Biomedical subjects

H Yasui

Publications and source records attributed to H Yasui.

At least 55 records · Page 3Linked to original sources

PubMed2001

Long-term inhalation of high-dose nitric oxide increases intraalveolar activation of coagulation system in mice.

Inhalation of nitric oxide (NO) is useful for the treatment of patients with pulmonary hypertension. However, the potential toxicity of inhaled NO is still unclear. Coagulation activation plays an important role in lung injury. We assessed the effect of low- and high-dose inhaled NO on the coagulation system in the intraalveolar space of mice. The animals were assigned to five groups (n = 6): [RA] group, mice exposed to fresh air alone; [RA+2 ppm NO] group, fresh air and 2 ppm NO; [RA+40 ppm NO] group, fresh air and 40 ppm NO; [RA+2 ppm NO+O(2)] group, fresh air, 2 ppm NO and O(2); and [RA+40 ppm NO+O(2)] group, fresh air, 40 ppm NO and O(2). Each group was treated for 3 wk. Lung specimens of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups showed significant nitrotyrosine immunoreactivity. BALF concentrations of total protein, thrombin and soluble tissue factor were significantly increased in mice of [RA+40 ppm NO] and [RA+40 ppm NO+O(2)] groups compared with [RA] group. However, BALF concentrations of total protein, thrombin, and soluble tissue factor were not significantly increased in mice of [RA+2 ppm NO] and [RA+2 ppm NO+O(2)] groups compared with [RA] group. Lung tissue factor mRNA expression was higher in the high-dose NO group than in the low-dose NO group. NO donor increased significantly tissue factor activity on alveolar epithelial cells. This study has shown for the first time that long-term inhalation of high, but not low, concentration of NO may activate the clotting system by increasing the lung expression of tissue factor.

Administration, Inhalation↗

PubMed2001

Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse.

It is well recognized that activation of the coagulation system plays an important role in bleomycin (BLM)-induced lung injury and fibrosis. The protein C (PC) pathway is an important regulator of the coagulation system. In this study, we evaluated the bronchoalveolar lavage fluid (BALF) concentration of activated PC (APC) and the therapeutic effect of the intratracheal administration of APC on BLM-induced lung fibrosis in mice. APC levels in BALF were significantly lower in BLM-treated animals than in the saline-treated group. Fibrotic changes were progressive in mice treated with BLM and intratracheal instillation of vehicle (BLM/Veh) after 14 and 21 d of BLM infusion. Compared with the BLM/Veh group, histologic findings on Days 14 and 21 in mice treated with BLM and intratracheal instillation of APC (BLM/APC) showed less fibrotic lesions in the subpleural and central areas of the lung. The mean Aschcroft's fibrosis score in the BLM/Veh group was significantly (p < 0.05) higher than in the BLM/APC group. The lung hydroxyproline content on Day 21 was significantly higher (p < 0.05) in the BLM/Veh group (1.78 +/- 0.07 micromol/lung weight) than in the BLM/APC (1.30 +/- 0.06 micromol/lung weight) group. The ratio of plasminogen activator activity to thrombin level in BALF was significantly increased in the BLM/APC group compared with the BLM/ Veh group on Day 21. The expression of tumor necrosis factor-alpha and interleukin-1beta was significantly decreased in the lungs of the BLM/APC group compared with the BLM/Veh group on Day 14 after BLM infusion. These results showed that intratracheal APC administration inhibits the development of lung fibrosis in BLM-induced lung injury, giving further support to the important role that the PC pathway plays in the mechanism of lung fibrosis.

Animals↗

PubMed2001

Pharmacokinetic study on gastrointestinal absorption of insulinomimetic vanadyl complexes in rats by ESR spectroscopy.

Recently, we have shown that oral administrations of vanadyl (+4 oxidation state of vanadium) complexes normalize the blood glucose level of streptozotocin-induced diabetic rats (STZ-rats). To develop clinically useful insulin-mimetic vanadyl complexes, clarification of the pharmacokinetic features of vanadyl compounds is essential. First, we investigated the absorption processes of three compounds, an ionic form of vanadyl sulfate (VS) and the complex forms of bis(picolinato)oxovanadium(IV) (VO(pic)2) and bis(6-methylpicolinato)oxovanadium(IV) (VO(6mpa)2), from the gastrointestinal tract of healthy rats. The concentration curves of paramagnetic vanadyl species in the blood of rats after oral administration of these compounds, as monitored by X-band electron spin resonance (ESR) spectroscopy, exhibited biphasic increasing patterns, indicating that these compounds were absorbed from more than two sites in the gastrointestinal tract. The bioavailability of the compounds was enhanced in the following order on both oral and intraperitoneal administration: VO(6mpa)2 > VO(pic)2 > VS. In addition, bioavailability of the VO(6mpa)2 on ileal administration was enhanced compared with that using other administration sites such as the stomach and jejunum, and resulted in an enhancement about 1.8 fold that compared with oral administration. On the basis of these results, we concluded that the bioavailability of the complex is enhanced most effectively by delivery of the VO(6mpa)2 complex to the ileum.

Administration, Oral↗

PubMed2001

Influence of cyclic variation of right ventricular volume on left ventricular mechanical parameters measured with conductance catheter.

The conductance catheter is widely used for the continuous measurement of the left ventricular (LV) pressure-volume loops. Cyclical change of the right ventricular (RV) volume may alter the parallel conductance volume, thereby affecting the LV mechanical parameters. Using 8 open-chest adult mongrel dogs, multiple LV pressure-volume loops were obtained by 2 methods: first with a vena cava occlusion (VCO) method, which involved RV volume alteration, and second with a right-heart-bypass (RHB) preparation, which decompressed the right ventricle completely. The slope of the end-systolic pressure-volume relation (Ees), the end-systolic volume associated with the end-systolic pressure of 100 mmHg (V100,es), stiffness constant (beta), and the end-diastolic volume associated with the end-diastolic pressure of 9 mmHg (V9,ed) were calculated from each loop. There was minimal influence from RV volume alteration on systolic-phase indices [Ees (VCO method, 6.37 +/- 1.91 mmHg/ml; RHB preparation, 6.60 +/- 1.66mmHg/ml; p=0.356), and V100,es (VCO method, 18.4 +/- 9.3ml; RHB preparation, 17.8 +/- 9.0 ml; p=0.681)], but there was a significant influence on diastolic-phase indices [beta (VCO method, 0.0599 +/- 0.0152; RHB preparation, 0.0839 +/- 0.0150; p=0.007), and V9,ed (VCO method, 35.6 +/- 11.3 ml; RHB preparation, 31.9 +/- 12.3 ml; p=0.001)]. The increase in the RV volume in the diastolic phase increased the parallel conductance volume, causing overestimation of the LV diastolic volume measured by the conductance catheter.

Animals↗

PubMed2001

[Case of protein-losing gastroenteropathy associated with scleroderma in which central serous chorioretinopathy developed].

A 44-year-old woman noticed edema of the lower limbs in May 1999 and visited our hospital in September 1999 to undergo further examination. On admission, severe hypoalbuminemia (1.9 g/dl) was detected with a negative urinary protein level. Protein leakage into the gastrointestinal tract and deposition of immune complex in the colonic mucosa were shown by the fluorescent antibody method. In addition, anti-centromere antibody, sclerodactyly, and findings indicative of histological sclerotic changes on a skin biopsy were observed. These findings supported a diagnosis of protein-losing gastroenteropathy complicated by scleroderma. Administration of oral corticosteroids was begun one month after admission and the patient experienced diminished visual acuity immediately after steroid pulse therapy in November. Central serous chorioretinopathy (CSC) was diagnosed at the Department of Ophthalmology of our hospital, and the administration of corticosteroids was suspected as a possible cause of CSC. Considering the severity of hypoproteinemia, the corticosteroid treatment was continued despite corticosteroids being strogly suspected as the primary cause of CSC. A complete disappearance of CSC was achieved in 30 days after the onset of symptoms despite continuation of the steroid therapy, and her serum albumin and complement levels both normalized. We concluded that damage to the retinal pigment epithelium secondary to the vascular lesion at the choroidal level plays a causative role in CSC. In the present case, the findings suggested that the deposition of immune complex in choroidal tissues as well as the gastrointestinal tract caused hyperpermeability of choroidal vessels and led to the development of CSC.

Adult↗

PubMed2001

[The surgical treatment of congenital valve disease].

The clinical results after surgical treatment of congenital valve disease have improved due to the use of several recently developed techniques. The replacement of tendinous cords using E-PTFE sutures has allowed the indications for the repair of mitral valve prolapse to be extended. The Ross procedure has made it possible to replace the aortic valve associated with small aortic annulus. However, replacement with a prosthetic valve remains the only option if repair is not possible or fails. Prosthetic valve replacement in the pediatric age-group remains challenging in patients with a small valve annulus. A number of techniques can be employed in such cases, including enlargement of the aortic annulus and translocation of the prosthetic valve in the left atrium, although there are limits on the size of the prosthesis. Further improvement of surgical techniques is necessary, along with the development of prosthetic valves using more nearly physiological materials.

Aortic Valve↗

PubMed2000

The properties of BCN films formed by ion beam assisted deposition.

A study has been made on the formation and the properties of boron carbonnitride (BCN) thin films. The BCN films were produced by ion beam assisted deposition, in which boron and carbon were deposited by electron beam heating and nitrogen was supplied by ion implantation simultaneously. The mechanical properties of BCN films were measured using a ultra micro hardness tester and a friction tester. The atomic ratio and the structure of BCN thin films were estimated by means of X-ray photoelectron spectroscopy, laser Raman spectroscopy and Fourier transform infrared spectroscopy. As preliminary results, it was found that the BCN films are higher in hardness and lower in friction coefficient than diamond-like carbon (DLC) films. The mechanical properties are discussed with the relation of surface composition and structure.

Journal Article↗

PubMed2000

Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.

We elucidated the possible role of chimerism in skin and heart allograft tolerance using cyclophosphamide (CP)-induced tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were i.v. primed with 1x10(8) spleen cells (SC) from H-2 matched AKR (H-2k; Thy1.1, Mls-1a) mice and then treated i.p. with 200 mg/kg of CP, the survivals of both AKR skin grafts and heart grafts (HG) were permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism, the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery, and the clonal deletion of Vbeta6+ thymocytes were all observed. When AKR SC and 100 mg/kg CP were used for conditioning, the AKR HG were permanently accepted, but the survival of the AKR skin grafts was only mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery and the intrathymic clonal deletion of Vbeta6+ thymocytes were induced in both the SC and the 100 mg/kg CP-treated C3H mice. A minimal degree of mixed chimerism was detectable at 4 and 12 weeks after AKR SC and 100 mg/kg CP treatment, and still did not disappear at 40 weeks. The degree of mixed chimerism induced with SC and 100 mg/kg CP was significantly lower than that with SC and 200 mg/kg CP during the observation. No posttransplant cardiac allograft vasculopathy (CAV) was observed to develop, while both the Th1 type (interferon-gamma) and Th2 type (interleukin-4 and -10) cytokine expressions decreased in the AKR HG of the tolerant C3H mice treated with both AKR SC plus 200 mg/kg CP, and AKR SC plus 100 mg/kg CP. A second set of skin grafts from donor AKR mice survived for more than 100 days in a tolerogen-specific fashion in all C3H mice treated with AKR SC and 200 mg/kg CP and also accepted the AKR HG for over 200 days, while 80% of the C3H mice treated with AKR SC and 100 mg/kg CP and accepted the AKR HG for more than 200 days. These results strongly suggested the following conclusions: 1) the degree of chimerism can strongly influence the induction of skin and heart allograft tolerance, 2) posttransplant CAV does not develop in the donor HG maintained by chimerism-based CP-induced tolerance, 3) the mRNA expression of both Th1 and Th2 type cytokine decreased in the donor HG maintained by chimerism-based CP-induced tolerance, and 4) the induction of skin allograft tolerance is more difficult than the prevention of posttransplant CAV.

Animals↗

PubMed2000

Induction of permanent mixed chimerism and skin allograft tolerance across fully MHC-mismatched barriers by the additional myelosuppressive treatments in mice primed with allogeneic spleen cells followed by cyclophosphamide.

A pure method of drug (cyclophosphamide plus busulfan)-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers in mice has been established. The components of the method are i.v. administration of 1 x 108 allogeneic spleen cells on day 0, i.p. injection of 200 mg/kg CP and 25 mg/kg busulfan on day 2, and i.v. injection of T cell-depleted 1 x 107 bone marrow cells from the same donor on day 3. Recipient B10 (H-2b; IE-) mice prepared with this conditioning developed donor-specific tolerance, and long-lasting survival of skin allografts was shown in almost of the recipient mice. In the tolerant B10 mice prepared with new conditioning, stable multilineage mixed chimerism was observed permanently, and IE-reactive Vbeta11+ T cells were reduced in periphery as seen in untreated B10.D2 (H-2d; IE+) mice. The specific tolerant state was confirmed by the specific abrogation against donor Ag in the assays of CTL activity and MLR and donor-specific acceptance in the second skin grafting. These results demonstrated that the limitation of standard protocol of cyclophosphamide-induced tolerance, which have been reported by us since 1984, can be overcome by the additional treatments with the myelosuppressive drug busulfan, followed by 1 x 107 T cell-depleted bone marrow cells. To our knowledge, this is the first report to induce allograft tolerance with a short course of the Ag plus immunosuppressive drug treatment without any kind of mAbs (pure drug-induced tolerance).

Animals↗

PubMed2000

An orally active antidiabetic vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), with VO(S2O2) coordination mode; in vitro and in vivo evaluations in rats.

According to Pearson's HSAB (hard and soft acids and bases) rule, the vanadyl ion is classified as a hard acid. However, vanadyl-cysteine methyl ester and dithiocarbamate complexes with VO(S2N2) and VO(S4) coordination modes, respectively, that contain bonds with a combination of hard acid (VO2+) and soft base (sulfur) have been found to form stable complexes and exhibit insulin-mimetic activities in in vitro and in vivo evaluations. Based on such observations, a purple bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) (VO(OPT)) complex with VO(S2O2) coordination mode was prepared and found to have a strong insulin-mimetic activity in in vitro evaluation, which followed in vivo effectiveness on intraperitoneal injection and oral administration. Then, we examined the real-time ESR analysis of vanadyl species in the blood of live rats given VO(OPT) by use of the blood circulation monitoring-ESR method. The clearance of vanadyl species from the blood in terms of half-life (t(1/2)) was determined as 15 min in VO(OPT)-treated rats, while t(1/2) of VOSO4-treated rats was 5 min, indicating the long-term acting character of VO(OPT). On the basis of the results, VO(OPT) with VO(S2O2) coordination mode is proposed to be a potent orally active insulin-mimetic complex in treating insulin-dependent diabetes mellitus in experimental animals.

Adipocytes↗

PubMed2000

Molecular decipherment of Rho effector pathways regulating tight-junction permeability.

We reported recently that the activation of RhoA induced an increase in transepithelial electrical resistance (TER). To clarify effectors of Rho for this RhoA-induced regulation of tight-junction permeability, we introduced two effector-loop mutants of constitutively active RhoA(V14), RhoA(V14/L40) and RhoA(V14/C42), into Mardin-Darby canine kidney cells in an isopropyl beta-D-thiogalactoside-inducible expression system. RhoA(V14) and the two effector-loop mutants interacted in vitro with the Rho-binding domain of Rho-associated kinase, ROKalpha. Next we examined two parameters of Rho functions, stress-fibre formation and TER elevation, induced by RhoA(V14). Stress-fibre formation was induced by RhoA(V14/C42) but not by RhoA(V14/L40). On the other hand, TER elevation was induced by neither RhoA(V14/L40) nor RhoA(V14/C42). RhoA-associated kinase inhibitor, Y-27632, inhibited both stress-fibre formation and TER elevation induced by RhoA(V14). These results demonstrated that RhoA-induced regulation of tight-junction permeability is mediated by Rho-associated kinase and at least one other unidentified effector, the coupling to RhoA being disrupted by mutation at position 40 or 42 in the effector loop.

Animals↗

PubMed2000

Chemiluminescent detection and imaging of reactive oxygen species in live mouse skin exposed to UVA.

The recent increase of ultraviolet (UV) rays on Earth due to the increasing size of the ozone hole is suggested to be harmful to life and to accelerate premature photoaging of the skin. The detrimental effects of UV radiation on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical (*O(-)(2)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (*OH), and singlet oxygen ((1)O(2)). However, direct proof of such ROS produced in the skin under UV irradiation has been elusive. In this study, we report first in vivo detection and imaging of the generated ROS in the skin of live mice following UVA irradiation, in which both a sensitive and specific chemiluminescence probe (CLA) and an ultralow-light-imaging apparatus with a CCD camera were used. In addition, we found that *O(-)(2) is formed spontaneously and (1)O(2) is generated in the UVA-irradiated skin. This method should be useful not only for noninvasive investigation of the spatial distribution and quantitative determination of ROS in the skin of live animals, but also for in vivo evaluation of the protective ability of free radical scavengers and antioxidants.

Animals↗

PubMed2000

Risk factors for posttransfusion graft versus host disease, mediastinitis, and late cardiac tamponade in heart surgery. Survey of 119 Japanese institutions.

OBJECTIVE: Correlations and risk factors remain to be unclarified for post-heart-surgery posttransfusion graft-versus-host disease, mediastinitis, and late cardiac tamponade caused by deteriorated host-defense mechanisms due to cardiopulmonary bypass both with and without steroid usage. METHODS: We sent questionnaires to 298 Japanese cardiovascular institutions asking for institution profiles, including infection control, steroid use in cardiopulmonary bypass, and prevalence of mediastinitis, late cardiac tamponade, and posttransfusion graft-versus-host disease during 1994. The overall prevalence of posttransfusion graft-versus-host disease since the start of service (from establishment of institution to date) was also requested. RESULTS: The number of pump cases at the 119 institutions responding (40%) were 91.6 +/- 67.9 cases/institution (total = 10,904). The prevalence of mediastinitis was 1.2 +/- 1.8 and that of late cardiac tamponade 1.0 +/- 1.8%. Posttransfusion graft-versus-host disease occurred in 1 of 10,904 patients (0.01%) during 1994 at an institution where steroids and nonirradiated blood were used in surgery. The simple institutional mean prevalence of posttransfusion graft-versus-host disease since establishing institutions was 0.08 +/- 0.13%. Of the 119 institutions surveyed, 86 used steroids in all pump cases (72%); 11 institutions used steroids in a limited number of cases (9%). The institutional mean of methylprednisolone-converted steroid dose was 21.5 +/- 16.4 mg/kg (n = 119). In multivariate regression analysis, operation time (p = 0.005) for mediastinitis, steroid usage (all, limited, or no cases) (p = 0.01) and % aneurysm (p = 0.05) for late cardiac tamponade, and steroid dosage (p = 0.002) for posttransfusion graft-versus-host disease were identified as significant risk factors. CONCLUSION: Our results suggest that massive steroid administration for cardiopulmonary bypass may increase the risk of posttransfusion graft-versus-host disease and late cardiac tamponade, but not mediastinitis.

Aged↗

PubMed2000

Mitral valve replacement using bileaflet mechanical prosthetic valve in the first year of life.

OBJECTIVE: The operative management and long term outcome of mitral valve replacement in infancy remain a therapeutic challenge. The selection of a prosthetic valve for this particular age group might affect the clinical outcome. Here we present our experience of mitral valve replacement in 6 infants using small bileaflet mechanical prosthetic valves. METHODS: Between January 1994 and August 1997, 6 infants (their age ranged from 3 months to 11 months, and their body weight from 2978 g to 7403 g) underwent mitral valve replacement using a mechanical valve prosthesis (16 mm CarboMedics prosthetic valve in 5, and 17 mm St. Jude Medical prosthetic valve Hemodynamic Plus in 1). The preoperative morphological features of the mitral valve were stenosis in 1, regurgitation in 3, and a combination of these in 2. The prosthesis was fixed at the annulus in 3, and at the supra-annular position in 3. Anticoagulation was performed using warfarin. RESULTS: There was no operative mortality. Postoperative catheterization revealed an acceptable wedge pressure in the pulmonary arteries, ranging from 10 to 12 mmHg. During the mean follow-up period of 36 months, late death due to residual pulmonary hypertension occurred in 1 patient at 10 months after surgery. Excluding this patient, all remaining patients are doing well with no need for repeated operation with no thromboembolic complication. The actuarial survival rate and the reoperation free rate at 70 months are 83 +/- 15% and 100%, respectively. CONCLUSION: Mitral valve replacement using a small size bileaflet mechanical prosthetic valves in infancy can be performed with low operative mortality and with satisfactory mid-term results.

Follow-Up Studies↗

PubMed2000

Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy.

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia.

Aged↗

PubMed2000

Current techniques of hyperthermic isolated limb perfusion for malignant melanoma.

A retrospective study was conducted examining 25 patients with malignant melanoma who were treated by our new protocol for hyperthermic isolated limb perfusion. The characteristics of our techniques include: a lower priming volume of the extracorporeal circuit; a therapeutic temperature range of 40-41 degrees C with 60 min hyperthermic perfusion; a nominal perfusion flow rate of 500 ml/min in the lower limb and 200 ml/min in the upper limb; and combined carboplatin with interferon-beta as the adjuvant chemotherapy drug. In the lower extremity group, the arterial cannula size ranged from 8 to 14 F, while the venous cannula size ranged from 14 to 16 F. In the upper limb group, the arterial cannula size ranged from 6 to 8F and the venous cannula size ranged from 10 to 12F. No patient required any homologous blood transfusion postoperatively. No operative death or major complications occurred during the early postoperative period, confirming the safety of this treatment. Both optimal cannula size selection and maintaining perfusion temperature below 41 degrees C were judged to be important in elimination of vascular and deep tissue injury.

Adult↗

PubMed2000

The differential cardioprotective effects of nucleoside transport inhibitor on moderate and deep hypothermic ischemia with cold cardioplegia.

The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.

Adenine Nucleotides↗

PubMed2000

Human skin xenograft rejection in CD45 exon-6 knockout mice: the implication of involvement of a direct pathway.

The results of previous studies indicate that only CD4+ T cells generated via the indirect pathway play an essential role in causing discordant skin xenograft rejection. The present study was conducted in an attempt to clarify further the roles of effector T cells generated via direct pathways on discordant xenograft rejection using CD45 exon-6 knockout (CD45-/-; C57BL/6 (B6): H-2b) mice. It has been strongly suggested that CD45 exon-6 knockout mice have profound impairment in T-cell functions via an indirect pathway. When human skin was grafted onto untreated normal C57BL/6 (B6; H-2b) mice, rejection occurred within 12 days; however, in the CD45 exon-6 knockout mice, the grafts lasted for slightly longer as in fully allogeneic C3H (H-2k) skin rejection, with a mean survival time +/- SD of 19.4 +/- 1.5 days and median survival times of 19 days. The difference in survival periods between the human and C3H skin grafts in the CD45 knockout mice was not statistically significant. Both CD4+ and CD8+ T cells seemed activated in the spleens of these CD45 exon-6 knockout mice 10 days after the human skin grafting. These results suggest that effector T cells generated via a direct pathway can cause discordant skin xenograft rejection, and that CD45 exon-6 knockout mice can generate effector T cells via a direct pathway to reject discordant skin xenografts, similarly to fully allogeneic skin allografts.

Animals↗