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Biomedical subjects

Y Misawa

Publications and source records attributed to Y Misawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs.

The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized by two successive cyclization reactions, 11,12-cyclic carbamate formation by intramolecular Michael addition and 9,11-diazaheptene ring construction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromycin-susceptible strains but also erythromycin-resistant Staphylococcus aureus and Streptococcus pneumoniae, which are problematic pathogens of nosocomial and community-acquired respiratory tract infections, respectively.

Anti-Bacterial Agents↗
PubMed2001

Development of a new method to induce angiogenesis at subcutaneous site of streptozotocin-induced diabetic rats for islet transplantation.

The subcutaneous space is a potential site for clinical islet transplantation. Even though there are several advantages, poor blood supply at this site mainly causes failure of islet survival. In this study, angiogenesis was induced in advance at the diabetic rats subcutis for islet transplantation by implanting a polyethylene terephthalate (PET) mesh bag containing gelatin microspheres incorporating basic fibroblast growth factor (bFGF) (MS/bFGF) and a collagen sponge. The bFGF was incorporated into gelatin microspheres for controlled release of bFGF. As controls, a PET mesh bag with or without either collagen sponges or MS/bFGF was implanted at the subcutaneous site of diabetic rats. Macroscopic and microscopic examinations revealed the formation of capillary network in and around the PET mesh bag containing MS/bFGF and collagen sponges 7 days after implantation when compare with other control groups. When tissue hemoglobin level was also measured, a significantly high level of hemoglobin amount was observed compared with that of control groups. When allogeneic islets mixed with 5% agarose were transplanted into the prevascularized rat subcutis, normoglycemia was maintained for more than 40 days, while other control groups were ineffective. This study demonstrated that combination of gelatin microspheres incorporating bFGF and collagen sponges enabled the mesh to induce neovascularization even at the subcutaneous site of streptozotocin-induced diabetic rats, resulting in improved function of islet transplantation.

Animals↗
PubMed2001

Isolation, culture, and characterization of endocrine cells from 6-month-old porcine pancreas.

Porcine endocrine cells were isolated from pancreas of 6-month-old pigs by two-step enzymatic digestion procedures. They were separated by the density gradient (isopycnic) centrifugation method using Histopaque-1077. Isolated cells were cultured and divided into two groups: suspension cells and adhesion cells. Suspension cells maintained their cell numbers on and after 7 days in culture. Approximately 1 x 10(7) cells were obtained from single pancreas of a 6-month-old pig. The cultured suspension cells took up dithizone (DTZ) staining 14 days after isolation in culture and indicated the presence of beta-cells. In in vitro study, the suspension cells were capable of secreting insulin into the culture medium. The suspension cells were tested for insulin and glucagon staining by Western blot analysis. These results indicated the maintenance of endocrine cell function after isolation. However, cultured adhesion cells failed to maintain their function during culture. In in vivo study, the suspension cells were transplanted into diabetes-induced nude mice. Reduction in blood glucose level was obtained after transplantation. Intraperitoneal glucose tolerance test (IPGTT) results showed a normal pattern of blood glucose clearance. After 1 week, the transplanted endocrine cells were detected with anti-insulin antibody by immunostaining and it showed the presence of viable beta-cells under the renal capsule of nude mice. Collectively, our results suggest that isolated and cultured suspension porcine endocrine cells maintained their endocrine function. These endocrine cells can be used as isolated islets for further study, including transplantation experiments.

Animals↗
PubMed2001

Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor.

Rats fed a semipurified diet supplemented with 3% (w/w) safflower oil [Saf, n-3 fatty acid deficient, high linoleic acid (18:2n-6)] through two generations exhibit decreased correct response ratios in a brightness-discrimination learning test compared with rats fed 3% perilla oil [Per, high alpha-linolenic acid (18:3n-3)]. This is associated with a decreased DHA (22:6n-3)-to-arachidonic acid (20:4n-6) ratio in brain lipids. In the first set of experiments, dietary oil was shifted from Saf to a mixture of 2.4% safflower oil plus 0.6% DHA after weaning (Saf-DHA), but all parameters measured in the learning test were essentially unchanged. Brain 22:6n-3 content of the Saf-DHA group reached that of the Per group but the levels of 20:4n-6 and docosatetraenoic acid (22:4n-6) did not decrease to those of the Per group at the start of the test. In the second set of experiments, dietary oil was shifted to a mixture of 0.6% safflower oil plus 1.2% oleic acid (OA) plus 1.2% DHA (Saf-OA-DHA group) with 18:2n-6 content comparable to that of the Per group. The Saf-OA-DHA group exhibited a learning performance similar to that of the Per group; brain 22:6n-3, 20:4n-6, and 22:4n-6 contents were also comparable to those of the Per group. These results indicate that the altered learning behavior associated with a long-term n-3 fatty acid deficiency is reversed by supplementing 22:6n-3 after weaning, when the levels of competing n-6 fatty acids in the diet and brain lipids are limited.

Aging↗
PubMed2000

Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin.

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.

Animals↗
PubMed2000

Effect of n-3 fatty acid deficiency on fatty acid composition and metabolism of aminophospholipids in rat brain synaptosomes.

Docosahexaenoic acid (DHA, 22:6n-3) is one of the major polyunsaturated fatty acids esterified predominantly in aminophospholipids such as ethanolamine glycerophospholipid (EtnGpl) and serine glycerophospholipid (SerGpl) in the brain. Synaptosomes prepared from rats fed an n-3 fatty acid-deficient safflower oil (Saf) diet had significantly decreased 22:6n-3 content with a compensatory increased 22:5n-6 content when compared with rats fed an n-3 fatty acid-sufficient perilla oil (Per) diet. When the Saf group was shifted to a diet supplemented with safflower oil plus 22:6n-3 (Saf + DHA) after weaning, 22:6n-3 content was found to be restored to the level of the Per group. The uptake of [3H]ethanolamine and its conversion to [3H]EtnGpl did not differ significantly among the three dietary groups, whereas the formation of [3H]lysoEtnGpl from [3H]ethanolamine was significantly lower in the Saf group than in the other groups. The uptake of [3H]serine, its incorporation into [3H]SerGpl, and the conversion into [3H]EtnGpl by decarboxylation of [3H]SerGpl did not differ among the three dietary groups. The observed decrease in lysoEtnGpl formation associated with a reduction of 22:6n-3 content in rat brain synaptosomes by n-3 fatty acid deprivation may provide a clue to reveal biochemical bases for the dietary fatty acids-behavior link.

Animals↗
PubMed2000

Allozymic variation of Hynobius kimurae Dunn (Amphibia, Caudata).

An electrophoretic survey was conducted to examine genetic divergence among 21 populations of a lotic-breeding salamander Hynobius kimurae from Honshu, Japan. Genetically H. kimurae proved to be specifically distinct from H. naevius. Hynobius kimurae is divided genetically into two groups of local populations, and the five populations from the eastern area are genetically distinct from the remaining populations of the central and western areas. Less prominent genetic differentiation was revealed between the western and central populations. Separation of the eastern and central-western groups are discussed in relation to the formation of the Japanese mainland.

Animals↗
PubMed2000

Dietary docosahexaenoic acid can alter the surface expression of CD4 and CD8 on T cells in peripheral blood.

The effect of dietary docosahexaenoic acid (DHA) on T cell states in peripheral blood was investigated. Weanling male C57Bl/6N mice were kept on one of three 10% fat diets containing various amounts of DHA and linoleic acid for 4 weeks. Changing the concentration of dietary DHA did not alter the proportion of T cells expressing CD4 or CD8. However, increasing the concentration of dietary DHA lowered the expression of CD4 and CD8 on the cell surface. The decreased expression of these surface molecules involved in T cell proliferation has serious implications in the role of DHA as an immunosuppressant.

Animals↗
PubMed2000

Transient rise in serum soluble Fas (APO-1/CD95) in patients undergoing cardiac surgery.

The Fas molecule, also designated APO-1/CD95, belongs to the tumor necrosis factor (TNF) receptor family. It is a widely expressed membrane-anchored protein that induces apoptosis by Fas/Fas ligand (Fas-L) mediation. It was reported that Fas-mediated apoptosis plays an important role in regulation of the immune system, systemic inflammatory response, and ischemia/reperfusion injury. A soluble form of Fas (sFas) is produced either through the proteolytic cleavage of membrane-bound receptors or by alternative splicing, and sFas is thought to be implicated in apoptosis. In addition, sFas released damaged cells, and elevated serum levels of sFas reflect systemic tissue damage. To examine the specificity of sFas production during cardiac surgery with cardiopulmonary bypass, we serially measured the serum sFas levels in 13 patients during and after surgery. Blood samples were obtained before surgery, at the end of cardiopulmonary bypass, at the end of surgery, and at 12 h after surgery. Levels of serum sFas were determined by sandwich ELISA. Seven patients undergoing other types of surgeries served as controls. Although increased sFas was not observed in the control group, a significantly higher sFas level was detected in cardiac surgical patients at the end of surgery than before surgery (p = 0. 028), and the level decreased at 12 h after surgery. A significant correlation was observed between the maximum sFas values and the length of surgery (r = 0.659, p = 0.012) and cardioplegic arrest (r = 0.559, p = 0.046). Elevated serum sFas levels were observed in patients undergoing cardiac surgery, and these serum sFas levels reflect the severity of a surgery. sFas may play an important role in the pathophysiology of surgical damage caused by cardiac surgery with cardiopulmonary bypass.

Adult↗
PubMed2000

Dietary docosahexaenoic acid but not eicosapentaenoic acid suppresses lipopolysaccharide-induced interleukin-1 beta mRNA induction in mouse spleen leukocytes.

Mice were fed a diet supplemented either with beef tallow (BT), BT plus ethyl eicosapentaenoate (EPA) or BT plus ethyl docosahexaenoate (DHA) for 9 weeks. EPA and DHA supplementation increased the content of the respective fatty acid in spleen leukocyte lipids, which was associated with the reduction in the arachidonate content. IL-1beta mRNA induction upon lipopolysaccharide (LPS) stimulation in spleen leukocytes in the DHA diet group was significantly lower than in the BT diet group, but the EPA diet was without any significant effect. The amount of prostaglandin E2 (PGE2) released from LPS-stimulated spleen leukocytes was significantly lower in both the EPA and DHA groups than in the BT group. Thus, dietary EPA and DHA inhibited arachidonate metabolism similarly but had different effects on IL-1beta mRNA induction in mouse spleen leukocytes.

Animals↗
PubMed2000

Mechanical circulatory assist for pulmonary embolism.

Optimal management of acute pulmonary embolism remains controversial, despite advances in thrombolytic therapy. Haemodynamic instability and, in particular, right ventricular dysfunction is associated with poor outcomes. Urgent surgical embolectomy has been the treatment of choice in this category of patients. We present two cases in which percutaneous cardiopulmonary support (PCPS) was used as an adjunct to thrombolytic therapy for progressive circulatory collapse secondary to massive acute pulmonary embolism. This experience suggests that PCPS may offer an attractive option for a condition which continues to carry significant morbidity and mortality.

Adult↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 11). Testicular toxicity of 2- or 4-week repeated or single-dose administration of a novel platinum complex.

A novel platinum complex, compound C, developed as an antitumor agent, was intravenously administered at 10 mg/kg/day to 6-week-old and 8-week-old rats. After 4 weeks of administration to the former, testicular enlargement was observed at a similar incidence as testicular atrophy and dilatation or atrophy of the seminiferous tubules was observed. Degeneration/necrosis of the seminiferous epithelium, decrease of seminiferous epithelium, formation of multinucleated giant cells, and vacuolar degeneration of Sertoli cells were also seen. These lesions were more marked in seminiferous tubules with atrophy than in those without atrophy. After 2-week administration to 8-week-old rats, slight initial-phase findings such as dilatation of seminiferous tubules and degeneration/necrosis of the seminiferous epithelium were noted in all rats. In rats administered 20 mg/kg/day, for which the administration period was shortened to 1 week due to marked weight loss, very slight initial lesions were similarly observed. However, these lesions were not easy to detect in these rats. Following single administration of a sublethal dose (80 mg/kg), testicular lesions were clearly observed 14 days after administration, but the incidence and grade of lesions were very low at 7 days. In conclusion, testicular toxicity of compound C can be clearly detected after 2-week administration, although the progression of lesions differed from the case with 4-week administration.

Animals↗
PubMed2000

[Effect of low dose aprotinin on reduction of blood loss after extracorpreal circulation].

Aprotinin administration during open heart surgery has been reported to reduce blood loss after extracorporeal circulation (ECC). We administered aprotinin to 12 patients undergoing CABG or prosthetic valve replacement. We examined the blood loss, the coagulation, and the fibrinolytic system in comparison with that in non-aprotinin group of 12 patients. In the aprotinin group, 1,000,000 units of aprotinin was infused intravenously before initiation of ECC and mixed with priming volume of ECC. After ECC, 250,000 units/hr was continuously infused until 1 hour after operation. The aprotinin group showed a significantly enhanced level of alpha 2 plasmin inhibitor and a significantly reduced level of plasmin-alpha 2 plasmin inhibitor complex and D-dimer. Post operative blood loss was not different between two groups. Operation time and closure time after heparinneutralization was shorter and postoperative blood use was lower in the aprotinin group. In conclusion, The administration of low dosed of aprotinin suppresses the fibrinolytic system resulting in the reduction of operation and closure time.

Adult↗
PubMed1999

Role of P-glycoprotein in human natural killer-like cell line-mediated cytotoxicity.

Natural killer (NK) cells express the highest amount of P-glycoprotein (Pgp), a product of the multidrug resistance (MDR) 1 gene, among lymphoid cells, and our previous studies demonstrated that Pgp is required for NK cell-mediated cytotoxicity. In this study we examined the role of Pgp in NK cell-mediated cytotoxicity using a human NK-like cell line, i.e., YTN cells and two MDR reversing agents, nicardipine and its structural analog, AHC-93. These two agents inhibited the Pgp function (rhodamine-123 excretion) as well as cell-mediated cytotoxicity, confirming that Pgp is critical for NK cell-mediated cytotoxicity. As revealed by video-rate ultraviolet laser-scanning confocal microscopy, AHC-93 did not inhibit the increase in the intracellular calcium concentration upon binding to target cells, whereas nicardipine did, as reported previously. These two reagents relocated acridine orange dye from lysosomes to the cytoplasm at concentrations similar to those required for the inhibition of cell-mediated cytotoxicity. These results suggest that Pgp is directly or indirectly involved in pH regulation in lysosomes, but not in calcium homeostasis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Effects of dietary docosahexaenoic acid on surface molecules involved in T cell proliferation.

It is known that n-3 polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA) suppress immunity as compared with n-6 PUFA such as linoleic acid (LA), but the mechanism involved in this phenomenon is still unclear. The present study was designed to assess the effect of dietary DHA on the surface molecules involved in T cell proliferation. Weanling male C57BL/6 mice were divided into four dietary groups that were fed a 10% fat diet for 4 weeks varying in amounts of DHA and LA. As the dietary DHA concentration increased, the surface expression of CD4 and CD8 on splenic T cells decreased, while that of CD28 increased. The surface expression of CD3, however, was invariable in all dietary groups. DNA synthesis of splenic T cells, induced by CD3 crosslinkage with anti-CD3 epsilon monoclonal antibody in the presence of CD28-mediated costimulation, increased as the DHA concentration was elevated. These observations suggest that diets rich in DHA exert some of their immunomodulatory effects by a downregulation of surface expression of CD4 and CD8 and by an upregulation of CD28-mediated costimulatory signal.

Adjuvants, Immunologic↗
PubMed1999

Assessment of the myocardial protective effect of antegrade warm blood cardioplegia by measuring the release of biochemical markers.

Intermittent warm blood cardioplegia has been reported as a valuable alternative for myocardial protection in cardiac surgery; however, conflicting experimental data have been published. To assess the clinical effectiveness of intermittent warm cardioplegia, we measured the release of troponin-T (Tn-T), a highly sensitive and specific marker of myocardial damage, and creatine kinase MB isoenzyme (CK-MB), in 12 patients who underwent elective coronary artery bypass grafting (CABG) with antegrade intermittent warm blood cardioplegia (37 degrees C) being the warm group, in comparison with 16 patients who underwent CABG with antegrade intermittent cold blood cardioplegia (4 degrees C) being the cold group. Blood samples were taken to determine the serum concentrations of CK-MB and Tn-T, at the induction of anesthesia, then 3, 6, 12, and 24h after the termination of cardiopulmonary bypass (CPB). The peak increase in serum CK-MB levels, 3h after CPB, was significantly lower in the warm group than in the cold group, at 27.8+/-7.8 IU/l vs. 40.8+/-12.6 IU/l, respectively (P = 0.0042). The serum Tn-T 12 h after CPB was significantly lower in the warm group than in the cold group, at 1.40+/-0.71 ng/ml vs. 2.06+/-0.95 ng/ml, respectively (P = 0.049). In conclusion, intermittent antegrade warm blood cardioplegia showed effective myocardial protection in elective CABG.

Biomarkers↗
PubMed1999

Platelet aggregation during cardiopulmonary bypass evaluated by a laser light-scattering method.

BACKGROUND: In regard to postoperative bleeding, the most important consequence of cardiopulmonary bypass (CPB) is the loss of aggregability. However, the mechanism of platelet aggregation loss during CPB is unclear. Newly developed particle-counting methods that use light scattering can be used to quantify changes in the number of platelet aggregates of different sizes after application of an aggregating stimulus. Using a light-scattering method, we investigated changes in platelet aggregation during cardiac operation. METHODS: Nineteen patients undergoing CPB were evaluated. Blood samples were obtained before the operation, 1 hour after initiation of CPB, at the end of CPB, at the end of the operation, and on day 1 after the operation. Platelet aggregation after stimulation by 2.5 micromol/L adenosine diphosphate and 2.0 microg/mL collagen was determined; small (9 to 25 microm), medium (25 to 50 microm), and large (50 to 70 microm) aggregates were counted. RESULTS: Generation of medium and large aggregates after stimulation with adenosine diphosphate and collagen were significantly decreased with CPB, whereas, in spite of hemodilution, the quantity of the small aggregates was maintained at the elevated level. CONCLUSIONS: These results reflect the fact that CPB does not affect the first phase of aggregation. It suggests that platelet dysfunction associated with CPB is mainly caused by an inhibition in the development of small aggregates into larger aggregates.

Adult↗