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Yoshitaka Hayashi

Publications and source records attributed to Yoshitaka Hayashi.

29 records · Page 2Linked to original sources
PubMed2002

Identification and recombinant production of human laminin alpha4 subunit splice variants.

Laminins, the major basement membrane glycoproteins, are composed of three subunits. We identified a splice variant of the human laminin alpha4 subunit transcript containing 21 extra nucleotides. A heptapeptide sequence, MDCPTIS, was inserted close to the two cysteine residues possibly involved in the intersubunit disulfide bonds. Both the authentic alpha4 subunit (alpha4A) and the variant with the heptapeptide insertion (alpha4B) were readily secreted as laminin-8 trimers (alpha4Abeta1gamma1 or alpha4Bbeta1gamma1) upon cotransfection with expression vectors for the beta1 and gamma1 subunits. The purified recombinant laminin-8 containing the alpha4B subunit was more potent in promoting cell spreading than that containing alpha4A, raising the possibility that the alternative splicing of the alpha4 subunit transcript regulates the cell-adhesive activity of laminin-8. Since both alpha4A and alpha4B transcripts were detected by RT-PCR in several human cell lines, these two isoforms of laminin-8 with differing cell-adhesive activities are present in the basement membranes of human tissues.

Alternative Splicing↗
PubMed2002

Preoperative glutamine administration induces heat-shock protein 70 expression and attenuates cardiopulmonary bypass-induced inflammatory response by regulating nitric oxide synthase activity.

BACKGROUND: Heat-shock protein 70 (HSP70) plays a major role in the pathophysiology of inflammation, and the induction of HSP70 before the onset of inflammation can reduce organ damage through a self-protective system. Glutamine is known to be an inducer of HSP70, and its preoperative administration seems useful in attenuating cardiopulmonary bypass (CPB)-induced inflammatory response. METHODS AND RESULTS: Adult male Sprague-Dawley rats (group G, received 100 mg/kg of glutamine via the right jugular vein 3 times per day for 1 week and just before the initiation of CPB; group C served as control) underwent CPB (60 minutes, 100 mL/kg per minute, 34 degrees C) and were killed 3 hours after the termination of CPB. Group G showed significantly lower plasma concentrations of interleukin-6 and interleukin-8 after CPB termination. Myocardial and respiratory damages were significantly attenuated in group G, as evidenced by Langendorff perfusion, respiratory index, and neutrophil adherence. HSP70 expressions in the heart, lung, and liver were detected only in group G before CPB and were markedly stronger in group G 3 hours after CPB termination. Although plasma nitrate+nitrite concentrations were not significantly different between the groups, endothelial-constitutive nitric oxide synthase (NOS) activity was markedly preserved and inducible NOS activity was markedly attenuated in the tissues of group G. CONCLUSIONS: These results suggest that preoperative glutamine administration induces HSP70 expression before CPB and attenuates CPB-induced inflammation by regulating NOS activity, which may be a prospective management for conferring tolerance to CPB-induced inflammatory response through a self-protective mechanism.

Animals↗
PubMed2002

Type 1 iodothyronine deiodinase in the house musk shrew (Suncus murinus, Insectivora: Soricidae): cloning and characterization of complementary DNA, unique tissue distribution and regulation by T(3).

The house musk shrew Suncus murinus (Insectivora: Soricidae) has been reported as having low thyroxine to 3,3'5-triiodothyronine (T(3)) converting activity in liver and kidney homogenates and was assumed to be type 1 iodothyronine deiodinase (D1)-deficient. To study whether this is due to structural abnormality of shrew D1, we cloned the cDNA and characterized the enzyme. The deduced amino acid sequence of shrew D1 was found to be highly homologous to other known D1s and the enzyme itself to have similar catalytic activity. However, unlike in other species, the D1 activity was detected only in liver. Moreover, the D1 activity in liver of the shrew was less than half of that in rat liver and its expression was not up-regulated by T(3). In contrast, a very high activity of D2 was demonstrated in brain and brown adipose tissue. The present study also revealed that the serum level of T(3) in the shrew was in the same range as these in other mammals. These results suggest that D2 contributes to the production and maintenance of T(3) levels in the house musk shrew.

Adipose Tissue, Brown↗
PubMed2002

Steroid receptor coactivator-1 deficiency causes variable alterations in the modulation of T(3)-regulated transcription of genes in vivo.

Thyroid hormone exerts its biological effect by binding to a TR. Both liganded and unliganded TRs regulate the transcription of T(3)-responsive genes. Cofactors with activating or repressing function modulate the transcriptional regulation by TRs. We showed that steroid receptor coactivator 1 (SRC-1)-deficient mice (SRC-1(-/-)) exhibit partial resistance to thyroid hormone at the level of the pituitary thyrotrophs. To determine whether SRC-1 deficiency affects globally T(3)-dependent transcriptional regulation, we studied the effects of thyroid hormone deprivation and replacement on the expression of several genes in different tissues of SRC-1(-/-) and wild-type mice (SRC-1(+/+)). Thyroid hormone deficiency was induced by a low iodine diet (LoI) supplemented with propylthiouracil (PTU) for 2 wk. L-T(3) was injected ip for the last 4 d in one group (PTU+T(3) group), and another group (PTU group) received only vehicle. Levels of mRNAs for T(3)-responsive genes were determined by Northern blotting: GH and TSH beta in pituitary; type 1 iodothyronine 5'-deiodinase, spot 14 (S14), and malic enzyme in liver; and sarcoplasmic reticulum calcium adenosine triphosphatase 2 and myosin heavy chain alpha and beta in heart. Serum parameters, TSH, total cholesterol, creatine kinase, and alkaline phosphatase (AP), were also measured. Hypothyroidism produced a comparable increase in TSH beta mRNA in both genotypes, but its suppression by L-T(3) was attenuated in SRC-1(-/-) mice. In contrast, hypothyroidism failed to reduce S14 mRNA levels in SRC-1(-/-) mice. As a consequence, the response to L-T(3) was not observed in these mice. SRC-1 deficiency had no effect on the expression of the rest of the T(3)-responsive genes examined. Of the four serum parameters, the T(3)-mediated decrease in TSH and changes in AP were attenuated in SRC-1(-/-) mice. We conclude that SRC-1 deficiency altered the expression of only some of the T(3)-responsive genes. SRC-1 appears to be involved not only in transcriptional activation by liganded TRs, but also in the suppression by liganded or unliganded TRs. Some of the effects of SRC-1 may be TR isoform specific.

Alkaline Phosphatase↗
PubMed2002

Clinical significance of coronary calcification.

Coronary artery calcification (CAC) was assessed by cinefluoroscopy and its extent was scored (CAC score) in 2,163 consecutive patients undergoing coronary angiography, based on the angiographic and clinical data, the patients were categorized into 8 types of coronary artery disease (CAD). The CAC score was lowest in angiographically normal subjects (0.12+/-0.60) and highest in patients with silent myocardial ischemia (14.31+/-8.61). Risk factors for CAC were advanced age, male sex (at age <80 years), hypertension, diabetes mellitus, and a high grade of organic coronary stenosis. The CAC score in patients with acute coronary syndrome (unstable angina+acute myocardial infarction; 5.48+/-7.42) was significantly lower than that in those with chronic CAD (silent ischemia+stable angina; 9.72+/-8.73; p<0.0001), but was still higher than that in normal subjects or those with vasospastic angina (0.92+/-2.88; p<0.0001). The results indicate that CAC is a manifestation of coronary atherosclerosis and its appearance depends on the pathological type of ischemic heart disease. Fixed stenosis with a slow and chronic process tends to be associated with CAC. The clinical implication of extensive CAC in acute coronary syndrome compared with normal subjects should be further investigated.

Age Distribution↗
PubMedDate not supplied

Improvement of bypass circuit biocompatibility: comparison and combination of heparin-coated circuit and nitric oxide gas infusion.

OBJECTIVES: Nitric oxide (NO) gas infusion to the oxygenator, as well as heparin-coated bypass circuits, have been reported to attenuate blood activation induced by the interaction with the artificial surfaces of an extracorporeal bypass circuit. Using a mock circulation model, we compared the effect of each and also evaluated the effect of their combination on attenuating bypass-induced blood activation. METHODS: A miniature closed bypass circuit was primed with diluted fresh human blood and perfused for 180 minutes using a centrifugal pump. NO gas (0, 50, or 100 ppm) was infused to the oxygenator sweep gas of either a non-heparin-coated or a heparin-coated circuit. Platelet counts, beta-thromboglobulin, platelet factor 4, complement-3 activation products and granulocyte elastase were measured at 0, 30, 60, 120, and 180 minutes after starting the perfusion. RESULTS: One hundred ppm of NO was statistically equivalent to the heparin-coated circuit for attenuating bypass-induced blood activation, and a combination of the two significantly surpassed the results of either modification alone. Fifty ppm of NO alone provided only a slight attenuation of blood activation as compared with the non-heparin-coated circuit, though the difference was not significant. A combination of 50 ppm NO and the heparin-coated circuit did not significantly enhance the effects of the heparin-coated circuit alone. CONCLUSIONS: The combination of NO gas infusion and heparin-coated circuits appears to be a useful and promising modification for enhancing the attenuation of bypass-induced blood activation, though the optimal dose of NO infusion in terms of effectiveness and adverse effects to the whole body remains to be established.

Anticoagulants↗
PubMedDate not supplied

Avoidance of full-sternotomy: effect on inflammatory cytokine production during cardiopulmonary bypass in rats.

BACKGROUND AND AIM OF THE STUDY: Although open heart operations via a mini-sternotomy or mini-thoracotomy are considered "less invasive" cosmetically and are hopeful for early social recovery, clinical experiences have not shown less invasiveness toward systemic inflammatory response, because of the wide variety of patients and operative procedures encountered. We examined the effect of a mini-sternotomy on an inflammatory response during a cardiopulmonary bypass (CPB) procedure performed in rats. METHODS: Thirty-two adult Sprague-Dawley (SD) rats, each of which underwent a 120-minute CPB, were randomly divided into four groups according to the method of exposing the pericardial cavity; no sternotomy (Group N [0 cm], n = 8), right para-sternal thoracotomy (Group P [2 cm], n = 8), lower mini-sternotomy (Group M [2 cm], n = 8), and full-sternotomy (Group F [4 cm], n = 8). Blood samples were obtained (1) just prior to the initiation of CPB, and then (2) 30, (3) 60, and (4) 120 minutes after the initiation of CPB. RESULTS: Thirty minutes after the initiation of CPB, there were significant differences in plasma interleukin [IL]-6 levels between groups, except for Groups P and M; whereas at 60 minutes the only significant difference occurred between Groups N and F, and at 120 minutes there were no significant differences between any of the groups. Further, plasma IL-8 levels were not significantly different at each sampling point between all of the groups. CONCLUSIONS: These results first demonstrate experimentally that the avoidance of a full-sternotomy can be considered a less invasive strategy in terms of reducing the systemic inflammatory response that accompanies a shorter CPB duration.

Animals↗
PubMedDate not supplied

Synthetic human alpha-atrial natriuretic peptide infusion in management after open heart operations.

Cardiopulmonary bypass (CPB) induces water retention in the third space, and the mechanism is partially associated with the activation of the renin-angiotensin-aldosterone system (RAAS). Atrial natriuretic peptide (ANP) has a gradual but strong diuretic effect and suppresses the RAAS activation. We examined the efficacy of synthetic human alpha-ANP (hANP) infusion in the management of the postoperative water balance control. Thirty patients (male:female = 18:12, 65.2 +/- 9.5 years) undergoing elective open heart operations in 2001 were allocated into one of two groups. Group H (n = 14) received 0.025 microg/kg/minute of synthetic hANP (HANP; Suntory Inc., Zeria Pharmaceutical, Tokyo, Japan) from the termination of CPB; the dose was gradually reduced to 0 until the 72nd postoperative hour. Group C (n = 16) served as control subjects. Twenty-four hours after operation, the central venous pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure were significantly lower in group H than in group C, and the cardiac index was significantly higher in group H. Total volume of plasma solution infused during the initial 24 postoperative hours was significantly smaller in group H. The total dosages of furosemide and potassium-chloride added during the first 72 postoperative hours were significantly smaller in group H. On the first postoperative day, plasma levels of renin activity and aldosterone were significantly lower in group H. These results suggest that postoperative hANP infusion, which provides a sufficient diuretic effect and suppresses CPB induced RAAS activation, may simplify management after open heart operations.

Aged↗
PubMedDate not supplied

Freestyle stentless bioprosthesis for active aortic infectious endocarditis with undetermined causative organism.

A 52-year-old woman developed congestive heart failure and was diagnosed with aortic regurgitation with approximately 20 mm of vegetation located on the noncoronary cusp of the aortic valve. The patient had undergone tooth extraction 3 months earlier, and various antibiotics had been given in the treatment of refractory high fever for 1 month. The damage to the aortic valve extended to the fibrous trigone near the mitral valve, and aggressive debridement of necrotic and infected tissue was done. The excised defect was repaired and reinforced with a pericardial patch, and the Freestyle stentless bioprosthesis was implanted using the full-root technique. Although the causative organism was never isolated, recurrent endocarditis has not occurred during 3 years of follow-up. The Freestyle stentless bioprosthesis was useful in the management of active aortic infectious endocarditis with undetermined causative organism for the prevention of recurrent endocarditis in the early postoperative period.

Aortic Valve↗