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Biomedical subjects

Y Fujimoto

Publications and source records attributed to Y Fujimoto.

At least 19 recordsLinked to original sources

Liver transplantation from an identical twin without immunosuppression, with early recurrence of hepatitis C.

Hepatitis C virus reinfection after liver transplantation is universal and more severe than in nontransplant patients. Rejection episodes and immunosuppressive agents are considered risk factors for deterioration of recurrent hepatitis C. We report 2 cases of living donor liver transplantation for patients with hepatitis C-related cirrhosis who received right-lobe grafts from an identical twin. Thanks to genetic identity, no immunosuppressive drugs were administered during or after transplantation without rejection. Hepatitis C virus RNA kinetics showed a rapid increase following transplantation and liver biopsies 1 month after transplantation showed acute lobular hepatitis in both cases. Antiviral therapy using interferon alpha and ribavirin was started immediately, and both cases showed virological and histological response. In conclusion, avoidance of immunosuppression did not delay hepatitis C recurrence following transplantation, while early antiviral therapy without risk of rejection or immunosuppression led to successful viral eradication.

Adult↗

Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain.

Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Toll-like receptors, NOD1, and NOD2 in oral epithelial cells.

Oral epithelium might be the first barrier against oral bacteria in periodontal tissue. We hypothesized that oral epithelium is endowed with innate immune receptors for bacterial components, which play roles in host defense against bacterial infection without being accompanied by excessive inflammatory responses. We found clear expression of Toll-like receptor (TLR)4 as well as TLR2, and strong expression of NOD1 and NOD2 in normal oral epithelial tissues by immunohistochemical analysis. We also showed that primary oral epithelial cells in culture expressed these molecules using PCR, flow cytometry, and immunostaining. In inflamed oral epithelium, cell-surface localizations of TLR2 and TLR4 were more clearly observed than in healthy tissue. Upon stimulation with synthetic ligands for these receptors, the expression of beta-defensin 2 was markedly up-regulated. These findings indicate that these molecules in oral epithelial cells are functional receptors that induce antibacterial responses.

Adaptor Proteins, Signal Transducing↗

Importance of phosphorylation for osteopontin regulation of biomineralization.

Previous in vitro and in vivo studies demonstrated that osteopontin (OPN) is an inhibitor of the formation and growth of hydroxyapatite (HA) and other biominerals. The present study tests the hypotheses that the interaction of OPN with HA is determined by the extent of protein phosphorylation and that this interaction regulates the mineralization process. Bone OPN as previously reported inhibited HA formation and HA-seeded growth in a gelatin-gel system. A transglutaminase-linked OPN polymer had similar effects. Recombinant, nonphosphorylated OPN and chemically dephosphorylated OPN, had no effect on HA formation or growth in this system. In contrast, highly phosphorylated milk OPN (mOPN) promoted HA formation. The mOPN stabilized the conversion of amorphous calcium phosphate (a non-crystalline constituent of milk) to HA, whereas bone OPN had a lesser effect on this conversion. Mixtures of OPN and osteocalcin known to form a complex in vitro, unexpectedly promoted HA formation. To test the hypothesis that small alterations in protein conformation caused by phosphorylation account for the differences in the observed ability of OPN to interact with HA, the conformation of bone OPN and mOPN in the presence and absence of crystalline HA was determined by attenuated total reflection (ATR) infrared (IR) spectroscopy. Both proteins exhibited a predominantly random coil structure, which was unaffected by the addition of Ca(2+). Binding to HA did not alter the secondary structure of bone OPN, but induced a small increase of beta-sheet (few percent) in mOPN. These data taken together suggest that the phosphorylation of OPN is an important factor in regulating the OPN-mediated mineralization process.

Animals↗

Radiofrequency thermal ablation for recurrent meningioma extending extracranially.

BACKGROUND: Image-guided and temperature-controlled radiofrequency thermal ablation techniques were applied to reduce tumor volume and relieve the symptoms caused by extracranial extension of recurrent meningioma. METHOD: We treated two patients with recurrent meningioma, an 81-year-old woman presenting with bulging of the temple and a 68-year-old woman presenting with visual disturbance, facial disfigurement, and sensory disturbance. Neuroimaging in both patients, revealed a large tumor extending extracranially and involving the infratemporal fossa. To avoid injury to important anatomical structures either compressed or entrapped by the tumor, the spatial relation between the planned ablation volume and these structures was confirmed by 3-D reconstruction of the ablation target. During the ablation procedure, local temperatures over the tissue being cauterized were continuously monitored to limit the ablation area to that within the planned volume adjusting RF power. FINDING: Radiofrequency ablation produced tumor necrosis as planned without adverse effects and resulted in swift relief of symptoms and signs with shrinkage of the tumor. CONCLUSION: This technique may be an effective alternative for recurrent meningiomas extending extracranially and for which radical surgical procedures are not indicated.

Aged↗

Adsorption of gaseous formaldehyde and carboxylic acids by ammonium-ion-exchanged alpha-zirconium phosphate.

Ammonium-ion-exchanged alpha-Zr(HPO(4))(2)H(2)O (alpha-ZrP) was obtained as a single phase with the interlayer distance of 9.4 A by the ion-exchange of proton with ammonium ion. The ammonium ion-exchanged alpha-ZrP could adsorb ill-smelling gases, such as formaldehyde and carboxylic acids (formic acid, acetic acid, propionic acid, and butyric acid). The adsorption amounts of carboxylic acids increased in the order, butyric acid<propionic acid<acetic acid<formic acid, whereas the adsorption amount of formaldehyde was the same as that of butyric acid. It was cleared that the adsorbed formaldehyde was partially decomposed to formic acid and methanol by self oxidation-reduction reaction in the interlayer region as evidenced by solid-state NMR. Thereby the interlayer distance after the adsorption of formaldehyde expanded to 14.4 A. In the case of formic acid, it was cointercalated into the interlayer region, and the interlayer distance expanded to 11.1 A. On the other hand, the interlayer distance of the other carboxylic acid-adsorbed compounds decreased to 7.6 A due to release by the evacuation.

Acetic Acid↗

Portal vein complications in the long-term course after pediatric living donor liver transplantation.

The frequency and the outcome of patients with portal vein (PV) complications in the long-term course after pediatric living donor liver transplantation (LDLT) have rarely been reported. Between June 1990 and September 2003, 527 pediatric patients underwent primary LDLT with left lobe grafts, among which 479 patients with functioning grafts at 3 months after LDLT were included in this analysis. The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and body weight from 3.1 kg to 62.4 kg (median: 9.6 kg). Biliary cirrhosis was the most common cause for LDLT (81%). The PV was anastomosed with or without a vein graft. Thirty-nine patients (8%) showed a PV complication (stenosis: 16; obstruction: 17; thrombus: 2; twist: 3). Their ages ranged from 4 months to 17 years, 3 months (median: 1 year) and their body weight from 3.8 kg to 44.8 kg (median: 8.5 kg) at operation. PV complications were detected between 4 and 116 months (median: 14 months) after the transplant. Splenomegaly and decreased platelet counts were observed in more than 90% of the patients with a PV complication. In 27 patients (71%), interventional venoplasty was successful. Eleven patients had obstruction of the PV (2.3%) including three who showed cirrhosis; one with severe pulmonary hypertension; one death after retransplantation; and one alive after retransplantation. Moderate fibrosis was found in two patients at 3 and 2 years after the procedure, one of whom had the complication of a moderate intrapulmonary shunt. Early detection of PV stenosis with these two markers can lead to successful angioplasty and avoid graft loss.

Adolescent↗

Open radiofrequency ablation for the management of intractable epilepsy associated with sessile hypothalamic hamartoma.

Sessile hypothalamic hamartoma (HH) often causes intractable epilepsy, which is difficult to control even by microsurgical resection and gamma knife surgery (GKS), especially when the hamartoma is intrahypothalamic, large, or irregularly shaped. We successfully applied radiofrequency ablation (RFA) to reduce its epileptogenicity and to disconnect seizure propagation. The patient was a 26-year-old man who presented with refractory epilepsy and severe mental retardation from age 6 months. He had undergone three surgeries yielding partial resection and conventional irradiation treatments. The residual HH was thin and shaped like a bent plate, attached widely to the floor of the third ventricle. He underwent open RFA via the transcallosal sub-choroidal approach under strict image guidance, which resulted in immediate and remarkable seizure remission without complications. This suggests that open RFA is a minimally invasive technique for an irregularly shaped HH that is difficult to treat by other modalities.

Adult↗

Endoscope assisted removal of jugular foramen schwannoma; report of 3 cases.

Removal of the intraforaminal portion of a jugular foramen schwannoma under direct vision requires resection of the adjacent bone. Extensive resection of the bone around the jugular foramen, however, involves a potential danger for cerebrospinal fluid (CSF) leakage and for damage to the adjacent cranial nerves as well as venous outflow. To avoid such bone resection, we applied the endoscope during the removal of a jugular foramen schwannoma through the lateral suboccipital approach. Three patients with schwannomas in the jugular foramen were treated using the lateral suboccipital approach with endoscopic assistance. After the intracranial portion was first removed under the microscope, the residual tumor in the jugular foramen was subsequently removed under the side-viewing endoscope. In all cases the tumor was removed successfully without major complications. The authors conclude that if the cases are selected properly, removal of the schwannoma extending into the jugular foramen is feasible through the conventional lateral suboccipital window under endoscopic assistance.

Adult↗

Steroidal and triterpenoidal saponins from the fruits of Diploclisia glaucescens.

Chemical investigation of methanol extract of the fruits of Diploclisia glaucescens furnished 3-O-beta-D-glucopyranosyl-20-hydroxyecdysone, 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]serjanic acid 28-O-beta-D-glucopyranosyl ester and 3-O-[beta-xylopyranosyl(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl]serjanic acid 28-O-beta-D-glucopyranosyl ester. The latter saponin was found to be a new natural product while the other two are reported for the first time from the family Menispermaceae.

Fruit↗

The ecdysteroidogenic P450 Cyp302a1/disembodied from the silkworm, Bombyx mori, is transcriptionally regulated by prothoracicotropic hormone.

During larval and pupal development of insects, ecdysone is synthesized in the prothoracic gland (PG). Although several Drosophila genes, including Halloween P450 genes, are known to be important for ecdysteroidogenesis in PG, little is known of the ecdysteroidogenic genes in other insects. Here we report on Cyp302a1/disembodied (dib-Bm), one of the Halloween P450s in the silkworm Bombyx mori that is a carbon-22 hydroxylase. dib-Bm is predominantly expressed in PG and its developmental expression profile is correlated with a change in the ecdysteroid titre in the haemolymph. Furthermore, dib-Bm expression in cultured PGs is significantly induced by treatment with prothoracicotropic hormone. This is the first report on the transcriptional induction of a steroidogenic gene by the tropic hormone in insects.

Amino Acid Sequence↗

Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture.

Two types of synthetic peptidoglycan fragments, diaminopimelic acid (DAP)-containing desmuramylpeptides (DMP) and muramyldipeptide (MDP), induced secretion of interleukin (IL)-8 in a dose-dependent manner in human monocytic THP-1 cells, although high concentrations of compounds are required as compared with chemically synthesized Toll-like receptor (TLR) agonists mimicking bacterial components: TLR2 agonistic lipopeptide (Pam3CSSNA), TLR4 agonistic lipid A (LA-15-PP) and TLR9 agonistic bacterial CpG DNA. We found marked synergistic IL-8 secretion induced by MDP or DAP-containing DMP in combination with synthetic TLR agonists in THP-1 cells. Suppression of the mRNA expression of nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the synergistic IL-8 secretion induced by DMP and MDP with these TLR agonists respectively. In accordance with the above results, enhanced IL-8 mRNA expression and the activation of nuclear factor (NF)-kappaB induced by MDP or DMP in combination with synthetic TLR agonists were markedly suppressed in NOD2- and NOD1-silenced cells respectively. These findings indicated that NOD2 and NOD1 are specifically responsible for the synergistic effects of MDP and DMP with TLR agonists, and suggested that in host innate immune responses to invading bacteria, combinatory dual signalling through extracellular TLRs and intracellular NODs might lead to the synergistic activation of host cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via toll-like receptors, NOD1 and NOD2 in human oral epithelial cells.

Peptidoglycan recognition proteins (PGRPs), a novel family of pattern recognition molecules (PRMs) in innate immunity conserved from insects to mammals, recognize bacterial cell wall peptidoglycan (PGN) and are suggested to act as anti-bacterial factors. In humans, four kinds of PGRPs (PGRP-L, -Ialpha, -Ibeta and -S) have been cloned and all four human PGRPs bind PGN. In this study, we examined the possible regulation of the expression of PGRPs in oral epithelial cells upon stimulation with chemically synthesized pathogen-associated molecular patterns (PAMPs) in bacterial cell surface components: Escherichia coli-type tryacyl lipopeptide (Pam3CSSNA), E. coli-type lipid A (LA-15-PP), diaminopimelic acid containing desmuramyl peptide (gamma-D-glutamyl-meso-DAP; iE-DAP), and muramyldipeptide (MDP). These synthetic PAMPs markedly upregulated the mRNA expression of the four PGRPs and cell surface expression of PGRP-Ialpha and -Ibeta, but did not induce either mRNA expression or secretion of inflammatory cytokines, in oral epithelial cells. Suppression of the expression of Toll-like receptor (TLR)2, TLR4, nucleotide-binding oligomerization domain (NOD)1 and NOD2 by RNA interference specifically inhibited the upregulation of PGRP mRNA expression induced by Pam3CSSNA, LA-15-PP, iE-DAP and MDP respectively. These PAMPs definitely activated nuclear factor (NF)-kappaB in the epithelial cells, and suppression of NF-kappaB activation clearly prevented the induction of PGRP mRNA expression induced by these PAMPs in the cells. These findings suggested that bacterial PAMPs induced the expression of PGRPs, but not proinflammatory cytokines, in oral epithelial cells, and the PGRPs might be involved in host defence against bacterial invasion without accompanying inflammatory responses.

Acetylmuramyl-Alanyl-Isoglutamine↗

Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion.

BACKGROUND/AIMS: In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC remain controversial, the morphology and immunohistochemical staining patterns of neoplastic GC cells were compared with those of other gliomas. METHODS: An immunohistochemical analysis of neoplastic cells from four patients with GC and 20 with astrocytic tumours using antibodies against Ki-67, GFAP, and L1, the last of which is a neural cell adhesion molecule putatively related to glioma invasion. RESULTS: GC tumour cells can be divided into two types, those mainly composed of strongly GFAP and L1 positive gemistocytic cells, the other composed of small, GFAP and L1 negative spindle shaped cells. The two types did not differ with respect to Ki-67 positivity. Cells from patients with other gliomas were positive for GFAP but concurrent L1 expression was negative or weakly positive. CONCLUSION: The strong expression of L1 in patients with GC and its poor expression in the 20 patients with other types of glioma, including those with GFAP positive gemistocytic astrocytomas, suggest that L1 expression may play a role in the histogenesis of GC.

Adult↗

[Norwood procedure after colostomy; report of a case].

We encountered a baby who was diagnosed with anal atresia, interruption of aortic arch (type B), aortic stenosis, mitral stenosis, single atrium, large ventricular septal defects, aberrant origin right subclavian artery. We operated on him using the Norwood procedure after a colostomy. Aortic arch was reconstructed by interposing with an 8 mm graft and the right ventricular-pulmonary artery (RV-PA) conduit was chosen for pulmonary flow. We closed the sternum 6 days after the Norwood procedure. We extubated him 16 days after delayed sternal closure. There was no trouble with his stoma and no sign of infection. The postoperative echocardiography didn't show the finding which left pulmonary artery was stenotic, but the lung perfusion schintigraphy revealed an imbalance in the distribution of lung perfusion. He was discharged 70 days after undergoing the Norwood procedure.

Anastomosis, Surgical↗

Glycosides from Grewia damine and Filicium decipiens.

Chemical investigation of n-butanol extract from the methanol extract of leaves of Grewia damine furnished lupeol, sitosterol beta-D-glucoside, flavone C-glycosides vitexin, isovitexin where as the same extracts from the leaves of Filicium decipiens furnished sitosterol beta-D-glucoside, 3-O-beta-D-glucopyranosyl kaempferol, 3-O-beta-D-glucopyranosylquercetin and 3-O-alpha-L-rhamnopyranosyl(1--> 2)-beta-D-glucopyranosylkaempferol.

Glycosides↗

Beddomeilactone: a new triterpene from Dysoxylum beddomei.

An investigation of the leaves of Dysoxylum beddomei has yielded a novel triterpene, named beddomeilactone, together with six known triterpenoids: 3-oxotirucalla-7,24-dien-23-ol, dipterocarpol, niloticin, melianone, melianodiol and 24-epi-melianodiol. The structure and stereochemistry of the new compound were determined on the basis of mass, 1D and 2D NMR spectroscopies including NOE difference and spin-spin decoupling studies.

Humans↗

Stilbene derivatives with antifungal and radical scavenging properties from the stem bark of Artocarpus nobilis.

Antifungal activity-guided fractionation of the n-butanol extract from the methanol extract of the stem bark of Artocarpus nobilis furnished two stilbene derivatives (E)-4-isopentenyl-3,5,2',4'-tetrahydroxystilbene and (E)-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene. Both compounds showed strong antifungal activity against Cladosporium cladosporioides and high radical scavenging activity towards the DPPH radical in TLC bio-autography method.

Antifungal Agents↗