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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 433 records · Page 24Linked to original sources

Relationship between turnover of cesium-137 and dietary potassium content in potassium-restricted mice.

The biological half-life of 137Cs and its organ distribution were investigated in mice fed various potassium-deficient diets. The biological half-life, which was 6.1 days in mice receiving the normal level of potassium, became longer as the dietary potassium content decreased, and 137Cs was hardly excreted from the body when dietary potassium content was restricted to 200 mg/kg or less. The muscle showed the highest concentration of 137Cs in both mice that had sufficient amounts of potassium and those that were potassium-deficient. Clearance of 137Cs from tissues was generally suppressed when mice were fed a potassium-deficient diet, but the relative distribution pattern of 137Cs was not affected by dietary potassium content. These results suggest that dietary potassium intake, which may vary with eating habits, affects the biological half-life of 137Cs in humans.

Animals↗

Endothelin-1 in the gastric mucosa in stress ulcers of critically ill patients.

OBJECTIVE: Gastric microcirculatory disturbances are involved in the pathogenesis of stress ulcers; however, vasomodulators causing this process are not fully understood. This study was conducted to investigate the role of endothelin 1 (ET-1), a potent vasoconstrictive peptide, in stress ulcers in critically ill patients. METHODS: Using sandwich enzyme immunoassay, we measured ET-1 content in plasma and the gastric mucosa of 16 critically ill patients with traumatic head injury on admission and of 11 healthy subjects. Gastric mucosal samples were obtained endoscopically. When gastric drainage contained occult blood, endoscopic examination was performed again, and ET-1 concentrations in injured and adjacent normal mucosa were compared. RESULTS: Plasma and mucosal ET-1 concentrations were significantly higher in critically ill patients on admission (6.1 +/- 0.6 pg/ml and 13.8 +/- 1.6 ng/g, respectively) compared with values in control subjects (2.7 +/- 0.4 pg/ml and 8.2 +/- 0.5 ng/g, respectively) (p < 0.01). The mucosal ET-1 concentration tended to be elevated in patients who had experienced hypoxia compared with those who had not (p = 0.07). In five patients who were again examined endoscopically, the ET-1 concentration in the injured mucosa was significantly higher than that in adjacent mucosa (19.2 +/- 3.2 and 10.1 +/- 1.6 ng/g, respectively; p < 0.05). CONCLUSIONS: These results suggest that endogenous ET-1 plays an important role in the local pathogenesis of stress ulcers, especially those caused by hypoxia.

Adult↗

[Clinical application of 31P-chemical shift image using 31P-volume coil to Moyamoya disease].

31P-MRS and 31P-Chemical Shift Image(CSI) using volume coil were applied to Moyamoya disease of 14 cases, data of which were compared with clinical manifestations and neuroimagings. In four asymptomatic cases, signal intensity of both total P and total ATP was almost equal in each voxel, but in other cases, both signal intensity of the lesion was relatively decreased, compared with non-lesion. Especially, signal intensity of total P and total ATP in ischemic lesion was significantly decreased. This showed that 31P-CSI is able to demonstrate cerebral ischemic lesion not detected by CT and MRI. We have reported on Moyamoya disease that 31P-MRS comparatively correlates to cerebral blood flow and 31P-CSI demonstrates ischemic lesion as not detected by CT and MRI less invasively.

Cerebrovascular Circulation↗

[The effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy].

We investigated changes in the blood velocity of the ophthalmic artery to observe its relationship to the complication of diabetes mellitus before and after hyperbaric oxygen therapy (HBO). Color Doppler imaging (Toshiba, SSA-260A) was used. In this study, there were 7 diabetic neuropathy patients, 3 diabetes patients without neuropathy, and 7 normal subjects for control. These patients were examined before and after HBO. The patients were made to breathe 100% oxygen at 2.0 atmosphere absolute (ATA) for one hour. HBO is sometimes used for treatment of diabetic neuropathy. HBO produced an average decrease in blood velocity of 15.0 +/- 9.0 (mean +/- standard deviation) % in normal subjects, 10.7 +/- 8.6% in diabetes patients without neuropathy, and returned to the baseline level 4 hours after the conclusion of HBO. On the other hand, the blood velocity increased by about 20.6 +/- 9.5% in diabetic neuropathy patients regardless the degree of severity of diabetic retinopathy. These results suggest that the increase in the blood velocity of the ophthalmic artery after HBO in diabetic neuropathy patients could be attributed to an imbalance in autonomic nervous function.

Blood Flow Velocity↗

[Bronchial hyperresponsiveness in patients with vasospastic angina pectoris (VSAP)].

To determine the relationship between airway and coronary artery spasmogenesity in patients with vasospastic angina pectoris (VSAP), we measured the bronchial responsiveness to inhaled methacholine in 21 VSAP patients (V-group) and compared it to that of 17 chest pain syndrome patients with normal coronary (N-group). In the V-group, logarithmic values of the minimum cumulative dose required to decrease respiratory conductance from the baseline (Log Dmin) was significantly lower than that in N-group (0.47 +/- 0.60 log units vs. 0.98 +/- 0.60 log units respectively, p < 0.05). Log Dmin was significantly correlated with the dose of acetylcholine which induced a greater than 90% stenosis of the coronary artery (r = 0.383, p < 0.05). We concluded that both the coronary artery and the airway show hyperresponsiveness to cholinergic agonists in patients with VSAP.

Aged↗

[An analysis of type 2 helper T cells in patients with atopic dermatitis].

In order to know the role of type 2 helper T (Th2) cells on patients with atopic dermatitis (AD), peripheral blood mononuclear cells were taken from the patients, stimulated with immobilized anti CD3 monoclonal antibody in the presence of monensin, and stained with fluorescein isothiocyanate-labeled anti IL-2 or IL-4 monoclonal antibody, followed by phycoerythrin labeled-anti CD4 monoclonal antibody. The fluorescent intensity was detected by FACScan. The results showed that the frequency of IL-4 producing CD4+ cells from AD patients was significantly higher than that from the healthy controls, whereas that of IL-2 producing CD4+ cells from patients were the same as healthy controls. The frequency of IL-4 producing cells was well correlated to the clinical severity of the disease, but that of IL-2 producing cells did not show any significance. Neither IL-2 nor IL-4 producing CD4+ cells had any relation to the serum IgE levels and the number of eosinophils in the patients. Our results indicate dominance of IL-4 producing CD4+ cells, which means Th2 cells in the peripheral mononuclear cells in the patients with AD, especially severe cases.

Adult↗

A phase I and II clinical trial of a newly developed ultrasound hyperthermia system with an improved planar transducer.

PURPOSE: The clinical usefulness of a newly developed ultrasound hyperthermia system was evaluated. METHODS AND MATERIALS: The hyperthermia system uses a modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The transducer has a nonvibrating part at the center to reduce the central hot spot. Frequency sweeping technique is also used to eliminate the annular hot spot around the center. Thirty-eight tumors in 29 patients were examined in this study. In 35 tumors, hyperthermia was given in conjunction with irradiation and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given. In all, a total of 153 hyperthermia sessions were performed. RESULTS: The number of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 +/- 1.3). The number of intratumor thermometry points per session ranged from 1 to 8 (mean, 4.3 +/- 1.5). The average intratumor temperature for tumors with a maximum depth of <3 cm, 3-6 cm, and >6 cm was 42.1 +/- 1.2, 41.7 +/- 1.4, and 39.9 +/- 2.0 degrees C, respectively. The percentage of monitored intratumor points with temperature exceeding 42 degrees C was 56 +/- 31%, 43 +/- 34%, and 21 +/- 24%, respectively. Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete response, 14 partial response, and 4 no change. Observed complications included pain at the treatment site in 13 of the 153 treatment sessions and vesicle formation in 3 of the 38 treatment sites. No serious complication was seen. CONCLUSIONS: These results indicate that the newly developed ultrasound hyperthermia system is clinically useful for the treatment of localized superficial and subsurface tumors with a maximum tumor depth of no more than 6 cm.

Adult↗

Optimal size criteria of malignant lymph nodes in the treatment planning of radiotherapy for esophageal cancer: evaluation by computed tomography and magnetic resonance imaging.

PURPOSE: To determine the optimal size criterion for detection of lymph node metastases from esophageal cancer for radiotherapy by computed tomography (CT) and magnetic resonance (MR) imaging. METHODS AMD MATERIALS: In 58 patients with esophageal cancer treated with subtotal esophagectomy and radical lymph node dissection the preoperative MR (n = 58) images and CT scans (n = 41) were reviewed. The relationship of the CT and MR findings for the neck and mediastinum to the surgical and histopathological results was examined. Five size criteria on malignant lymph nodes were used to construct receiver operating characteristic (ROC) curves for CT and MR, and their detectabilities were evaluated. RESULTS: The specificities of both modalities at the cutoff of 3 mm short-axis diameter were lower than those at the cutoff of 5 mm or more. In contrast, the sensitivities apparently decreased at the cutoff of 10 mm or more. The analysis of the ROC curves showed that the optimal size criterion for malignant lymph nodes was 5 mm for both CT and MR. When the criterion of 5 mm was used, the sensitivity, specificity, and accuracy for CT was 68, 92, and 87%, respectively, and the respective values for MR were 70, 93, and 89%. Although there was no significant difference between the two ROC curves, MR was useful in distinguishing lymph nodes from vascular structures because of the flow void. CONCLUSIONS: There was no significant difference between CT and MR in the detection of malignant lymph nodes from esophageal cancer. The optimal size criterion for both CT and MR in the detection of cervical and mediastinal lymph node metastases is 5 mm for short-axis diameter. These results suggest that all regional lymph nodes of 5 mm or more on CT or MR should be regarded as part of the gross tumor volume in the treatment planning of radiotherapy for esophageal cancer.

Adult↗

Altered TCR ligands affect antigen-presenting cell responses: up-regulation of IL-12 by an analogue peptide.

When examining the effects of analogue peptides on changes in response patterns of a human Th0 clone DT13.2 that recognizes a peptide fragment (18RSLRTVTPIRMQGG31) derived from a group I allergen in Dermatophagoides farinae in the context of HLA-DQ6 (DQA1*0102/DQB1*0602), we found that replacement of the 21st residue Arg to Lys resulted in a significant increase in IFN-gamma production, with no remarkable changes either in proliferative response or IL-4 production, at high doses of the peptide. Selective enhancement of IFN-gamma production by the analogue peptide was accompanied by an increased production of IL-12, which was suppressed by an anti-IL-12 Ab down to the level of IFN-gamma production induced by the wild-type peptide. On the contrary, co-incubation with neutralizing Abs to IFN-gamma and IFN-gamma receptor did not affect IL-12 production, indicating that increased production of IL-12 stimulated by the analogue peptide was not due to an effect of IFN-gamma from T cells. Peptide-induced up-regulation of CD40 ligand expression at high peptide concentrations showed no difference between the wild-type and analogue peptides. These data collectively indicate that certain T cell/APC interactions mediated through TCR and altered TCR ligands affect APC responses and that signals transmitted to APC are as indispensable as those to T cells in determining T cell response patterns.

Allergens↗

Genetic analysis of a Japanese cerebrotendinous xanthomatosis family: identification of a novel mutation in the adrenodoxin binding region of the CYP 27 gene.

Cerebrotendinous xanthomatosis (CTX), an autosomal recessive lipid-storage hereditary disorder, is caused by mutations in the sterol 27-hydroxylase gene (CYP 27). A 24-year-old female Japanese CTX patient and her parents were studied for a CYP 27 mutation. Multiple xanthomas were the main complaint of the patient and plasma cholestanol level was markedly elevated. Sterol analysis of a xanthoma biopsy confirmed cholesterol and cholestanol deposition, and the cholestanol accounted for 8.1% of the total sterols. Sterol 27-hydroxylase activity in fibroblasts derived from the patient was undetectable, while the activities in fibroblasts from her mother and father were 54% and 41% of the normal level, respectively. Direct sequence analysis showed a missense mutation of A for G substitution in the CYP 27 gene at codon 362 (CGT 362Arg to CAT 362His) with a homozygous pattern in the patient, and a heterozygous pattern in the parents. The mutation, which eliminates a normal HgaI endonuclease site at position 1195 of the cDNA and is located at the adrenodoxin binding region of the gene, is most probably responsible for the decreased sterol 27-hydroxylase activity in this Japanese CTX family. The combined data strongly support that the primary enzymatic defect in CTX is the disruption of sterol 27-hydroxylase and that the disease is inherited in an autosomal recessive trait.

Adrenodoxin↗

Response of a human T cell clone to a large panel of altered peptide ligands carrying single residue substitutions in an antigenic peptide: characterization and frequencies of TCR agonism and TCR antagonism with or without partial activation.

A CD4+ human T cell clone YN5-32 recognized a streptococcal M12p54-68 peptide in the context of HLA-DR4 and produced a large amount of IFN-gamma. We investigated responses of YN5-32 to 156 independent analogue peptides carrying single residue substitutions at residues 57 (position 1 (p1)) to 65 (p9) of the peptide. Approximately 30% of analogues at either Leu57 (p1), Ala60 (p4), or Asn62 (p6) residues exhibited TCR agonism to stimulate various magnitudes of proliferative responses in the T cell clone, and analogues exhibiting TCR antagonism are rare in these three residues. In analogues at either Glu58 (p2), Gln59 (p3), Tyr61 (p5), or Glu63 (p7) residue, 30 to 50% exhibited TCR antagonism. About 10% of analogues at Glu58 (p2) or Tyr61 (p5) stimulated proliferative responses, while 30 to 50% of analogues at Gln59 (p3) or Glu63 (p7) did so. Some of these TCR antagonistic analogues carrying relatively conservative amino acid substitutions partially activated the T cells to induce large increases in size and expression levels of CD4, CD11a (LFA-1), CD28, CD49d (VLA-4), and CD95 (Fas), and small increases in CD25 and CD44 expressions on the cell surface. None of the partially activating antagonistic analogues induced IFN-gamma production or anergy in T cells. Analogues with replacements of acidic amino acids at either Leu64 (p8) or Ser65 (p9) residue had dominant negative effects on T cell proliferation. Thus, altered peptide ligands with single residue substitutions in the antigenic peptide frequently stimulated the human T cell clone, in at least three different ways to exhibit agonism, antagonism, and antagonism with partial activation. Frequencies of analogue peptides exhibiting these three different effects on the T cell clone differed depending on the residue of the peptide substituted. Altered T cell responses induced by analogue peptides of a T cell epitope provide a system to analyze activation signals mediated by TCR, and to manipulate T cell responses.

Amino Acid Sequence↗

Cloning of a gene from Escherichia coli that confers resistance to fosmidomycin as a consequence of amplification.

A gene conferring resistance to fosmidomycin (Fs) was cloned from the gene pool of a wild-type strain of Escherichia coli. The cloned DNA fragment was sequenced and shown to encode a putative polypeptide of 406 amino acids (aa) with a molecular weight of 43303. The gene mapped at 10.9 min on the E. coli chromosome and was designated fsr (fosmidomycin resistance). Maxicell analysis revealed that the Fsr protein migrated in sodium dodecyl sulfate-polyacrylamide-gel electrophoresis as a broad band of 35 kDa. A comparison between the aa sequence of Fsr and sequences in a protein database revealed 18% homology to the bacterial drug-export proteins that mediate resistance to tetracycline and chloramphenicol. Hydropathy analysis of the Fsr protein revealed twelve putative transmembrane segments. The degree of FsR of transformants depended on the number of copies of the plasmid that contained fsr. The levels of ubiquinone-8 and undecaprenyl phosphate in cells that harbored a high-copy-number plasmid that included fsr were almost the same as those in the cells without the plasmid. These results suggest that Fsr does not have any direct effect on the biosynthesis of isoprenoid in E. coli, and that the mechanism for FsR involves the efflux of the drug by a process that is facilitated by Fsr.

Amino Acid Sequence↗

Polyprenyl diphosphate synthase essentially defines the length of the side chain of ubiquinone.

Ubiquinone, known as a component of the electron transfer system in many organisms, has a different length of the isoprenoid side chain depending on the species, e.g., Escherichia coli, Saccharomyces cerevisiae and humans have 8, 6, and 10 isoprene units in the side chain, respectively. No direct evidence has yet shown what factors define the length of the side chain of ubiquinone. Here we proved that the polyprenyl diphosphate that was available in cells determined the length of the side chain of ubiquinone. E. coli octaprenyl diphosphate synthase (IspB) was expressed with the mitochondrial import signal in S. cerevisiae. Such cells produced ubiquinone-8 in addition to the originally existing ubiquinone-6. When IspB was expressed in a S. cerevisiae COQ1 defective strain. IspB complemented the defect of the growth on the non-fermentable carbon source. Those cells had the activity of octaprenyl diphosphate synthase and produced only ubiquinone-8. These results opened the possibility of producing the type of ubiquinone that we need in S. cerevisiae simply by expressing the corresponding polyprenyl diphosphate synthase.

Alkyl and Aryl Transferases↗

The burst firing in the layer III and V pyramidal neurons of the cat sensorimotor cortex in vitro.

We identified the burst and single-spiking cells, and the repetitive bursting cells in layers III and V of the cat sensorimotor cortex with intracellular recording and staining techniques. Both types of the bursting cells were found in 22.7% of the recorded layer V neurons and in 23.1% of the recorded neurons in layer III. The bursting cells were characterized by the prominent afterdepolarization (ADP) which was usually reaching the threshold depolarization. Intracellular staining revealed that the morphology of the bursting cells was not so different from that of the regular-spiking cells in the cat.

Adenosine Diphosphate↗

A 19-kb CpG island associated with single-minded gene 2 in Down syndrome chromosomal region.

To help in isolating the genes involved in Down syndrome, we sought CpG islands in 4 Mb cosmid/PAC contigs spanning most of the 21q.22.2 band using seven rare cutting enzymes. A striking feature was observed upstream of hSIM2 where at least 41 rare-cutting sites were clustered within a 20-kb region. To investigate the structure of the cluster, a cosmid containing hSIM2 was submitted to shotgun sequencing. Sequence analysis revealed that the cluster was a long CpG island extending 19, 128 nucleotides which includes in the first and second exons of hSIM2. Taken together with our observation in which the CpG islands were concentrated within 1.2 Mb around hSIM2, we propose that this region functions as an R-band, and the cluster provides a unique element for marking of DNA for the spatial and temporal expression of the hSIM2 locus.

Amino Acid Sequence↗

Different apoptotic pathways mediated by Fas and the tumor-necrosis-factor receptor. Cytosolic phospholipase A2 is not involved in Fas-mediated apoptosis.

Fas is a cell-surface receptor that belongs to the tumor-necrosis factor (TNF)/nerve growth factor receptor family. Fas can transduce an apoptotic signal through the death domain in the cytoplasmic region, which has similarity with the corresponding region of the TNF type-I receptor. Here, we expressed human Fas in mouse L929 cells or its subline (C12), which express extremely low levels of cytosolic phospholipase A2 (cPLA2). L929 cells were sensitive to the cytotoxic activity of TNF, while C12 cells were resistant. Cross-linking of human Fas with anti-(human Fas antibody) Ig killed both L929 transformants and C12 transformants expressing human Fas. Various inhibitors of the arachidonate metabolism significantly inhibited the TNF-induced cytotoxicity in L929 cells, but they did not have any effect on Fas-mediated apoptosis. These results indicated that cPLA2 is required for TNF-induced apoptosis, whereas it is dispensable for Fas-mediated apoptosis, and suggested that the TNF receptor and Fas use different signaling pathways for apoptosis.

Animals↗