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Biomedical subjects

H Hagiwara

Publications and source records attributed to H Hagiwara.

At least 19 recordsLinked to original sources

Reduced amplitude of the sural nerve sensory action potential in PARK2 patients.

The authors performed nerve conduction studies in nine PARK2 and eight idiopathic Parkinson disease patients and found a significant reduction of sural sensory nerve action potential (SNAP) amplitude in eight PARK2 patients who mostly remained asymptomatic. These data suggest that sensory axonal neuropathy may be a common clinical feature of PARK2 and a reduced amplitude of sural SNAP could be a diagnostic indicator of PARK2.

Action Potentials↗

[The correlation between flow pattern during cardiopulmonary bypass and patency of the coronary artery bypass grafts].

Recently the availability of transit time flow measurement (TTFM) is reported especially in off-pump coronary artery bypass grafting (CABG). But little is known about TTFM findings in on-pump CABG. We examined the correlation between the TTFM flow pattern and the angiography findings in on-pump CABG. The subjects consisted of 52 patients who underwent on-pump CABG and angiography early after operation. In these patients, 55 internal thoracic artery (ITA), 17 gastroepiploic artery (GEA), 13 saphenous vein graft (SVG) and 41 radial artery (RA) were tested with TTFM during cardiopulmonary bypass (CPB). TTFM demonstrated a diastolic filling pattern in 53 ITA, 16 GEA, 13 SVG and 36 RA. The angiography revealed that all these grafts were perfectly patent with the exception of a GEA with a flow competition pattern. TTFM revealed an abnormal flow pattern in 2 ITA (these 2 grafts were revised during CPB and the angiography demonstrated their perfect patency), 1 GEA (to and fro pattern), 0 SVG and 5 RA (the abnormal pattern was due to graft spasm in 3 of 5, and the angiography revealed their perfect patency, however, the angiography detected stenosis in the remaining 2 grafts). The present study found that the TTFM flow pattern during CPB correlated well with the angiography findings. TTFM during CPB was useful to detect graft failure, and grafts were revised safely during CPB.

Aged↗

[Advantages of side-to-side anastomosis in the assessment and revision of coronary artery bypass grafting].

With the advent of drug eluting stents in percutaneous coronary intervention, required quality level of coronary artery bypass grafting (CABG) has been elevating. To obtain nearly perfect patency of bypass grafts, intraoperative assessment and repair of abnormal grafts are helpful. We report systematic revision and safe repair technique of arterial grafts in CABG. Side-to-side instead of commonly used end-to-side anastomosis of arterial grafts is the first step in this technique. When any abnormalities are noted in intraoperative flowmetry of a graft, the distal surgical clip is removed. Free flow of the graft is measured. A coronary probe is gently inserted into the graft and the coronary artery. Vasodilators can be injected into the graft if necessary. When direct revision of the anastomosis is indicated, the graft is cut longitudinally from the distal end up to just proximal to the anastomotic site. The shape of the anastomosis can be observed directly without removing sutures. When re-anastomosis is not indicated, the distal remnant graft tissue is folded back and utilized as a patch. Thus the graft can be easily closed without narrowing.

Anastomosis, Surgical↗

Inhibition of osteoclast formation by 3-methylcholanthrene, a ligand for arylhydrocarbon receptor: suppression of osteoclast differentiation factor in osteogenic cells.

We investigated the effects of 3-methylcholanthrene (3MC), a ligand for arylhydrocarbon receptor (AhR), on osteoclastogenesis. Osteoclast-like cells, in cocultures with mouse spleen cells and clonal osteogenic stromal ST2 cells, are formed from spleen cells by a combination of the receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) produced by ST2 cells in response to 1alpha,25(OH)(2) Vitamin D(3). 3MC dose-dependently inhibited the formation of mono- and multinuclear osteoclast-like cells. However, 3MC did not inhibit the formation of osteoclast-like cells from mouse spleen cells which was supported by the exogenous soluble RANKL and M-CSF. 3MC did not affect the formation of an actin ring and pits on slices of dentine by osteoclast-like cells, both of which are typical indices of osteoclast activity. These results suggest that 3MC affects osteoclast-supporting cells such as ST2 cells but not osteoclast precursor cells and mature osteoclastic cells. When we measured the expression levels of RANKL mRNA in ST2 cells, 3MC dose-dependently decreased the level of this mRNA. However, 3MC did not affect levels of mRNAs for osteoprotegerin (OPG), M-CSF, and the receptor of 1alpha,25(OH)(2) Vitamin D(3) in ST2 cells. Furthermore, soluble RANKL was able to counteract the inhibitory effect of 3MC on the formation of osteoclast-like cells. Our findings indicate that 3MC inhibits osteoclastogenesis via the inhibition of RANKL expression in osteoblastic cells.

Animals↗

Treatment of myoblastic C2C12 cells with BMP-2 stimulates vitamin D-induced formation of osteoclasts.

The interaction of osteoclast precursors with osteoblasts and/or stromal cells is essential for the formation of mature osteoclasts and the resorption of bone. We found that myoblastic C2C12 cells induced the differentiation of mouse spleen cells into tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated cells in the presence of 10(-7) M 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and that C2C12 cells that had been treated with bone morphogenetic protein-2 (BMP-2) dose-dependently stimulated the formation of osteoclasts. The newly developed TRAP-positive multinucleated cells were capable of resorbing mineralized tissues. Treatment of C2C12 cells with BMP-2 for 24 h enhanced the subsequent expression in C2C12 cells of mRNA for the receptor activator of nuclear factor-kappaB ligand (RANKL) in the presence of 1alpha,25(OH)2D3. Since the formation of osteoclasts was inhibited dose-dependently by exogenous OPG, the expression of RANKL in response to BMP-2 appeared to be critical for the formation of osteoclasts. Our findings suggest that BMP-2 might play an important role in the differentiation of cells that support osteoclastogenesis.

Acid Phosphatase↗

Identification of a novel osteoblastic gene, inducible by C-type natriuretic peptide, whose transcript might function in mineralization as a noncoding RNA.

We reported previously that C-type natriuretic peptide (CNP) promotes the differentiation and mineralization of osteoblast-like cells. However, little information is available about the mechanism of action of CNP in differentiating osteoblastic cells. In this study, using the technique known as differential display-polymerase chain reaction, we identified a novel cDNA fragment that corresponded to a transcript whose level was increased by CNP in mouse clonal preosteoblastic MC3T3-E1 cells. Northern blotting analysis revealed transcripts of 1.3 kb and 2.3 kb in MC3T3-E1 cells. Both these transcripts were also expressed at high levels in the heart and stomach. We isolated a full-length cDNA (2,135 bp) from a cDNA library derived from MC3T3-E1 cells using the original cDNA fragment. Analysis of the sequence and of products of transcription and translation in vitro indicated that the transcript of the gene did not include any extensive open reading frames. Enhanced expression, after transfection, of transcript in MC3T3-E1 cells stimulated the deposition of calcium of these cells and the formation of mineralized nodules, but did not affect the activity of alkaline phosphatase. Our results suggest that CNP promotes the expression of a novel transcript, which might stimulate the mineralization of MC3T3-E1 cells.

3T3 Cells↗

[Experience of coronary artery bypass grafting on the beating heart with right heart bypass; 3 cases of octogenarian].

Right heart bypass (RHB) yields more stable hemodynamics by increasing left ventricular preload and collapse right ventricular chamber during the displacement of the heart on beating heart coronary artery bypass grafting (CABG). Recently beating heart CABG gaining popularity, and the indications for CABG have increasingly expanded to elderly person. Using RHB while exposing posterior branches by displacing the beating heart, we have attempted to make total revascularization in beating heart CABG. We performed beating heart CABG with RHB in 3 cases of octogenarian. All patients had left main trunk lesion and needed revascularization of posterior vessels. Introduction of RHB enabled us to approach to posterior target vessels in better exposure and under greater hemodynamic stability. All three patients had no complications postoperatively. Strictly speaking CABG with RHB is not off-pump CABG, but RHB system does not include either artificial lung or manipulation of the aorta. Therefore we think it is very effective support system which enables multiple coronary revascularization for elderly person.

Aged↗

Stiff-person syndrome associated with invasive thymoma: a case report.

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

Adult↗

Induction of hepatic tissue-type plasminogen activator and type 1 plasminogen activator-inhibitor gene expressions and appearance of their translation products in the bile following acute liver injury in rats.

BACKGROUND/AIMS: The plasminogen activator (PA)-plasmin system is primarily involved in fibrinolysis, but is also in the patho/physiological events in which breakdown of extracellular matrices is evoked topically. In this present study, we examined the expression of fibrinolytic factors, tissue-type PA (t-PA) and Type 1 PA inhibitor (PAI-1), in acute liver injury. METHODS: Acute liver injury was produced in rats by the intraperitoneal administration of carbon tetrachloride (CCl(4)). Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured to verify the hepatocellular damage. t-PA and PAI-1 gene expressions were measured by Northern blotting, and the cell type(s) expressing these genes was identified by in situ hybridization. t-PA and PAI-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A single intraperitoneal administration of CCl(4) caused severe acute parenchymatous liver injury. Both t-PA and PAI-1 gene expressions were induced by the acute liver injury, and plasma t-PA and PAI-1 concentrations were also increased. In situ hybridization studies demonstrated that the hepatocytes were the cells expressing t-PA and PAI-1 genes during the acute liver injury. t-PA was also augmented in the bile, whereas PAI-1 was decreased there. CONCLUSIONS: t-PA and PAI-1 gene expressions are induced in the hepatocytes of rats with acute liver injury. These fibrinolytic factors induced by liver injury may play important roles in liver regeneration.

Animals↗

Crucial role of type 1, but not type 3, inositol 1,4,5-trisphosphate (IP(3)) receptors in IP(3)-induced Ca(2+) release, capacitative Ca(2+) entry, and proliferation of A7r5 vascular smooth muscle cells.

Stimulation of G protein- or tyrosine kinase-coupled receptors regulates cell proliferation through intracellular Ca(2+) ([Ca(2+)](i)) signaling. In A7r5 cells, we confirmed that inositol 1,4,5-trisphosphate (IP(3)) mediates vasopressin (VP)-evoked Ca(2+) release from intracellular stores and showed that types 1 (IP(3)R(1)) and 3 (IP(3)R(3)) IP(3) receptors were expressed. Using antisera selective for IP(3)R(1) or IP(3)R(3) and another that interacted equally well with both subtypes, together with membranes from SF:9 cells expressing only single IP(3)R subtypes to calibrate immunoblotting, we established that A7r5 cells express 81% IP(3)R(1) and 19% IP(3)R(3). To elucidate the contributions of IP(3)R(1) and IP(3)R(3) to Ca(2+) signaling and proliferation, stable clones expressing promoter-inducible antisense cDNA fragments (-90 to +9) corresponding to the two IP(3)R subtypes were selected. Mild inhibition of IP(3)R(1) (71+/-8% of control level) slightly attenuated the IP(3)-evoked Ca(2+) release (IICR) induced by VP but significantly decreased the subsequent capacitative Ca(2+) entry (CCE) and proliferation. Moderate inhibition (34+/-6%) strongly decreased both IICR and CCE and further blocked proliferation. Complete inhibition almost abolished IICR and CCE and arrested proliferation entirely. Complete inhibition of IP(3)R(3) expression slightly attenuated IICR without affecting CCE or proliferation. In cells microinjected with a low dose of heparin, VP-induced CCE was more susceptible than IICR to mild inhibition of both IP(3)R(1) and IP(3)R(3). A high dose of heparin had a similar effect to complete inhibition of IP(3)R(1) expression: it blocked VP-evoked IICR entirely and CCE by 90%. We conclude that IP(3)R(1), but not IP(3)R(3), is crucial for IICR, CCE, and proliferation of vascular smooth muscle cells.

Animals↗

The first total synthesis of (-)-solanapyrone E based on domino Michael strategy.

[figure: see text] A phytotoxin, solanapyrone E, has been synthesized from the decalone prepared by the domino Michael reaction of the kinetic enolate of optically pure acetylcyclohexene with methyl crotonate. After several transformations on the decalone ring, condensation of a methyl acetoacetate equivalent installed a pyrone moiety and introduction of a hydroxymethyl unit into the pyrone ring furnished solanapyrone E.

Alternaria↗

Preferential binding of polyethylene glycol-coated liposomes containing a novel cationic lipid, TRX-20, to human subendthelial cells via chondroitin sulfate.

PURPOSE: To design novel cationic liposomes, polyethylene glycol (PEG)-coated cationic liposomes containing a newly synthesized cationic lipid, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) were formulated and their cellular binding and uptake investigated in vitro in the following cells: human subendothelial cells (aortic smooth muscle cells and mesangial cells) and human endothelial cells. METHODS: Three different PEG-coated cationic liposomes were prepared by the extrusion method, and their mean particle size and zeta potential were determined. Rhodamine-labeled PEG-coated cationic liposomes were incubated with smooth muscle cells, mesangial cells, and endothelial cells at 37 degrees C for 24 h. The amounts of cellular binding and uptake of liposomes were estimated by measuring the cell-associated fluorescence intensity of rhodamine. To investigate the binding property of the liposomes, the changes of the binding to the cells pretreated by various kinds of glycosaminoglycan lyases were examined. Fluorescence microscopy-is used to seek localization of liposomes in the cells. RESULTS: The cellular binding and uptake of PEG-coated cationic liposomes to smooth muscle cells was depended strongly on the chemical species of cationic lipids in these liposomes. Smooth muscle cells bound higher amount of PEG-coated TRX-20 liposomes than other cationic liposomes containing N-(1-(2.3-dioleoyloxy) propyl)-N, N, N-trimethylammonium salts or N-(alpha-(trimethylammonio)acetyl)-D-glutamate chloride. Despite of the higher affinity of PEG-coated TRX-20 liposomes for subendothelial cells, their binding to endothelial cells was very small. The binding to subendothelial cells was inhibited when cells were pretreated by certain kinds of chondroitinase, but not by heparitinase. These results suggest that PEG-coated TRX-20 liposomes have strong and selective binding property to subendothelial cells by interacting with certain kinds of chondroitin sulfate proteoglycans (not with heparan sulfate proteoglycans) on the cell surface and in the extracellular matrix of the cells. This binding feature was different from that reported for other cationic liposomes. CONCLUSIONS: PEG-coated TRX-20 liposomes can strongly and selectively bind to subendothelial cells via certain kinds of chondroitin sulfate proteoglycans and would have an advantage to use as a specific drug delivery system.

Aorta, Thoracic↗

Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation.

Nineteen-hour variation of postural sway, alertness and rectal temperature during sleep deprivation were studied. Alertness decreased gradually at night and remained low until morning. Postural sway in the eyes-closed condition increased during early morning. In six of the eight subjects the greatest sway was observed during the 3-h period when rectal temperature was at its minimum. It is suggested that unbearable sleepiness during sleep deprivation will give rise to measurable impairment of postural balance especially during the time zone of temperature nadir.

Adult↗

Effect of adrenal and ovarian androgens on type 4 follicles unresponsive to FSH in immature mice.

The present study investigates the physiological significance of dehydroepiandrosterone, dehydroepiandrosterone sulfate, T, androstenedione (Delta(4)), dihydrotestosterone (DHT), estrone (E1), and E2 on recombinant human FSH- (rhFSH) resistant type 4 follicles obtained from immature mice. Type 4 follicles of a diameter of 100-120 microm with one or two granulosa cell layers around the oocyte and an intact basal lamina with theca cells were isolated from the ovaries of 11-d-old BDF-1 mice and cultured with medium alone (control) or with dehydroepiandrosterone, dehydroepiandrosterone sulfate, T, Delta(4), DHT, E1, or E2 at concentrations ranging from 1 x 10(-11) to 1 x 10(-7) M for 4 d. We examined the mean diameters of type 4 follicles, levels of immunoreactive (IR)-inhibin, and E2 and progesterone in the culture media on day 4. In addition, we evaluated follicular cell proliferation by immunofluorescence staining with 5-bromo-2'-deoxyuridine. All tested androgens significantly increased the diameter of type 4 follicles in a dose-dependent manner without the production of IR-inhibin and E2. The nuclei of granulosa cells in type 4 follicles cultured with all tested androgens exhibited intense 5-bromo-2'-deoxyuridine-positive staining, compared with those of controls. In contrast, neither E1 nor E2 had any stimulatory effects. The stimulatory effects of T, Delta(4), or DHT were inhibited by an AR antagonist in a dose-related fashion but not by an aromatase inhibitor. Furthermore, all tested androgens had a synergistic effect with rhFSH on follicular growth and the production of IR-inhibin and E2. These results demonstrated that neither adrenal nor ovarian androgens are arteriogenic but that they stimulate type 4 follicles unresponsive to rhFSH and augment the responsiveness of these follicles to rhFSH.

Adrenal Glands↗

Reciprocal control of expression of mRNAs for osteoclast differentiation factor and OPG in osteogenic stromal cells by genistein: evidence for the involvement of topoisomerase II in osteoclastogenesis.

Osteoclast-like cells, in cocultures with mouse spleen cells and clonal osteogenic stromal ST2 cells, are formed from spleen cells with monocyte/macrophage lineage in response to a combination of osteoclast differentiation factor (RANKL) and OPG, a decoy receptor for RANKL, produced by ST2 cells in response to 1alpha,25-dihydroxyvitamin D(3). Treatment of ST2 cells with the natural isoflavonoid genistein for 6 h before coculture with spleen cells inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclast-like cells. When we measured levels of RANKL mRNA in ST2 cells, we found that genistein decreased the level of this mRNA. By contrast, the level of OPG mRNA was enhanced by genistein. Genistein is a specific inhibitor of topoisomerase II (topo II) and an inhibitor of protein tyrosine kinase, as well as being a potent phytoestrogen. To characterize the mode of action of genistein, we examined the effects of an inactive form of genistein (daidzein), 17beta-estradiol, inhibitors of topo II, and inhibitors of tyrosine kinases on the formation of tartrate-resistant acid phosphatase-positive osteoclast-like cells. Among the compounds tested, two inhibitors of topo II, amsacrine and etoposide, attenuated the formation of osteoclast-like cells via reciprocal regulation of the expression of mRNAs for RANKL and OPG in ST2 cells, acting similarly to genistein. Our findings indicate that genistein might inhibit the formation of osteoclast-like cells via inhibition of the activity of topo II, suggesting the novel possibility that topo II might play an important role in osteoclastogenesis.

Animals↗

Novel syntheses of murrayaquinone A and furostifoline through 4-oxygenated carbazoles by allene-mediated electrocyclic reactions starting from 2-chloroindole-3-carbaldehyde.

The formal total synthesis of murrayaquinone A (1) and the total synthesis of furostifoline (5) were completed by the construction of 4-oxygenated 3-methylcarbazoles 7 based on a new type of electrocyclic reaction through 2-alkenyl-3-allenylindole intermediates 8 derived from the 2-alkenyl-3-propargylindoles 9, starting from 2-chloroindole-3-carbaldehyde (11). The N,O-bisbenzyloxymethyl group of 16c and 22 underwent a Birch reduction followed by treatment with Triton B to produce the known 4-hydroxy-3-methylcarbazole (7a) and 4-hydroxy-3-methylfuro[3,2-a]carbazole (7b) as precursors of murrayaquinone A (1) and furostifoline (5), respectively. The trifluoromethanesulfonyloxy-3-methylfuro[3,2-alcarbazole (24), prepared from 7b, was subjected to reductive cleavage to provide furostifoline (5).

Alkaloids↗

A topographical study of ERP correlates of semantic and syntactic violations in the Japanese language using the multichannel EEG system.

Language processing was investigated using event-related potentials obtained using a multichannel (58-channel) EEG system, with regard to semantic dependency (i.e., selectional restriction between a verb and the arguments it takes: the SR type) and syntactic dependency between sentence-final particles and interrogative phrases (the WH-Q type) in Japanese. It was found that semantic violations elicited the conventional N400, which was distributed in the bilateral occipital and the right temporal regions, and that the syntactic violations elicited the P600 in a broad area, predominantly in the centroparietal regions. Scalp current density mappings suggested that the right temporal cortex plays a significant role in integrating pieces of contextual information, especially when it is difficult to integrate a word in the context of a sentence, and that the P600 was connected to the syntactic processes conceivably indexed by the left temporal current sink with a relatively early onset.

Adult↗