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Biomedical subjects

A Mori

Publications and source records attributed to A Mori.

At least 145 records · Page 8Linked to original sources

Reoperation for graft failure of femoropopliteal bypass with externally supported knitted Dacron prosthesis.

BACKGROUND: Aggressive reoperation for failing or failed femoropopliteal (FP) bypass has been affirmative despite graft material. There has been no report regarding results of reoperation for FP bypass with externally supported knitted Dacron prosthesis (EXS). The aim of this study is to justify aggressive reoperation of FP bypass with EXS and to examine risk factors affecting the result of reoperation. METHODS: A retrospective review was performed on 204 patients undergoing 212 FP bypasses (with EXS between January 1982 and December 1997 and 34 FP EXSes of 32 patients underwent reoperation for graft failure until March 1998. The cumulative graft patency (GP) and limb salvage (LS) rate after first reoperation for 34 FP bypass EXS were calculated and the importance of each perioperative factor on GP or LS was estimated by uni- and multivariate analysis. RESULTS: Reoperated 34 FP EXSes included 12 failing and 22 failed grafts and 14 limbs with failed grafts underwent reoperation for limb salvage. The GP of 34 grafts and LS of 14 limbs rate were 58 and 67% at 2 years, respectively. Univariate analysis identified graft thrombosis (2 years GP; failing graft: failed graft=78: 48%) and continuance of smoking (2 years LS; smoker: non-smoker=43: 100%) as a significant risk factor of GP and IS, respectively, neither of which was significant by multivariate analysis. CONCLUSIONS: Early diagnosis and treatment, before graft thrombosis, can lead to superior durability of GP and discontinuance of smoking is important for LS.

Aged↗

Critical limb ischemia in a patient with von Recklinghausen's neurofibromatosis. Report of a case.

A 42-year-old woman complicated with neurofibromatosis underwent both balloon percutaneous transluminal angioplasty (PTA) of the iliac artery and femoropopliteal (FP) bypass grafting for critical lower limb ischemia. Seven months after the initial intervention, a recurrence of stenosis in the iliac artery and at the anastomoses of the FP bypass necessitated both PTA and a repeat thrombectomy and finally resulted in the amputation of her left thigh. This is a rarely documented case of chronic arterial occlusion associated with neurofibromatosis, in which the prognosis of arterial reconstruction for such patients is suggested to be poor.

Adult↗

[Change in skin reactivity to common allergens in allergic patients over a 30-year period. Association with aeroallergen load].

Five-year changes in the percentage of positive intradermal test to allergens in patients with bronchial asthma (BA) and allergic rhinitis (AR) over a period of 30 years from 1969 to 1998 were analyzed, with consideration of their association with the yearly changes in the levels of airborne pollens and molds over 30 years. Allergens used throughout the period were house dust, pollens from various plants (Japanese cedar, pine, oak, Japanese alder, Zelkova, orchard grass, ragweed, mugwort and Japanese hop) and molds (Alternaria, Cladosporium, Aspergillus, Penicillium and Candida). Overall percentages to house dust were higher in BA patients than in AR patients, but those to pollens were distinctly higher in the latter. Those to molds were higher in BA patients, except that those to Alternaria were about the same in both BA and AR patients. Therefore, the clinical expression of allergy may differ according to the type of allergen to which subjects are sensitized. Over the course of 30 years, the increase in the percentage of positive intradermal test to all of the allergens used was noted in both BA and AR patients, although this did not always reflect the aeroallergen load. This includes the two extremes to pollens from Japanese cedar and pine, either of which is the most common source of allergen in Japan. Significant increases in the percentages to Japanese cedar pollen (from 12.5% to 54.4% in BA patients, and from 35.1% to 81.5% in AR patients) appeared to be roughly correlated to marked increases in pollen count. In contrast, that to pine pollen was kept low at about 2%, because of their weak allergenicity, but abruptly increased to 5-6% in the last decade, despite the almost invariable pollen count over the last 30 years. Therefore, the increased sensitivity to aeroallergens may also be associated with other factors besides their load in the air.

Adult↗

Capillary electrophoretic behaviour of humic substances in physical gels.

We investigated the principles of the capillary electrophoretic behaviour of humic substances (HSs) in physical gels. Long chain (Mr 4000, 6000 and 20,000) polyethylene glycols (PEGs) at concentrations above their entanglement threshold caused the separation of HS fractions according to molecular size differences. Close linear relationships between effective mobilities and mean apparent molecular masses were observed at PEG concentrations between 2.5 and 15%. The efficiency of the separation does not increase in gels of increasing polymer concentrations. The possibility of interactions between HSs and gel-forming polymers was also investigated. Short chain (Mr 400) PEGs, added to the buffer at concentrations from 2.5 to 12.5%, increased the migration times of all HS fractions, but no separation was obtained even at large polymer concentrations, showing that gel formation was essential for the separation. In 2.5% polyvinyl alcohol (PVA) 49 000 all fractions show two unresolved, but well defined peaks. This separation is probably artefactual and depends on the relative concentration of HSs and PVA, as the relative abundance of the peaks changes with the sample concentration.

Electrophoresis, Capillary↗

Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue.

The retinoblastoma protein (pRB) and the related pocket proteins, p107 and p130, play crucial roles in mammalian cell cycle control. Recent studies indicate that these pocket proteins are also involved in cellular differentiation processes. We demonstrate in this work that the pRB-related p130 selectively accumulates during the in vitro differentiation of the myeloid progenitor cell, 32Dcl3, into granulocyte in response to granulocyte-colony stimulating factor (G-CSF). This G-CSF-dependent granulocytic differentiation is blocked by the adenovirus E1A oncoprotein, which binds to and inactivates the pRB family of pocket proteins including p130. Furthermore, enforced overexpression of p130 but not pRB inhibits the myeloid cell proliferation that is concomitantly associated with granulocytic differentiation morphologically characterized by nuclear segmentation. However, simple G1-cell cycle arrest induced by cytokine deprivation or ectopic overexpression of the p27 cyclin-dependent kinase inhibitor, or inhibition of E2F activities by dominant negative DP-1 is not sufficient to trigger granulocytic differentiation. The differentiation-promoting activity of p130 in myeloid cells requires both the pocket domain and the spacer domain. Our results indicate that the pRB-related p130 plays a critical role in myeloid cell differentiation and suggest that coupling of cell cycle exit with the cellular differentiation program may be specifically achieved by p130.

Adenovirus E1A Proteins↗

p38 mitogen-activated protein kinase regulates human T cell IL-5 synthesis.

Involvement of p38 mitogen-activated protein (MAP) kinase in human T cell cytokine synthesis was investigated. p38 MAP kinase was clearly induced in human Th cells activated through the TCR. SB203580, a highly selective inhibitor of p38 MAP kinase, inhibited the induction of p38 MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4, IL-5, and IFN-gamma, were produced by Der f 2-specific Th clones upon stimulation through the TCR. IL-5 synthesis alone was significantly inhibited by SB203580 in a dose-dependent manner, whereas the production of IL-2, IL-4, and IFN-gamma was not affected. The proliferation of activated T cells was not affected. IL-5 synthesis of human Th clones induced upon stimulation with rIL-2, phorbol ester plus anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble anti-CD28 mAb was also suppressed by SB203580 in the same concentration response relationship. The results clearly indicated that IL-5 synthesis by human Th cells is dependent on p38 MAP kinase activity, and is regulated distinctly from IL-2, IL-4, and IFN-gamma synthesis. Selective control of IL-5 synthesis will provide a novel treatment devoid of generalized immune suppression for bronchial asthma and atopic dermatitis that are characterized by eosinophilic inflammation.

Clone Cells↗

Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein receptor and TG phosphorylation.

Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes (Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A. , and Kohn, L. D. (1997) Proc. Natl. Acad. Sci. U. S. A. 95, 8251-8256). The ability of highly purified 27, 19, or 12 S follicular TG to suppress thyroid-restricted gene expression correlates with their ability to bind to FRTL-5 thyrocytes and is inhibited by a specific antibody to the thyroid apical membrane asialoglycoprotein receptor (ASGPR), which is related to the ASGPR of liver cells. Phosphorylating serine/threonine residues of TG, by autophosphorylation or protein kinase A, eliminates TG suppression and enhances transcript levels of the thyroid-restricted genes 2-fold in the absence of a change in TG binding to the ASGPR. Follicular TG suppression of thyroid-restricted genes is thus mediated by the ASPGR on the thyrocyte apical membrane and regulated by a signal system wherein phosphorylation of serine/threonine residues on the bound ligand is an important component. These data provide a hitherto unsuspected role for the ASGPR in transcriptional signaling, aside from its role in endocytosis. They establish a functional role for phosphorylated serine/threonine residues on the TG molecule.

Animals↗

The antioxidant EPC-K1 attenuates NO-induced mitochondrial dysfunction, lipid peroxidation and apoptosis in cerebellar granule cells.

In this study we investigated the effects of nitric oxide (NO) on cultured cerebellar granule cells. Exposure to NO donors, S-nitrosoglutathione (GSNO; 250 microM) or sodium nitroprusside (SNP; 500 microM), triggered apoptosis in immature cultures of cerebellar granule cells, which was characterized by chromatin condensation, nuclei fragmentation, and DNA laddering. Exposure of cerebellar granule cells to NO donors led to a decrease in the mitochondrial transmembrane potential and intracellular ATP content, which suggested that NO treatment caused mitochondrial dysfunction. NO treatment also induced oxidative stress in cerebellar granule cells as measured by thiobarbituric acid (TBA) assay. Pretreating cells with L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1-benzopyran-6-yl-hydrogen phosphate] potassium salt (EPC-K1), a novel antioxidant, attenuated NO-induced mitochondrial dysfunction and oxidative stress to some extent, and prevented the cells from apoptosis. The results of the present investigation suggest that a superoxide/peroxynitrite-mediated oxidative stress may be an important pathway leading to NO-associated neuronal damage. Pretreating cells with the antioxidant EPC-K1 attenuated NO-induced neurotoxicity by scavenging superoxide/peroxynitrite and/or its breakdown products.

Animals↗

Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys.

BACKGROUND: Chronic treatment with L-3,4-dihydroxyphenylalanine (L-dopa) is often associated with motor side effects in PD patients. The search for new therapeutic approaches has led to study the role of other neuromodulators including adenosine. Among the four adenosine receptors characterized so far, the A2A subtype is distinctively present on striatopallidal output neurons containing enkephalin and mainly bearing dopamine (DA) D2 receptors (indirect pathway). Studies in DA-denervated rats suggest that blockade of adenosine A2A receptors might be used in PD. OBJECTIVE: To evaluate the antiparkinsonian effect of a new selective adenosine A2A receptor antagonist, KW-6002, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. METHODS: In the present study, we used six MPTP-exposed cynomolgus monkeys already primed and exhibiting L-dopa-induced dyskinesias to evaluate both the antiparkinsonian and dyskinetic effect upon challenge with two oral doses (60 and 90 mg/kg) of KW-6002 administered alone or in combination with L-dopa/benserazide (50/12.5 mg). RESULTS: KW-6002 administered alone produced a dose-dependent antiparkinsonian response that reached the level of efficacy of L-dopa/benserazide but was less likely to reproduce dyskinesias in these animals. When co-administered, KW-6002 potentiated the effects of L-dopa/benserazide on motor activity (up to 30%) without affecting the dyskinetic response. CONCLUSION: Adenosine A2A receptor antagonists have antiparkinsonian effects of their own with a reduced propensity to elicit dyskinesias. They might therefore be useful agents in the treatment of PD.

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

Antioxidant properties of EPC-K1: a study on mechanisms.

Scavenging effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8- tetramethyl-2-(4,8,12-trimethytridecyl)-2H-1-benzopyran- 6-yl-hydrogen phosphate] potassium salt (EPC-K1) on hydroxyl radicals, alkyl radicals and lipid radicals were studied with ESR spin trapping techniques. The inhibition effects of EPC-K1 on lipid peroxidation were assessed by TBA assay. The kinetics of EPC-K1 reacting with hydroxyl radicals and linoleic acid radicals were studied by pulse radiolysis. The active site of EPC-K1 and the structure-antioxidative activity relationships were discussed. The superoxide radicals scavenging capacity of the brain homogenate of EPC-K1-treated rats was measured. The results revealed that in comparison with Trolox and vitamin C, EPC-K1 showed better overall antioxidative capacity in vitro and in vivo. EPC-K1 was a moderate scavenger on hydroxyl radicals and alkyl radicals, a potent scavenger on lipid radicals, and an effective inhibitor on lipid peroxidation. EPC-K1 could react with hydroxyl radicals with a rate constant of 7.1 x 10(8) dm3 mol-1 s-1 and react with linoleic acid radicals with a rate constant of 2.8 x 10(6) dm3 mol-1 s-1. The active site of EPC-K1 was the enolic hydroxyl group. After administration of EPC-K1, the ability of rat brain to scavenge superoxide radicals was significantly increased. The potent scavenging effects of EPC-K1 on both hydrophilic and hydrophobic radicals were relevant with its molecular structure, which consisted of both hydrophilic and hydrophobic groups.

Animals↗

Morphologic alteration of hepatocytes and sinusoidal endothelial cells in rat fatty liver during cold preservation and the protective effect of hepatocyte growth factor.

BACKGROUND: Fatty liver grafts are considered to be one of the main factors of primary nonfunctioning graft in transplantation. We investigated here, the hepatic damage during cold preservation in a rat fatty liver model by ultrastructural observation, and examined the effect of human recombinant hepatocyte growth factor (hrHGF) on amelioration of the cold-preserved graft condition. METHODS: Wistar rats were fed a choline-deficient diet (CDD) for 7 days. Livers were stored in cold University of Wisconsin (UW) solution for 0, 4, and 24 hr. We evaluated the ultrastructural alteration of the hepatocytes, sinusoidal architecture, and endothelial cells (SECs) by scanning and transmission electron microscopy. Ex vivo, we measured alanine aminotransferase (ALT) in first effluent as an index of hepatocyte injury and the hyaluronic uptake rate (HUR) as that of SEC damage. We injected hrHGF into rats fed CDD for 7 days through the portal vein and also added it to the UW solution to determine whether or not the agent ameliorated the hepatic damage in cold-preserved fatty livers. RESULTS: In rats fed CDD for 7 days, the lesion occupied by fat deposits appeared to enlarge with the duration of cold preservation leading to the disarrangement of sinusoidal architecture. Furthermore, sinusoidal endothelial damage, in which gaps, blebs, microvilli, and sinusoid denudation were detected, appeared to be more severe in these livers than in the corresponding control livers. ALT significantly increased in the 4-hr cold-preserved livers of rats fed CDD for 7 days. HUR decreased with 4-hr cold preservation and/or with CDD feeding. Administration of hrHGF prevented the expansion of fatty droplets and reduced SEC injury as detected by morphological observations. Increase of ALT in first effluent was inhibited to about one fourth the level observed in the 4-hr cold-preserved livers of rats fed CDD. Moreover, HUR significantly increased with the pretreatment of hrHGF. CONCLUSION: The hepatic injury in both hepatocytes and SECs in cold-preserved fatty liver graft developed more rapidly and severely than in the corresponding controls and demonstrated a protective effect of hrHGF.

Animals↗

Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides.

Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gammaIFN), i.e., ds polynucleotides increase class I much more than class II, whereas gammaIFN increases class II more than class I. The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the class II transactivator, RFX5, and the IFN regulatory factor 1 differently from gammaIFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene therapy.

3T3 Cells↗

Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model.

Although vascular endothelial growth factor (VEGF) is well known to be a potent mitogen for vascular endothelial cells, the role of VEGF in a developmental process of tumor angiogenesis and metastatic potential remains poorly understood. The present study was designed to investigate VEGF-induced vascular formation from a spatiotemporal viewpoint and to analyze VEGF-enhanced metastatic potential using stable clones of HT1080 human fibrosarcoma cells transfected with VEGF cDNA (S) or with vector alone (V). Microangiography revealed massive angiogenesis in the S cell-derived tumors and demonstrated that the angiogenesis occurred not in the tumor itself, but rather around the S cell tumor early after inoculation into the thigh muscles of mice. Thereafter, the angiogenesis extended in and around the tumor. The tumorigenicity of the S cells was higher than the V cells in the subcutaneous (s.c.) space, intraperitoneal space, liver and spleen. However, neither S cells nor V cells metastasized to the liver after an intrasplenic injection. Few apoptotic cells were detected in the S cell tumor, but many apoptotic cells were scattered in the V cell tumor. Our results indicate that VEGF facilitates tumorigenicity in various organs, possibly due to inducing angiogenesis in and around the tumor and preventing tumor cells from undergoing apoptosis, and suggest that VEGF may augment metastatic potential, by accelerating proliferative activity after reaching the target organ. Furthermore, VEGF-induced angiogenesis occurred preferentially around the tumor at an early period of tumor development, followed by neovascularization into the tumor.

Animals↗

Myocardial high-energy phosphates and hepatic redox state in jaundiced rats.

BACKGROUND: The mechanism underlying the fatal complications in jaundiced states after shock has not been fully clarified. The present study was designed to examine the effect of hemorrhagic shock on myocardial high-energy phosphate stores and the arterial ketone body ratio (AKBR:acetoacetate/beta-hydroxybutyrate), which reflects the redox state of the liver mitochondria, in normal and jaundiced rats. MATERIALS AND METHODS: At 1 week after ligation of the common bile duct, hemorrhagic shock was induced by exsanguination (mean arterial blood pressure = 40 mmHg) and maintained for 2 h. Serial changes in AKBR were measured. The myocardial adenine nucleotides phosphocreatine (PCr) and inorganic phosphate (Pi) were determined before and after hemorrhagic shock. RESULTS: Before shock, myocardial ATP in the jaundiced group was lower than that in the sham group. However, the myocardial PCr levels in the two groups did not differ. After reinfusion of the shed blood, ATP and PCr recovered to the preshock levels in the sham group. However, ATP and PCr were further increased in the jaundiced group. At 60 min after reinfusion, AKBR recovered to the normal level in the sham group, but decreased below 0.7 in the jaundiced group. Metabolic acidosis was more severe in the jaundiced group than in the sham group. CONCLUSIONS: The decrease in AKBR indicated irreversible metabolic acidosis. As a result, fatal circulatory failure occurred, although the phosphoenergetic level in the myocardium was sufficiently maintained.

Acidosis↗

Penetration by a huge abdominal aortic aneurysm into the lumbar vertebrae: report of a case.

We report herein the case of a 64-year-old man who underwent urgent surgery for a huge abdominal aortic aneurysm (AAA) with severe lumbago. At surgery, a defect in the posterior wall of the AAA, through which the adjacent lumbar vertebrae was seen after removal of intraluminal thrombi, was encountered with no evidence of blood leakage. This is a rare case of AAA that eroded the posterior wall and exposed the vertebrae.

Angiography↗

Combined catheter embolization and femorofemoral bypass for pseudoaneurysm of the right external iliac artery: report of a case.

Performing direct surgery for postoperative hemorrhage caused by intraperitoneal arterial injury is very difficult. We report herein the case of a 52-year-old woman who developed sudden right lower abdominal pain after numerous laparotomies and radiotherapy for advanced uterine cancer. A diagnosis of pseudoaneurysm of the right external iliac artery was made, and an emergency catheter embolization and femorofemoral bypass was successfully performed under local anesthesia. The patient was able to walk the next day. To the best of our knowledge, this is the first report of such a combined procedure in the literature.

Adenocarcinoma↗

Remodeling of patellar tendon grafts augmented with woven polyester after anterior cruciate ligament reconstruction in humans.

Arthroscopic and histological evaluations of anterior cruciate ligament (ACL) grafts were made in 38 patients at various intervals after reconstruction was performed with patellar tendons (PTs) augmented with woven polyester. The interval between the surgery and the examinations ranged from 3 to 36 months (mean, 14.1 months). Biopsy specimens with woven polyester were removed from the anterior mid-portion of the graft 5 mm in depth from the graft surface. Arthroscopically, all 38 grafts showed thick ligamentous tissues, but some polyester fibers had ruptured in 9 grafts. The transplanted grafts were arthroscopically very similar to normal ACL 12 months after reconstruction. Histologically, a marked inflammatory response to the woven polyester was observed in the first 4 months after the operation, but this decreased with time. Five of 6 grafts obtained 18-36 months postoperatively showed decreased cellularity, with longitudinally oriented fibrous bundles, suggesting approaching ligament maturity. The appearance of the fibroblasts in the grafts varied from patient to patient, with 13 of 37 grafts (35.1%) showing spindling fibroblasts, and 24 grafts (64.9%) oval ones. (The remaining graft consisted of mesenchynal cells). Clinically, postoperative KT 1000 arthrometer measurements showed that the mean injured-to-uninjured difference in anterior knee laxity was 1.7 +/- 2.6 mm. There was no chronic synovitis or effusion during the study period. These results suggest that grafts with PT augmented with woven polyester transform arthroscopically and histologically into a structure similar to that of normal ligaments after reconstruction, and may act as a substitute for the ACL. The advantage of woven polyester for the augmentation of PT grafts was that it allowed earlier mobilization and weight-bearing after reconstruction, without adverse effects on graft integrity.

Adolescent↗