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Biomedical subjects

Y Matsui

Publications and source records attributed to Y Matsui.

At least 505 records · Page 28Linked to original sources

[The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2].

We have studied the in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2 (rIL-2). LAK cells were generated by placing 5 X 10(7) fresh C 57 BL/6 splenocytes (erythrocytes were lysed osmotically) in 10-cm (diameter) dishes (Falcon) containing 10 ml of complete medium (CM). The CM consisted of RPMI 1640 with 0.1 mM non-essential amino acids, 1 microM sodium pyruvate, 5 X 10(-5)M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine, 10% heat-inactivated fetal calf serum (FCS) and 10 units/ml of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd). The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hr. The LAK cells were then harvested, washed three times, and resuspended in RPMI 1640 with 5% heat-inactivated FCS for the in vitro cytotoxicity assay. The antitumor cytotoxic activity of LAK cells was estimated in triplicate by 4 hr 51Cr release assays. The cytotoxic activity of LAK cells against syngeneic 203 glioma and normal syngeneic glioblasts was approximately 50% and a few %, respectively. The in vitro cytotoxicity of LAK cells against syngeneic EL-4 thymoma, allogeneic YAC-1 lymphoma and P-815 mastocytoma was 72%, 87% and 43%, respectively. Thus LAK cells have apparent tumor specificity in vitro and are easily generated. Fresh splenocytes of CBA/J mice were markedly lytic for natural killer (NK)-sensitive YAC-1 cells, but not for 203-glioma cells or NK-resistant P-815 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical studies of adoptive immunotherapy of human disseminated brain tumors with LAK cells and recombinant interleukin-2].

In previous in vitro studies, the authors showed that recombinant interleukin-2 (rIL-2) stimulated peripheral blood lymphocytes (PBL) from patients with malignant brain tumors to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. We then tried the adoptive transfer of such lymphokine-activated killer-(LAK) cells induced from patients with meningeal gliomatosis (MG) and meningeal carcinomatosis (MC). PBL fractions were separated into a plastic bag by leukophoreses using HEMONETICS V 50. PBL were then harvested by LSM (Litton Bionetics, Kensington, Md.) gradient centrifugation according to the standard method. Human LAK cells were generated by placing 5 X 10(7) PBL in 10-cm diameter plastic dishes (Falcon) holding 20 ml of complete medium (CM) containing 100 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI P640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml of gentamicin sulfate, 0.03% glutamine and 2% heat-inactivated human AB serum. The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks' balanced salt solution (HBSS) and resuspended in HBSS for transfer to patients. 1-2 X 10(8) LAK cells were injected intrathecally through Ommaya's reservoir or a V-P shunt reservoir twice a week. Portions of LAK cells were tested for cytotoxicity in vitro. During the adoptive transfer of LAK cells, patients were given intravenous injections of 500 units of rIL-2 every day. Case 1: A 29-year-old man with meningeal gliomatosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Antitumor efficacy of activated macrophages against murine glioma cells].

A crucial manifestation of malignant gliomas is the regrowth of already-invaded neoplastic cells after surgical intervention. One possible approach for inhibiting such tumor growth is to utilize the tumoricidal potential of macrophages. In order to investigate the clinical application of this concept, peritoneal exudate cells (PEC) activated in vitro and in vivo by immunomodulating agents were tested for cytotoxic activity against murine glioma (203-glioma) cells. As immunomodulating agents, heat-killed Propionibacterium acnes (P. acnes), OK-432 and Concanavilin A supernatant (Con A sup) were used in these experiments. P. acnes was provided by Kowa Pharmaceutical Co., Tokyo, and OK-432 by Chugai Pharmaceutical Co., Ltd., Tokyo. Klinische Einheit (KE) units were used to express the strength of the preparation, with 1 KE equal to 0.1 mg of dried streptococci. Con A sup was produced by Con A pulsing of BALB/c splenocytes resuspended in complete medium. PEC harvested from mice to which 5% glycogen in saline had been inoculated intraperitoneally 6 d previously were activated in vitro by P. acnes (P. acnes-PEC), OK-432 (OK-432-PEC) and Con A sup (Con A-PEC). The cytotoxic activities of P. acnes-PEC, OK-432-PEC and Con A-PEC were approximately 25%, 65% and 60%, respectively. PEC were then collected from mice into which either 100 micrograms of P. acnes or 1 KE of OK-432 had been injected intraperitoneally several times. The antitumor effects of P. acnes-PEC and OK-432-PEC were about 35% and 50%, respectively. These activated PEC demonstrated cytotoxic activity against murine glioma in the tumor neutralization assay (Winn assay). Also, the antitumor efficacy of OK-432-PEC belonged mainly to adherent cells. Meningeal gliomatosis (MG) models were prepared for clinical studies. Viable 203-glioma cells (5 X 10(6) were injected percutaneously into the cisterna magna of C57BL/6 mice. The median survival time (MST) of the untreated group was 8.5 days. The MST of the groups treated by intraperitoneal and intracisternal administration of P. acnes were 26 and 33 days. This therapy significantly prolonged the survival time of these models, particularly by the intracisternal treatment. The differential cell count by Giemsa staining and latexphagocytic cell findings revealed that macrophages accounted for more than 90% of the P. acnes-PEC. These results may indicate that activated (PEC) macrophages were induced intracisternally by P. acnes and that activated macrophages induced intraperitoneally exerted antitumor effects in MG models.

Animals↗

[Meningeal gliomatosis model in nude mice].

The nude mouse has been proposed as a model animal for testing the chemosensitivity of human cancer cells, and encouraging results have been obtained. Murine brain tumor models were successfully prepared by direct inoculation of glioma cells into the cerebral hemisphere, an immunologically privileged area. However, the blood-brain barrier was destroyed mechanically by this manipulation. Accordingly, experimental models of MG were established by intracisternal inoculation of human glioma cells (ONS-6, -12, and -16). These cell lines were established by primary explant technique from our biopsy specimens. The outgrown cells were trypsinized and cultured in monolayers. Tumor cells (10(7) in 0.1 ml) were inoculated transcutaneously into the cisterna magna of BALB/c nu/nu mice using a 27-gauge needle. Tumor growth generally occur in no more than 10-20% of nude mice transplanted subcutaneously. Also, nude mice which were transplanted with these 10(7) glioma cells rejected the tumor. MG models which were inoculated with the same tumors intrathecally, however, all died within a month after inoculation. In in vitro studies, the doubling time (DT) of ONS-6, -12, and -16 were 30.5 h, 41.5 h and 60.9 h, respectively. Median survival time (MST) of MG models inoculated with ONS-6, -12, and -16 glioma cells were 8.5 days, 15.5 days and 18.5 days, respectively. These DTs were well correlated with the MST. Clinicopathological features observed in MG models were similar to those seen in diffuse leptomeningeal involvement of glioma in human beings. Tumor cells were disseminated in the diffuse arachnoid space, involving the cerebral hemisphere, spinal cord and throughout the cauda equina. Some tumor cells infiltrated the cerebral parenchyma and Virchow-Robin space. The models will be useful for investigating the pathophysiology of MG and the efficacy of chemotherapeutic agents.

Animals↗

[The prevention of spinal cord ischemia during the operation on the thoracic aorta utilizing the evoked spinal cord potential (ESP)].

The evoked spinal cord potential was used for the moniter of the spinal cord ischemia during the operation on the thoracic aorta. At first, experiments were performed on 23 dogs. Following laminectomy and 1t. thoracotomy, evoked spinal cord potential to the stimulation from bipoler electrodes in the midline dorsal subdural space at the level of near L1 were recorded from needle electrode in the intervertebral disk at the level of Th4-5. After baseline measurements, the thoracic aorta was occluded in all dogs by aortic cross-clamping (AXC) distral to the origin of the left subclavian artery. Then 3 types of changes were detected. TYPE-I (n = 8) showed loss of the ESPs during AXC and return after reperfusion. TYPE-II (n = 10) showed no changes during and after AXC. TYPE-III (n = 5) showed return of ESPs after transient loss of them even during AXC. Five of 7 dogs (71%) in TYPE-I and 1 of 5 dogs (20%) in TYPE-III developed paraplegia, but all of them in TYPE-II avoided paraplegia. Secondly, ESP was used for the moniter of spinal cord ischemia during operation on 13 patients. Ten patients showed no changes of ESPs, but 3 showed loss of ESPs during AXC and return after reperfusion of them. No paraplegia appeared. We have concluded that intraoperative ESP monitering is a more reliable indicator of the spinal cord ischemia than other methods previously reported.

Adult↗

Systemic and regional hemodynamic effects of E614 (tripamide) as studied in conscious SHR.

Experiments were conducted on 53 conscious young male spontaneously hypertensive rats utilizing radiolabeled microspheres to analyze the acute and chronic hemodynamic effects of a newly synthesized antihypertensive drug, E614. The hemodynamic variables were observed on the 1st and 6th days of E614 treatment (p.o., once daily) in separate groups of rats. When the drug was given at a smaller dose (10 mg/kg body weight) over 6 days, the hypotensive action of E614 was found to be due mainly to a reduction of the total peripheral vascular resistance with no significant change in the cardiac output (CO). A supra-pharmacological dose (100 mg/kg), however, lowered the mean arterial pressure (AP) due mainly to a significant reduction of the CO in both the acute and chronic treatments. We found little influence of the drug on heart rate, and the coronary and renal vascular beds in any of the present experimental settings. The cerebral blood flow appeared not to change significantly unless the AP fell to such an extent that a fall in cerebral blood flow took place despite the autoregulatory mechanism of the brain blood vessels. The tissue perfusion was also well preserved in the gastrointestinal tract.

Animals↗

HLA-DR-4-associated alloreactivity of an HLA-DR-3-restricted human tetanus toxoid-specific T cell clone: inhibition of both reactivities by an alloantiserum.

We present here the first report of a human helper/inducer T cell clone (F6) that specifically recognizes tetanus toxoid (TT) in the context of self-major histocompatibility complex (MHC) determinant(s) (HLA-DR3), and in addition recognizes a specific but unrelated MHC determinant(s) in the absence of conventional antigen. Extensive subcloning insured that the cells were progeny of a single cell. Furthermore, removal of the cells proliferating to the alloantigen with bromodeoxyuridine and light removed cells responding to both TT plus self-MHC and to the stimulating alloantigen, again indicating that F6 was the progeny of a single cell. The alloantigen recognized by this TT-specific clone appears to be closely linked to HLA-DR4 since cells from 13 of 14 HLA-DR4+ donors stimulated F6. An antiserum which recognizes HLA-DR4, when added to cultures, blocked the alloreactivity of F6, and in addition blocked its proliferation to TT plus HLA-DR3. Absorption of this antiserum with HLA-DR4+ cells or with TT-pulsed HLA-DR3+ cells removed its capacity to inhibit the proliferation of F6. These results suggest that the antigen recognition unit on F6 is stimulated both by allodeterminants expressed on HLA-DR4 cells and by TT plus HLA-DR3. These moieties cross-react at the T cell recognition level as well as at the antibody level.

Clone Cells↗

Cisplatin, vinblastine, and bleomycin therapy of yolk sac (endodermal sinus) tumor of the ovary.

Five patients with yolk sac (endodermal sinus) tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin combination therapy (PVB). Four of five achieved a complete remission and remain free from disease 24 to 53 months from start of PVB therapy. One patient did not respond well to PVB and died 11 months after start of PVB therapy. One patient who was treated with PVB after unilateral salpingo-oophorectomy has delivered a normal term infant. Serum alpha-fetoprotein levels were monitored in all patients during and after therapy. Serum alpha-fetoprotein was correlated with clinical course.

Adolescent↗

Establishment of a new ovarian tumor line in nude mice and its application to treatment of the donor patient.

A new line of the human ovarian tumor (poorly differentiated adenocarcinoma), designated OVA-2, has been established by heterotransplantation of the original tumor into athymic nude mice. The donor patient, a 38-year-old woman with stage IV disease, was treated with cis-diamminedichloroplatinum II, Adriamycin, 5-fluorouracil, and VM-26, which were selected in consideration of the results, obtained by experimental chemotherapy of this heterotransplanted tumor. She achieved a complete remission and is alive 15 months after diagnosis. Usefulness of the human tumor-nude mouse system in chemotherapy is reemphasized.

Adenocarcinoma↗

Induction of glycophorin gene expression in cultured murine erythroleukemia cells.

In order to identify the mRNA for mouse glycophorin, mRNA was isolated from immature erythroid cells obtained from the spleens of anemic mice, translated in vitro in mRNA-dependent rabbit reticulocyte lysate, and then immunoprecipitated with a specific antiserum. Glycophorin mRNA was shown to be present only in erythroid cells. In immunofluorescent and in vitro translation studies, it was shown that glycophorin mRNA is absent in uninduced murine erythroleukemia (MEL) cells, but is induced in dimethylsulfoxide-treated differentiating cells.

Animals↗

[The attachment structure and the heterosexual relationship among university students].

Research on adolescents in romantic love has suggested that their heterosexual relationship may be influenced by their attachment to their mothers and to friends of the same sex. Three hundred fifty-nine college students responded to a questionnaire designed to explore this correlation. The results indicated that male sexual behavior and feelings of romantic love towards their girl friends were not influenced by the attachment to their mothers nor to their friends whereas those of the females were. Females who were involved in intimate sexual relationship had weaker attachment to their mothers; on the other hand, females who had strong romantic feelings, yet without sexual relationships, tended to have strong attachment to their friends of the same sex.

Adolescent↗