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Biomedical subjects

H Akiho

Publications and source records attributed to H Akiho.

At least 19 recordsLinked to original sources
PubMed2006

An increase in the serum amylase level in patients after peroral double-balloon enteroscopy: an association with the development of pancreatitis.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a novel technique that allows the enteroscope to be inserted deep into the small intestine. The procedure has been thought to be safe, but cases of acute pancreatitis after peroral DBE have recently been observed. The aim of this study was to confirm the occurrence of hyperamylasemia after peroral DBE. PATIENTS AND METHODS: Peroral DBE was carried out in 13 patients from July 2005 to February 2006. Blood samples were taken before and 3 h after the procedure, and serum pancreatic amylase levels were measured. The patients were also evaluated for pancreatic-type abdominal pain after the procedure. Hyperamylasemia after peroral DBE was defined as an elevation of the serum pancreatic amylase level to more than the upper normal limit and twice the level before the procedure. Pancreatitis was diagnosed on the basis of both pancreatic-type abdominal pain and hyperamylasemia. RESULTS: Hyperamylasemia after peroral DBE occurred in six patients (46.2 %). One of the six patients with hyperamylasemia had pancreatic-type abdominal pain after the procedure and developed acute pancreatitis. The average procedure time was 105 min (range 65 - 155 min) in the patients with hyperamylasemia, and did not significantly differ from that in the group without hyperamylasemia (99 min). CONCLUSIONS: Hyperamylasemia after peroral DBE occurs frequently and may be associated with development of pancreatitis.

Adolescent↗
PubMed2003

Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections.

Immune responses associated with intestinal nematode infections are characterized by the activation of T-helper 2 (Th2) cells. Previous studies demonstrated that during Trichinella spiralis infection, Th2 cells contribute to the development of intestinal muscle hypercontractility and to worm eviction from the gut, in part through signal transducer and activator of transcription factor 6 (Stat6). Interleukin-9 (IL-9), a Th2-cell-derived cytokine, has pleiotropic activities on various cells that are not mediated through Stat6. In this study, we investigated the role of IL-9 in the generation of enteric muscle hypercontractility in mice infected with the intestinal parasite T. spiralis and the cecal parasite Trichuris muris. Treatment of mice with IL-9 enhanced infection-induced jejunal muscle hypercontractility and accelerated worm expulsion in T. spiralis infection. These effects were associated with an up-regulation of IL-4 and IL-13 production from in vitro-stimulated spleen cells. In addition, increases in the level of intestinal goblet cells and in the level of mouse mucosal mast cell protease 1 (MMCP-1) in serum were observed in infected mice following IL-9 administration. However, the neutralization of IL-9 by anti-IL-9 vaccination or by anti-IL-9 antibody had no significant effect on worm expulsion or muscle contraction in T. spiralis-infected mice. In contrast, the neutralization of IL-9 significantly attenuated T. muris infection-induced colonic muscle hypercontractility and inhibited worm expulsion. The attenuated expulsion of the parasite by IL-9 neutralization was not accompanied by changes in goblet cell hyperplasia or the MMCP-1 level. These findings suggest that IL-9 contributes to intestinal muscle function and to host protective immunity and that its importance and contribution may differ depending on the type of nematode infection.

Animals↗
PubMed2001

Large thrombus in the ascending aorta successfully treated by thrombolysis--an unusual cause of acute massive myocardial infarction.

A 52-year-old woman suffered from acute massive myocardial infarction in association with a large thrombus in the ascending aorta. She was a moderate smoker and was taking hormone supplement therapy for menopausal hormone insufficiency and the contraceptive pill for endometriosis. Cardiac angiography revealed a large mobile filling defect close to the orifice of the left coronary artery, but the left coronary artery could not be visualized. Her hemodynamic condition was impaired so greatly that intraarterial counterpulsation and intravenous thrombolysis was immediately performed. The thrombus dissolved in 1 h and recanalization of the left coronary artery was achieved without serious systemic thromboembolism. She has been doing well with no cardiac events for 7 years. This is the second report of a large thrombus in ascending aorta being the cause of acute myocardial infarction in the whole territory of the left coronary artery, and the first to diagnose such a thrombus antemortem and treat it successfully.

Aorta↗
PubMed1998

Effect of orotic acid on the metabolism of cerebral cortical astrocytes during hypoxia and reoxygenation: an NMR spectroscopy study.

Astrocytes were incubated under normoxic or hypoxic conditions in Dulbecco's minimum essential medium containing [2-13C]acetate, unlabeled glucose and in some cases orotic acid, an intermediate in pyrimidine biosynthesis. After 12 hr the medium was replaced by fresh medium without drug and incubation was continued for 17 hr in a normal oxygen atmosphere (reoxygenation). Thereafter, medium was removed, cell extracts were prepared, and metabolism in the treatment group was compared to the untreated hypoxia group and to control. 13C and 1H NMR spectra revealed that 13C enrichment in citrate and glutamine C-4 in the initial medium were increased in the presence of orotic acid, compared to the untreated hypoxia group but lower than control. The drug increased acetate utilization during hypoxia to normoxic levels. Thus it appears that the treatment group had a more active mitochondrial metabolism, which was also reflected in higher intracellular uridine diphosphoryl sugars and ADP concentrations. Glutamine labeling was increased in the cell extracts in the presence of orotic acid. Thus it appears that, in the presence of the pyrimidine nucleotide precursor, astrocytes are capable of normal metabolism during hypoxia which might have implications for neuronal survival during low oxygen insults, since neurons are dependent on astrocyte produced precursors for their neurotransmitter synthesis.

Animals↗
PubMed1998

Neuroprotective effect of YM-39558 in focal cerebral ischemia in cats.

We studied the effect of YM-39558, orotic acid ethylester, in a focal cerebral ischemia model in anesthetized cats. YM-39558 has good permeability across the blood brain barrier, and in the brain is hydrolyzed to orotic acid, the main active substance. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. Treatment with YM-39558 (intravenous infusion of 11.8 mg (10 mg as orotic acid)/6 ml per kg per h) starting 15 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2450 +/- 82 mm3 of the cerebral hemisphere in the saline-treated cats to 1644 +/- 123 mm3 in the YM-39558-treated cats, P < 0.01). In contrast, YM-39558 (2.26 and 1.18 mg/0.8 ml per kg per h) showed no significant protective effect on ischemic damage. No significant differences were observed between saline- and YM-39558-treated cats concerning physiological variables including brain temperature. This evidence for the neuroprotective efficacy of YM-39558 in gyrencephalic species suggests its therapeutic potential in the treatment of stroke in humans.

Animals↗
PubMed1998

Neuroprotective effect of YM-39558, orotic acid ethylester, in gerbil forebrain ischemia.

We studied the effects of orotic acid and YM-39558 (2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl ester), orotic acid ethylester, on delayed neuronal death of hippocampal CA1 neurons induced by transient forebrain ischemia. Our data indicated that YM-39558 had high permeability across the blood brain barrier and was hydrolyzed to orotic acid, the active substance, in the brain. The neuronal damage was reduced significantly in animals intraperitoneally treated with YM-39558 (100 mg/kg x 3) after ischemia, but not with orotic acid in the same way. The results also suggested that the maintenance of a few ten micromolar orotic acid in cerebrospinal fluid were needed for its neuroprotective effects.

Animals↗
PubMed1997

Post-ischaemic treatment with orotic acid prevents neuronal injury in gerbil brain ischaemia.

We studied the effects of orotic acid, a precursor of pyrimidine nucleotide, on delayed neuronal death of hippocampal CA1 neurones induced by global cerebral ischaemia in Mongolian gerbils. Neuronal damage was significantly reduced in animals treated with orotic acid 2 h before ischaemia at doses of 100, 200 or 300 mg kg-1, i.p. A dose of 300 mg kg-1 given 24 h after ischaemia also suppressed CA1 neuronal damage, but had no effect when given at 48 or 72 h. These results demonstrate a protective effect of orotic acid on ischaemic neuronal damage with a wide therapeutic time window.

Animals↗
PubMed1996

Low stringency hybridization study of the dopamine D4 receptor revealed D4-like mRNA distribution of the orphan seven-transmembrane receptor, APJ, in human brain.

We recently reported that the density of mRNA for the dopamine D4 receptor was extremely low in human cerebral cortex but unexpectedly higher in the corpus callosum and spinal cord both of which contain substantial white-matter area. Under low stringency conditions, Northern blot analysis using the D4 probe detected cross-hybridized mRNAs having a similar distributional profile to the D4 mRNA in human brain regions, suggesting the mRNA distributional profile is not peculiar to the D4 receptor. Homology screening revealed one of the mRNAs to be an orphan seven-transmembrane receptor, APJ, abundantly expressed in the corpus callosum and spinal cord. In porcine spinal cord the APJ mRNA was detected at a higher level in white-matter rather than in gray-matter area. These data suggest that a group of seven-transmembrane receptors, including the D4 and APJ receptor, is preferentially expressed in the white-matter area probably in non-neuronal glial cells.

Animals↗
PubMed1996

Inactivation of a novel neuropeptide Y/peptide YY receptor gene in primate species.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) belong to a family of structurally related peptides which have numerous functions in both neural and endocrine signaling. By homology screening, we cloned a novel gene sharing the highest homology with the NPY Y1 receptor gene from humans, rabbits, and several other species. This novel gene of rabbit encodes a functional NPY/PYY receptor, designated Y2b, which prefers NPY13-36 rather than [Leu31,Pro34]NPY despite its higher identity with the Y1 receptor. Although, at low levels, mRNA was detected in the tissues and brain regions, including hypothalamus. Further, sequence data revealed that this gene is the orthologue of the recently cloned mouse novel NPY receptor, Y5. However, our study demonstrates that the receptor function of this gene has been inactivated in primates by a frameshift mutation occurring early in primate evolution. This novel NPY receptor represents the first neurotransmitter receptor identified that has universally lost its receptor function in primate species. Interestingly, despite its inactivation in humans, the transcripts were abundantly detected in the heart and skeletal muscle, suggesting a novel function of the human gene.

Amino Acid Sequence↗
PubMed1996

Direct inhibitory effect of corticotropin releasing hormone on isolated caecal circular smooth muscle cells of guinea pig via adenylate cyclase system.

Smooth muscle cells isolated separately from the caecal circular smooth muscle layer of the guinea pig were used to investigate whether corticotropin releasing hormone (CRH) can inhibit directly the contraction produced by cholecystokinin octapeptide (CCK-8). In addition, the role of adenylate cyclase and guanylate cyclase in the direct inhibitory effect of CRH was examined. CRH inhibited the contractile response produced by 10(-9)M CCK-8 in a concentration-dependent manner, with an IC50 value of 0.16nM. An inhibitor of particulate guanylate cyclase and an inhibitor of soluble guanylate cyclase had no significant effect of the relaxation produced by CRH. In contrast, an inhibitor of adenylate cyclase and an inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by CRH. This is the first report demonstrating the direct inhibitory action of CRH on the isolated caecal smooth muscle cells via adenylate cyclase system.

Adenylyl Cyclase Inhibitors↗
PubMed1996

Direct inhibitory effect of thyrotropin-releasing hormone on isolated cecal circular smooth muscle cells of guinea pig.

Smooth muscle cells isolated from cecal circular smooth muscle of the guinea pig were used to determine whether thyrotropin-releasing hormone (TRH) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine (an inhibitor of adenylate cyclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of nitric oxide synthase) on the TRH-induced relaxation of cecal circular smooth muscle cells was examined. TRH inhibited the contractile response produced by 10(-6) M carbachol in a concentration-dependent manner, with an IC50 value of 4 nM, 2',5'-Dideoxyadenosine and phorbol 12-myristate 13-acetate did not have any significant effect on the TRH-induced relaxation. On the other hand, 6-anilinoquinoline-5,8-quinone and N omega-nitro-L-arginine methyl ester significantly inhibited the relaxation produced by TRH. Our findings show that TRH has a direct inhibitory effect on the isolated cecal circular smooth muscle cells via activation of nitric oxide synthase and soluble guanylate cyclase.

Aminoquinolines↗
PubMed1995

Two endothelin receptors (ETA and ETB) expressed on circular smooth muscle cells of guinea pig cecum.

BACKGROUND/AIMS: The functional receptors for endothelin (ET) in colonic smooth muscle are still unknown. This study investigated the expression of ET receptors in isolated circular smooth muscle cells of guinea pig cecum. METHODS: Inhibition of 125I-ET-1 binding was examined using unlabeled ET-1, ET-2, ET-3, sarafotoxin 6c (S6c), and ETA antagonists. Expression of the ET-receptor message was investigated using reverse-transcription polymerase chain reaction. The contractile potency of the ET family and the inhibitory effect of ETA antagonists on ET-1-induced contraction were also investigated. RESULTS: Unlabeled ET-1, ET-2, and ET-3 inhibited the specific binding of 125I-ET-1 in a concentration-dependent manner, but the inhibitory effect of ET-3 was smaller than those of ET-1 and ET-2. At a 10(-6) mol/L concentration of S6c, the specific binding of 125I-ET-1 was 24.7%. S6c had clearly reached maximal inhibition. Abundant polymerase chain reaction products for both the ETA and the ETB message were observed. ET-1 and ET-2 showed similar contractile potency, but ET-3-induced and S6c-induced contractions were significantly less potent than the ET-1-induced contraction. A significant response to S6c was obtained at a concentration as low as 10(-10) mol/L. The ETA antagonists BQ-123 and FR 139317 significantly inhibited ET-1-induced contraction. CONCLUSIONS: The results show a direct contractile effect of ETs on circular smooth muscle of guinea pig cecum and the presence of both ETA- and ETB-receptor subtypes.

Animals↗
PubMed1995

Interaction between atrial natriuretic peptide and vasoactive intestinal peptide in guinea pig cecal smooth muscle.

BACKGROUNDS & AIMS: The role of atrial natriuretic peptide (ANP) in gastrointestinal motility is still unclear. The aim of this study was to investigate the relationship between ANP and vasoactive intestinal peptide (VIP) in guinea pig cecal circular smooth muscle cells. METHODS: The inhibition of 125I-ANP binding or 125I-VIP binding to cecal smooth muscle cells was assessed using unlabeled peptides (i.e., ANP, ANP fragments, VIP, secretin, and peptide histidine isoleucine); the effect of ANP, ANP fragments, and VIP on muscle contraction stimulated by 1 mumol/L carbachol was assessed; and the inhibitory effects of ANP 1-11 on VIP-induced relaxation, ANP 1-11 and VIP 10-28 (a VIP antagonist) on ANP-induced relaxation, and nitric oxide production inhibitors on ANP-induced relaxation were assessed. RESULTS: The specific binding of 125I-ANP was inhibited completely by unlabeled ANP and VIP in a dose-dependent manner but only slightly inhibited by secretin and peptide histidine isoleucine. ANP 1-11 and C-atrial natriuretic factor inhibited the binding of 125I-ANP with a lower affinity than ANP. ANP only partly inhibited 125I-VIP binding. ANP and VIP inhibited 1 mumol/L carbachol-induced contraction in a dose-dependent manner. ANP 1-11 significantly inhibited VIP-induced relaxation. ANP 1-11, VIP 10-28, and NO production inhibitors completely inhibited ANP-induced relaxation. CONCLUSIONS: The results of the study showed that ANP 1-11 antagonized ANP-induced relaxation and that ANP stimulated NO production and subsequently induced relaxation via a receptor to which VIP binds.

Animals↗
PubMed1995

Fractal dimension analysis of the oscillated blood flow with a vibrating flow pump.

To analyze the hemodynamic parameters during circulation with oscillated blood flow, nonlinear mathematical analyzing techniques, including fractal theory, were utilized. Vibrating flow pumps (VFP) were implanted as a left heart bypass, and the ascending aorta was clamped to constitute the total left heart circulation with oscillated blood flow in acute animal experiments using 7 adult goats. Using nonlinear mathematical analyzing techniques, reconstructed attractors of the arterial blood pressure waveform in the phase space during natural circulation and oscillated circulation were analyzed. Using the Grassberger-Procaccia correlation dimension analyzing technique, fractal dimension analysis of the reconstructed attractor was performed. During VFP bypass, lower fractal dimensions of the reconstructed attractor were shown compared with those during natural heart circulation. The results suggest that lower dimensional chaotic dynamics contributed to the circulation with oscillated blood flow.

Animals↗
PubMed1995

Functional endothelin A receptor on gastric smooth muscle cells.

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to examine the functional endothelin receptor subtype responsible for gastric smooth muscle contraction by endothelin. Endothelin-1 induced the contraction of these cells in a dose-dependent manner, with an ED50 value of 0.2 nM. Endothelin-3-induced contraction was significantly less than that of endothelin-1. Sarafotoxin 6c (10(-11)-10(-7) M), endothelinB highly selective agonist, did not elicit the contraction of gastric smooth muscle cells. BQ-123, endothelinA selective antagonist, inhibited the contractile response produced by 10(-7) M endothelin-1 in a dose-dependent manner, with an IC50 value of 5 nM. These results strongly suggest that endothelin elicited the contraction of gastric smooth muscle cells via functional endothelinA receptor subtype.

Animals↗
PubMed1995

Chaotic behavior of hemodynamics with ventricular assist system.

In order to analyze hemodynamic parameters during left ventricular assistance as an entity and not as decomposed parts, non-linear mathematical techniques were utilized. Pneumatically actuated ventricular assist systems (VAS) were implanted as left heart bypasses in acute animal experiments, using healthy adult mongrel dogs. By the use of the non-linear mathematical technique, the arterial blood pressure waveform (AP) was embedded into the four-dimensional phase space and projected into the three-dimensional phase space. The Lyapunov numerical method was used as an adjunct to the graphical analysis of the state space. The phase portrait of the attractor showed a complex structure; a three dimensional solid torus with a screw type structure as a part, suggesting deterministic chaos in the AP without left ventricular assistance. Positive lyapunov exponents confirmed the existence of chaos. During counterpulsation mode left ventricular assistance, the phase portrait of the attractor showed a more complex structure, and positive Lyapunov exponents suggested a greater dimensional deterministic chaos. However, non-structured patterns were seen in the phase space during internal mode VAS driving, suggesting the possibility of dissipative dynamics in the four dimensional phase space. These results suggest that the cardiovascular system with counterpulsation mode VAS driving is in a homeochaotic state, which is thought to be a flexible and intelligent control system. And there is greater dimensional complex dynamics in the circulatory regulatory system with VAD during internal mode assistance.

Animals↗