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Biomedical subjects

T Maki

Publications and source records attributed to T Maki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of neutral endopeptidase inhibitor on endogenous atrial natriuretic peptide as a paracrine factor in cultured cardiac fibroblasts.

1. Cardiac remodelling is a fundamental response to hypertension, myocardial infarction and chronic heart failure, and involves cardiac fibroblast proliferation and production of extracellular matrix components such as collagen. The present study was performed to examine the role of endogenous atrial natriuretic peptide (ANP) as a possible paracrine factor for cardiac fibroblasts, and to examine the effects of three neutral endopeptidase (NEP) inhibitors, thiorphan, phosphoramidon and ONO-BB-039-02 (ONO-BB) on endogenous ANP-induced changes in collagen synthesis by cultured neonatal rat cardiac fibroblasts. 2. Each NEP inhibitor singly had no significant effect on collagen synthesis by cardiac fibroblasts, except for maximum concentration (10(-3) M) of thiorphan. 3. Exogenous ANP inhibited collagen synthesis in a concentration-dependent manner (10(-8) - 10(-6) M). Thiorphan (10(-4) and 10(-3) M) and phosphoramidon (10(-5) and 10(-4) M) enhanced the ANP (10(-7) M)-induced decrease in collagen synthesis. ONO-BB (10(-5) and 10(-4) M) slightly enhanced the ANP-induced decrease in collagen synthesis. 4. Myocyte-conditioned medium (MC-CM), as well as exogenous ANP, inhibited collagen synthesis dose-dependently. The decrease in collagen synthesis at 100% MC-CM was augmented by thiorphan (10(-3) M), phosphoramidon (10(-4) M) and ONO-BB (10(-4) M). 5. HS-142-1, a natriuretic peptide receptor antagonist, significantly reduced the MC-CM plus thiorphan- and MC-CM plus ONO-BB-induced decrease in collagen synthesis, by 92 and 62%, respectively and showed a tendency to attenuate the MC-CM plus phosphoramidon-induced decrease in collagen synthesis by 40%. 6. Our observations suggested that endogenous ANP released from cardiomyocytes inhibited collagen synthesis as a paracrine factor and that NEP inhibitors enhanced the activity of this peptide in cardiac fibroblasts.

Animals↗
PubMed2000

CD4(+) Valpha14 natural killer T cells are essential for acceptance of rat islet xenografts in mice.

Pancreatic islet transplantation represents a potential treatment for insulin-dependent diabetes mellitus. However, the precise cellular and molecular mechanisms of the immune reactions against allogeneic and xenogeneic transplanted islets remain unclear. Here, we demonstrate that CD4(+) Valpha14 natural killer T (NKT) cells, a recently identified lymphoid cell lineage, are required for the acceptance of intrahepatic rat islet xenografts. An anti-CD4 mAb, administrated after transplantation, allowed islet xenografts to be accepted by C57BL/6 mice, with no need for immunosuppressive drugs. The dose of anti-CD4 mAb was critical, and the beneficial effect appeared to be associated with the reappearance of CD4(+) NKT cells at around 14 days after transplantation. Interestingly, rat islet xenografts were rejected, despite the anti-CD4 mAb treatment, in Valpha14 NKT cell-deficient mice, which exhibit the normal complement of conventional lymphoid cells; adoptive transfer of Valpha14 NKT cells into Valpha14 NKT cell-deficient mice restored the acceptance of rat islet xenografts. In addition, rat islet xenografts were accepted by Valpha14 NKT mice having only Valpha14 NKT cells and no other lymphoid cells. These results indicate that Valpha14 NKT cells play a crucial role in the acceptance of rat islet xenografts in mice treated with anti-CD4 antibody, probably by serving as immunosuppressive regulatory cells.

Animals↗
PubMed2000

Depressor effect of wheat germ hydrolysate and its novel angiotensin I-converting enzyme inhibitory peptide, Ile-Val-Tyr, and the metabolism in rat and human plasma.

We report here the antihypertensive effect of wheat germ (WG) hydrolysate and its dominant peptide, Ile-Val-Tyr (IVY), with potent angiotensin I-converting enzyme (ACE) inhibitory activity. The toxicity test of AG50W fraction purified from the WG hydrolysate and IVY in ddy mice revealed that 1 week median lethal concentrations of AG fraction and IVY were less than 100 and 10 mg/kg, respectively. As a result of an intravenous administration test of both inhibitors in spontaneously hypertensive rat (SHR), the mean arterial blood pressure (MAP) significantly decreased with the dose; the MAP reduction of 10.3 and 19.2 mmHg was observed at a dose of 50 mg/kg of AG fraction and 5 mg/kg of IVY, respectively. In addition to this behavior, the MAP gradually decreased after the 5 mg/kg of IVY injection (time to give a maximum reduction; 8 min), and the reduction was held for 20 min. By using rat and human plasma, IVY was found to be metabolized by the action of aminopeptidase in plasma to form a subsequent ACE inhibitor, Val-Tyr (VY). Thus, the intake of IVY as a physiologically functional food would serve in the lowering of blood pressure (BP) by the combined depressor effect of itself and its metabolite after the absorption.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Dissolution profiles of principal ingredients in Kampo medicinal powders by high-performance liquid chromatography.

We describe here a method using HPLC for the simultaneous determination of albiflorin, paeoniflorin, glycyrrhizin and six flavanone glycosides (liquiritin, liquiritin apioside, naringin, neohesperidin, hesperidin and narirutin) in the Kampo medicines, Shigyaku-san and Haino-san. All nine components were separated in less than 40 min by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile. The dissolution of these components from powders of Shigyaku-san in aqueous solution at pH 1.80, 4.08 and 6.89 was examined. All of the components except glycyrrhizin were dissolved entirely within 5 min regardless of pH. Dissolution of glycyrrhizin was dependent on the pH of the aqueous solution, and increased with increasing pH.

Chromatography, High Pressure Liquid↗
PubMed1999

Resistance of established porcine islet xenografts to humoral rejection by hyperimmune sera.

BACKGROUND: Although preformed natural antibodies cause hyperacute rejection of primarily vascularized xenografts, tissue grafts such as skin or islets are revascularized by in-growth of host capillaries and therefore might be resistant to circulating antibodies. We examined the effect of hyperimmune serum and primed T cells on the survival of long-term porcine islet xenografts in diabetic nude mice. METHODS: Porcine islets were transplanted beneath the kidney capsule of streptozotocin-induced diabetic BALB/c athymic mice. Hyperimmune serum and sensitized splenocytes were prepared by repeated immunization of BALB/c mice with porcine lymph node cells. Splenic T cells were enriched by nylon wool column separation. Tissues were examined by immunohistology using murine- and porcine-specific monoclonal antibodies. RESULTS: Porcine islets survived in nude mice for > 100 days with high levels of circulating porcine C-peptide and maintenance of normoglycemia. Injection of the hyperimmune sera (IgG) into normoglycemic nude mice bearing porcine islets for > 70 days failed to induce rejection despite the continued presence of circulating anti-porcine cytotoxic antibody. Injection of sensitized T cells caused acute rejection of long-term (>140 days) porcine islets, whereas injection of naive T cells had no effect. Histologically, porcine islets removed from mice treated with hyperimmune serum showed no staining for IgG. Long-surviving porcine islet grafts showed strong staining for interleukin (IL)-10 and a lesser amount of IL-4 but no staining for IL-2 or interferon-gamma. Although fresh porcine islets were positive for swine leukocyte antigen class 1 antigen and intercellular adhesion molecule (ICAM)-1 but negative for mouse platelet endothelial cell adhesion molecule and ICAM-2, long-surviving porcine islets showed positive endothelial staining for mouse platelet endothelial cell adhesion molecule and ICAM-2. CONCLUSIONS: Established islet xenografts are resistant to hyperimmune serum as a result of a lack of target endothelial antigens, whereas they remain susceptible to rejection caused by primed T cells. Local production of Th2 cytokines may explain the inability of long-surviving islet xenografts to activate injected naive T cells.

Animals↗
PubMed1999

A convenient method for synthesis of enantiomerically enriched methylphenidate from N-methoxycarbonylpiperidine.

[formula: see text] This report describes a new method to prepare optically active methylphenidate starting from piperidine. The method consists of a transformation of N-methoxycarbonylpiperidine to the corresponding alpha-methoxylated carbamate I by utilizing electrochemical oxidation followed by the coupling reaction with optically active Evans imides II to produce optically active methylphenidate derivatives III with high stereoselectivities, threo-(2R,2'R)-Methylphenidate (IV; Ar = Ph; Ritalin) was easily prepared from III in three steps.

Adrenergic Agents↗
PubMed1999

Islet mass plays a critical role in initiation, but not progression, of the diabetogenic process in NOD mice.

Pancreatectomy (90%) at a preinsulitis age (7 weeks) protects NOD mice from diabetes while pancreatectomy at a mid-insulitis age (13 weeks) has no such protective effect. The present study examined the effects of islet transplantation in pancreatectomized diabetes-free NOD mice. Transplantation of syngeneic NOD islets as well as allogeneic C3H/He and C57BL/6 islets 3 weeks after pancreatectomy-induced spontaneous diabetes whereas transplantation of xenogeneic Sprague-Dawley rat islets or allogeneic C3H/He skin failed to induce diabetes, demonstrating that the diabetogenic antigen(s) of NOD islets is also expressed by islets of diabetes-resistant mouse strains but not by xenogeneic rat islets. Removal of NOD islet grafts by nephrectomy 7-14 days after transplantation had no effect on the subsequent chronic development of diabetes, while graft removal 3 days after transplantation completely abolished the diabetogenic effect of islet transplantation. Thus, activation of the diabetogenic response by islet isografting takes less than 7 days and the continuous presence of a large islet mass is not required for progression to diabetes. While islet transplantation at 10 and 15 weeks of age caused diabetes, delayed islet transplantation at 23 and 35 weeks of age failed to induce diabetes in pancreatectomized diabetes-free NOD mice, suggesting that initiation of the diabetogenic autoimmune process must take place within a certain window of time. The pancreatectomy/islet transplantation model is excellent for studying the immunological events surrounding activation and progression of the diabetogenic autoimmune process and for identifying the diabetogenic islet antigen(s).

Animals↗
PubMed1999

A magnetic resonance abnormality correlating with permeability of the blood-brain barrier in a child with chemical meningitis during central nervous system prophylaxis for acute leukemia.

Chemical meningitis developed in a boy with acute lymphoblastic leukemia during central nervous system (CNS) prophylaxis. Cerebrospinal fluid examination showed pleocytosis and a high protein level. There were no malignant cytological findings. Calculated permeability of albumin across the blood-brain barrier (BBB) was more elevated than that of immunoglobulin or alfa2-macroglobulin. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement without any intracerebral lesion. Subsequent CNS prophylaxis was postponed. CSF findings and BBB permeability returned to normal, correlating well with the decrease of MRI abnormality.

Albumins↗
PubMed1999

Improvement of exercise capacity of rats with chronic heart failure by long-term treatment with trandolapril.

1. The effects of long-term treatment with trandolapril, an angiotensin I-converting enzyme inhibitor, on exercise capacity of rats with chronic heart failure (CHF) following coronary artery ligation were examined. CHF was developed by 8 weeks after the coronary artery ligation. 2. The running time of rats with CHF in the treadmill test was shortened to approximately 65% of that of sham-operated rats (16.3+/-1.2 vs. 25.1+/-1.6 min, n = 7; P<0.05). ATP, creatine phosphate (CP), and lactate contents of the gracilis muscle of rats with CHF were similar to those of sham-operated rats before running. After running, ATP and CP were decreased and lactate was increased in both rats with CHF and sham-operated rats. There were no significant differences in the levels of energy metabolites between rats with CHF and sham-operated rats. The rates of decrease in ATP and CP and rate of increase in lactate in the gracilis muscle of rats with CHF during exercise were greater than those of sham operated rats (2.5, 2.0 and 1.5 fold high, respectively), suggesting wastage of energy during exercise in the animals with CHF. 3. Myofibrillar Ca2+ -stimulated ATPase (Ca-ATPase) activity of skeletal muscle of rats with CHF was increased over that of the sham-operated control (62.03+/-1.88 vs. 52.34+/-1.19 micromol Pi mg(-1) protein h(-1) n = 7; P<0.05). The compositions of myosin heavy chain (MHC) isoforms of gracilis muscle were altered by CHF; decreases in MHC types I and IIb and an increase in MHC type IIa were found (P<0.05). 4. Rats with CHF were treated with 1 mg kg(-1) day(-1) trandolapril from the 2nd to 8th week after surgery. Treatment with trandolapril prolonged the running time, reversed the rates of decrease in ATP and CP and the rate of increase in lactate, and restored the Ca-ATPase activity (51.11+/-0.56 micromol Pi mg(-1) protein h(-1), n = 7; P<0.05) and composition ratio of MHC isoforms in the gracilis muscle. 5. The results suggest that long-term trandolapril treatment of rats with CHF may restore their ability to utilize energy without wastage and thus improve exercise capacity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[Chlamydia pneumoniae infection and Mycoplasma pneumoniae infection in pediatric patients].

We evaluated a total of 1104 pediatric patients with acute lower respiratory tract infection for C. pneumoniae infection and M. pneumoniae infection by serology during July 1995 to December 1998. A microimmunofluorescence test was used for diagnosis of C. pneumoniae infection and a high density particle agglutination test for that of M. pneumoniae infection. Acute C. pneumoniae infection was found in 149 patients (13.5%), acute M. pneumoniae infection in 118 patients (10.7%), and dual infection in 27 patients (2.4%). Among 305 patients with pneumonia, M. pneumoniae infection (83 patients, 27.2%) was more common than C. pneumoniae infection (47 patients, 15.4%). However among 799 patients with bronchitis. C. pneumoniae infection (102 patients, 12.8%) was more common than M. pneumoniae infection (35 patients, 4.4%). Patients with C. pneumoniae infection were more younger and more frequently wheezing than patients with M. pneumoniae infection. These findings demonstrate that C. pneumoniae infection in very common pathogen of pediatric lower respiratory tract infection as M. pneumoniae infection in Japan.

Acute Disease↗
PubMed1998

Indefinite survival of skin allografts in adult thymectomized, antilymphocyte serum-treated mice given bone marrow and thymus grafts of donor origin: tolerance induction by donor bone marrow and thymus.

BACKGROUND: Perigraft immunosuppression with antilymphocyte serum (ALS) and postgraft infusion of donor bone marrow cells (BMC), which induces allograft unresponsiveness in a class I major histocompatibility complex (MHC)-disparate mouse combination, is much less effective in class I and II MHC-disparate strain combinations. Because the thymus plays a central role in the maturation, differentiation, and education of T lymphocytes, which are the principal mediator of allograft responses, we examined whether transplantation of donor-specific thymus combined with adult thymectomy of recipients enhances the tolerogenic effect of ALS and donor BMC infusion in a strongly histoincompatible class I and II MHC-disparate DBA/2-to-B6AF1 mouse strain combination. METHODS: Adult thymectomy was performed 4 weeks before grafting. B6AF1 mice received ALS (days -1 and 2), skin allografts (day 0), and BMC and/or thymus grafts (ThyTx) (day 7). Flow cytometric analysis was used to detect donor cells in tolerant mice. Limiting dilution assay was used to calculate the frequencies of precursor cytotoxic T lymphocytes against donor and third-party alloantigens. The presence of suppressor cells was determined by in vivo adoptive transfer assay and in vitro coculture mixed lymphocyte culture. RESULTS: When adult thymectomy and postgraft donor ThyTx were combined with ALS and donor BMC, DBA/2 allograft survival was prolonged with all grafts surviving for >122 days. Third-party (DBA/1) or recipient ThyTx was not effective. The tolerant mice accepted the second donor skin allografts but acutely rejected the third-party grafts. No significant chimerism was detected. Marked reduction of precursor cytotoxic T lymphocyte frequencies continued only against donor alloantigens after second donor and third-party skin grafting. No suppressor cell activity was detected. Immunopathological analysis revealed that the cells in the ThyTx of tolerant mice are of donor origin. CONCLUSION: Donor ThyTx combined with donor BMC infusion in adult thymectomized, ALS-treated mice induced clonal deletion of donor-reactive T cells.

Animals↗
PubMed1998

Importance of natural killer cells in the rejection of hamster skin xenografts.

BACKGROUND: In the hamster to rat xenogeneic combination, antibodies, T cells, and natural killer (NK) cells have all been implicated in the process of rejection. 3.2.3 is a mouse IgG1kappa monoclonal antibody (mAb) directed against NKR-P1A on rat NK cells. The purpose of this study was to evaluate the effect of this mAb independently and in combination with other immunosuppressive agents in a hamster to rat skin graft model in order to elucidate the mechanisms involved in xenograft rejection. METHODS: Lewis rats were recipients of hamster skin grafts. Various groups received antilymphocyte serum (ALS) (days -1, 0, and +2), rapamycin (3 mg/kg; alternate days from day +1 through day +13), and 3.2.3 mAb (days 0, +1, and +2). Anti-hamster antibody production was determined serially with a complement-dependent cytotoxicity assay. Lewis anti-hamster mixed lymphocyte reaction and cell-mediated lympholysis assays were performed within 7 days after rejection of the skin graft. NK cell function was tested using a cytotoxicity assay versus YAC-1 target cells on day 14 or day 15 after skin grafting. RESULTS: Median graft survival in untreated animals was 7 days. There was only modest prolongation in rats treated with rapamycin alone (median survival time [MST]=9 days) or ALS alone (MST=10 days). The use of 3.2.3 mAb in untreated rats (3.2.3 alone MST=7 days) and in ALS-treated rats (ALS+3.2.3 MST=9.5 days) did not improve graft survival. The combination of ALS+rapamycin substantially improved graft survival (MST=13 days), and even greater prolongation was seen with the addition of 3.2.3 mAb (ALS+rapamycin+3.2.3 MST=18.5 days). Cytotoxic antibodies, secondary mixed lymphocyte reaction responses, cytotoxic T cells, and normal NK activity were seen at the time of rejection in untreated rats as well as those treated with 3.2.3 mAb alone, ALS alone, ALS+3.2.3 mAb, and rapamycin alone. ALS+rapamycin completely blocked the formation of anti-hamster antibodies and cytotoxic T cells but did not suppress NK activity. The use of 3.2.3 mAb produced a marked but transient suppression of NK activity in all groups. CONCLUSION: Hamster skin xenografts can be rejected by Lewis rats in the absence of cytotoxic antibodies and cytotoxic T cells. ALS, rapamycin, and ALS+rapamycin do not suppress NK activity in Lewis rats, although their use produces a modest prolongation of hamster skin graft survival. The administration of 3.2.3 mAb to Lewis rats results in a marked but transient suppression of NK cell function, which substantially prolongs hamster skin graft survival only when antibody and cytotoxic T-cell production have also been suppressed.

Animals↗
PubMed1998

Determination of an improved sirolimus (rapamycin)-based regimen for induction of allograft tolerance in mice treated with antilymphocyte serum and donor-specific bone marrow.

BACKGROUND: Posttransplant donor-specific bone marrow (BM) infusion in mice treated with antilymphocyte serum (ALS) induces specific unresponsiveness (tolerance) to skin allografts, which can be augmented by the adjuvant administration of chemotherapeutic immunosuppressive agents. The purpose of this study was to determine the optimal dose and timing of administration of sirolimus (rapamycin) to induce maximal skin allograft survival in ALS-treated, BM-infused recipients. METHODS: DBA/2 donor skin grafts were placed on B6AF1 recipients (class I- and II-disparate). Groups of recipient mice (n=10 each) received combinations of the following treatment protocols: ALS, 0.5 ml on days -1 and 2; BM, 25x10(6) donor-specific cells on day 7; sirolimus, 6, 12, 18, or 24 mg/kg at times indicated; and cyclosporine, 50 mg/kg at times indicated. The immune status of putatively tolerant animals was examined with mixed lymphocyte cultures, cell-mediated lympholysis assays (CML), and limiting dilution analyses. RESULTS: When administered in conjunction with ALS/BM, a single dose of sirolimus (6 mg/kg) on days 21, 18, 14, 10, or 7 resulted in median skin graft survival times of 35, 26, 40, 46, and 103 days, respectively, versus a median survival of 27 days in mice given ALS and BM alone. The addition of cyclosporine to sirolimus (6 mg/kg) given on day 7 or days 7 and 10 did not significantly increase graft survival over that achieved with sirolimus alone. A single dose (18 or 24 mg/kg) of sirolimus administered on day 7 to ALS/BM-treated recipients resulted in 100% 200-day skin graft acceptance. Tolerant mice demonstrated nonspecific suppression of the mixed lymphocyte culture assays at 90 and 200 days and a nonspecific reduction of the CML assay at 50 days. By 200 days, the third-party CML response was restored, whereas donor-specific cell-mediated cytotoxicity remained suppressed. There was a donor-specific reduction in the number of alloreactive cytotoxic T lymphocyte clones by limiting dilution assay at 120 days. In vivo specificity of immunosuppression induced with this protocol was demonstrated by indefinite survival of second donor-specific skin grafts placed on putatively tolerant mice at day 90, whereas third-party skin grafts were rejected in 14 days. CONCLUSION: A single dose of sirolimus (18-24 mg/kg) administered on day 7, within the context of an ALS/BM immunosuppressive regimen, reliably induces permanent skin allograft acceptance in this model. In vitro measures of immunocompetence demonstrated an early nonspecific suppression of the recipients immune status and later recovery of third-party immunoreactivity. In vivo testing indicates an operationally tolerant state that is donor-specific 90 days after treatment.

Animals↗
PubMed1998

Use of pharmacologic immunosuppression to augment the specific unresponsiveness (tolerance) to skin allografts induced by donor-specific bone marrow in antilymphocyte serum-treated mice: the unique effect of sirolimus.

Tolerance produced with ALS treatment, DSBM, and sirolimus involves multiple mechanisms of a specific and nonspecific nature. In eventual clinical application for tolerance induction, sirolimus (rapamycin) has great potential for augmenting the tolerogenicity of the ALS/BM regimen.

Animals↗
PubMed1998

Simultaneous determination of an active metabolite and open-ring metabolites by high performance liquid chromatography and pharmacokinetic studies of a penem antibiotic, FCE22891, in dogs.

A sensitive high performance liquid chromatographic method for the simultaneous determination of an active metabolite (FCE22101) and open-ring metabolites (P1, P2) of a penem antibiotic, FCE22891, in dog plasma was developed. Plasma samples were pretreated only by ultrafiltration for the determination of the metabolites. The filtrates were directly analyzed by a reversed-phase high-performance liquid chromatographic system using a two-sided bracketing injection technique. The quantitation limits of FCE22101, P1 and P2 were 0.03, 0.1 and 0.15 microgram ml-1, respectively. Analysis of the spiked plasma samples demonstrated the good accuracy and precision of the method. The proposed method was applied to the pharmacokinetic studies of an active metabolite and open-ring metabolites after oral administration of a penem antibiotic, FCE22891, in dogs. In addition, the plasma levels of unchanged FCE22891 and the possible changes of formaldehyde and acyl-L-carnitine levels in plasma, which will be generated from the ester group of FCE22891, were also investigated.

Acetylcarnitine↗
PubMed1998

Oral supplementation with branched-chain amino acids improves survival rate of rats with carbon tetrachloride-induced liver cirrhosis.

We investigated whether supplementation with branched-chain amino acids (BCAA) improves survival of rats with carbon tetrachloride (CCl4) -induced cirrhosis. Liver cirrhosis was induced in 40 male Sprague-Dawley rats by administering CCl4 for 15 weeks. Twenty rats each were then assigned to the control and BCAA group and fed a casein diet or a BCAA-supplemented casein diet, respectively, for an additional 17 weeks with repeated injections of CCl4. No significant difference occurred in either mean energy or nitrogen intake or in body or liver weight between the two groups. BCAA-supplementation significantly preserved plasma albumin concentrations (P < 0.05) and inhibited significantly the occurrence of ascites and hyperammonemia (P < 0.05). The survival rate was significantly higher in the BCAA group (P=0.03), while no significant difference was found in liver histology between the groups. These results suggest that BCAA improved survival of rats with CCl4-induced cirrhosis by preventing hypoalbuminemia and hyperammonemia without directly reducing hepatic necrosis and fibrosis.

Administration, Oral↗