Biomedical subjects

M Goto

Publications and source records attributed to M Goto.

At least 289 records · Page 16Linked to original sources

PubMed1998

Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL.

Osteoclasts, the multinucleated cells that resorb bone, develop from hematopoietic cells of monocyte/macrophage lineage. Osteoclast-like cells (OCLs) are formed by coculturing spleen cells with osteoblasts or bone marrow stromal cells in the presence of bone-resorbing factors. The cell-to-cell interaction between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL formation. Recently, we purified and molecularly cloned osteoclastogenesis-inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF is a secreted member of the tumor necrosis factor receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction. Here we report the expression cloning of a ligand for OPG/OCIF from a complementary DNA library of mouse stromal cells. The protein was found to be a member of the membrane-associated tumor necrosis factor ligand family and induced OCL formation from osteoclast progenitors. A genetically engineered soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation induced by the protein. Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors. We conclude that the membrane-bound protein is osteoclast differentiation factor (ODF), a long-sought ligand mediating an essential signal to osteoclast progenitors for their differentiation into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system.

Animals↗

PubMed1998

A significant reduction of macrophages expressing inducible nitric oxide synthase in rat hepatic allografts pretreated with donor-specific blood.

BACKGROUND: A single intravenous injection of donor-specific blood (DST) 7 days before transplantation significantly prolongs survival of hepatic allografts from fully allogeneic ACI(RT1a)-->LEW(RT1(1)) rats. The aim of this study was to investigate the kinetics of nitric oxide synthesis by macrophages in rat hepatic allografts treated with DST. METHODS: We investigated macrophages expressing inducible nitric oxide synthase in animal group I (receiving isografts), group II (hepatic allografts), and group III (hepatic allografts after donor-specific blood). RESULTS: Serum nitrite/nitrate, interferon-gamma, and tumor necrosis factor-alpha concentrations increased significantly in group II for 7 days after transplantation but were significantly much lower in groups I and III. Numbers of macrophages immunostained with an anti-macrophage nitric oxide synthase monoclonal antibody and inducible nitric oxide synthase mRNA levels in liver specimens also were much lower in groups I and III than in group II. In addition, Northern blot analysis demonstrated abundant interleukin-10 mRNA transcripts in the DST-treated hepatic allografts compared to untreated allografts. Double immunostaining revealed anti-macrophage synthase-containing cells, including both ED1+ and ED2+ cells, in liver and spleen as more numerous in group II. CONCLUSIONS: Inducible nitric oxide synthase is suppressed in immunologic unresponsiveness to grafts after donor-specific blood transfusion.

Animals↗

PubMed1998

Midkine exists in astrocytes in the early stage of cerebral infarction.

Midkine (MK), a heparin-binding neurotrophic factor, is expressed in the early stage of experimental cerebral infarction in the zone surrounding the infarct. Double immunostaining with anti-MK and anti-glial fibrillary acidic protein showed existence of MK in astrocytic cytoplasm on postoperative day 2. Immunoelectron microscopic analysis revealed the presence of MK in the swollen astrocytic processes on postoperative day 4.

Acute Disease↗

PubMed1998

Protein refolding by reversed micelles utilizing solid-liquid extraction technique.

This article reports that a reversed micellar solution is useful for refolding proteins directly from a solid source. The solubilization of denatured RNase A, which had been prepared by reprecipitation from the denaturant protein solution, into reversed micelles formulated with sodium di-2-ethylhexyl sulfosuccinate (AOT) has been investigated by a solid-liquid extraction system. This method is an alternative to the ordinary protein extraction in reversed micelles based on the liquid-liquid extraction. The solid-liquid extraction method was found to facilitate the solubilization of denatured proteins more efficiently in the reversed micellar media than the ordinary phase transfer method of liquid extraction. The refolding of denatured RNase A entrapped in reversed micelles was attained by adding a redox reagent (reduced and oxidized glutathion). Enzymatic activity of RNase A was gradually recovered with time in the reversed micelles. The denatured RNase A was completely refolded within 30 h. In addition, the efficiency of protein refolding was enhanced when reversed micelles were applied to denatured RNase A containing a higher protein concentration that, in the case of aqueous media, would lead to protein aggregation. The solid-liquid extraction technique using reversed micelles affords better scale-up advantages in the direct refolding process of insoluble protein aggregates.

Acetone↗

PubMed1998

Characterization of structural domains of human osteoclastogenesis inhibitory factor.

Osteoclastogenesis inhibitory factor (OCIF) is a heparin-binding secretory glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) family. OCIF is present both as a approximately 60-kDa monomer and a disulfide-linked homodimer. We attempted to characterize the seven structural domains of OCIF by determining the capabilities of various OCIF mutants to inhibit osteoclastogenesis, to interact with heparin, and to form dimers. We also examined a potential of domains 5 and 6, death domain homologous regions (DDHs), for inducing cell death by expressing OCIF/Fas fusion proteins. Our results show that: (i) the N-terminal portion of OCIF containing domains 1-4, which have structural similarity to the extracellular domains of the TNFR family proteins, is sufficient to inhibit osteoclastogenesis; (ii) a heparin-binding site is located in domain 7, and affinity for heparin does not correlate with the inhibitory activity; (iii) Cys-400 in domain 7 is the residue responsible for dimer formation; and (iv) the C-terminal portion containing domains 5 and 6, DDHs, has a high potential for mediating a cytotoxic signal when it is expressed in cells as an OCIF/Fas fusion protein in which the transmembrane region of Fas is inserted in front of DDHs.

Apoptosis↗

PubMed1998

A comparative analysis of the proteins between the fibroblasts from Werner's syndrome patients and age-matched normal individuals using two-dimensional gel electrophoresis.

Werner's syndrome (WS) is an autosomal recessive disorder causing symptoms of premature aging. The fibroblasts of WS patients have a shorter life-span than normal fibroblasts. We analyzed the fibroblast proteins from three WS patients and from three age-matched normal individuals using two-dimensional gel electrophoresis and image processing. The expressions of 12 proteins were shown to be augmented or suppressed in WS fibroblasts compared with normal fibroblasts: 11 of 12 spots on the electrophoresis gel of WS fibroblasts were denser than the corresponding spots of normal individual fibroblasts, while the remaining one spot was fainter in WS fibroblasts than in normal fibroblasts. The abundance of these proteins were compared to those of the corresponding proteins from normal fibroblasts at various cell passages in vitro reported in the TMIG-2DPAGE database. The result shows that the change in the protein patterns in in vitro aging did not necessarily correspond to the change in WS fibroblasts, except for three proteins abundant in WS fibroblasts, which increased their abundance during in vitro aging. These results suggest that the premature aging process of WS fibroblasts shares only part of the in vitro aging process of normal fibroblasts.

Adult↗

PubMed1998

Effects of Microwave Heating on the Loss of Vitamin B(12) in Foods.

To clarify the effects of microwave heating on the loss of vitamin B(12) in foods, raw beef, pork, and milk were treated by microwave heating and then their vitamin B(12) contents were determined according to a chemiluminescent vitamin B(12) assay with hog intrinsic factor. Appreciable loss ( approximately 30-40%) of vitamin B(12) occurred in the foods during microwave heating due to the degradation of vitamin B(12) molecule by microwave heating. When hydroxo vitamin B(12), which predominates in foods, was treated by microwave heating and then analyzed by silica gel 60 thin layer chromatography, two vitamin B(12) degradation products were found. One of the compounds with a R(f)() of 0.16 was purified and partially characterized. The vitamin B(12) degradation product did not show any biological activity in the growth of a vitamin B(12) requiring microorganism, Euglena gracilis Z, and was not bound to hog intrinsic factor, a mammalian vitamin B(12) binding protein. Intravenous administration of the compound (1 µg/day) for 7 days to rats showed that the compound neither has toxicity nor acts as a vitamin B(12) antagonist in mammals. These results indicate that the conversion of vitamin B(12) to the inactive vitamin B(12) degradation products occurs in foods during microwave heating.

Journal Article↗

PubMed1998

Inhibition of NF-kappa B transcriptional activity by alpha-tocopheryl succinate.

The role of vitamin E in cell regulation in addition to its function as an antioxidant has attracted attention. The effects of alpha-tocopherol (T) and alpha-tocopheryl succinate (TS) on transcriptional activation of the tumor necrosis factor alpha (TNF-alpha) gene and nuclear factor kappa B (NF-kappa B) activation were examined. Two stable transformants were used: TR-1 cells derived from THP-1 cells transfected with a vector contains the human TNF-alpha promoter (1.4-kb) joined to the human placental alkaline phosphatase (PLAP) coding sequence, and B164 cells derived from the same cell line but carrying the vector containing the human beta-actin promoter (4.3-kb) as a control. The transfectants were cultured in the presence of TS, followed by stimulation with lipopolysaccharide (LPS). After stimulation, PLAP activity secreted into the culture medium was measured. TS reduced TNF-alpha transcriptional activity in a concentration-dependent manner, while no effect was observed on that of the beta-actin promoter. Gel shift assay revealed that THP-1 cells pretreated with TS and then with LPS showed inhibition of NF-kappa B activity by 43% at 50 microM versus the TS-untreated group. Since TS did not affect activator protein-1 (AP-1) activity under the same conditions, the inhibitory effect of TS on NF-kappa B activation might be specific. However, T had no effect on the results of the gel shift assay. Vitamin E transportation was analyzed by simultaneous determination of vitamin E and its derivatives using HPLC. The vitamin E recovered from culture pellets showed almost the same amounts of T and TS transferred and was recovered in unchanged form. These observations indicated that TS inhibited NF-kappa B activation and/or translocation to the nuclei in its unchanged form under the culture conditions used here. These results suggested that vitamin E is involved in signal transduction via an effect distinct from its antioxidant function. To explain the lack of activity with T, it remains to be clarified whether physiological incorporation of T occurred.

Actins↗

PubMed1998

Xanthine oxidase inhibition attenuates kupffer cell production of neutrophil chemoattractant following ischemia-reperfusion in rat liver.

We investigated the effects of the xanthine oxidase inhibitor, BOF-4272, on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF-4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF-4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF-4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF-4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF-4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF-4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.

Animals↗

PubMed1998

Dynamic contrast-enhanced MR imaging of the entire breast with spectral-selective inversion fast three dimensional sequence.

Dynamic contrast-enhanced images with high spatial and temporal resolutions were acquired with a fast 3D spoiled gradient echo (SPGR) sequence using spectral selective inversion recovery (IR) pulse. Five healthy volunteers and 12 patients with 14 pathologically proven breast lesions were studied. Fat suppressed volume image data covering the entire breast were obtained with a sufficient spatial resolution (0.9 x 1.5 x 3.0 mm3) and an imaging time of 57 s. By using the criteria including peripheral enhancement and presence of spiculation, sensitivity, specificity, and accuracy in detecting malignant lesions were 88.9, 80.0 and 85.7%, respectively. Although the C/N and S/N ratios were approximately 30% less than those of the conventional fat suppressed 3D technique, fast 3D SPGR imaging with spectral IR method demonstrated sufficient image quality for both time intensity analysis and morphological evaluation of the breast lesions with a data acquisition time less than half of the conventional method. This technique can substantially improve spatial and temporal resolutions of dynamic MR images of the breast and will be useful in evaluating malignant and benign breast lesions.

Adipose Tissue↗

PubMed1998

[Pseudo-aneurysm of aortic arch and rupture into pericardium, a case report of successful surgical management].

This is a case report of 50 years old male suffering from pyrexia and epigastralgia 2 weeks prior to admission. On the 15th hospital day, he complained chest pain. Chest roentgenography revealed marked expansion of the mediastinum which was not existed upon admission. CT and MRI of the chest demonstrated a pseudoaneurysm of aortic arch at lesser curvature with extension into the pericardium. Exploration of the pericardium through median sternotomy disclosed fully filling with purulent effusion and blood clots. Following irrigation of the pericardial space and tube drainage, chest was closed. Repair of the aneurysm was postponded. Following continues irrigation of the pericardial space for 19 days, tube graft replacement of the aneurysm was performed under femorofemoral bypass and circuratory arrest through left thoracotomy. The aneurysmal space was filled with the omental pedicle to control infection. However, repeated bacteriological examination of the pericardium and aneurysm revealed no growth. Behçet disease was most suspected in report of the pathology.

Aneurysm, False↗

PubMed1998

[Surgical treatment for chronic dissecting aneurysm (DeBakey type I)--a case using "elephant trunk" and "aortic tailoring"].

We present a surgical case of a 54-year-old man with chronic dissecting aortic aneurysm (Type I). At the first operation, ascending aorta and aortic arch were replaced with a tube graft under cardiopulmonary bypass and selective cerebral perfusion. Elephant trunk method was employed for the second operation. At the second operation, graft replacement of the proximal two-thirds of the descending aorta was performed, and the lower third of the descending aorta was tailored. Aortic tailoring consisted of the longitudinal aortomy and the removal of the initimal flap from the distal part of the descending aorta from the level of the 9th intercostal artery down to the diaphragm. The aorta was closed creating single channel 21 mm in diameter and containing the origins of the important intercostal arteries. He discharged the hospital without any complication including paraplegia or visceral ischemia, and his follow-up CT scan (1 year-later) did not show any dilatation of the tailored segment of the descending aorta and abdominal aorta.

Aortic Dissection↗

PubMed1998

[Postoperative compartment syndrome in a patient with acute aortic dissection (DeBakey type I)].

We report a case of compartment syndrome caused by femoral arterial cannulation during cardiopulmonary bypass. A 62-year-old man who had been diagnosed as acute aortic dissection (type I) received a operation of partial arch replacement with reconstruction of brachiocephalic and left carotid arteries. Compartment syndrome was noticed just after the operation, which was caused by long-term ischemia during femoral arterial cannulation combined with poor collateral circulation by the dissection of iliac arteries. The emergency fascitomy was performed, therefore, he could be discharged without any complications. It is concluded that in case of acute aorte aortic dissection, the back-flow of blood should be checked at the time of femoral arterial cannulation, and whenever the back-flow is poor, some procedures should be added to increase distal blood flow.

Acute Disease↗

PubMed1998

[Aortic root replacement by cryopreserved homograft for prosthetic valve detachment case due to aortitis].

We present a surgical case of a 35-year-old man with aortitis. He had been performed the reconstruction of the right common carotid artery with a saphenous vein graft at 23 years old for his ruptured aneurysm by aortitis. The aortic valve replacement and CABG (LITA to LAD, SVG to D1 and SVG to RCA) were performed for aortic regurgitation and aneurysms of coronary arteries two years ago. The diastolic murmur was first heard at 18 months after the operation. The echocardiography on admission showed an abnormal movement of the prosthetic valve with perivalvular leakage. At the second operation, the valve dehiscence was observed. Although the tissues around the dehiscence was friable and edematous, there were no signs of vegetation nor abscess formation. His aortic root was replaced with a cryopreserved aortic allograft conduit. His postoperative course was uneventful and aortography revealed neither aortic regurgitation nor stenosis of the coronary artery or SVGs. We think the softness of the allograft valve ring is favorable in valve detachment cases due to not only infection but also aortitis, to prevent redetachment.

Adult↗

PubMed1998

Does Helicobacter pylori eradication depend on the period of amoxicillin treatment? A retrospective study.

In this study, the effect of different periods of amoxicillin (AMPC) treatment on the eradication rate of Helicobacter pylori in 173 patients with peptic ulcers (gastric ulcer, 109; duodenal ulcer, 64) was investigated. AMPC (1.5 g/day) was administered for 2, 4, or 6 weeks with omeprazole (20mg/day) and plaunotol (240mg/day), a mucoprotective drug, for 8 weeks. The H. pylori eradication rate was 46.7% for 2 weeks' treatment, 83.4% for 4 weeks' treatment, and 100% for 6 weeks' treatment. The eradication rate had a good correlation with the period of AMPC treatment. The healing rates of peptic ulcer at 4 and 8 weeks were 93.3% and 100%, respectively, in the 2-week group, 98.0% and 99.3% in the 4-week group, and 85.7% and 100% in the 6-week group. The recurrence rate of gastric and duodenal ulcers was 3.5% and 0% respectively, in the patients in whom H. pylori was eradicated and 30.0% and 40%, respectively, in the patients in whom H. pylori was not eradicated for 12 months after the H. pylori eradication treatment. Adverse effects of this regimen were observed in 5 (2.9%) of the 173 patients. Diarrhea was observed in 3 patients and eruption in 2. These adverse effects disappeared within a few days after only AMPC was withdrawn. Therefore, these may be caused by AMPC. The eradication rate of H. pylori depends on the period of AMPC treatment. This regiment, AMPC (1.5g/day) + omeprazole (20mg/day) + plaunotol (240mg/day), is safe and well tolerated for eradication of H. pylori.

Adult↗

PubMed1998

In vivo somatic mutations in Werner's syndrome.

The frequencies of mutant erythrocytes with loss of heterozygosity at the glycophorin A (GPA) locus and mutant CD4+ T cells lacking surface expression of the T-cell receptor alphabeta (TCR)/CD3 complex were measured by flow cytometry for Japanese Werner's syndrome (WRN) patients. The hemizygous and homozygous GPA mutant frequencies (GPA Mfs) and the TCR/CD3-defective mutant frequency (TCR Mf) in WRN patients were found to be significantly higher than those in normal controls in the same age range. However, because these Mfs in the patients are only about twice those in controls, it is difficult to conclude that the WRN gene mutations cause instability of somatic genes. This contrasts markedly with Bloom's syndrome (BLM) patients, whose GPA and TCR Mfs were previously reported to increase about 50- and 15-fold, respectively. The difference in Mfs is one aspect of the large variation in the phenotype observed between WRN and BLM patients, suggesting a different role of the responsible genes, both of which belong to the RecQ DNA helicase gene family, in the control of somatic mutagenesis.

Adult↗

PubMed1998

Effect of protein kinase C inhibitors on cardioprotection by ischemic preconditioning depends on the number of preconditioning episodes.

OBJECTIVES: This study examined the possibility that the role of PKC in [corrected] PC, and thus the response to PFC inhibitors, may differ depending on how many ischemic episodes are employed to precondition the heart. METHODS: In the first series of experiments, myocardial infarct was induced by 30 min of coronary occlusion and 3 h of reperfusion in the rabbit. Infarct size was determined by tetrazolium staining and expressed as a percentage of area at risk (%IS/AR). Prior to the 30-min ischemia, rabbits were subjected to no PC, single PC (i.e., PC with an episode of 5 min ischemia/5 min reperfusion), and repetitive PC (2 cycles of 5 min ischemia/5 min reperfusion) with or without one of three treatments: polymyxin B (PolyB), staurosporine (Stauro), and 8-sulfophenylthephylline (SPT). In the second series of experiments, the rabbits received 5 min of coronary occlusion after repetitive PC with or without PolyB or Stauro treatment. Then, myocardial tissue in the ischemic region was sampled for assay of PKC activity. Untreated rabbits served as controls. RESULTS: Single and repetitive PC limited %IS/AR to the same extent (%IS/AR = 9.8 +/- 1.9 and 10.4 +/- 2.3, both p < 0.05, vs. the control value of 44.5 +/- 3.4), and single PC was blocked by PolyB (%IS/AR = 43.9 +/- 2.7) and Stauro (%IS/AR = 31.5 +/- 3.2). Although the protocol of PolyB injection maintained the plasma PolyB level during sustained ischemia well above its Ki for PKC, this agent and also Stauro failed to abolish the protection by repetitive PC (%IS/AR = 21.6 +/- 3.0 and 11.4 +/- 4.3, respectively). SPT, an adenosine receptor antagonist, not only blocked single PC (%IS/AR = 44.4 +/- 4.4) but also attenuated protection by repetitive PC (%IS/AR = 28.3 +/- 3.6). Infarct sizes in non-preconditioned hearts were not modified by PolyB, Stauro, or SPT. The ratio of membrane fraction PKC activity to cytosolic fraction PKC activity was elevated by repetitive PC plus 5 min ischemia, and this change in PKC was inhibited in hearts given PolyB and Stauro. CONCLUSIONS: In contrast to single PC, repetitive PC protects the heart against infarction even when PolyB and Stauro are administered to inhibit PKC during ischemic insult. This difference may be attributable to a PKC-independent mechanism, in which the adenosine receptor may be partly involved.

Animals↗

PubMed1998

Theta rhythms associated with sucking, crying, gazing and handling in infants.

In order to specify the locations and to clarify the electrophysiological significance of the transitory rhythmic theta activities detected on scalp electrodes in infants, we performed simultaneous EEG and video recording with power spectral map analysis in 29 normal infants of less than 1 year of age. The rhythmic theta activities appeared in posterior temporal regions with sucking or crying, in the parietal region with gazing, and in the frontal region with handling. Each specific location of the theta rhythm seemed to correspond to the functional localization in the infant's brain. We thus concluded that these rhythmic theta activities might originate from direct cortical activation, or from the cortical activation driven by the neuronal impulses from the limbic system through the connection between that system and the cortex.

Brain Mapping↗