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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 37 records · Page 2Linked to original sources

Hemodynamic influence of peripheral vascular occlusive disease on abdominal aortic aneurysms.

AIM: Clinical evidence indicates that hemodynamic conditions such as peripheral vascular occlusive disease (PVOD) influence abdominal aortic aneurysm (AAA) disease. METHODS: We retrospectively analyzed 406 operated cases of AAA at our institute over the last 15 years, and compared 39 patients with PVOD to those without, to examine hemodynamic effects and risk factors. Aneurysm size at operation, rupture, shape, expansion rate and several preoperative risk factors were compared. RESULTS: Mean aortic diameter in the AAA with PVOD patients (56.8+/-17.8 mm) showed no significant difference to that in the AAA without PVOD group (60.4+/-14.8 mm). However, the subgroup of AAA with PVOD in whom the aneurysm was found prior to PVOD diagnosis (67.8+/-18.1 mm) (n=19) showed a larger mean AAA diameter compared to the AAA (not followed up until operative indication/prior to operation) without PVOD group (60.4+/-14.8 mm), (n=340), (p=0.04). Smoking was the only preoperative risk factor to show a difference between AAA patients with and without PVOD. The aneurysm expansion rate was determined retrospectively in 13 patients with PVOD who had been followed for at least 1 year by CT scan and 17 patients without PVOD. The rate in the PVOD group was 8.1 mm/year, which was significantly faster than that in PVOD-free patients (4.6 mm/year), (p=0.03). CONCLUSIONS: The findings of a large diameter and fast expansion rate in AAA patients with concomitant PVOD suggest that the hemodynamic effects of PVOD have a great influence on AAA development.

Adult↗

Contralateral stenosis as a risk factor for carotid endarterectomy measured by near infrared spectroscopy.

AIM: It is still controversial whether the existence of a contralateral stenosis is a risk factor during carotid endarterectomy (CEA). We used a near infrared spectroscopy (NIRS) monitoring system during CEA to evaluate the hemodynamic effect of contralateral stenosis during cross clamping of the carotid arteries. METHODS: We monitored 34 consecutive cases of CEA, using NIRS. Tissue oxygen index (TOI), as a parameter of oxygenation, and total hemoglobin index (THI), as a parameter of blood volume, were measured during cross-clamping the carotid arteries. We evaluated the relationship between these results and the pre- and intraoperative characteristics including the existence of a contralateral stenosis and the results of single-photon emission computed tomography (SPECT). RESULTS: Bilateral TOI and THI correlated well with the severity of the stenosis of the contralateral internal carotid artery, and ipsilateral THI correlated with the cerebrovascular reserve measured by SPECT. CONCLUSIONS: A contralateral stenosis is a risk factor for CEA from the hemodynamical point of view, and extreme care should be taken when performing CEA in patients with bilateral stenoses.

Aged↗

The role of inducible co-stimulator (ICOS)/B7-related protein-1 (B7RP-1) interaction in the functional development of Peyer's patches.

T-cell co-stimulatory molecule, inducible co-stimulator (ICOS)/B7-related protein-1 (B7RP-1) interactions play an essential role of T-cell-dependent B-cell activation in peripheral lymphoid organs such as spleen and lymph nodes. Here, we investigate the role of ICOS/B7RP-1 interactions in the development of Peyer's patches (PPs). In ICOS(-/-) mice, the number of PPs was not decreased, although PPs in ICOS(-/-) mice were significantly reduced in size. Phenotypic analysis showed no obvious differences between ICOS(-/-) and ICOS(+/-) mice in the distribution of T-cells, B-cells, macrophages and dendritic cells. However, PNA(+) cells characteristic of intestinal germinal centers were totally absent in ICOS(-/-) mice. Moreover, production of IgA and IgG, but not IgM was significantly reduced in PPs in ICOS(-/-) mice. These data suggest that ICOS/B7RP-1 interactions may not affect the organogenesis, but involve in the functional development of PPs.

Animals↗

In vivo activation of pro-form Bombyx cysteine protease (BCP) in silkmoth eggs: localization of yolk proteins and BCP, and acidification of yolk granules.

The present study was designed to investigate the process of acidification of yolk granules during embryogenesis. In oocytes of mature Bombyx mori silkmoth, yolk proteins and a cysteine protease (pro-form BCP) were found in yolk granules. BCP was localized in small sized yolk granules (SYG, 3-6 microm in diameter) and yolk proteins in large sized granules (LYG, 6-11 microm in diameter), which might result in a spatial separation of protease and its substrates to avoid unnecessary hydrolysis. The granules were isolated on Percoll density gradient centrifugation. Although separation of LYG and SYG was incomplete, the granules sedimented in different fractions when using unfertilized egg extract, in which LYG was recovered from heavier fractions and BCP from lighter fractions. Acid phosphatase, as well as other lysosomal marker enzymes tested, was recovered from LYG-containing fractions. When extracts were prepared from developing eggs (day 3), some BCP-containing granules co-sedimented with LYG. The inactive pro-form BCP was activated in vivo, in parallel with yolk protein degradation, and as demonstrated previously in vitro under acidic conditions (). These results suggest that acidification occurs in yolk granules during embryogenesis. This was also confirmed using acridine orange fluorescent dye. In early development, most yolk granules were neutral, but became acidic during embryonic development. SYG were progressively recovered in heavier density fractions, displaying acidic interior. In this fraction, BCP-containing granules seem to be associated with larger granules (6-11 microm in size). In addition, SYG (BCP containing granules) were likely to be acidified earlier than LYG. Our results suggest that acidification initiates yolk degradation through activation of pro-form BCP.

Animals↗

Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model.

We previously reported adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor (bFGF) as a new treatment for leg ischemia. This time, we tested this method on a swine myocardial ischemia model, seeking the possibility of its application for ischemic heart disease. An ameroid constrictor was placed around the proximal left circumflex branch of pigs to induce myocardial ischemia. Simultaneously, a skin section was harvested and fibroblasts were cultured. Fibroblasts were then infected with adenovirus vector containing a bFGF cDNA with a secretory signal sequence (bFGF group, n=8) or a LacZ cDNA (control group, n=8). At 28 days after constrictor implantation, 2.5 x 10(6) fibroblasts were administered into each of the right and left coronary arteries. The injected fibroblasts accumulated in the myocardium without causing myocardial ischemia. Echocardiography, electromechanical mapping and coronary arteriography were conducted just before and 28 days after fibroblast injection, and regional left ventricular myocardial blood flow was measured 28 days after fibroblast injection. These evaluations revealed that the bFGF group exhibited significant development of collateral vessels and improvement of myocardial contraction in the ischemic area compared with the control group. We believe that this method is a promising treatment strategy for ischemic heart disease.

Adenoviridae↗

Population-based distribution of plasminogen activity and estimated prevalence and relevance to thrombotic diseases of plasminogen deficiency in the Japanese: the Suita Study.

Reduced plasminogen activity with a normal level of antigen is commonly observed in Japanese individuals. The first reported patient with plasminogen deficiency was accompanied with deep vein thrombosis. The present study examines whether heterozygous or homozygous deficiency of plasminogen is a risk factor for thrombotic disease. This study measures the plasminogen activity of 4517 individuals in the general population, determines the cut-off to define plasminogen deficiency, and identifies plasminogen deficiencies in the control groups and thrombotic disease groups. In another study, we examined the phenotypes of consecutive patients with homozygous plasminogen deficiency detected in our hospital. We found 173 and two of 4517 individuals to have heterozygous and homozygous deficiency with normal plasminogen antigen level, respectively, and 19 to have heterozygous deficiency with reduced antigen levels. The incidence of plasminogen deficiency in an age- and sex-matched control group (13/324, 4.01% for deep vein thrombosis or 13/330, 3.94% for stroke) selected from the 4517 individuals was not significantly different from those in patients with deep vein thrombosis (3/108, 2.78%) or cardioembolic stroke (6/110, 5.55%). Among 19 patients with homozygous plasminogen deficiency showing about 10% plasminogen activity, none had deep vein thrombosis. These findings indicate that neither heterozygous nor homozygous plasminogen deficiency constitutes a significant risk factor for thrombotic disease.

Aged↗

Infrainguinal arterial reconstruction for limb salvage in patients with end-stage renal disease.

OBJECTIVES: to evaluate the efficacy of infrainguinal bypass for limb-threatening ischaemia in patients with end-stage renal disease (ESRD). MATERIALS AND METHODS: from 1991 through 2000, 28 limbs in 22 patients with ESRD received 33 infrainguinal bypasses, while 65 limbs in 57 patients with functioning kidneys underwent 77 bypasses for limb salvage. The prevalence of diabetes is higher in the ESRD group (p = 0.03). RESULTS: perioperative mortality and patient survival rate in the follow-up period were significantly poorer in patients with ESRD (18% vs 0%; p = 0.001, and 45% vs 85%, p < 0.001, respectively). Most causes of death were related to atherosclerosis or respiratory diseases. In spite of no significant difference in 2-year primary and secondary graft patency rates and limb salvage between the ESRD and non-ESRD groups (76% vs 83%; p = 0.12, 85% vs 91%; p = 0.06, and 83% vs 93%; p = 0.06, respectively), two cases of early limb loss occurred as a result of uncontrolled infection in the ESRD group. In contrast to autogenous conduits, nonautogenous conduits revealed a poorer outcome in ESRD patients (p = 0.03). CONCLUSIONS: perioperative mortality and patient survival rate were significantly poorer in the ESRD group. Preoperative full evaluation of myocardial and brain ischaemia, revascularisation with autogenous conduits, appropriate treatment of wound infection, and strict follow-up for accompanying diseases may be needed in these patients.

Adult↗

Successful en-bloc resection of large superficial tumors in the stomach and colon using sodium hyaluronate and small-caliber-tip transparent hood.

En-bloc resection is desirable for accurate histopathological assessment of tissue specimens obtained using endoscopic mucosal resection (EMR). A new EMR method using sodium hyaluronate and a small-caliber-tip transparent hood has been developed. This is a peeling-off method using a needle-knife for mucosal and submucosal incisions. Long-lasting submucosal thickening resulting from an injection of sodium hyaluronate, and good visualization of the submucosal tissue with the aid of a small-caliber-tip transparent hood, make the cutting procedures easy and safe. A large superficial gastric cancer and a large villous tumor of the sigmoid colon were endoscopically resected using this method. En-bloc endoscopic resection was successful in both patients. The gastric lesion was an well-differentiated intramucosal adenocarcinoma, completely resected in a specimen measuring 97 x 50 mm. The colonic lesion was an intramucosal well-differentiated adenocarcinoma in adenoma, completely resected in a specimen measuring 70 x 55 mm in diameter. No significant complications were noted in either patient. The new method of EMR using sodium hyaluronate and the small-caliber-tip transparent hood is a promising method for endoscopic en-bloc resection of large superficial neoplastic lesions, both in the stomach and the colon.

Adenocarcinoma↗

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice.

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed. However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is critically involved in the development of GALT in adult mice.

Adaptor Proteins, Signal Transducing↗

Activin A is an autocrine activator of rat pancreatic stellate cells: potential therapeutic role of follistatin for pancreatic fibrosis.

BACKGROUND AND AIM: The present study was conducted to examine the effect of activin A on activation of rat pancreatic stellate cells (PSCs). METHODS: PSCs were prepared from rat pancreas using collagenase digestion and centrifugation with Nycodenz gradient. Activation of PSCs was examined by determining smooth muscle actin expression with western blotting. The presence of activin A receptors in PSCs was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunocytochemistry. Expression of activin A and transforming growth factor beta (TGF-beta) mRNA was examined by RT-PCR. Activin A and TGF-beta peptide concentrations were examined with ELISA. Existence of activin A peptide in PSCs was investigated by immunocytochemistry. Collagen secretion was determined by Sirius red dye binding. RESULTS: Activin A receptors I and IIa were present in PSCs. PSCs expressed activin A mRNA and secreted activin A. Activin A enhanced PSC activation and collagen secretion in a dose dependent manner. TGF-beta and activin A increased each other's secretion and mRNA expression of PSCs. Follistatin decreased TGF-beta mRNA expression and TGF-beta secretion of PSCs, and inhibited both PSC activation and collagen secretion. CONCLUSION: Activin A is an autocrine activator of PSCs. Follistatin can inhibit PSC activation and collagen secretion by blocking autocrined activin A and decreasing TGF-beta expression and secretion of PSCs.

Actins↗

Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis.

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-gamma production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-alpha and IL-1beta production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation.

Adoptive Transfer↗

Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats.

Neural progenitor cells, including neural stem cells, are a potential expandable source of graft material for transplantation aimed at repairing the damaged CNS. Here we present the first evidence that in vitro-expanded fetus-derived neurosphere cells were able to generate neurons in vivo and improve motor function upon transplantation into an adult rat spinal-cord-contusion injury model. As the source of graft material, we used a neural stem cell-enriched population that was derived from rat embryonic spinal cord (E14.5) and expanded in vitro by neurosphere formation. Nine days after contusion injury, these neurosphere cells were transplanted into adult rat spinal cord at the injury site. Histological analysis 5 weeks after the transplantation showed that mitotic neurogenesis occurred from the transplanted donor progenitor cells within the adult rat spinal cord, a nonneurogenic region; that these donor-derived neurons extended their processes into the host tissues; and that the neurites formed synaptic structures. Furthermore, analysis of motor behavior using a skilled reaching task indicated that the treated rats showed functional recovery. These results indicate that in vitro-expanded neurosphere cells derived from the fetal spinal cord are a potential source for transplantable material for treatment of spinal cord injury.

Age Factors↗

Oxygen saturation measurement of calf muscle during exercise in intermittent claudication.

OBJECTIVES: to evaluate the oxygen saturation of the calf muscle measured by means of spatially resolved spectroscopy (SRS) in claudicants. METHODS: a total of 150 legs in 84 consecutive patients with calf claudication were studied by SRS. Oxygen saturation (SmO(2)) and the relative changes in oxygenated haemoglobin (HbO(2)) and deoxygenated haemoglobin (Hb) of the gastrocnemius muscle were measured during a treadmill walking test (2.4 km/h, 12%, 5 min). RESULTS: exercise was associated with a decrease in HbO(2) and an increase in Hb. There was no difference in SmO(2) at rest among all groups. The decrease oxygen saturation correlated well with the severity of symptoms of IC. CONCLUSION: muscle oxygen saturation measurement by SRS can be used clinically to provide objective information regarding the severity of IC.

Adult↗

Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis ("carbonyl stress").

Aging is accompanied by a progressive and irreversible non-enzymatic modification of protein by carbohydrates, eventually yielding the advanced glycation end products (AGEs). Age generation (Maillard reaction) is markedly augmented in diabetes with sustained hyperglycemia but also in normoglycemic uremia and atherosclerosis. Recent studies have brought new insights into broad derangements in non-enzymatic biochemistry involving not only carbohydrates but also lipids, present in diabetes, uremia, and atherosclerosis. The latter have in common increased levels of reactive carbonyl compounds (RCOs) with attendant protein modifications ("carbonyl stress"). Carbonyl stress might be derived from 1) hyperglycemia (lipemia), 2) oxidative stress, and/or 3) impaired detoxification of RCOs. Manipulation of carbonyl stress in diabetes, uremia and atherosclerosis opens new therapeutic approaches including redox modulation, RCO detoxification, and carbonyl stress inhibition. The first generation of carbonyl stress inhibitors such as aminoguanidine trap RCOs with its hydrazine group. Unfortunately, aminoguanidine (AG) traps pyridoxal as well as noxious RCOs, so that its long-term administration in animals results in vitamin B6 deficiency and neurotoxicity. Fortunately, newer compounds devoid of such side effects, have opened exciting prospects. Widely used hypotensive agents, such as angiotensin converting enzyme (ACE) inhibitor and angiotensin II receptor antagonist, but not calcium blockers, prove more effective than AG in attenuating the production of AGEs. Unlike AG, they do not act as RCO trapping agents, but impact upon the production of RCO precursors by scavenging a variety of radicals and altering oxidative stress, a mechanism similar to that involved in the inhibitory action of nitric oxide on AGE formation. These results provide a new framework to assess families of compounds according to their mechanisms of action.

Aging↗

Extremely reduced evolutionary rate of TATA-box binding protein in higher vertebrates and its evolutionary implications.

Previously we showed that the evolutionary rates of the Pax proteins are markedly reduced in higher vertebrates, as compared with those in the ancestral lineage of vertebrates, and we suggested that the reduced Pax protein evolution might be explained by increased functional constraints due to gene recruitment for other purposes or repeated expression in different developmental stages. To clarify the problem of whether the evolutionary rate variation found in the Pax proteins is an evolutionary feature generally recognized in most transcription factors, we have cloned and sequenced cDNAs encoding the TATA-box binding protein (TBP), a general transcription factor of eukaryotes, from Oryzias latipes, a Japanese medaka, Lampetra reissneri, a lamprey, and Ephydatia fluviatilis, a freshwater sponge. An evolutionary rate analysis of TBP has revealed that the evolutionary rate of TBP is extremely low in higher vertebrates, but not in the ancestral lineage of vertebrates, as found in the Pax proteins. In contrast, no marked reduction of the evolutionary rate in higher vertebrates is observed in the aldolase C, a house keeping enzyme. It is therefore likely that the increased functional constraint on TBP is responsible for the extremely low evolutionary rate in higher vertebrates. The temporal pattern of the evolutionary rate variation during vertebrate evolution was discussed.

Animals↗

Overlapping genes in parasitic protist Giardia lamblia.

The parasitic protist Giardia lamblia lacks mitochondria and peroxisomes, as well as many typical membrane-bound organella characteristics of higher eukaryotic cells, together with extremely economized usage of DNA sequence, as demonstrated by the lack of introns. We describe here the presence of overlapping genes in G. lamblia, in which a part of the protein coding sequence of one mRNA exists in a region corresponding to the 3'-noncoding region of another mRNA transcribed from a gene on the opposite strand. Recently we isolated 13 kinesin-related cDNAs from G. lamblia. Nine of these cDNAs contain long 3'-noncoding sequences in which long open reading frames (ORFs) exist (in the remaining four cDNAs, the lengths of the 3'-noncoding sequences are very short). The predicted amino acid sequences of these ORFs were subjected to a search for homologies with sequences in databases. The amino acid sequences of the six ORFs exhibited significant sequence similarities with known sequences. These lines of evidence suggest the frequent occurrence of gene overlap in Giardial genome.

Animals↗