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Biomedical subjects

A Yamashita

Publications and source records attributed to A Yamashita.

At least 19 recordsLinked to original sources
PubMed2002

Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis.

The etiology of steroid-induced osteonecrosis (ON) is unclear. This study was designed to determine whether bone marrow fat cell size, intraosseous pressure, and blood flow rate differed between steroid-treated rabbits with ON and those without. Twenty-nine rabbits were intramuscularly injected once with 20 mg/kg of methylprednisolone acetate (MPSL), and five rabbits were injected once with physiologic saline (PS) as a control. Intraosseous pressure and blood flow rate in the proximal femur were determined before and at 2 weeks after the injection. After these measurements, both femora and humeri were histopathologically examined for the presence of ON, and size of bone marrow fat cells were morphologically examined. At 2 weeks after steroid injection, the intraosseous pressure was significantly higher in rabbits with ON than in those without (p = 0.0251), and the blood flow rate had decreased significantly more in rabbits with ON than in those without (p = 0.0051). The size of the bone marrow fat cells was significantly (p = 0.0004) larger in rabbits with ON (diameter, 63.5 +/- 5.8 microm) than in those without (diameter, 53.3 +/- 6.9 microm). Injection of PS (5 rabbits), 1 (10 rabbits), 5 (10 rabbits), and 20 (10 rabbits) mg/kg of body weight of MPSL showed that a larger dose of steroid increased both fat cell size and prevalence of ON. These results suggest that bone marrow fat cell enlargement and a rise in intraosseous pressure may be important when considering the pathophysiology of steroid-induced ON in rabbits.

Adipocytes↗
PubMed2002

[Off-pump coronary artery bypass grafting/beating coronary artery bypass grafting for a patient with low left ventricular ejection fraction].

Beating coronary artery bypass grafting could be performed for a 47-year-old man with left ventricular ejection fraction (LVEF) of 9.3%. Post-operative LVEF was improved to 51.6%. Conventional coronary artery bypass grafting (CABG) used to be contraindicative for patients with LVEF below 20%. Recently, such patients are involved to indication of off-pump CABG (OPCAB) or beating CABG, because we consider OPCAB are lower complications than conventional CABG. We were able to bypass the circumflex for the patient while we had been used percutaneous cardio-pulmonary support (PCPS). We could perform beating coronary artery bypass grafting for a patient of the low LVEF.

Coronary Artery Bypass↗
PubMed2001

Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a conserved surveillance mechanism that eliminates imperfect mRNAs that contain premature translation termination codons (PTCs) and code for nonfunctional or potentially harmful polypeptides. We show that a novel phosphatidylinositol 3-kinase-related protein kinase, hSMG-1, is a human ortholog of a product of Caenorhabditis elegans smg-1, one of seven smg genes involved in NMD. hSMG-1 phosphorylates hUPF1/SMG-2 in vivo and in vitro at specific serine residues in SQ motifs. hSMG-1 can associate with hUPF1/SMG-2 and other components of the surveillance complex. In particular, overexpression of a kinase-deficient point mutant of hSMG-1, hSMG-1-DA, results in a marked suppression of the PTC-dependent beta-globin mRNA degradation; whereas that of wild-type hSMG-1 enhances it. We also show that inhibitors of hSMG-1 induce the accumulation of truncated p53 proteins in human cancer cell lines with p53 PTC mutation. Taken together, we conclude that hSMG-1 plays a critical role in NMD through the direct phosphorylation of hUPF1/SMG-2 in the evolutionally conserved mRNA surveillance complex.

Amino Acid Sequence↗
PubMed2001

The fission yeast meiotic regulator Mei2p undergoes nucleocytoplasmic shuttling.

Schizosaccharomyces pombe Mei2p is an RNA-binding protein that switches the cell cycle from mitotic to meiotic. Mei2p forms a unique dot in the nucleus prior to meiosis I, aided by a non-coding RNA molecule termed meiRNA. Here we show that Mei2p intrinsically undergoes nucleocytoplasmic shuttling. Artificial acceleration of nuclear migration of Mei2p advances nuclear dot formation, but meiRNA does not appear to promote the dot formation by modulating the migration rate of Mei2p into the nucleus. Rather, this RNA is likely to facilitate the assembly of Mei2p into a dot structure and trap the protein as such in the nucleus.

Active Transport, Cell Nucleus↗
PubMed2001

ATP-independent fatty acyl-coenzyme A synthesis from phospholipid: coenzyme A-dependent transacylation activity toward lysophosphatidic acid catalyzed by acyl-coenzyme A:lysophosphatidic acid acyltransferase.

CoA-dependent transacylation activity in microsomes is known to catalyze the transfer of fatty acids between phospholipids and lysophospholipids in the presence of CoA without the generation of free fatty acids. We previously found a novel acyl-CoA synthetic pathway, ATP-independent acyl-CoA synthesis from phospholipids. We proposed that: 1) the ATP-independent acyl-CoA synthesis is due to the reverse reaction of acyl-CoA:lysophospholipid acyltransferases and 2) the reverse and forward reactions of acyltransferases can combine to form a CoA-dependent transacylation system. To test these proposals, we examined whether or not recombinant mouse acyl-CoA:1-acyl-sn-glycero-3-phosphate (lysophosphatidic acid, LPA) acyltransferase (LPAAT) could catalyze ATP-independent acyl-CoA synthetic activity and CoA-dependent transacylation activity. ATP-independent acyl-CoA synthesis was indeed found in the membrane fraction from Escherichia coli cells expressing mouse LPAAT, whereas negligible activity was observed in mock-transfected cells. Phosphatidic acid (PA), but not free fatty acids, served as an acyl donor for the reaction, and LPA was formed from PA in a CoA-dependent manner during acyl-CoA synthesis. These results indicate that the ATP-independent acyl-CoA synthesis was due to the reverse reaction of LPAAT. In addition, bacterial membranes containing LPAAT catalyzed CoA-dependent acylation of LPA; PA but not free fatty acid served as an acyl donor. These results indicate that the CoA-dependent transacylation of LPA consists of 1) acyl-CoA synthesis from PA through the reverse action of LPAAT and 2) the transfer of the fatty acyl moiety of the newly formed acyl-CoA to LPA through the forward reaction of LPAAT.

Acyl Coenzyme A↗
PubMed2001

Whole genome sequencing of meticillin-resistant Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism. METHODS: Whole genome sequences of two related S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction. FINDINGS: The Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors. INTERPRETATION: The remarkable ability of S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by S aureus.

Animals↗
PubMed2001

Involvement of polyamines in B cell receptor-mediated apoptosis: spermine functions as a negative modulator.

The B cell lymphoma WEHI231 has been used as a model for studying clonal deletion of B cells on the basis of its ability to undergo growth arrest and apoptosis by B cell antigen receptor (BCR) cross-linking. To comprehensively analyze the genes involved in BCR-mediated apoptosis, we applied the technique of serial analysis of gene expression (SAGE) to WEHI231. Comparison of expression patterns revealed that BCR cross-linking caused coordinate changes in the expression of genes involved in polyamine metabolism. Polyamines are ubiquitous compounds required for cell proliferation and homeostasis. The coordinate expression of the polyamine-related genes was confirmed by semiquantitative reverse transcriptase-polymerase chain reaction analysis. During apoptosis, the genes involved in polyamine biosynthesis were downregulated, whereas those involved in polyamine catabolism were upregulated, suggesting that intracellular polyamines play a role in BCR-mediated apoptosis. Levels of intracellular putrescine, spermidine, and spermine were reduced after BCR cross-linking. These effects were prevented by concurrent CD40 stimulation, which blocked BCR-mediated apoptosis. Furthermore, addition of spermine could repress the BCR-mediated apoptosis by attenuating the mitochondrial membrane potential (Deltapsim) loss and activation of caspase-7 induced by BCR signaling. These findings strongly suggest that polyamine regulation is involved in apoptosis during B cell clonal deletion.

Animals↗
PubMed2001

CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation.

Immune and inflammatory systems are controlled by multiple cytokines, including interleukins (ILs) and interferons. These cytokines exert their biological functions through Janus tyrosine kinases and signal transducer and activator of transcription (STAT) transcription factors. We recently identified two intrinsic Janus kinase (JAK) inhibitors, JAK binding protein (JAB; also referred to as suppressor of cytokine signaling [SOCS1]/STAT-induced STAT inhibitor [SSI1]) and cytokine-inducible SH2 protein (CIS)3 (or SOCS3/SSI3), which play an essential role in the negative regulation of cytokine signaling. We have investigated the role of STATs and these JAK inhibitors in intestinal inflammation. Among STAT family members, STAT3 was most strongly tyrosine phosphorylated in human ulcerative colitis and Crohn's disease patients as well as in dextran sulfate sodium (DSS)-induced colitis in mice. Development of colitis as well as STAT3 activation was significantly reduced in IL-6-deficient mice treated with DSS, suggesting that STAT3 plays an important role in the perpetuation of colitis. CIS3, but not JAB, was highly expressed in the colon of DSS-treated mice as well as several T cell-dependent colitis models. To define the physiological role of CIS3 induction in colitis, we developed a JAB mutant (F59D-JAB) that overcame the inhibitory effect of both JAB and CIS3 and created transgenic mice. DSS induced stronger STAT3 activation and more severe colitis in F59D-JAB transgenic mice than in their wild-type littermates. These data suggest that hyperactivation of STAT3 results in severe colitis and that CIS3 plays a negative regulatory role in intestinal inflammation by downregulating STAT3 activity.

Animals↗
PubMed2001

IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II.

Human T cell leukemia virus type I (HTLV-I) is etiologically associated with adult T cell leukemia (ATL) and chronic neurological disease, tropical spastic paraparesis (TSP). In our study, a unique IL-2 dependent human T cell line, designated TY8-3, was established from a thymoma obtained from a myasthenia gravis patient. The cells were heterogeneous and mainly consisted of those with CD4 , CD8 as well as activation markers and adhesion molecules including IL-2Ralpha,beta,gamma, CD45RO, Tf-R, HLA-DR, LFA-1alpha,beta, LFA-3, ICAM-1 and OX40 but without CD3 surface markers. Furthermore, these cells underwent an efficient and reproducible IL-2 independent transformation upon cocultivation with HTLV-I/II producing cell lines. Interestingly, although the infected cells became IL-2 independent, the growth rate of infected cells was significantly lower than those of parental TY8-3 cells. Clonal HTLV-I proviral DNA and viral particles were detected in the cells. Down-regulation of the lck and fyn genes and activation of the lyn gene was demonstrated in the IL-2 independent HTLV-positive TY8-3 cells. Subclones of TY8-3 cells were again able to be efficiently transformed and became IL-2 independent several months after coculture. Our results thus exhibit that TY8-3 cells and its subclones provide us with a very unique model whereby IL-2 independent transformation events of human T cells by HTLV-I/II in vitro can be studied at a clonal level.

CD4 Antigens↗
PubMed2001

Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.

Aged↗
PubMed2001

Fatal diffuse atheromatous embolization following endovascular grafting for an abdominal aortic aneurysm: report of a case.

A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

Aged↗
PubMed2001

Intramuscular haemodynamic responses to different durations of sustained extension in normal human masseter.

Ten healthy non-smoking males (mean age 24.3+/-0.8 years) with no history of chronic muscle pain or migraine participated in this study. Intramuscular total haemoglobin (Hb), an indicator of blood volume in the illuminated area, was measured with a non-invasive, near-infrared spectroscopic device. Each participant was told to maintain maximal mouth opening to extend the masseter muscle for 30, 60 or 120 s in random order. Data were continuously recorded from the right masseter 1 min before, at set times during and for 5 min after sustained muscle extension in each trial. Each trial was separated by a 10-min interval. Heart rate (HR) and blood pressure (BP) were also recorded. The mean normalized Hb decreased during muscle extension and rebound hyperaemia was observed after it in each trial (P=0.0001). Hb returned to baseline within 60 s. The magnitude of the decremental change during extension and of the incremental change in the rebound hyperaemia was not significantly different among the three trials (P=0.9071); neither were mean normalized HR and BP. These data suggest that sustained extension of the masseter produces a reduction in total intramuscular Hb during extension and a secondary increase in Hb following a return to the resting muscle's normal length.

Adult↗
PubMed2001

Axon trajectories in local circuits of the primary motor cortex in the macaque monkey (Macaca fuscata).

The intrinsic trajectories and terminal arbors of two axons and one horizontal axon collateral within the primary motor cortex (M1) were studied in the macaque monkey using injections of biotinylated dextran amine (BDA) into the putative primary forelimb motor cortex, and two-dimensional (2-D) reconstruction of the individually labeled axons and collateral. (1) A long collateral of the main axon from a large pyramidal cell in layer Vb of the putative forelimb area on the anterior bank of the central sulcus coursed horizontally anteriorly for 3 mm and formed a terminal arbor in layer III of M1. (2) The main axon of a pyramidal cell in layer IIIa+b of the putative forelimb area on the precentral gyrus descended into the white matter and then entered the anterior bank of the central sulcus to form a terminal arbor in layers III and V. (3) The main axon of a pyramidal cell in layer IIIc of the putative forelimb area on the precentral gyrus descended and bifurcated in the white matter. One branch entered the anterior bank of the central sulcus to form a terminal field in layer VI. These results indicate that some local axons and horizontal axon collaterals arising from M1 reach their single targets within M1 to form single terminal fields.

Animals↗
PubMed2001

Somatotopic arrangement and corticocortical inputs of the hindlimb region of the primary motor cortex in the macaque monkey.

Using Japanese monkeys, we examined the somatotopic organization of the hindlimb region of the primary motor cortex (MI) with intracortical microstimulation. In the hindlimb region of the MI, areas representing distal movements (digits and ankle joints) were basically surrounded by those representing proximal movements (knee and hip joints). Thus, the hindlimb region of the MI has a nested or horseshoe-like somatotopic representation. We then examined the topographic organization of corticocortical projections to the hindlimb region of the MI by the retrograde double-labeling technique: one monkey received paired injections of Fast blue (FB) and Diamidino yellow (DY) into hindlimb or forelimb representation of the MI, respectively, while two monkeys received those of FB and DY into proximal or distal representation of the hindlimb region of the MI, respectively. The neurons projecting to the hindlimb region of the MI were located in cortical areas largely separate from those projecting to the forelimb region of the MI. On the other hand, we found a substantial overlap of corticocortical neurons projecting to the proximal and distal parts of the hindlimb region of the MI in the dorsal division of the premotor cortex and the cingulate motor areas.

Animals↗
PubMed2001

Involvement of GTP-binding protein in the induction of phytoalexin biosynthesis in cultured carrot cells.

Biosynthetic activity of carrot phytoalexin 6-methoxymellen was induced in cell suspension culture by the treatment with oligogalacturonide elicitor; however, the elicitor-induced activity appreciably reduced in the presence of suramin, a potent inhibitor of GTP-binding proteins. In contrast, addition of G-protein activators, such as mastoparan or GTP-gamma-S, to carrot cell culture triggered 6-methoxymellein production even in the absence of uronide elicitor. An appreciable GTPase activity was found in purified plasma membrane of cultured carrot cells, and the hydrolytic activity was significantly increased by the addition of elicitor. Carrot plasma membrane was capable of associating with GTP-gamma-S, and the binding ability was markedly increased in the presence of elicitor. However, the binding activity markedly decreased when the membrane preparation was pre-incubated with GTP but not with ATP. These observations strongly suggest that a certain GTP-binding protein located at plasma membrane of cultured carrot cells plays an important role in the oligogalacturonide elicitor-induced 6-methoxymellein production.

Journal Article↗