[Is It possible to accomplish artificial heart within 10 years].
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Biocompatible Materials↗
Biomedical subjects
H Takano
Publications and source records attributed to H Takano.
Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27.
An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at D6S305 (theta = .03) and D6S253 (theta = .02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons.
Adolescent↗
[Expression of ATP binding cassette superfamily (multidrug resistance-1, multidrug resistance-associated protein, human canalicular multispecific organ anion transporter) mRNA in etoposide and m-AMSA resistant cell lines].
The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to etoposide or m-AMSA. Subsequently, a population of cells from each sublines was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Quantitative aspects of MRP and C-MOAT were studied by Northern blotting in 66 resistant cell lines. Increased MRP mRNA was observed in 48.5% of resistant cell lines (64.7% of etoposide resistant cells and 31.3% of m-AMSA resistant cell lines). Increased C-MOAT mRNA was also observed in 39.4% of resistant cell lines (41.2% in etoposide resistant cell lines and 37.5% in m-AMSA resistant cell lines). To characterize the function of C-MOAT, cellular accumulation assay for 3H-etoposide was performed in three resistant cell lines which overexpress C-MOAT but do not express MRP. Accumulation of etoposide was reduced in the cell lines. Our findings suggest that increased MRP and O-MOAT mRNA seems to be an important mechanism of resistance to topo II inhibitors.
ATP-Binding Cassette Transporters↗
Gastrointestinal tumors of childhood.
Tumors of the gastrointestinal tract in children are divided into tumors involving the solid organs that bud from the gastrointestinal tract, principally the liver, and tumors intrinsic to the alimentary tract. This article presents a review of the current state of understanding of solid tissue tumors. The human genome project and better understanding of human genetics have led to remarkable changes in the classification and description of tumors of the alimentary tract. This article attempts to summarize these changes to a current classification of the gastrointestinal polyposis syndromes.
Child↗
[Expression of DNA topoisomerases (I, II alpha, II beta) mRNA in etoposide- and mAMSA-resistant cell lines].
The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to etoposide or m-AMSA. Subsequently, a population of cells from each subline was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. Quantitative aspects of topo I, II alpha, and II beta were studied by Northern blotting in 66 resistant cell lines. Reduced topo II alpha mRNA was observed in 95.5% of resistant cell lines, and median topo II alpha mRNA was lower (38.0 +/- 28.1%) in resistant cell lines in comparison to parental cell lines, while increased topo I and II beta were observed (145.5 +/- 89.3%, and 165 +/- 105.9% of that of parental cell lines). But the expression of the topo I and II beta gene were not correlated to that of topo II alpha. Our findings suggest that reduced topo II alpha mRNA seems to be the most important mechanism of resistance to topo II inhibitors.
Amsacrine↗
G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.
Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.
Animals↗
Characterization of a human glycoprotein with a potential role in sperm-egg fusion: cDNA cloning, immunohistochemical localization, and chromosomal assignment of the gene (AEGL1).
Acidic epididymal glycoprotein (AEG), thus far identified only in rodents, is one of the sperm surface proteins involved in the fusion of the sperm and egg plasma membranes. In the present study, we describe the isolation and characterization of cDNA encoding a human glycoprotein related to AEG. Although this protein, designated ARP (AEG-related protein), is not the ortholog of rodent AEG, it resembles AEG in that it is an epididymal secretory glycoprotein that binds to the postacrosomal region of the sperm head. The fact that no AEG mRNA can be detected in the human epididymis suggests that ARP might be the functional counterpart of rodent AEG. The gene encoding ARP (AEGL1) was mapped by fluorescence in situ hybridization to 6p21.1-p21.2. This result indicates that AEGL1 and the mouse gene for AEG are located in the chromosomal segments with conserved syntenies.
Acrosome↗
Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy.
We have recently shown that mechanical stress induces cardiomyocyte hypertrophy partly through the enhanced secretion of angiotensin II (ATII). Endothelin-1 (ET-1) has been reported to be a potent growth factor for a variety of cells, including cardiomyocytes. In this study, we examined the role of ET-1 in mechanical stress-induced cardiac hypertrophy by using cultured cardiomyocytes of neonatal rats. ET-1 (10(-8) approximately 10(-7) M) maximally induced the activation of both Raf-1 kinase and mitogen-activated protein (MAP) kinases at 4 and 8 min, respectively, followed by an increase in protein synthesis at 24 h. All of these hypertrophic responses were completely blocked by pretreatment with BQ123, an antagonist selective for the ET-1 type A receptor subtype, but not by BQ788, an ET-1 type B receptor-specific antagonist. BQ123 also suppressed stretch-induced activation of MAP kinases and an increase in phenylalanine uptake by approximately 60 and 50%, respectively, but BQ788 did not. ET-1 was constitutively secreted from cultured cardiomyocytes, and a significant increase in ET-1 concentration was observed in the culture medium of cardiomyocytes after stretching for 10 min. After 24 h, an approximately 3-fold increase in ET-1 concentration was observed in the conditioned medium of stretched cardiomyocytes compared with that of unstretched cardiomyocytes. ET-1 mRNA levels were also increased at 30 min after stretching. Moreover, ET-1 and ATII synergistically activated Raf-1 kinase and MAP kinases in cultured cardiomyocytes. In conclusion, mechanical stretching stimulates secretion and production of ET-1 in cultured cardiomyocytes, and vasoconstrictive peptides such as ATII and ET-1 may play an important role in mechanical stress-induced cardiac hypertrophy.
Animals↗
Activation of p70 S6 protein kinase is necessary for angiotensin II-induced hypertrophy in neonatal rat cardiac myocytes.
Although many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in development of cardiac hypertrophy, the mechanism by which Ang II increases protein synthesis in cardiac myocytes remains unclear. It has been reported that the phosphorylation of S6 protein in 40 S ribosome is correlated to the efficiency of protein synthesis. In the present study, we have examined whether Ang II activates p70 S6 kinase (p70S6K), which has been reported to phosphorylate S6 protein. Ang II activated p70S6K through AT1 receptor. An immunosuppressant agent, rapamycin, inhibited Ang II-induced p70S6K activation but not the activation of MAP kinases or the induction of c-fos gene expression. Rapamycin also abolished Ang II-induced increase in protein synthesis. These results suggest that Ang II induces cardiac hypertrophy by activating p70S6K.
Angiotensin I↗
Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptor.
The inositol 1,4,5-trisphosphate (InsP3) receptor acts as an InsP3-gated Ca2+ release channel in a variety of cell types. Type 1 InsP3 receptor (IP3R1) is the major neuronal member of the IP3R family in the central nervous system, predominantly enriched in cerebellar Purkinje cells but also concentrated in neurons in the hippocampal CA1 region, caudate-putamen, and cerebral cortex. Here we report that most IP3R1-deficient mice generated by gene targeting die in utero, and born animals have severe ataxia and tonic or tonic-clonic seizures and die by the weaning period. An electroencephalogram showed that they suffer from epilepsy, indicating that IP3R1 is essential for proper brain function. However, observation by light microscope of the haematoxylin-eosin staining of the brain and peripheral tissues of IP3R1-deficient mice showed no abnormality, and the unique electrophysiological properties of the cerebellar Purkinje cells of IP3R1-deficient mice were not severely impaired.
Animals↗
Interleukin-6 (IL-6) production in carcinoma of the cervix.
Interleukin-6 (IL-6) is a pleiotropic cytokine that is not only a mediator in major immunologic reactions but also a growth factor of keratinocytes. We studied the IL-6 secretion in vitro of 15 human cell lines derived from both squamous cell carcinoma (SCC) and adenocarcinoma of the uterine cervix. Four of the eight well differentiated SCC secreted a large amount (> 1500 pg/48 h/10(6) cells) of IL-6 in nude mice. In contrast, poorly differentiated SCC cell lines and all of the 7 adenocarcinoma cell lines secreted a small amount (< 500 pg/48 h/10(6) cells of IL-6). The expression of IL-6 mRNA of the cell lines correlated well with their IL-6 secretion potential. However, the expression of IL-6 receptor did not correlate with the IL-6 secretory potential. We also studied the IL-6 secretion of freshly isolated normal squamous epithelium and of dysplastic epithelium. In culture, two normal squamous epithelia secreted a large amount (> 2000 pg/48 h/10(6) cells), whereas 8 dysplasia epithelia secreted an extremely small amount (< 10 pg/48 h/10(6) cells). About one-third of patients with SCC had a raised serum IL-6 value. IL-6 production may help to differentiate between SCC and adenocarcinoma of the uterine cervix. IL-6 regulation seems to change in the course of SCC carcinogenesis.
Adenocarcinoma↗
Venopelvic fistula: a rare complication of hyperalimentation.
The prolonged placement of a hyperalimentation catheter via the left great saphenous vein resulted in obstruction of the inferior vena cava and in the formation of a venopelvic fistula. Administration of hyperosmolar fluid via this catheter might be the cause of this complication.
Arteriovenous Fistula↗
Rearrangements of mitochondrial DNA and the mitochondrial fusion-promoting plasmid (mF) are associated with defective mitochondrial fusion in Physarum polycephalum.
A specific linear mitochondrial plasmid (mF) is genetically associated with the fusion of mitochondria in the true slime mould, Physarum polycephalum. In matings between mF+ and mF- strains, which respectively carry and do not carry the mF plasmid, mitochondrial fusion occurs in the zygote. Mitochondrial fusion induces recombination between specific sites in the mitochondrial DNA (mtDNA) and in the mF plasmid. To detect a region which is associated with the mitochondrial fusion in the mF plasmid, we isolated, by fluorescence microscopy, strains which showed defective mitochondrial fusion (delta mif-) from those which showed normal mitochondrial fusion (mif+). Analysis of the mitochondrial genomes of delta mif- strains showed only mtDNA which recombined with the mF plasmid in mitochondria. Comparison of this recombinant mtDNA in one delta mif- strain (NG 15) with that of a mif+ strain showed that a 2.2-kbp region, which included the integration site of the mF plasmid, was deleted in the delta mif- strain by recombination between the main mtDNA and the mF plasmid. In other strains, in addition to this deletion, a 6-kbp region which included both termini was deleted by recombination at six repeats of AAT sequences in the mF plasmid. Moreover, transcripts of the mF plasmid were not detected in NG15 by slot hybridization.
Animals↗
Ventricular assist systems: experience in Japan with Toyobo pump and Zeon pump.
BACKGROUND: Two types of ventricular assist systems have been approved for use by the Japanese government. METHODS: The two government-approved ventricular assist systems, the Toyobo pump (National Cardiovascular Center type) and the Zeon pump (Tokyo University type), were applied to 219 patients in Japan as of October 20, 1994. RESULTS: Adult-sized were used in 211 patients and pediatric ones in 8 patients. Left ventricular assist systems was performed in most cases (82.6%). The predominant indication was failure to be weaned from cardiopulmonary bypass (65.8%). The duration of ventricular assist system application ranged from 1 hour to 70 days, and the mean was 7.3 days, excluding the patients with cardiomyopathy. The weaning rate was 48.8% and the survival rate was 25.6%. Main causes of death were heart failure including unrecoverable heart failure and multiple organ failure. In 12 cardiomyopathy patients, Toyobo pumps were applied as left ventricular assist systems. Support duration was from 13 days to 192 days (ongoing). One patient was bridged to transplantation successfully and 1 was weaned after 3 months of support. CONCLUSIONS: From these data, the Toyobo pump and the Zeon pump are useful for short-term support for acute, profound heart failure. The Toyobo pump also may provide sufficient support as a bridge to transplantation for the medium term.
Adolescent↗
Influence of prolonged ventricular assistance on myocardial histopathology in intact heart.
BACKGROUND: The unloading effect of ventricular assistance on the injured myocardium may adversely affect the compensatory hypertrophy of the residual intact myocardium because myocardial protein synthesis is partly controlled by cardiac work. The influence of prolonged ventricular assistance on normal myocardium was evaluated from a pathologic point of view. METHODS: A ventricular assist device was chronically implanted in 5 goats using left atrium-aorta bypass. The pumping ratio was fixed at 70 beats/min. Left ventricular biopsy samples were taken before and 1 month after assistance. RESULTS: Although the volume densities of myocytes and interstitial tissue in the myocardium showed no significant changes after 1 month of support, the myocyte volume density to nuclear volume density ratio and the interstitial tissue volume density to nuclear volume density ratio decreased significantly (p < 0.01 and p < 0.05, respectively). A cross-sectional area of myocyte showed decreases of 20.9% to 49.5%, whereas the nuclear cross-sectional area showed no significant changes. In addition, myofibrillar volume density in the cytoplasm decreased from 54.9 +/- 2.3% to 49.1 +/- 4.4%. CONCLUSIONS: The results indicate that long-term ventricular assistance in the intact heart leads to myocardial atrophy. This suggests that in the damaged heart subjected to prolonged unloading by ventricular assistance, there is the possibility of limiting compensatory hypertrophic changes in the residual intact myocardium.
Animals↗
Impact of systemic depulsation on tissue perfusion and sympathetic nerve activity.
BACKGROUND: We postulated that pathophysiologic processes under nonpulsatile circulation are related to the behavior of the sympathetic nerve activity that regulates tissue perfusion. METHODS: Pulsatile and nonpulsatile pumps were installed in parallel in the left heart bypass circuit of anesthetized goats (n = 9) so that pulsatile circulation could be converted to nonpulsatile circulation instantly. At 5 minutes before and after systemic depulsation, we measured hemodynamic indices, renal nerve activity, and regional blood flow of the brain, heart, and renal cortex. RESULTS: Renal nerve activity was significantly elevated after systemic depulsation (15.6 +/- 9.3 versus 19.4 +/- 9.8 microV), when mean aortic pressure remained almost constant. The renal cortical flow was significantly reduced after depulsation (3.61 +/- 1.23 versus 2.93 +/- 1.19 mL.min-1.g-1), whereas no significant difference was found in the regional blood flow of the brain or the heart. CONCLUSIONS: The significant reduction of renal cortical blood flow after systemic depulsation is associated with a significant increase in renal nerve activity. Our results suggest that increased renal nerve activity plays an important role in the reduction of renal function after systemic depulsation.
Animals↗
Elevated levels of nitric oxide in synovial fluid from patients with temporomandibular disorders.
OBJECTIVE: The objective of this study was to measure nitric oxide activity in synovial fluid samples taken from patients with temporomandibular disorders. STUDY DESIGN: We investigated six volunteers without symptoms and 56 patients with temporomandibular disorders. Nitric oxide activity was measured in temporomandibular joint synovial fluid with a highly sensitive and specific chemiluminescence detection method. RESULTS: A detectable nitrite concentration was found in only 1 of 10 joints in the control group. Measurable levels (> 0.001 mol/l) of nitrites in the synovial fluid were found in 8 (72.7%) of 11 joints with disk derangement with clicking, 24 (85.7%) of 28 joints with disk derangement with locking, and all 26 (100%) joints with osteoarthritis. The mean nitrite concentrations in the temporomandibular joint synovial fluid in the disk derangement with clicking, disk derangement with locking, and osteoarthritis groups were significantly higher than that in the control group (p < 0.05, p < 0.001, p < 0.001, respectively). CONCLUSIONS: These data clearly show increased nitric oxide production in certain temporomandibular disorders and suggest that nitric oxide may play a role in the pathogenesis of synovitis and degenerative changes of cartilaginous tissue and bone of the temporomandibular joint.
Adolescent↗
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↗