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Biomedical subjects

M Kasai

Publications and source records attributed to M Kasai.

At least 163 records · Page 9Linked to original sources

The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease.

We have investigated cytokine mRNA expression in the peripheral blood mononuclear cells of 20 patients who received allogeneic hematopoietic stem cell transplants to assess the cytokine network after transplantation. IL-4 mRNA expression decreased in five of five (100%) patients with > or = grade III (severe) acute GVHD and increased in 10 of 22 (45%) patients without severe GVHD. In contrast, IL-12 mRNA expression increased in two of two (100%) patients with severe GVHD, but increased in only six of 18 (33%) patients without severe GVHD. Furthermore, IL-10 and/or IL-13 mRNA expression increased in 19 of 22 (86%) patients without severe GVHD, but increased in only one of three (33%) patients with severe GVHD. In patients with allogeneic PBSCT who had severe acute GVHD, the cytokine mRNA expression in patients with allogeneic PBSCT, who had no severe GVHD, showed a similar pattern to that in patients with allogeneic BMT. IL-4 mRNA expression increased in three of five (60%) patients and IL-10 and/or IL-13 mRNA expression increased in five of five (100%) patients. In contrast, IL-12 mRNA expression increased in only one of three (33%) patients. Serum IL-4 concentration in allogeneic PBSCT patients in the early engraftment phase was relatively high, while serum IL-12 concentration was low. These findings suggest that severe GVHD may be related to the cytokine imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells.

Adult↗

Kinetics of depolarization-induced calcium release from skeletal muscle triads in vitro.

Calcium release from the sarcoplasmic reticulum (SR) depending on depolarization of the transverse tubular membrane (TTM) caused by rapid ionic replacement was measured in skeletal muscle triadic vesicles using a stopped-flow apparatus and Fura-2, a membrane-impermeable Ca2+ indicator. Calcium release was triggered by an increase in the magnitude of depolarization. This Ca2+ release was inhibited by ruthenium red, digoxin and dantrolene, and enhanced by caffeine. Thus, Ca2+ release was found to occur through the SR Ca2+ release channel via TTM depolarization and to be able to cause skeletal muscle contraction. Calcium release curves could be divided into two phases. In contrast to other previous studies, in the fast phase the amount of released Ca2+ increased with an increase in the magnitude of depolarization but the Ca2+ release rate did not; on the other hand, in the slow phase the Ca2+ release rate increased but the amount of Ca2+ did not. Furthermore, the Ca2+ release rate was controlled by the luminal Ca2+ concentration of the SR only in the fast phase. These independent dual kinetics of Ca2+ release were explained by the calsequestrin regulation model.

Animals↗

Dietary safflower phospholipid reduces liver lipids in laying hens.

This experiment was conducted to determine the effects of dietary safflower phospholipids (crude safflower phospholipid and purified safflower phospholipid) on performance and lipid metabolism of laying hens. Sixty-week-old Single Comb White Leghorn laying hens were divided into four groups of seven birds each, and were given one of four experimental diets containing 5% beef tallow (served as a control, tallow), a mixture of safflower oil and palm oil (SP-oil), crude safflower phospholipid (Saf-PLcrude), or purified safflower phospholipid (Saf-PL) for 7 wk. Egg production ratio and daily egg mass were significantly higher in hens fed Saf-PLcrude diets than in hens of the other diet groups. There were no significant differences in egg weight among groups. Liver cholesterol and triglyceride contents were significantly decreased in all treated groups as compared with the control. The activity of hepatic 3-hydroxy-3 methylglutaryl coenzyme A reductase was the highest in hens fed the Saf-PLcrude diet. Serum esterified cholesterol concentration was decreased by feeding of SP-oil, Saf-PLcrude, or Saf-PL diets. Serum lecithin-cholesterol acyltransferase activity was highest in hens fed the tallow diet. Excreta neutral steroid excretion was significantly increased in the Saf-PLcrude or Saf-PL diet groups, although acidic steroid excretion was not affected by dietary treatments. Total cholesterol, triglyceride, and phospholipid contents in egg yolks were not different for any dietary treatments. The fatty acid compositions of egg yolks from hens fed Saf-PLcrude diets were not different with those fed the SP-oil diet, although eggs of hens fed the Saf-PL diet showed lower total polyunsaturated fatty acids. These results suggest that dietary safflower phospholipids may be a valuable ingredient to layers for reducing liver triglycerides and serum cholesterol without any adverse effects.

Animals↗

Genetic and clinical features of sensorineural hearing loss associated with the 1555 mitochondrial mutation.

Five Japanese families showing aminoglycoside-induced hearing loss were genetically as well as clinically investigated. A mitochondrial mutation at nucleotide 1555 was found in 28 out of 32 subjects. One hundred American control subjects did not show any evidence of the mutation at nucleotide 1555, suggesting that the 1555 A-->G (A1555G) mitochondrial mutation may be found more frequently among populations in the Asian continent. Many subjects who harbor this mitochondrial mutation exhibit a mild, high-frequency, progressive hearing loss even without aminoglycoside injection. The results presented here appear to support the hypothesis that the A1555G mutation may play a more general role in causing hearing loss.

Aminoglycosides↗

Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells.

The selective induction of effector functions of a T-cell clone (DB14), specific to pigeon cytochrome c 43-58 (p 43-58) and restricted to I-Ab, was analyzed using a professional antigen-presenting cell, B hybridoma (Th 2.58), and various non-professional antigen-presenting cells (APC), L cells transfected with I-Ab (I-Ab L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC, and c-TEC expressed I-Ab upon induction with interferon gamma (IFN-gamma). When stimulated with p 43-58 in the presence of I-Ab L cells as well as Th 2.58 cells, the DB14 cells showed marked proliferation and, after 18 hr of culturing, exhibited significant cytotoxicity against the APC. By contrast, in the presence of m, c-TEC, the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity towards them. Furthermore, DB14 cells became expressed activation markers CD69 or CD44) following stimulation with p 43-58 plus m-TEC or c-TEC. The addition of rIL-2 to the culture of DC14 cells, p 43-58 and m-TEC or c-TEC, restored the proliferative responses. However, it was shown that anergy was not involved in the negligible proliferative responses of DB14 cells after stimulation with p 43-58 plus m, c-TEC. The present findings indicate that differences in APC functions are present among the non-professional APC and suggest that the selective induction of T-cell functions can be achieved using the appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.

Animals↗

Invasive pulmonary aspergillosis complicated by subclavian artery occlusion following allogeneic stem cell transplantation.

We describe an unusual case of invasive pulmonary aspergillosis (IPA) complicated by subclavian artery occlusion in a 32-year-old man with severe aplastic anemia, who underwent allogeneic stem cell transplantation. He was severely neutropenic after the conditioning for transplantation, but he had no history of fungal infection. Five days after the transplantation, he developed IPA in the left upper lung, complicated by left subclavian artery occlusion. Extensive chronic graft-versus-host disease, which required the administration of potent immunosuppressants for a long period of time, interfered with the resolution of the IPA.

Adult↗

A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt's type (FAB-L3) leukemia.

We report a case of B-cell acute lymphocytic leukemia which showed histological transformation from an FAB-L2 into a Burkitt's type (FAB-L3). Both leukemias had identical immunoglobulin heavy-chain joining gene and kappa light-chain joining gene rearrangements, indicating the clonal identity of the two leukemias. A chromosomal analysis of leukemia cells on the onset indicated normal karyotype, whereas that of the transformed FAB-L3 showed t(8;14)(q24;q32). Furthermore, the proto-oncogene c-myc was in the germline configuration in the initial leukemia but in the rearranged configuration after transformation. Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.

Adolescent↗

Low levels of serum soluble c-kit relates to delayed engraftment after bone marrow transplantation.

Serum soluble c-kit concentrations were measured in 28 patients undergoing bone marrow transplantation (BMT). The c-kit levels in patients with delayed engraftment (time to leukocyte recovery > 1.0 x 10(9)/L being more than 20 days after BMT) were significantly lower than those in patients with early engraftment (time to leukocyte recovery being less than 19 days after BMT) from the start of conditioning until day 100 after BMT. The data from this study indicates that the measurement of serum soluble c-kit concentrations may be a useful indicator of engraftment.

Adolescent↗

[Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis. After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320. Thereafter, the graft consisting of mononuclear cells was transplanted. TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT. Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause.

Adult↗

Improvement of circulation in pedicled intestinal grafts: hemodynamics of the intestine after preparation of a sacrificial colonic graft.

BACKGROUND: To preserve postoperative digestive function in patients with esophageal carcinoma, jejunal or colonic segments on long vascular pedicles are transplanted and anastomosed between the esophagus and residual stomach. A postoperative survey showed pedicled jejunum transplantation to be superior in terms of digestive and absorptive functions, intraesophageal pressure, pH, and the quality of life of long-term postoperative survivors. Anastomotic leakage and necrosis of the pedicled intestinal graft are occasional complications; circulatory disorders of the pedicled intestine are a probable cause of both complications. STUDY DESIGN: To simulate pedicled jejunum transplantation, we prepared pedicled colonic segments from dogs and measured blood flow volume at the cut end of the oral side of the colonic segments using the hydrogen clearance method and at the nutrient vascular pedicle with an electromagnetic blood flowmeter. RESULTS: Resection of excess colon increased blood flow volume per unit weight of the colonic segment. CONCLUSIONS: It is essential to resect excess intestine and keep only the minimum length of pedicled intestinal graft needed for reconstruction of the esophagus.

Anastomosis, Surgical↗

Biochemical characterization of calsequestrin-binding 30-kDa protein in sarcoplasmic reticulum of skeletal muscle.

Calsequestrin (CSQ)-binding 30-kDa protein in the sarcoplasmic reticulum (SR) of rabbit skeletal muscle was purified from the junctional face membrane (JFM) in the SR. Analysis of proteins which bound to the affinity column conjugated with the purified 30-kDa protein was performed. As a result, in the heavy fraction of the SR (HSR), four proteins including CSQ proved to be adsorbed on the column, and in the JFM, one protein, whose molecular weight was about 25-kDa. was mainly adsorbed. Furthermore, the same 25-kDa protein was found to be adsorbed on the CSQ affinity column. This 25-kDa protein is probably the CSQ-binding 26-kDa protein (junctin) recently reported [Jones, L. R., et al. (1995) J. Biol. Chem. 270, 30787] judging from the molecular weight and the CSQ-binding property. These results suggest that three proteins, CSQ, 30-kDa protein, and 25-kDa protein, form a protein complex in the terminal cisternae of the SR.

Animals↗

Structural studies of mitomycins. VIII. Mitomycin D hydrate, C15H18N4O5.1.5H2O.

The title compound, [1aS]-6-amino-1, 1a,2,4,7,8,8a,8b-octahydro-8a-hydroxy-1,5-dimethyl-4,7-dioxoazirino++ +[2',-3': 3,4]pyrrolo[1,2-a]indol-7-ylmethyl, is a mitomycin derivative, mitomycins being antitumor antibiotics. The O atoms of the quinone ring deviate significantly from the least-squares plane through the quinone ring.

Antibiotics, Antineoplastic↗

Novel 5-aminoflavone derivatives as specific antitumor agents in breast cancer.

In the course of our search for new antitumor agents in breast cancer, novel amino-substituted flavone derivatives were synthesized and examined for antitumor activities. Among them, 5,4'-diaminoflavone and some of its congeners showed remarkable antiproliferative activity against the estrogen receptor (ER)-positive and estrogen-responsive human breast cancer cell line MCF-7. The activity was observed irrespective of the presence or absence of estrogen. The 5-aminoflavone derivatives (5-AFs) are not classical anti-estrogens because they did not compete with [3H]estradiol to bind the estrogen receptor. Moreover, 5-AFs showed antitumor activity highly selective to the ER-positive breast cancer cell line, and they showed no effects against the ER-negative human cancer cell lines HeLa S3, WiDr, and MDA-MB-453. Although the mechanism of their selective antitumor activity to ER-positive breast cancer cells is unclear, 5-AFs are expected to be a new type of antitumor agents in breast cancer.

Antineoplastic Agents↗

Structural studies of mitomycins. VII. Mitomycin G.

The title compound, [1aS-(1a alpha, 8a alpha, 8b alpha)]-6-amino-1, 1a,2,8,8a,8b-hexahydro-8a-methoxy-1,5-dimethyl-8-methyleneazirino [2',3':3,4]pyrrolo[1,2-a]indole-4,7-dione, C15H17N3O3, is a derivative of the mitomycins, which are antitumor antibiotics. The quinone O atoms deviate significantly from the least-squares plane of the quinone ring.

Antibiotics, Antineoplastic↗