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Biomedical subjects

Y Ishikawa

Publications and source records attributed to Y Ishikawa.

At least 109 records · Page 6Linked to original sources
PubMed2001

The distribution and production of cholesteryl ester transfer protein in the human aortic wall.

Cholesteryl ester transfer protein (CETP) has been considered to mediate the transfer of cholesteryl ester from arterial wall, however, the distribution and production of CETP in human arterial wall remains unclear. Present study histopathologically demonstrated the distribution of CETP and CETP mRNA in the human aortic wall by immunohistochemistry and in situ hybridization. While CETP was constantly distributed in the media, the protein was recognized within the intima with fibrocellular thickening and atherosclerotic intima. Double immunostaining methods demonstrated CETP expression in smooth muscle cells in the intima and media. CETP mRNA was detected not only in intimal cells but medial smooth muscle cells. Intimal cells expressing CETP mRNA were considered to be monocyte-derived macrophages and smooth muscle cells by immunohistochemistries using two antibodies against smooth muscle actin and human macrophage on the subserial sections. Our in vivo study provides that CETP is produced by smooth muscle cells in the intima and media of human aorta, and it is suggested that arterial smooth muscle cells positively participate in the removal of excessive cholesteryl ester from the arterial wall by CETP production.

Aorta↗
PubMed2001

Immunolocalization of apolipoproteins in aortic atherosclerosis in American youths and young adults: findings from the PDAY study.

The immunohistochemical distribution of apolipoproteins in the abdominal aortas of 142 men, 15-34 years of age, collected in a cooperative multicenter study group (Pathobiological Determinants of Atherosclerosis in Youth) was examined in relationship to serum VLDL+LDL+HDL cholesterol levels. ApoB deposits were limited to the intima of specimens with intimal fibro cellular thickening or atherosclerotic lesions. Apo A-I, E and J were observed in both the intima and media of the aortas with intimal lesions. The pattern of apoJ distribution was similar to that of apoA-I and E. The distribution patterns of these apolipoproteins in these young adults were very similar to those in adults and old men seen in an earlier study. The extent of apolipoprotein distribution in the intima and media increased with age and the stage of atherosclerosis development, but was not correlated significantly with serum VLDL+LDL or HDL cholesterol levels. The infiltration of lipoprotein particles into the aortic wall seems to be more strongly associated with the progression of intimal lesions rather than with serum cholesterol levels.

Adolescent↗
PubMed2001

Suppression of tumor necrosis factor-alpha production and neutrophil infiltration during ischemia-reperfusion injury of the liver after heat shock preconditioning.

BACKGROUND/AIMS: Heat shock preconditioning provides the liver with ischemic tolerance. In this study we examined the effects of heat shock preconditioning on hepatic nonparenchymal cells in light of tumor necrosis factor-alpha (TNF-alpha) production and neutrophil infiltration. METHODS: Rats were exposed to heat shock pretreatment at 42 degrees C in the heat shock group (group HS) and at 37 degrees C in the control group (group C). After a 48-h recovery, the left hepatic lobes were given a 90-min ischemia and reperfused. Plasma concentrations of TNF-alpha, cytokine-induced neutrophil chemoattractant (CINC) and alanine aminotransferase (ALT) were measured. Liver tissues were checked for the presence of TNF-alpha mRNA. Histological staining for CINC and polymorphonuclear leukocyte (PMN) was also evaluated. RESULTS: In group HS, plasma TNF-alpha levels were significantly more suppressed than in group C (P<0.0001). Expressions of TNF-alpha mRNA in the liver was suppressed in group HS. Production of CINC 2 h after reperfusion was reduced in group HS (P<0.05). PMN infiltration was significantly reduced in group HS (P<0.01). In group HS, liver histology revealed less cellular damage and the plasma level of ALT was significantly reduced (P<0.0001). CONCLUSIONS: Heat shock preconditioning suppressed the production of TNF-alpha and CINC in the liver during reperfusion and consequently reduced neutrophil infiltration.

Alanine Transaminase↗
PubMed2001

In situ pedicle resection in left trisegmentectomy of the liver combined with reconstruction of the right hepatic vein to an inferior vena caval segment transpositioned from the infrahepatic portion.

A combination of an in situ pedicle resection of the liver and a hepatic vein reconstruction using a cranially transpositioned segment of the IVC after implantation of an ePTFE graft at the missing IVC was useful in treating a patient who suffered from a huge liver tumor involving all of the hepatic venous confluence and the IVC. Although early tumor recurrence remains an unresolved problem for such patients, a surgical approach is feasible. This technique can be justified as a therapeutic modality, not only because it improves quality of life, but also because it provides patients with an opportunity for additional treatment.

Anastomosis, Surgical↗
PubMed2001

Wide distribution of the MICA-MICB null haplotype in East Asians.

Stress-inducible MICA (MHC class I chain-related A) is known to bind to NKG2D, which is one of the natural killer (NK) cell receptors, and plays a role in immune surveillance. We have reported that a MICA-MICB null haplotype is in linkage disequilibrium with HLA-B*4801 in the Japanese population. In the haplotype, an approximately 100-kb deletion, including the entire MICA gene, was observed and MICB possessed a premature stop codon. In this study, a multiplex polymerase chain reaction (PCR) method was developed for detecting the MICA deletion. MICB alleles were typed by PCR-single-strand conformation polymorphism (SSCP) method and direct sequencing. The frequency of the MICA-MICB null haplotype was 3.7% on the average, and was strongly associated with HLA-B48 in seven East Asian populations. It was presumed that the stop codon of MICB gene generated after the large-scale deletion. The wide distribution of the null haplotype at polymorphic frequencies suggests that the haplotype has been conservatively maintained because of some selective advantage.

Alleles↗
PubMed2001

Allele frequency of HLA-B39 in the Japanese population and identification of a novel B39 allele, B*3923.

A new HLA-B39 allele, B*3923, was found in the Japanese population. Compared with B*39022, the new allele had a single point mutation at position 503 in exon 3 with an amino acid substitution, Gln144Arg. To determine B39 allele frequency in Japanese, 275 B39-positive samples from 3277 Japanese individuals were examined by polymerase chain reaction using microtitre plate hydribization (PCR-MPH) and single-strand conformation polymorphism (PCR-SSCP). The frequency of B*3923 was estimated to be 0.4% in B39 alleles of the Japanese population. B*3923 was found in samples from four Japanese individuals, all of whom have DRB1*1406.

Asian People↗
PubMed2001

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

Bone Marrow Transplantation↗
PubMed2001

Profiling of genes expressed in human monocytes and monocyte-derived dendritic cells using cDNA expression array.

Using a human cDNA expression array, we obtained expression profiles of 588 genes in CD14+ monocytes and monocyte-derived dendritic cells (DCs). Overall, 22 genes were upregulated, and nine genes were downregulated in DCs of both samples from two different individuals. Many of the genes that were upregulated in DCs encode proteins that are related to differentiation, cell structure, migration, termination of cell cycle as well as proliferation, e.g. tumour necrosis factor-alpha (TNF-alpha), tumour necrosis factor receptor II (TNFRII), thymosin beta-10, epithelial discoidin domain receptor 1, replication factor C, putative transcription factor DB1, alpha catenin, transforming growth factor-beta 1, prohibitin, p53-regulating protein and neu differentiation factor. Among the downregulated genes in DCs were genes that encode proteins of cell cycle regulation: mitotic growth and transcription activator, platelet-derived growth factor receptor-beta subunit, interleukin 2 receptor (IL-2R)-gamma subunit, IL-7R-alpha subunit, leucocyte interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR). Semi-quantitative reverse transcription-polymerase chain reaction method confirmed the upregulated expression levels in DCs for TNFRII, TNF-alpha, alpha catenin and downregulation of IFN-gamma, GM-CSFR on four different donor samples of DCs and monocytes. Moreover, our data show the presence of a 'switch-on' step for the TNF-alpha and TNFRII gene expression in immature DCs for further differentiation into mature DCs.

Cell Cycle↗
PubMed2001

Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy.

BACKGROUND: Nonenzymatic glycation of neural proteins and their end-products (advanced glycation end-products, AGE) have been implicated in the pathogenesis of diabetic neuropathy. We need a development of effective ant-glycation agents for future clinical use. MATERIALS AND METHODS: We examined the effects of OPB-9195 (OPB), a new inhibitor of glycation, on the peripheral nerve structure and function in diabetic rats. Eight-week-old Wistar rats were made diabetic by streptozotocin (40 mg kg(-1), i.v.) and OPB (60 mg kg(-1) day(-1)) was given by gavage for 24 weeks. Age- and sex-matched normal Wistar rats were used for comparison. RESULTS: During the experimental period, OPB treatment did not affect the reduced body weight, elevated levels of blood glucose and glycated haemoglobin in diabetic rats. At the end of the experiment, delayed tibial motor nerve conduction velocity was significantly improved (by 60%) in treated diabetic rats, with reduction of serum AGE levels. Expression of immunoreactive AGE in the sciatic nerve was reduced in treated diabetic rats compared with those in untreated rats. Sciatic nerve (Na+, K+)-ATPase activity was also restored in treated diabetic rats. On the cross-sectioned sciatic nerves, positive cells with oxidative stress-related DNA damage, as expressed by 8-hydroxy-2'-deoxyguanosine, were less in the peripheral nerve of treated diabetic rats compared with those of untreated rats. CONCLUSION: The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.

Animals↗
PubMed2001

Retroperitoneal cystic metastasis from a small clear cell renal carcinoma.

A 39-year-old housewife was referred to our hospital for the treatment of a small renal tumor. A 25 x 35 mm cystic mass that had been detected by computerized tomography scan just caudal to the renal hilus proved to be a metastasis from the renal carcinoma of clear cell type. The pathogenesis may have been due to tumor cells obstructing a lymphatic vessel draining the kidney. Cystic metastasis from renal cell carcinoma is very rare and this appears to be the second published case in the world.

Adult↗
PubMed2001

Differences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons.

Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) act on various neurons of the CNS as neurotrophic factors promoting neuronal differentiation and survival. We examined the survival-promoting effects of BDNF and IGF-1 on serum deprivation-induced death in cultured cerebral cortical neurons, and compared the intracellular signaling pathways stimulated by BDNF and IGF-1 in the neurons. We found that the survival-promoting effect of BDNF was much weaker than that of IGF-1 in serum deprivation-induced death of cultured cortical neurons. We found no differences in the levels of phosphatidylinositol 3-kinase (PtdIns3-K) activity or Akt (also called PKB) phosphorylation induced by BDNF and IGF-1 in the cultured cortical neurons, although many reports suggest that PtdIns3-K and Akt are involved in survival promotion. In addition, phosphorylation signals of mitogen-activated protein kinase (MAPK) and cAMP responsive element-binding protein (CREB), which have also been reported to be involved in survival promotion, were stimulated by BDNF much more potently than by IGF-1. These results show that there may be, as yet unidentified, intracellular signaling pathways other than the PtdIns3-K-Akt, MAPK and CREB signaling, to regulate survival promotion. These unidentified signaling pathways may be responsible for the distinct strengths of the survival-promoting effects of BDNF and IGF-1.

Animals↗
PubMed2001

Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.

Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.

Animals↗
PubMed2001

E variants found in Japanese and c antigenicity alteration without substitution in the second extracellular loop.

BACKGROUND: The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out. STUDY DESIGN AND METHODS: E variants from healthy Japanese blood donors were screened by serologic analysis using E MoAbs. Fifteen E variant samples were divided into three types--EFM, EKH, and EKK-on the basis of patterns of reactivity with five distinct E antibodies. The entire coding region of the Rh cDNAs from the E variant samples was analyzed by sequencing. RESULTS: Although the Rh cDNA sequences of the three types were different from each other, those of the EFM-type variants (RHEFM) had a partial DNA exchange in exon 5 between the RHCE and RHD genes, generating an RHcE variant (Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a point mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg154Thr substitution in the third external loop of the RhcE peptide. The EKK-type variant (RHEKK) carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene. The RHD gene of a person possessing an E variant of the EKK type was also a hybrid gene, D-cE(2-3)-D or cE(1-3)-D (RHDKK). The E variants of types EKH and EKK showed weak c antigenicity. CONCLUSION: In serologic screening of 140,723 Japanese blood donors, 15 were found to possess E variants (0.011%). A new RHCE variant, RHEKH, was identified. On the basis of the variants found in this study, the c antigenicity seemed to be determined not only by Pro-103 but also by the structure of the third extracellular loop or the amino acids contained in it.

Amino Acid Substitution↗
PubMed2001

gammadelta T-cell lymphoma with tropism for various types of epithelium in a cow.

A 2-year-old Holstein cow developed multiple cutaneous masses, up to 10 cm in diameter, over the neck and trunk. The animal also had neoplastic lesions in internal organs, and epitheliotropism was observed not only in the skin but also in the conjunctiva, mammary glands, trachea, abomasum, small intestine, gall bladder, uterus and urinary bladder. Moreover, the neoplastic cells showed preferential homing to T-zones of lymphatic tissues. Because the lymphoma cells were positive for CD3 but not CD79a, and a few were CD2- or WC1-positive, this lymphoma was thought to be of gammadelta T-cell origin. Helicobacter -like organisms, found in the abomasum and small intestine, were considered to be associated with the severe neoplastic involvement of these organs, on the basis of the intense immunolabelling for major histocompatibility complex class II in the epithelial cells, and the presence of increased numbers of apparently normal intraepithelial T lymphocytes.

Animals↗
PubMed2001

Insecticidal diarylheptanoid from Alpinia oxyphylla against larvae of Drosophila melanogaster.

In the course of screening for novel naturally occurring insecticides from Chinese crude drugs, a MeOH extract of Alpinia oxyphylla was found to give an insecticidal activity against larvae of Drosophila melanogaster Meigen. From the extract, an insecticidal compound was isolated by bioassay-guided fractionation and identified as yakuchinone A (1) by GC, GC/MS, 1H and 13C NMR spectroscopy.

Animals↗
PubMed2001

Interaction of porphyrins bearing peripheral cationic heterocycles with G-quadruplex DNA.

Telomere-interactive compounds such as TMPyP4 are expected to inhibit telomerase and thus to be potential anti-cancer drugs. We investigated the interaction of porphyrins bearing peripheral cationic heterocycles with G-quadruplex DNA, which contained human telomeric repeats (GGGTTA)4. One of the porphyrins, pPyTTP, was found to bind to the G-quadruplex DNA and to increase the Tm of the G-quadruplex. The positive sign of induced CD for the complex suggested pPyTTP bound to and stabilized the G-quadruplex DNA possibly by groove binding, distinct from that of TMPyP4.

Antineoplastic Agents↗