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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 433 records · Page 24Linked to original sources
PubMed1997

Role of serotonin receptor subtypes in the development of amygdaloid kindling in rats.

The present study was conducted to identify serotonin (5-HT) receptor subtypes involved in the development of amygdala (AM) kindling. We used 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, both of which were injected subcutaneously 15 min prior to each daily electrical stimulation to the rat AM. Treatment with 8-OH-DPAT (1 mg/kg) slightly suppressed behavioral and electrographic seizure development during the course of kindling. In contrast, DOI (1 mg/kg) strongly facilitated kindling development and reduced the number of stimulations needed to produce generalized seizures. These facilitatory effects of DOI were completely blocked by pretreatment with a 5-HT2 antagonist ketanserin. The present results suggest that the activation of 5-HT1A receptors can retard the development of AM kindling, whereas 5-HT2 receptors play a facilitatory role in this developmental seizure process.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Glucocorticoid induced the expression of mRNA and the secretion of lipocortin 1 in rat astrocytoma cells.

The lipocortins are a family of structurally related proteins that have been shown to be implicated in multiple aspects of cell biology. Subsequent research has shown that lipocortin 1 (LC1) participates in the physiological and pathological functioning of the CNS and neuroendocrine system. In the present study, the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), dibutyryl cyclic AMP (Bt2cAMP) or dexamethasone (DEX) on expression of LC1 were investigated by a sandwich enzyme immunoassay and reverse transcription polymerase chain reaction (RT-PCR) in rat astrocytoma (C6) cells. Time-dependent experiments revealed that the intracellular protein content and the mRNA of rat LC1 increased significantly 4 h after TPA (10 mM) or DEX (1 microM) addition. TPA and DEX elicited a prominent induction of LC1 at 10(-8) M and 10(-6) M, respectively. Bt2cAMP (0.5 mM) also appeared to induce, but the induction was not statistically significant. In addition, DEX increased the extracellular secretion of LC1 without cytotoxicity. These results suggest that LC1 synthesis is chemically induced and selectively released from C6 cells by dexamethasone.

Animals↗
PubMed1997

Electroencephalographic abnormalities in patients with presenile dementia of the Alzheimer type: quantitative analysis at rest and during photic stimulation.

In the present study, quantitative electroencephalographic (EEG) analysis was performed at rest and during photic stimulation (5, 10, and 15 Hz) in nine patients with presenile dementia of the Alzheimer type (AD; mean age at onset, 55 years) and nine sex- and age-matched control subjects. Compared with the normal controls, the AD patients had a significantly lower alpha-2 and beta band power in the resting EEG as well as a significant increase in delta and theta band power. EEG analysis during the photic stimulation demonstrated that the AD patients had a significantly lower EEG power during photic stimulation for the alpha (9.8-10.2 Hz) and beta bands (14.8-15.2 Hz) corresponding to photic stimulation at 10 Hz and 15 Hz, respectively. In addition, when we examined EEG changes from rest to the stimulus condition, the AD patients were found to show significantly smaller changes in EEG power mainly over the posterior regions, irrespective of the stimulus frequency. These findings provide evidence that AD patients have EEG abnormalities in both non-stimulus and stimulus conditions, and suggest diminished EEG reactivity to photic stimulation.

Alzheimer Disease↗
PubMed1997

Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans.

BACKGROUND: Although long-term lipid-lowering therapy improves endothelium-dependent vasodilatation in humans, it remains unknown whether the short-term removal of LDL per se ameliorates endothelial dysfunction. METHODS AND RESULTS: To examine the effects of a single session of LDL apheresis on endothelial function in patients with hypercholesterolemia, we measured forearm blood flow (FBF) by strain-gauge plethysmography before and after single LDL apheresis while infusing acetylcholine (ACh; 4 to 24 micrograms/min) and sodium nitroprusside (SNP; 0.2 to 1.2 micrograms/min). The single session of LDL apheresis reduced total LDL (from 142.2 +/- 15.0 to 32.6 +/- 5.0 mg/mL, P < .0005) and oxidized LDL (from 111.6 +/- 22.8 to 30.0 +/- 5.4 ng/mL, P < .005). Although ACh and SNP increased FBF dose-dependently before and after LDL apheresis, the endothelium-dependent vasodilatation responses to ACh were significantly augmented (P < .01) after the single session of LDL apheresis without changes in the endothelium-independent vasodilatation responses to SNP. The plasma levels of total and oxidized LDL correlated with the degree of ACh-induced vasodilatation. Furthermore, the local production of nitrate/nitrite, metabolites of NO, during ACh infusion was significantly (P < .05) augmented by LDL apheresis, and there was a significant correlation between the degree of ACh-induced vasodilatation and the production in nitrate/nitrite (r = .99, P < .0005). CONCLUSIONS: We demonstrated that even a single session of LDL apheresis with the reduction of total LDL and oxidized LDL improved endothelial function. Our results suggest that total LDL and/or oxidized LDL may directly impair endothelial function in the human forearm vessel.

Acetylcholine↗
PubMed1997

Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human.

Sipa1, previously called Spa1, is transcriptionally induced in the murine lymphoid cells following mitogenic stimulation and encodes a protein with a domain related to Rap1 GTPase activating protein (Rap1GAP) at the N-terminus and to PEST sequences followed by a leucine zipper motif at the C-terminus. Herein mouse genomic Sipa1, which consisted of 16 exons, was cloned. Gene linkage analysis using (BXD) recombinant inbred strains indicated that Sipa1 was mapped to the most centromeric region of chromosome 19 syntenic with the long arm of human chromosome 11. Human SIPA1 cDNA exhibited a striking homology to that of mouse throughout the entire region, with the overall identity being 90% at the amino acid level. Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated. Fluorescence in situ hybridization (FISH) analysis using the human genomic clones indicated that SIPA1 was indeed mapped to chromosome 11q13, most likely to the 11q13.3 subregion. It was further indicated by double-color FISH that SIPA1 was located in the centromeric neighborhood of CCND1/ PRAD1, a presumed BCL1 oncogene.

Animals↗
PubMed1997

Detection of single-nucleotide mutations including substitutions and deletions by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was applied to the detection of mutations involving single nucleotides. For detection of a single-nucleotide deletion, a normally 44 bp region of the L1CAM gene was amplified in a 50 microL solution, and measurement was carried out on the DNA sample after phenol extraction and ethanol precipitation. A molecular mass decrease of 300 Da corresponding to a single nucleotide was identified in the amplified product of patient DNA. For detection of a substitution, an amplified product from a 50 bp region of the human beta-globin gene was cleaved with restriction endonucleases HaeIII and Bsp12861. Measurement of a mixture of digested fragments, or restriction fragment mass mapping, clearly identified a heterozygous G/C mutation in the molecular ion signals for both sense and antisense single-stranded DNAs. The results indicate that MALTI-TOFMS is feasible for genetic diagnosis of point mutations.

DNA↗
PubMed1997

An effective chemotherapy regimen for liver metastasis from retroperitoneal fibrosarcoma: report of a case.

Retroperitoneal fibrosarcoma is a rare disease that has proven difficult to treat due to its high incidence of postoperative local recurrence. We recently experienced a patient in whom retroperitoneal fibrosarcoma was followed by liver metastasis without local recurrence. A 34-year-old woman who initially presented with right upper quadrant pain was found to have a retroperitoneal tumor by diagnostic imaging techniques. Extirpation of the tumor was performed and the histopathological diagnosis was fibrosarcoma. A solitary metastasis was detected in the lateral segment 1 year after this operation and a lateral segmentectomy was carried out; however, a short time later, multiple liver metastases were found. Initially, ethanol injections were given with little effect, following which CYVADIC chemotherapy, consisting of cyclophosphamide, vincristine, farmorubicin, and dacarbazine was administered. An excellent responsiveness without severe toxicity was achieved after five cycles, with a significant reduction in tumor size, being estimated as a complete response. Thus, we consider that this chemotherapy regimen could be a promising mode of treatment for liver metastasis from retroperitoneal fibrosarcoma without local recurrence.

Adult↗
PubMed1997

Delayed enhancement of myocardial FDG uptake on glucose loading FDG-PET in NIDDM patient.

We report a case of delayed enhancement of myocardial FDG uptake in NIDDM patient after oral glucose loading. A 65-year-old man who had a past history of NIDDM received FDG-PET examination during fasting and glucose loading. In neither condition, was an accumulation of FDG in the myocardium, and myocardial blood flow was normal. An oral glucose tolerance test (OGTT) was performed to find the best time for FDG injection and 3 hours after loading, the serum insulin concentration was increased significantly. When the interval between glucose loading and the injection of FDG was set at 3 hours, enhancement of myocardial FDG uptake was demonstrated. To know the best time for the FDG injection in advance is thought to be important in obtaining better image quality and interpreting the myocardial viability when FDG-PET examination during glucose loading is performed in NIDDM patients.

Aged↗
PubMed1997

Pituitary adenoma with prolactin and growth hormone production in a sheep.

A pituitary adenoma was found in a 6-year-old ewe. This tumour was composed mainly of chromophobic cells, but acidophilic cells predominated in a few areas. Prolactin was demonstrated in the cytoplasm of some chromophobic cells by means of the immunoperoxidase technique, and secretory granules ranging in size from 100 to 900 nm in diameter were seen in all chromophobic cells examined. Almost all acidophilic cells were positive for growth hormone (GH), and a few of them were also positive for prolactin (PRL). This tumour resembled a human mixed GH cell-PRL cell adenoma.

Adenoma↗
PubMed1997

Electrophysiological evidence of an increase in cold tolerance of cardiac muscles in mice after energy restriction.

Life-prolonging energy restriction (ER) has been known to extend longevity. The heart was selected as the target organ of ER and the electrophysiological properties of ER on the heart were investigated. Action potential parameters were measured on ventricular papillary muscles of C57BL/6 mice (2-6 months of age). Resting membrane potential (Rm) did not change even when the temperature was lowered to 20 degrees C in ER mice (-67.5 +/- 0.8 mV), however, the membrane was depolarized in the control (-61.1 +/- 1.1 mV). Action potential duration measured at 30 and 50% repolarization was significantly prolonged in ER mice at 20-35 degrees C. Ouabain (10 microM) decreased Rm in ER mice at 20 degrees C (-68.6 +/- 1.0 to -63.6 +/- 0.8 mV), but failed to decrease Rm in the control (-60.6 +/- 1.8 to -62.1 +/- 1.2 mV). There were no significant differences in extracted Na, K-ATPase activity or affinity and binding capacity of ouabain between ER and control hearts. These results indicate that in ER mice the lack of effect of temperature on Rm was not due to a change in the physicochemical properties of Na, K-ATPase. The present study collectively suggests that ER increases cold tolerance in the heart of mice.

Acclimatization↗
PubMed1997

Chromosome aberrations in renal tumors detected by fluorescence in situ hybridization.

The aim of this study was to investigate the relationship between chromosome aberrations detected by fluorescence in situ hybridization (FISH) and tumor grade, stage, venous involvement, and DNA ploidy status in 18 renal tumors. Using FISH with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 3, 7, 9, and 17 was detected within interphase nuclei in touch preparations from tumor specimens. Monosomy for chromosome 3 was detected in seven of 9 DNA diploid tumors, whereas all DNA aneuploid tumors demonstrated trisomy or tetrasomy for chromosome 7. Moreover, monosomy for chromosome 3 was more frequently shown in the diploid and low-stage tumors than in the aneuploid and high-stage tumors. The percentage of hyperdiploid cells significantly correlated with DNA ploidy status in the case of chromosomes 3 and 7 (p = 0.030, p = 0.007, respectively). The percentage of hyperdiploid cells for chromosome 3 had borderline significance with tumor stage. On the other hand, the percentage of diploid cells for chromosome 17 was significantly correlated with DNA ploidy status and tumor stage (p = 0.030, p = 0.027, respectively). Moreover, the percentage of diploid cells for chromosome 7 in renal cell carcinoma (RCC) with venous involvement was significantly lower than those without venous involvement (p = 0.023). These results suggest that the incidence of chromosomal aberrations detected by FISH is more frequent than the chromosomal aneuploidy reported previously by conventional cytogenetics. Therefore, loss of chromosome 3 may be associated with an early event in RCC carcinogenesis. Gain of chromosomes 3 and 7 is correlated with tumor progression as well as gain and loss of chromosome 17. Study of the chromosomal aberrations may provide a greater understanding of tumor carcinogenesis and progression in RCC.

Adult↗
PubMed1997

Unilateral meningoencephalitis with hemispheric slowing on EEG.

We report a 12-year-old boy with unilateral meningoencephalitis due to non-herpes simplex virus. He experienced secondarily generalized partial seizures of the left extremities with loss of consciousness. In contrast with normal neuroimaging findings, interictal electroencephalograms (EEGs) showed prolonged slowing in the right hemisphere. This laterality agreed with the right brain dysfunction verified on neuropsychological examination. Follow-up EEG is important in such a subtle case with normal neuroimaging.

Child↗
PubMed1997

Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure.

Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in (beta2m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N epsilon-(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and pentosidine. In vitro incubation of beta2m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of beta2m into AGE-modified beta2m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in beta2m and beta2m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 +/- 0.16 vs. 0.35 +/- 0.11, P < 0.0001), suggesting the presence of an increased oxidative stress. Interestingly, plasma level of oxiAA was correlated with the plasma levels of protein linked (P < 0.01, r2 = 0.25) and free (P < 0.05, r2 = 0.22) pentosidine. Altogether these results demonstrate that AGE, that is, CML and pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.

Amino Acid Sequence↗
PubMed1997

FP-21399 blocks HIV envelope protein-mediated membrane fusion and concentrates in lymph nodes.

The identification of fusin and other chemokine receptors as coreceptors for HIV-1 has renewed the interest in agents that may prevent viral entry. Polyanionic compounds such as dextran sulfate, curdian sulfate, and suramin act on the V3 loop of the viral envelope and may prevent its interaction with fusin. These agents show activity against a wide range of HIV-1 strains, but have undesirable circulating half-life, bioavailability, and toxicity. We have developed a small molecule inhibitor of HIV-1 that has several advantages over these other agents. FP-21399 is a novel compound of the bis(disulfonaphthalene) dimethoxybenzene class that blocks entry of HIV into CD4+ cells and blocks fusion of infected and noninfected CD4+ cells. This compound only weakly inhibits binding of CD4 and gp120, at concentrations much greater than are required to block viral entry. Furthermore, FP-21399 can block the interaction between gp120 and antibodies directed against the V3 loop, but does not block binding of antibodies directed against the V4 loop. Animal studies demonstrate that FP-21399 is concentrated in lymph nodes, making it a promising compound for anti-HIV therapy. In SCID mice reconstituted with human immune cells, maintenance of HIV-1 infection was blocked by a 5-day treatment with low doses of FP-21399, suggesting that lymph node accumulation may contribute to antiviral activity. Finally, attempts to generate drug-resistant virus in cell culture resulted in only weakly resistant variants with IC90 values that are much lower than concentrations of FP-21399 found in lymph nodes.

Animals↗
PubMed1997

Successful prevention of hematological relapse for a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic bone marrow transplantation by donor leukocyte infusion.

Donor leukocyte infusion (DLI) was carried out on a 12-year-old girl with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who received allogeneic bone marrow transplantation from an HLA-identical sibling. This is the first report of DLI use before the onset of hematological relapse monitored by the results of RT-PCR. This patient has been in CR for 11 months after BMT, suggesting this alternative treatment is promising for Ph+ ALL with positive reverse transcriptase-polymerase chain reaction (RT-PCR) following BMT.

Bone Marrow Transplantation↗