Xenogeneic humoral graft-Vs-host disease following hamster-to-Rat bone marrow transplantation.
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Animals↗
Biomedical subjects
T Miki
Publications and source records attributed to T Miki.
Concordant hamster-to-rat liver xenotransplantation leads to hyperlipidemia.
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Animals↗
Loss of serum bicarbonate after discordant liver xenotransplantation.
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Animals↗
Correlation of histological inflammation in needle biopsy specimens with serum prostate- specific antigen levels in men with negative biopsy for prostate cancer.
OBJECTIVES: To reveal the possible contribution of histological inflammation within the prostate to the abnormal elevation of serum prostate-specific antigen (PSA) levels in patients with needle biopsy negative for prostate cancer. METHODS: We reviewed negative needle biopsy specimens obtained in 93 patients. The degree of acute and chronic inflammation as evaluated histologically was compared with serum PSA levels in conjunction with age and prostate volume. RESULTS: Both age (P <0.01) and prostate volume (P <0.0001) correlated significantly with serum PSA levels and were significantly greater in patients with abnormal serum PSA levels (greater than 4.0 ng/mL) than in those with normal serum PSA levels (4.0 ng/mL or less) (P <0.01). The presence of histological inflammation within the prostate also correlated significantly with serum PSA levels. Multiple regression analysis demonstrated prostate volume to be the only independent determinant of serum PSA levels (P <0.01). In patients with a prostate volume larger than 25 mL, only prostate volume correlated significantly with serum PSA levels (P <0. 05). On the other hand, the degree of acute inflammation as represented by polymorphonuclear leukocyte infiltration was the only parameter correlating significantly with serum PSA levels (P <0.05) in patients with a prostate volume smaller than 25 mL. CONCLUSIONS: Histologically defined acute inflammation within the prostate is a significant contributor to elevated serum PSA levels, especially in patients with small prostates. In the assessment of needle biopsy results negative for prostate cancer, it might be helpful to evaluate the degree of histological inflammation, especially in terms of the necessity of subsequent repeated biopsies.
Aged↗
Augmentation by interleukin-18 of MHC-nonrestricted killer activity of human peripheral blood mononuclear cells in response to interleukin-12.
Interleukin (IL)-18 is a novel cytokine with pleiotropic functions. In the present study, we examined the induction of the killer activity of peripheral blood mononuclear cells (MNC) against lung cancer cell lines upon treatment with IL-18 in combination with IL-12. Cytotoxic activity was measured by standard (51)Cr release assay. IL-18 (100 ng/ml) was found to significantly augment IL-12-induced killer activity in a MHC-nonrestricted manner against allogeneic NK-resistant Daudi cells and lung cancer cell lines: SBC-3, RERF-LC-AI and A549. IL-18 could augment IL-12-induced killer activity both at the optimal as well as suboptimal doses of the latter. However, IL-18 was found to have little effect on the killer activity of MNC induced by optimal or suboptimal dose of IL-2 or IL-15. Treatment of MNC with IL-18 in combination with IL-12 for a period of more than 4 days was observed to optimally induce the killer activity. As for induction of IFN-gamma production by MNC, IL-18 augmented that induced by IL-2 and IL-15, as well as that induced by IL-12. These results show the potential of IL-18 in combination with IL-12 for clinical application in treatment of cancer.
Cytotoxicity, Immunologic↗
Significant changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension.
The present study was conducted to reveal the possible changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension. When analyzed together for 51 men, all measurements but area changed statistically significantly as the rectal wall was distended by a balloon covering a probe. Ultrasonic measurements concerning the prostatic shape changed more remarkably than those concerning its size. More importantly, changes in ultrasonic measurements were much more remarkable in patients with a healthy prostate than in those with an advanced BPH. These results suggest that possible changes in prostatic shape with the rectal wall distension has to be taken into account when evaluating transrectal prostatic ultrasonograms in terms of changes in shape, especially in patients with a healthy prostate. This is also the case when the diagnosis of BPH is made based on the change in shape, such as presumed circle area ratio, which is a parameter representing the roundness of the horizontal sonogram of the prostate.
Adult↗
Functional genomics of Escherichia coli in Japan.
Completion of the genome sequence of the model bacterium Escherichia coli has produced nearly 2000 open reading frames (ORFs) that remain to be functionally characterized. To accomplish this goal, we have organized a working project team in Japan and have begun construction of clones containing each of the putative ORFs. The procedure has been conceived such that we shall be able to perform systematic analysis of the shut-off as well as forced expression in vivo of each ORF and purification of its protein product for further biochemical studies. In addition, we have started a collection of various genetic and biochemical data of E. coli published in the past, and analyses of the data from a bio-informatics point of view. Thus, we aim at reaching complete understanding of this model organism in the near future.
Bacterial Proteins↗
Infarct size limitation by bradykinin receptor activation is mediated by the mitochondrial but not by the sarcolemmal K(ATP) channel.
Earlier studies have shown that activation of bradykinin B2 receptor triggers protein kinase C (PKC)-mediated cardioprotective mechanism in ischemic preconditioning (PC). In the present study, we examined whether the effector in this B2-receptor triggered pathway of PC is the ATP sensitive potassium (K(ATP)) channel in the mitochondria (mito-K(ATP) channel) or K(ATP) channel in the sarcolemma (sarc-K(ATP) channel). Isolated rabbit hearts were perfused with modified Krebs-Henseleit buffer in a Langendorff mode, and regional myocardial ischemia was induced by occluding a left coronary artery for 30 min and then reperfusing for 2 hours. Infarct size was determined by triphenyltetrazolium chloride staining and expressed as a percentage of area at risk (% IS/AR). Infusion of bradykinin (500 nmol/L) for 15 min prior to ischemia significantly reduced % IS/AR from 37.4 +/- 2.9 (SE) of the untreated controls to 12.0 +/- 3.3%. This protective effect of bradykinin was completely abolished by coinfusion of 5-hydroxydecanoate (5-HD, 50 micromol/L), a selective mito-K(ATP) channel blocker (% IS/AR = 44.2 +/- 6.4). In contrast, a high dose of HMR1098 (20 micromol/L), which is a newly developed sarc-K(ATP) channel selective blocker with IC50 of 0.6 micromol/L, failed to modify the infarct size limitation by preischemic infusion of bradykinin (% IS/AR = 11.7 +/- 3.4). Neither 5-HD nor HMR1098 alone modified infarct size (% IS/AR = 37.8 +/- 3.8 and 35.1 +/- 6.2, respectively). These results suggest that opening of the mito-K(ATP) channel but not the sarc-K(ATP) channel is involved in infarct size limitation by a mechanism triggered by bradykinin B2 receptor activation.
Analysis of Variance↗
Adenosine A1 agonist at reperfusion trial (AART): results of a three-center, blinded, randomized, controlled experimental infarct study.
Adenosine A1 receptor agonists given prior to myocardial ischemia limit ischemic injury in several species. However, the ability of adenosine receptor agonists to limit infarct size when given at reperfusion has proved controversial. We designed a three-center experimental study using a blinded, randomized treatment protocol to test the hypothesis that adenosine A1 receptor activation during early reperfusion can attenuate lethal reperfusion injury, thereby reducing infarct size. Sixty anesthetized rabbits (20 in each laboratory) underwent 30 minutes coronary artery occlusion followed by 120 minutes reperfusion. The selective adenosine A1 receptor agonist GR79236 (10.5 microg/kg, a dose shown to limit infarction in this model when given before ischemia) or vehicle were administered IV 10 minutes before reperfusion. Infarct size was assessed by tetrazolium staining and, after the randomization code was revealed, data from the three laboratories were pooled for statistical analysis. Infarct size was not modified by administration of GR79236. In the vehicle-treated group, the infarct-to-risk ratio was 28.9 +/- 2.7% (n = 24) compared with 31.9 +/- 2.6% (n = 26) in the GR79236-treated group (not significant). Risk zone volume was similar in the two groups (1.06 +/- 0.05 cm3 vs 1.00 +/- 0.05 cm3, respectively). A modest reduction in rate-pressure product was noted following the administration of GR79236, but this effect was transient. The same dose of GR79236 was found to limit infarct size when given prior to coronary artery occlusion. We conclude that A1 receptor activation does not modify lethal reperfusion injury in myocardium.
Adenosine↗
Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966.
serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC.
Animals↗
Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population.
Low density lipoprotein (LDL) receptor-related protein (LRP) gene polymorphisms located in the 5' region and in exon 3, and the apolipoprotein E (APOE) genotype were determined in 100 Japanese patients affected by late-onset Alzheimer's disease (AD). We matched 246 controls for age and found no association between the polymorphism located in the 5' region of the LRP gene. The distribution of LRP exon 3 genotypes and alleles did not differ between AD and the control groups. However, the frequency of T allele in the Alzheimer's group having APOE-epsilon4 was lower than that in the control group having APOE-epsilon4, but it was only marginally significant (p = 0.022). Age of onset was significantly younger in the patients with CC genotype than those carrying the T allele (p = 0.03), and this trend was more evident among non-APOE-epsilon4 carriers (p = 0.008). These results support the possibility that ApoE and LRP may contribute to the development of AD.
Age of Onset↗
cAMP-GEFII is a direct target of cAMP in regulated exocytosis.
Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.
Animals↗
Mutant DnaA proteins defective in duplex opening of oriC, the origin of chromosomal DNA replication in Escherichia coli.
We characterized three mutant DnaA proteins with an amino acid substitution of R334H, R342H and E361G that renders chromosomal replication cold (20 degrees C) sensitive. Each mutant DnaA protein was highly purified from overproducers, and replication activities were assayed in in vitro oriC replication systems. At 30 degrees C, all three mutant proteins exhibited specific activity similar to that seen with the wild-type protein, whereas at 20 degrees C, there was much less activity in a replication system using a crude replicative extract. Regarding the affinity for ATP, the dissociation rate of bound ATP and binding to oriC DNA, the three mutant DnaA proteins showed a capacity indistinguishable from that of the wild-type DnaA protein. Activity for oriC DNA unwinding of the two mutant DnaA proteins, R334H and R342H, was more sensitive to low temperature than that of the wild-type DnaA protein. We propose that R334H and R342H have a defect in their potential to unwind oriC DNA at low temperatures, the result being the cold-sensitive phenotype in oriC DNA replication. The two amino acid residues of DnaA protein, located in a motif homologous to that of NtrC protein, may play a role in the formation of the open complex. The E361 residue may be related to interaction with another protein present in a crude cell extract.
Adenosine Triphosphate↗
Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.
1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.
Adult↗
Are micturition systems influenced by sleep-arousal system?
To clarify a relation between contractile condition of the urinary bladder and vigilance condition, bladder pressure was monitored simultaneously with cortical electroencephalogram (EEG) in urethane-anesthetized rats. Slow waves of large amplitude and those of lower amplitude appeared in EEG alternately. The bladder showed no contractile activity in the former EEG condition, while it contracted intermittently or continuously to urinate in the latter EEG condition. The relative power of EEG delta waves was significantly different in these two conditions. These results suggest that activity of the micturition system changes according to vigilance conditions, which may serve to prevent enuresis during sleep.
Animals↗
Transrectal power Doppler imaging in the detection of prostate cancer.
OBJECTIVES: To evaluate the clinical utility of transrectal power Doppler imaging (PDI) of the prostate for detecting prostate cancer in patients with abnormally high serum levels of prostate specific antigen (PSA). PATIENTS AND METHODS: Patients (107) with abnormally high serum PSA levels were assessed using a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and PDI. Any hypervascular lesion on PDI was graded on a scale of 0-3, where grade 1-3 was considered positive and grade 0 negative. Patients were then diagnosed by prostatic needle biopsy and the results compared with the other detection methods. RESULTS: Needle biopsy confirmed prostate cancer in 41 (24%) of the 170 patients. PDI was positive in 68, of whom 40 (59%) had prostate cancer; all those but one having prostate cancer were positive on PDI. Thus, PDI had a high sensitivity of 98% (40/41) and a negative predictive value of 99% (101/102). PDI could have saved a significant number of patients from undergoing unnecessary biopsies, compared with DRE and TRUS (P < 0.001). CONCLUSION: The use of PDI in detecting prostate cancer might reduce the number of unnecessary needle biopsies of the prostate in patients with abnormally high serum PSA levels.
Aged↗
Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells.
The involvement of the phosphatidylinositol 3-kinase pathway in the regulation of melanogenesis was examined using human G361 melanoma cells. In the cells treated with wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, the melanin content increased concomitant with the elevated protein level of tyrosinase, a key enzyme in melanogenesis. Northern blot analysis revealed that the mRNA level of tyrosinase increased transiently on treatment of the cells with the phosphatidylinositol 3-kinase inhibitor. When the cells were infected with the adenovirus vector encoding the mutant adapter subunit of phosphatidylinositol 3-kinase, which acts as a dominant negative of phosphatidylinositol 3-kinase, both the melanin content and the expression of tyrosinase increased. In cells infected with the adenovirus vector encoding the constitutively active mutant of the lipid kinase, a decrease in melanin content as well as reduced expression of tyrosinase was observed. In cells expressing the constitutively active mutant of the serine-threonine protein kinase Akt, one of the downstream targets of phosphatidylinositol 3-kinase, the melanin content decreased as in the cells overproducing the constitutively active mutant of phosphatidylinositol 3-kinase. These results indicate that phosphatidylinositol 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and that activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells.
Androstadienes↗
A Rho-specific exchange factor Ect2 is induced from S to M phases in regenerating mouse liver.
The ect2 oncogene was originally identified as a transforming complementary DNA (cDNA) from mouse epithelial cells in an expression cloning approach and encodes a product related to Rho-specific exchange factors and yeast cell cycle regulators. To explore the potential role of ect2 in the cell cycle, we examined the expression of the ect2 proto-oncogene in a liver regeneration model in mice after partial (two thirds) hepatectomy. We found that the expression of the ect2 transcript and protein were markedly elevated with the onset of DNA synthesis and remained elevated during G2 and M phases. The timing of ect2 expression matched that of proliferating cell nuclear antigen (PCNA) and partially overlapped cell division cycle 2 (Cdc2) expression. In situ hybridization analysis showed that ect2 was expressed at a high level in cells undergoing mitosis in regenerating liver. Moreover, expression of a dominant negative or an oncogenic mutant of ect2 in cultured mouse hepatocytes resulted in a large increase in the number of binucleated cells. These findings showed that Ect2 is expressed in a cell cycle-dependent manner during liver regeneration, and suggest that it has an important role in the regulation of cytokinesis.
Animals↗