lymphoid stroma (UCLS) arising in the salivary gland is a rare tumor, except for its geographic concentration among Eskimo and southern Chinese populations. Five cases of salivary gland UCLS in Japanese patients are presented here and compared with benign lymphoepithelial lesions (BLELs) with regard to their association with Epstein-Barr virus (EBV), p53 expression, and cell proliferative activity. METHODS: Formalin fixed, paraffin embedded sections of 5 cases of UCLS selected from 1676 patients with primary tumors of the major salivary gland and 7 cases of BLEL were examined using in situ hybridization for EBV-encoded RNAs (EBERs), along with immunostaining for p53 and Ki-67 (MIB-1). RESULTS: The incidence of UCLS was 0.3% among patients with major salivary gland tumors. EBER hybridization signals were strongly expressed in most of the neoplastic cells in all five cases of UCLS, whereas there was no signal in BLEL and surrounding nontumorous salivary gland tissues. All cases of UCLS showed strongly positive immunostaining for p53 in the tumor cell nuclei. By contrast, only one case of BLEL was positively stained for p53 in dysplastic epimyoepithelial cells, which showed focal immunostaining. Cell proliferative activity assessed using the Ki-67 labeling index was significantly higher in tumor cells of UCLS than in epimyoepithelial cells of BLEL. CONCLUSIONS: UCLS of the salivary gland is an extremely rare tumor in Japanese patients characterized by consistent association with EBV. Distinction between BLEL and UCLS is possible by examining for evidence of EBV infection, expression of p53, and cell proliferative activity.

Adult↗

A combination chemotherapy with low doses of cytarabine and etoposide for high risk myelodysplastic syndromes and their leukemic stage. A pilot study.

BACKGROUND: Even now, no definitely effective therapy is inducted to high risk myelodysplastic syndromes (MDS) and their leukemic stage (MDS-AML) except bone marrow transplantation. METHODS: Ten patients with high risk MDS and 6 with MDS-AML were treated with daily low doses of cytarabine (10 mg/m2/12h, infused over 2h) etoposide (50 mg/m2/day, infused over 2h). RESULTS: Fourteen of these patients were finally evaluated among whom 6 with high risk MDS and 3 with MDS-AML (64.3%) had complete remission, and 2 with high risk MDS (14.3%) achieved partial remission after this chemotherapy for 9 to 21 days. Three of 11 responders were resistant to the prior chemotherapies with single and low dose cytotoxic agents including cytarabine, etoposide, or aclarubicin. Although all of the patients who could be assessed developed severe marrow hypoplasia after chemotherapy, the nonhematologic side effects were mild enough to be tolerated. CONCLUSIONS: This combination chemotherapy must be effective and useful in high risk MDS and MDS-AML not only without prior chemotherapy but in cases which have been resistant to single and low dose oncostatic agent.

Adult↗

Dopaminergic transplants suppress L-DOPA-induced Fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease.

We examined the effects of MK-801, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and fetal ventral mesencephalic (VM) transplants on L-3,4-dihydroxyphenylalanine (L-DOPA)-induced Fos protein expression in the dopamine (DA)-depleted striatum. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were produced in young adult female rats and grafting was performed 3 weeks later. Methamphetamine-induced rotational behavior recovered significantly on the 4th week after grafting. Immunohistochemical examinations of c-Fos and tyrosine hydroxylase (TH) were performed 3-4 months after grafting. L-DOPA (100 mg/kg, i.p.) markedly induced Fos-like immunoreactivity (FLI) in the DA-depleted striatum. Pretreatment with a large dose of MK-801 (3-4.5 mg/kg, i.p.) dose-dependently suppressed L-DOPA-induced FLI in the striatum. The stimulatory effect of L-DOPA on c-Fos expression observed within the lesioned striatum was suppressed by fetal VM transplants. It seemed that the graft-induced effect on FLI extended over a considerably larger area than that covered by the graft-derived TH-immunoreactive innervation. Taken together, these findings suggest that glutamatergic modulation is involved in the L-DOPA-induced c-Fos expression in the denervated striatum which is normalized by fetal VM transplants. It also seems likely that VM grafts suppress the L-DOPA-induced expression of transcriptional factors which might be involved in the mechanisms underlying various side effects of chronic L-DOPA therapy.

Animals↗

Dopaminergic transplants alter in vivo activity of tryptophan hydroxylase in the striatum in a rat model of Parkinson's disease.

L-3,4-Dihydroxyphenylalanine (L-DOPA) inhibits the activity of tryptophan hydroxylase (TRH) and thus serotonin synthesis. This inhibitory effect of L-DOPA may be related to some side effects in the patients under L-DOPA therapy. The effects of transplantation of fetal ventral mesencephalon (VM) on extracellular 5-hydroxytryptophan (5-HTP) accumulation was examined by microdialysis as an index of in vivo activity of TRH in the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rats. In the rat striatum perfused with m-hydroxybenzylhydrazine (NSD-1015; an inhibitor of aromatic L-amino acid decarboxylase), L-DOPA and 5-HTP in dialysate were measured simultaneously. In response to NSD-1015, 5-HTP levels were substantially elevated in the lesion plus VM-grafted striata as compared with those in the lesion plus sham-grafted striata. The results indicate that implantation of dopamine-rich VM grafts into the 6-OHDA-lesioned striatum of rats induces hyperactivity of TRH.

Adrenergic Agents↗

Inactivation of human immunodeficiency virus (HIV)-1 envelope-specific CD8+ cytotoxic T lymphocytes by free antigenic peptide: a self-veto mechanism?

Free peptide has been found to inhibit cytotoxic T lymphocyte (CTL) activity, and veto cells bearing peptide-major histocompatibility complex (MHC) complexes have been found to inactivate CTL, but the two phenomena have not been connected. Here we show that a common mechanism may apply to both. CD8+ CTL lines or clones specific for a determinant of the human immunodeficiency virus (HIV) 1 IIIB envelope protein gp160, P18IIIB, are inhibited by as little as 10 min exposure to the minimal 10-mer peptide, I-10, within P18IIIB, free in solution, in contrast to peptide already bound to antigen-presenting cells (APC), which does not inhibit. Several lines of evidence suggest that the peptide must be processed and presented by H-2Dd on the CTL itself to the specific T cell receptor (TCR) to be inhibitory. The inhibition was not killing, in that CTL did not kill 51Cr-labeled sister CTL in the presence of free peptide, and in mixing experiments with CTL lines of different specificities restricted by the same MHC molecule, Dd, the presence of free peptide recognized by one CTL line did not inhibit the activity of the other CTL line that could present the peptide. Also, partial recovery of activity could be elicited by restimulation with cell-bound peptide, supporting the conclusion that neither fratricide nor suicide (apoptosis) was involved. The classic veto phenomenon was ruled out by failure of peptide-bearing CTL to inactivate others. Using pairs of CTL lines of differing specificity but similar MHC restriction, each pulsed with the peptide for which the other is specific, we showed that the minimal requirement is simultaneous engagement of the TCR and class I MHC molecules of the same cell. This could occur in single cells or pairs of cells presenting peptide to each other. Thus, mechanistically, the inhibition is analogous to veto, and might be called self-veto. As a clue to a possible mechanism, we found that free I-10 peptide induced apparent downregulation of expression of specific TCR as well as interleukin 2 receptor, CD69, lymphocyte function-associated antigen 1, and CD8. This self-veto effect also has implications for in vivo immunization and mechanisms of viral escape from CTL immunity.

3T3 Cells↗

Progesterone and dexamethasone stimulate proliferation and differentiation of osteoprogenitors and progenitors for adipocytes and macrophages in cell populations derived from adult rat vertebrae.

We investigated the effects of the sex hormone progesterone (Prog) and the synthetic glucocorticoid dexamethasone (Dex) on proliferation and differentiation of progenitor cells of osteogenic, adipocytic, and hemopoietic lineages in cell populations derived from explants of adult female rat lumbar vertebrae. The cell populations were obtained by culturing bone explants in plasma clots immersed in alpha-minimum essential medium plus 10% fetal calf serum (standard medium) and then subculturing the outgrowth cells in standard medium plus 50 micrograms/ml of ascorbic acid, 5 mM beta-glycerophosphate, and with or without Prog or Dex. On day 6 of culture, these populations were analyzed for cAMP responses to parathyroid hormone (PTH), prostaglandin E2 (PGE2), and isoproterenol (IPT). Increases in intracellular cAMP were seen in response to PTH, PGE2, and IPT, and culturing in medium containing Prog increased these responses. At various time periods between days 4-27 of culture, the cultures were evaluated for the presence of bone nodules, alkaline phosphatase (AP)-positive colonies, adipocytes, monocytes, and macrophages. Prog and Dex increased the number of bone nodules and AP-positive colonies. The effect of Prog on bone nodule formation was smaller than that of Dex. In addition, the effect of Dex on bone nodule formation was evident after 10 days of culture, while the Prog-induced effects became significant at days 16-20 of culture. Both hormones also increased the number of Sudan IV-positive colonies (adipocytes), certain types of alpha-naphthyl butyrate esterase (alpha-NBE)-positive colonies (monocytes, macrophages, and T-lymphocytes), and ED2-positive colonies (macrophages). Prog-treated cultures contained more colonies of small spindle-shaped alpha-NBE-positive cells and fewer colonies of small round alpha-NBE-positive cells when compared with Dex-treated cultures. These data indicate that cell populations derived from adult rat lumbar vertebrae contain, among others, osteoprogenitors and progenitors for adipocytes and macrophages that are stimulated to proliferate and differentiate by Prog and Dex. The data also suggest that the effects of Prog and Dex differ qualitatively and quantitatively.

Adipocytes↗

Morphological analysis of the cervical spinal canal, dural tube and spinal cord in normal individuals using CT myelography.

To verify the conventional concept of "developmental stenosis of the cervical spinal canal", we performed a morphological analysis of the relations of the cervical spinal canal, dural tube and spinal cord in normal individuals. The sagittal diameter, area and circularity of the three structures, and the dispersion of each parameter, were examined on axial sections of CT myelograms of 36 normal subjects. The spinal canal was narrowest at C4, followed by C5, while the spinal cord was largest at C4/5. The area and circularity of the cervical spinal cord were not significantly correlated with any parameter of the spinal canal nor with the sagittal diameter and area of the dural tube at any level examined, and the spinal cord showed less individual variation than the bony canal. Compression of the spinal cord might be expected whenever the sagittal diameter of the spinal canal is below the lower limit of normal, that is about 12 mm on plain radiographs. Thus, we concluded that the concept of "developmental stenosis of the cervical spinal canal" was reasonable and acceptable.

Adolescent↗

Prognosis of hypertrophic cardiomyopathy: assessment by 123I-BMIPP (beta-methyl-p-(123I)iodophenyl pentadecanoic acid) myocardial single photon emission computed tomography.

123I-BMIPP (beta-methyl-iodophenyl pentadecanoic acid) has shown unique properties for potential use in assessing myocardial metabolism. Previous basic and clinical studies demonstrated that the disturbances of myocardial metabolism precede the occurrence of myocardial perfusion abnormalities by using 201Tl in hypertrophic myocardium. The present study was therefore undertaken to determine whether or not 123I-BMIPP myocardial SPECT is useful in predicting the prognosis of hypertrophic cardiomyopathy (HCM) in 65 patients in 6 facilities. There were 33 patients with non-obstructive HCM, 12 with obstructive HCM, 12 with apical HCM and 8 with dilated-phase HCM. Fasted patients at rest received an intravenous injection of 111 MBq of 123I-BMIPP. Twenty to thirty minutes later, myocardial SPECT was carried out. The BMIPP severity score (BMIPP SS) was evaluated semiquantitatively by using representative short axial SPECT images. We followed up the incidence of cardiac events for a mean period of 3.0 +/- 0.6 years. Cardiac events occurred in 13 patients. Of these, 11 developed heart failure and 6 died (4 from heart failure and 2 from sudden death). The BMIPP SS in the dilated-phase HCM was significantly lower than that for the nonsurvivors. The BMIPP SS was particularly high in patients with fatal heart failure. Furthermore, there was a close negative correlation between the BMIPP SS and percent fractional shortening measured by echocardiography (r = -0.49). Finally, the mortality over the three years increased according to the extent of the BMIPP SS. In conclusion, these results indicate that BMIPP SS is useful in evaluating the severity of HCM. We conclude that 123I-BMIPP is a valuable metabolic tracer in predicting the outcome of HCM.

Adult↗

Paradoxical uptake of F-18 fluorodeoxyglucose by successfully reperfused myocardium during the sub-acute phase in patients with acute myocardial infarction.

The myocardial uptake of F-18 fluorodeoxyglucose (FDG) has been shown to indicate ischemia. To elucidate whether this is applicable to reperfused myocardium in patients with acute myocardial infarction (AMI), Tl-201 SPECT and F-18 FDG PET were performed in 10 patients with successfully recanalized AMI (male myocardial perfusion on the infarct-related area was classified, on the basis of Tl-201 images, into 2 groups (normal and defect) during the sub-acute phase, and into 3 grades (normal, redistribution (RD), and persistent defect) during the chronic phase (1 and 3 months after onset). Regional FDG uptake was calculated as FDG uptake in the region of interest normalized relative to that in a normal area. During the chronic phase, FDG accumulated only in the region of RD, indicating ischemia, but during the sub-acute phase, FDG accumulated mainly in the peri-infarct area. To elucidate whether the reperfused myocardium itself shows signs of accelerated glucose uptake, an experimental study was performed in rats. Glucose uptake in the isolated heart was measured by deoxyglucose and 31P-NMR spectroscopy, and was significantly increased after reperfusion compared with the pre-ischemic level. In conclusion, the enhancement of FDG uptake during the sub-acute phase was observed in successfully reperfused myocardium of patients with acute myocardial infarction. Such augmentation disappeared during the chronic phase. An experimental study in rats indicated that ischemia and reperfusion themselves augment glucose uptake. This mechanism may be responsible for the increase in FDG uptake of reperfused myocardium observed clinically.

Aged↗

A nitric oxide-sensitive electrode: requirement of lower oxygen concentration for detecting nitric oxide from the tissue.

In order to directly detect nitric oxide (NO) liberated from isolated tissue, a practical and convenient method using a nitric oxide-sensitive electrode is described. To avoid the nonselective signal caused by ionic substances, the electrode was covered with three layers but remains permeable for gaseous substances. In a solution bubbled with 20% oxygen (pO2, approximately 150 mm Hg), administration of S-nitroso-N-acetyl-d, l-penicillamine (SNAP) at concentrations greater than 10(-7) mol/L elicited an electrode response. Based on a comparison with the chemical determination of NO released from SNAP, the electrode may be able to detect nitric oxide around nmol/L. At least 30 nmol NO per liter in anoxic conditions was reported to be detected by this electrode (Matsui, 1995). In a specially designed small chamber, the electrode was attached on the surface of endothelial side of the isolated aorta of the guinea pig. When carbachol was added to the chamber, the electrode responded when the solution was bubbled with 20% but not with 40% or 95% of oxygen, suggesting a much faster decomposition of nitric oxide in the presence of higher concentrations of oxygen. The electrode response to carbachol was abolished in the presence of NG-monomethyl-L-arginine or nitro arginine. These results suggest that the electrode method described in this manuscript is suitable for detecting nitric oxide liberated from isolated tissues when comparatively low oxygen levels are present in the physiological salt solution.

Animals↗

Hypereosinophilic syndrome with generalized myasthenia gravis.

A patient with hypereosinophilic syndrome simultaneously had generalized myasthenia gravis. Ultrastructural and functional studies demonstrated an increase of the activated hypodense eosinophils. The eosinophilic cationic protein level in plasma and whole blood paralleled the severity of congestive heart failure. A high level of interleukin-5 was detected in both serum and in conditioned medium of T cells by interleukin-2 stimulation before therapy. The findings indicate that both diseases may be associated with a common T-cell abnormality.

Blood Proteins↗

Electrophysiological responses of three chemosensory systems in the carp to pesticides.

Responses of three chemical senses, olfaction, taste, and pit organ sense, to three pesticides were studied electrophysiologically in carp, Cyprinus carpio. Only olfaction was responsive to the three pesticides at behavioral avoidance levels, which were determined in a previous study. The olfactory thresholds for benthiocarb, isoprothiolane, and fenitrothion were 1.7 x 10(-1) micrograms/l (4 log units lower concentration than 48-h LC50), 6.7 x 10(-3) micrograms/l (6 log units lower than 48-h LC50), and 4.9 x 10(2) micrograms/l (1 log unit lower than 48-h LC50), respectively. There were two distinctive features in the olfactory response to pesticides. One is that these pesticides barely indicated the concentration dependency that is usually recognized in the olfactory response to a typical stimulant such as L-alanine or NaCl. Another is that these pesticides indicated a power spectrum with an overall increase in frequency ranges of less than 10.0 Hz, unlike L-alanine or NaCl, which show a marked peak ranging from 8.0 to 12.0 Hz. These findings suggest that there is a specific mechanism in the chemoreception for these pesticides.

Animals↗

High efficiency transformation of maize (Zea mays L.) mediated by Agrobacterium tumefaciens.

Transformants of maize inbred A188 were efficiently produced from immature embryos cocultivated with Agrobacterium tumefaciens that carried "super-binary" vectors. Frequencies of transformation (independent transgenic plants/embryos) were between 5% and 30%. Almost all transformants were normal in morphology, and more than 70% were fertile. Stable integration, expression, and inheritance of the transgenes were confirmed by molecular and genetic analysis. Between one and three copies of the transgenes were integrated with little rearrangement, and the boundaries of T-DNA were similar to those in transgenic dicotyledons and rice. F1 hybrids between A188 and five other inbreds were transformed at low frequencies.

Agrobacterium tumefaciens↗

Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant, neurodegenerative disorder that affects the cerebellum and other areas of the central nervous system. We have devised a novel strategy, the direct identification of repeat expansion and cloning technique (DIRECT), which allows selective detection of expanded CAG repeats and cloning of the genes involved. By applying DIRECT, we identified an expanded CAG repeat of the gene for SCA2. CAG repeats of normal alleles range in size from 15 to 24 repeat units, while those of SCA2 chromosomes are expanded to 35 to 59 repeat units. The SCA2 cDNA is predicted to code for 1,313 amino acids-with the CAG repeats coding for a polyglutamine tract. DIRECT is a robust strategy for identification of pathologically expanded trinucleotide repeats and will dramatically accelerate the search for causative genes of neuropsychiatric diseases caused by trinucleotide repeat expansions.

Amino Acid Sequence↗

Recombinant human c-Mpl ligand is not a direct stimulator of proplatelet formation in mature human megakaryocytes.

To evaluate the effect of the c-Mpl ligand on platelet production by megakaryocytes, we investigated proplatelet formation in isolated human megakaryocytes cultured in serum-free medium, with or without the c-Mpl ligand, interleukin-6 and erythropoietin. When interleukin-6 was added to the culture medium, the percentage of megakaryocytes displaying proplatelets was approximately 1.5-fold the control value; whereas, in the presence of the c-Mpl ligand, the percentage of megakaryocytes displaying proplatelets decreased in a dose-dependent manner and did not increase compared to control values at any dose tested. However, the viability of megakaryocytes after a 4 d culture in the presence of the c-Mpl ligand was significantly higher than that of the cells cultured without it. The c-Mpl ligand did not stimulate the proplatelet formation in megakaryocytes in vitro.

Blood Platelets↗

Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes.

A mAb J43 has been produced against the product of the mouse PD-1 gene, a member of the Ig gene superfamily, which was previously isolated from an apoptosis-induced T cell hybridoma (2B4.11) by using subtractive hybridization. Analyses by flow cytometry and immunoprecipitation using the J43 mAb revealed that the PD-1 gene product is a 50-55 kDa membrane protein expressed on the cell surface of several PD-1 cDNA transfectants and 2B4.11 cells. Since the molecular weight calculated from the amino acid sequence is 29, 310, the PD-1 protein appears to be heavily glycosylated. Normal murine lymphoid tissues such as thymus, spleen, lymph node and bone marrow contained very small numbers of PD-1(+) cells. However, a significant PD-1(+) population appeared in the thymocytes as well as T cells in spleen and lymph nodes by the in vivo anti-CD3 mAb treatment. Furthermore, the PD-1 antigen expression was strongly induced in distinct subsets of thymocytes and spleen T cells by in vitro stimulation with either anti-CD3 mAb or concanavalin A (Con A) which could lead T cells to both activation and cell death. Similarly, PD-1 expression was induced on spleen B cells by in vitro stimulation with anti-IgM antibody. By contrast, PD-1 was not significantly expressed on lymphocytes by treatment with growth factor deprivation, dexamethasone or lipopolysaccharide. These results suggest that the expression of the PD-1 antigen is tightly regulated and induced by signal transduction through the antigen receptor and do not exclude the possibility that the PD-1 antigen may play a role in clonal selection of lymphocytes although PD-1 expression is not required for the common pathway of apoptosis.

Animals↗

Effect of resistance training volume on strength and muscle thickness.

The purpose of this study was to determine the effects of different volumes of high-intensity resistance training on isometric torque and muscle thickness. Training was conducted three times per week using one set (low volume, EX-1, N = 18) or three sets (high volume, EX-3, N = 20) of dynamic variable resistance exercise. Ten subjects acted as nontraining controls (CONT). Bilateral knee extension (KEXT) and flexion (KFLEX) exercise was performed to fatigue within 8-12 repetitions for 14 wk. Maximal isometric KEXT and KFLEX torque was tested at 6 degrees, 24 degrees, 42 degrees, 60 degrees, 78 degrees, 96 degrees, and 108 degrees of KFLEX using a MedX (Ocala, FL) KEXT/KFLEX ergometer. The anterior (ANT), lateral (LAT), and posterior (POST) right thigh, the medialis muscle (MED), and the lateralis muscle (LATER) were assessed for thickness by B-mode ultrasound (ULTRA). Both training groups improved torque output at most angles, but there was no difference between EX-1 and EX-3 (P > or = 0.05). ULTRA detected increases in muscle thickness for EX-1 at 60% LAT and 40% and 60% POST. EX-3 increased muscle thickness at the MED, and 40% and 60% POST. In conclusion, one set of high intensity resistance training was as effective as three sets for increasing KEXT and KFLEX isometric torque and muscle thickness in previously untrained adults.

Adolescent↗