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Biomedical subjects

K Akimoto

Publications and source records attributed to K Akimoto.

At least 37 records · Page 2Linked to original sources

Restenosis after balloon angioplasty of coarctation: relationship with ductus arteriosus.

BACKGROUND: Recently, balloon angioplasty (BA) has been used for the treatment of coarctation of the aorta (CoA) and the effectiveness of this treatment has been reported. However, the restenosis rate following BA in native CoA in the infant is high and the cause may be related to tissue properties at the origin of the ductus arteriosus (DA). However, the mechanisms responsible for restenosis remain uncertain. METHODS/RESULTS: The present study was designed to examine transformation of the smooth muscle cell (SMC) phenotypes using immunohistologic studies and to investigate the cause of restenosis of CoA following BA. A CoA model was surgically created in 15 newborn pigs (10-14-days-old; 2.4-4.1 kg). Balloon angioplasty was performed 1 month after the initial operation. One or 3 months after BA, animals were killed and immunohistologic studies on smooth muscle cell (SMC) antibodies against SM1, SM2 and SMemb of the myosin heavy chain (MHC) isoform were performed in the aorta at the CoA and DA. In the neointima, only SMemb was positive. In the SMC layer of the DA, only SM2 was positive. One month after BA, the external layer of the tunica media was strongly positive for SM2 only in the area around the origin of the DA. CONCLUSIONS: The first cause of restenosis is obstructive neointimal formation caused by the proliferation of undifferentiated SMC into the subendothelial tissue. This proliferation seems to be triggered by BA. The distribution of SM2 1 month after balloon angioplasty showed a similar pattern of proliferation of SMC in the external layer around the DA. This may represent a second mechanism of restenosis.

Angioplasty, Balloon↗

Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes.

The asymmetric distribution of cellular components is an important clue for understanding cell fate decision during embryonic patterning and cell functioning after differentiation. In C. elegans embryos, PAR-3 and aPKC form a complex that colocalizes to the anterior periphery of the one-cell embryo, and are indispensable for anterior-posterior polarity that is formed prior to asymmetric cell division. In mammals, ASIP (PAR-3 homologue) and aPKCgamma form a complex and colocalize to the epithelial tight junctions, which play critical roles in epithelial cell polarity. Although the mechanism by which PAR-3/ASIP and aPKC regulate cell polarization remains to be clarified, evolutionary conservation of the PAR-3/ASIP-aPKC complex suggests their general role in cell polarity organization. Here, we show the presence of the protein complex in Xenopus laevis. In epithelial cells, XASIP and XaPKC colocalize to the cell-cell contact region. To our surprise, they also colocalize to the animal hemisphere of mature oocytes, whereas they localize uniformly in immature oocytes. Moreover, hormonal stimulation of immature oocytes results in a change in the distribution of XaPKC 2-3 hours after the completion of germinal vesicle breakdown, which requires the kinase activity of aPKC. These results suggest that meiotic maturation induces the animal-vegetal asymmetry of aPKC.

Adaptor Proteins, Signal Transducing↗

Rate enhancement with high ratio of the monoalkylated product to the dialkylated product in the alkylation of the lithium enolate of 1-tetralone with reactive alkyl halides.

The reactions of the lithium enolate of 1-tetralone with reactive alkyl halides were examined in the absence and in the presence of 3 eq of various ligands for the lithium. It is shown that the rates of the reactions are enhanced greatly in the presence a tetradentate amine (1,1,4,7,10,10-hexamethyltriethylenetetramine), and the ratio of the monoalkylated product to the dialkylated product is increased under shorter reaction times.

Alkylation↗

A mitochondrial DNA mutation cosegregates with the pathophysiological U wave.

In a family with long QT syndrome (LQT2), some individuals who did not harbor the HERG mutation had a prolonged QTU interval on electrocardiograms after exercise. It may be determined or modified by other gene(s) or factor(s). The sequence analysis of mtDNA in these individuals of this family showed a candidate pathogenic mutation at 3394 in the ND1 gene. The cybrids (mutation at 3394) showed significantly reduced NADH-CoQ reductase (complex I) activity and O2 consumption to normal levels. These inhibitory effects on respiratory function may result in the depletion of ATP and could possibly produce an increase in Ca2+ concentration in cytosol, and it may lead to the prolongation of the QTU intervals on electrocardiograms. Therefore, we stated that the 3394 mutation in the ND1 gene is pathogenic and could be the cause of prolongation of the QTU intervals or modification of the phenotypes of not only congenital but also so-called "acquired drug-induced long QT syndrome."

Adolescent↗

Effects of 3alpha- and 3beta-galactosylated alpha-galactosylceramides on the immune system.

We compared effects of alpha-galactosylceramide (alpha-GalCer) and its 3alpha- or 3beta-galactosylated derivatives on the proliferation of murine spleen cells. The 3alpha-galactosylated alpha-GalCer showed stronger proliferative response than the parental alpha-GalCer, but the 3beta-galactosylated alpha-GalCer possessed weaker activity than the alpha-GalCer. In addition, alpha-Gal-3-Cer did not show immunostimulatory activity.

Adjuvants, Immunologic↗

Transcriptional regulation of adrenomedullin in rat vascular smooth muscle cells.

Adrenomedullin (AM), a potent vasorelaxant peptide recently identified in extracts of pheochromocytoma, is actively secreted from vascular smooth muscle cells (VSMC). AM production in rat VSMC is potently stimulated by proinflammatory cytokines including TNF alpha, and glucocorticoids and many vasoactive substances have also been shown to alter AM synthesis. To study AM promoter function, we cloned the 5'-flanking region of the rat AM gene, and AM promoter function was assessed in rat VSMC stably transfected with a construct containing the cloned fragment. This 1.4 kb AM promoter region includes a number of putative transcriptional control elements. The promoter activity in VSMC was stimulated by TNF alpha and dexamethasone, and was suppressed by 8-bromo-cAMP and forskolin. These data indicate that transcriptional regulation is an important mechanism for AM production in VSMC.

8-Bromo Cyclic Adenosine Monophosphate↗

Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with polyanions, and involvement of interferon-gamma in the regulation of cytokine secretion.

When macrophages derived from rat bone marrow were cultured in the presence of polyanions such as acetyl lignin (EP3), sulfonyl lignin (LS) or dextran sulfate (DS), the cells secreted TNF-alpha, IL-8 and nitric oxide (NO). EP3 had a dose-dependent effect on the secretion of TNF-alpha, IL-8 and NO. EP3 significantly affected secretion at concentrations greater than 5 microg/ml. The EP3 effect was at its maximum between concentrations of 50 and 100 microg/ml. LS and DS induced a slight increase in the secretion of cytokines and NO at a concentration of 100 microg/ml. The use of the reverse-transcription polymerase chain reaction (RT-PCR) showed that the increases in cytokine and NO secretion were due to an increase in cytokine mRNAs or NO synthase mRNA. Anti-TNF-alpha antibodies partially inhibited NO secretion by EP3-activated macrophages, although IL-8 secretion was independent of antibody treatment. The secretion of TNF-alpha and NO was also unaffected by the addition of anti-IL-8 antibodies. The addition of interferon-gamma (IFN-gamma) to the culture medium did not alter TNF-alpha and NO secretion by the EP3-activated macrophages, however, IL-8 secretion was increased when a low concentration of IFN-gamma (0.2 U/ml) was added, but was reduced in the presence of a high concentration of IFN-gamma (2000 U/ml). IFN-gamma produced similar effects on cytokine and NO secretion in macrophages activated with lipopolysaccharide (LPS). Therefore, it is concluded that macrophages treated with polyanions secrete cytokines and NO, and that INF-gamma is involved in the regulatory mechanism of cytokine and NO secretion.

Animals↗

Formation of bone around titanium implants placed into zero wall defects: pilot project using reinforced e-PTFE membrane and autogenous bone grafts.

BACKGROUND: Guided bone regeneration (GBR) frequently is used to augment implants with various types of bone defects. The defects often are grafted with different materials, yet there is insufficient evidence that these materials enhance bone-to-implant contacts. PURPOSE: The purpose of this pilot project was to test the principle of GBR to promote bone formation adjacent to commercially pure titanium implants placed within zero-wall defects. Histologic and histomorphometric measurements were used to evaluate new bone formation. MATERIALS AND METHODS: Under appropriate anesthesia, deep, wide defects were created within the mandibles of two large dogs. Buccolingual bone was removed to the depth of the defects leaving only the mesial and distal walls. Of the eight implants placed, three were augmented with titanium-reinforced expanded polytetrafluoroethylene (e-PTFE) barriers and autogenous bone chips. Three sites were augmented with barrier membranes only, and two sites were not augmented or grafted and served as controls. Seven months after surgery the dogs were sacrificed and block sections were taken for histologic evaluation. RESULTS: Histologic and histomorphometric measurements were used to evaluate new bone formation. Results from this evaluation revealed bone formation at the membrane-only sites and the membrane-plus-bone grafted sites. The bone grafts were completely incorporated by the newly formed marginal compact bone. For all treated sites, there was poor bone-to-implant contact. Histomorphometric measurements showed a trend toward greater bone formation at membrane-treated sites compared with control sites. However, autogenous bone grafting did not seem to affect the amount of newly regenerated bone. CONCLUSIONS: Within the limits of this pilot project, findings show trends toward bone healing, indicating constant and enhanced bone regeneration over the exposed implant. Bone contact to the implant surface generally was poor.

Animals↗

Sudden death in a rat subarachnoid hemorrhage model.

The pathogenesis of sudden death during subarachnoid hemorrhage (SAH) still remains to be elucidated. A new rat common carotid artery-prechiasmal extracorporeal shunt model was designed to study the effect of different severities of SAH on intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mortality. Different severities of SAH were induced by controlling the bleeding period (from 30 to 90 sec) and number of bleedings (one or three times). SAH caused a dramatic increase in ICP and immediate depression of rCBF, which recovered slowly to a certain extent. ICP increased sharply within the first 30 seconds and reached a plateau concomitant with nearly zero rCBF, which suggested the occurrence of cerebral circulation arrest. Bleeding of more than 60 seconds and increased ICP over 80 mmHg were directly correlated with the mortality. Respiratory arrest was the first sign of death, immediately followed by cardiac depression resulting in sudden death. This model combines arterial bleeding with systemic blood pressure and controlled bleeding time to simulate the acute period of SAH.

Acute Disease↗

[Histidine buffered cardioplegic solution (HBS) provides effective myocardial preservation with wider safety margin in patients with prolonged ischemia].

Increasingly complex techniques of cardiac surgery often require prolonged myocardial ischemia. We previously reported a better myocardial preservation with histidine containing cardioplegia (HBS) in human open heart surgery. To see a safety margin of this cardioplegia for prolonged myocardial preservation, this study was retrospectively done. One hundred twenty-six patients received either intermittent multidose (20-30 minute) cold blood cardioplegia (CBC) plus topical cooling (aotric cross clamp time (ACC) < 120 minutes, n = 63) or HBS (n = 63). HBS group was divided into two groups with either short ACC (< or = 120 minutes, HBS-S, n = 46) or long ACC (> 120 minutes, HBS-L, n = 17). Cardiac index (C.I.) and dopamin/dobutamine requirement were measured 3, 6, and 12 hours post-bypass. Incidence of homologous blood transfusion was also studied. There was two deaths due to LOS in HBS-S group; four patients in HBS group required 5 DC cardioversion, whereas six patients required a total of 12 DC cardioversion in CBC group. Functional recovery were significantly better with significantly lower inotropic requirements in HBS-S group than CBC group and HBS-L group. Although preoperative ejection fraction and C.I. were significantly lower in HBS-L group, post-operative cardiac function and inotropic requirements in HBS-L was comparable to that seen in CBC group. We conclude that the highly buffered histidine crystalloid cardioplegia solution provides effective myocardial preservation with a wider safety margin for prolonged myocardial preservation in open heart surgery.

Adult↗

Atypical protein kinase Clambda binds and regulates p70 S6 kinase.

p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, the mechanism of its activation is not fully understood. In the present work, evidence is provided that an atypical protein kinase C (PKC) isotype, PKClambda, is indispensable, but not sufficient, for the activation of p70 S6K. Both the regulatory and kinase domains of PKClambda associate directly with p70 S6K. Overexpression of the kinase domain without kinase activity or the regulatory domain of PKClambda results in the suppression of the serum-induced activation of p70 S6K. In addition, two types of dominant-negative mutants of PKClambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum-induced DNA synthesis and E2F activation. The overexpresion of the active form of PKClambda, however, fails to activate p70 S6K. These results suggest that PKClambda is a mediator in the regulation of p70 S6K activity and plays an important role in cell cycle progression.

Amino Acid Sequence↗

Observation of the strain field near the Si(111) 7 x 7 surface with a new X-ray diffraction technique.

A new X-ray diffraction technique has been developed in order to measure the strain field near a solid surface under ultrahigh vacuum (UHV) conditions. The X-ray optics use an extremely asymmetric Bragg-case bulk reflection. The glancing angle of the X-rays can be set near the critical angle of total reflection by tuning the X-ray energy. Using this technique, rocking curves for Si surfaces with different surface structures, i.e. a native oxide surface, a slightly oxide surface and an Si(111) 7 x 7 surface, were measured. It was found that the widths of the rocking curves depend on the surface structures. This technique is efficient in distinguishing the strain field corresponding to each surface structure.

Journal Article↗

Combined angioplasty and valvuloplasty for coexisting coarctation of the aorta and aortic stenosis in an infant.

The patient was a 1-month-old male infant. Echocardiography showed left ventricular hypertrophy with coarctation of the aorta (CoA) and aortic valve stenosis (AVS). Left ventricular systolic function was poor. At catheterization, the gradient of AVS was 25 mmHg and the annulus size of the aortic valve was 7 mm. There was a CoA measuring 2.1 mm in diameter. Balloon valvuloplasty of the CoA was then performed using the same balloon; the pressure gradient decreased to 0 mmHg, and CoA diameter decreased from 2.1 to 5.5 mm.

Angioplasty, Balloon↗

Multinucleation and preservation of nucleolar integrity of macrophages.

Rat bone marrow-derived macrophages formed multinucleated giant cells spontaneously when cultured in slide glass chambers or when induced with the polyanion acetyl lignin. Nuclei in such cells tended to cluster in distinct rings. DNA fragmentation appeared to occur in multinucleated cells, as detected by 3' end-labeling. Southern blot analyses, using probes specific for nucleolar and non-nucleolar genes, indicated that chromatin DNA was fragmented whereas nucleolar DNA was relatively intact. Autoradiography revealed preservation, in multinucleated cells, of nucleoli into which radiolabeled uridine was incorporated. Multinucleated macrophages appeared to eventually fragment. Preserved integrity of nucleoli seems to be a feature of macrophage multinucleation, a process which apparently culminates in cell death.

Animals↗

Hydatidiform moles associated with multiple gestations after assisted reproduction: diagnosis by analysis of DNA fingerprint.

In spite of the widespread use of assisted reproductive technology, there have been, to our knowledge, only two reported cases of molar pregnancies after gamete intra-Fallopian transfer and five reported cases after in-vitro fertilization and embryo transfer. We report here a case of a complete hydatidiform mole in a twin pregnancy after gamete intra-Fallopian transfer, as well as a case of a complete hydatidiform mole in a triplet pregnancy after in-vitro fertilization and embryo transfer. The genetic constitution of each conceptus was determined by examination of the restriction fragment length polymorphism of the DNA with four different single-locus probes. This analysis revealed that both hydatidiform moles were of androgenetic origin and probably of monospermic origin. Moreover, the analysis confirmed that the pregnancies were dizygotic and trizygotic pregnancies respectively. The diagnostic utility of the analysis of DNA polymorphism is discussed in cases of a molar pregnancy with coexisting fetuses.

Adult↗

Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats.

Vesicular transport inhibitors have been reported to inhibit biliary excretion of some organic anions, suggesting that vesicular transport has a role in intracellular transport of these compounds. However, these inhibitors are substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats. Colchicine treatment slightly but significantly inhibited biliary excretion of indocyanine green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine treatment did not affect biliary excretion of indocyanine green and pravastatin, but it increased biliary sulphobromophthalein-glutathione excretion. In conclusion, the present findings suggest that P-glycoprotein plays an additive role on biliary excretion of some organic anions in addition to the canalicular multispecific organic anion transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗