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Biomedical subjects

T Ebina

Publications and source records attributed to T Ebina.

At least 55 records · Page 3Linked to original sources
PubMed1995

Regulation of adenylyl cyclase by protein kinase A.

The changing relationship between stimuli and responses after prolonged receptor stimulation is a general feature of hormonal signaling systems, termed desensitization. This phenomenon has been best exemplified in the covalent modification of the G protein-linked catecholamine receptors. However, other components within this signaling pathway can be involved in desensitization. Here we present evidence that desensitization occurs at the level of the effector enzyme itself through phosphorylation. Type V adenylyl cyclase (AC) is the major isoform expressed in the heart. Using purified enzymes, we demonstrate that protein kinase A (PKA) directly phosphorylates and thereby inhibits type V AC catalytic activity. This inhibition was negated in the presence of PKA inhibitor. Analysis of enzyme kinetics revealed that this inhibition was due to a decrease in the catalytic rate, not to a decrease in the affinity for the substrate ATP. Our results indicate that AC catalytic activity can be regulated through PKA-mediated phosphorylation, suggesting another mechanism of desensitization for receptor pathways which signal via increases in intracellular cAMP.

Adenosine Triphosphate↗
PubMed1995

High-grade surface osteosarcoma of the humerus.

We presented a case of high-grade surface osteosarcoma of the humerus in a 12-year-old girl and the results of our analysis of 26 cases reported in the literature. Twelve of the 21 patients for whom substantial follow-up information was reported had died of the disease, and the results of the analysis regarding the efficacy of chemotherapy and medullary involvement were ambiguous. It is emphasized that high-grade surface osteosarcoma is a distinct entity, since it is associated with a poorer prognosis than other osteosarcomas arising on the surface of bone.

Bone Neoplasms↗
PubMed1995

[Antitumor effect of intratumoral administration of BRM: inhibition of tumor cell invasion in vitro].

The effect of intratumoral administration of BRMs in Meth-A solid tumor has been analyzed in BALB/c mice. The effect of BRMs on in vitro invasion by murine RL male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton Dickinson Labware). We determined the ability of tumor cells to penetrate matrigel-coated filters in the presence or absence of BRM. PSK or OK-432 inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent manner. PSK, OK-432 and Cepharanthin inhibited invasion of murine Colon 26 carcinoma cells and human A 375. S2 melanoma cells. On the other hand, polysaccharide preparations without protein, Lentinan or Sonifilan inhibited neither tumor growth nor tumor cell invasion.

Animals↗
PubMed1994

A novel peptide inhibitor of adenylyl cyclase (AC). A peptide from type V AC directly inhibits AC catalytic activity.

Peptides derived from various regions of type V adenylyl cyclase (AC) were studied to determine their effect on AC catalytic activity. Out of 10 examined, only one peptide, peptide 2 (Lys425-Cys444), significantly inhibited both basal and stimulated (forskolin or GTP gamma S (guanosine 5'-O-thiotriphosphate)) type V AC catalytic activity overexpressed in CMT cells. The sequence of this peptide was taken from the first cytoplasmic domain of type V AC, which has a high sequence homology to other AC isoforms. Competition studies performed between the peptide and the substrate ATP showed that the inhibition was noncompetitive. Mutation or truncation of the peptide designed to destroy its secondary structure totally negated the inhibitory effect. This peptide also inhibited the catalytic activity of purified types II and V AC, as well as that of various cells, including S49 cyc- cells. Our data indicate that the peptide directly interacts with AC to inhibit catalytic activity; this provides new information regarding regions of the enzyme involved in its catalytic activation.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Differential activation of adenylyl cyclase by protein kinase C isoenzymes.

Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC isoenzymes, we demonstrate that PKC zeta directly phosphorylates type VAC, leading to an approximate 20-fold increase in its catalytic activity, a significantly larger enhancement than that achieved with forskolin (approximately 5-fold), the most potent activator of AC. When forskolin and PKC phosphorylation are combined, type V AC catalytic activity is increased 100-fold over basal levels. The two PKC isoenzymes (alpha and zeta) are additive in their capacity to activate AC, although PKC alpha is less potent than PKC zeta. Our data indicate that PKC can directly and potently regulate AC activity in an isoenzyme-specific manner, suggesting that direct cross-talk plays a major role in coordinating the activity of these two principal signal transduction pathways.

Adenylyl Cyclases↗
PubMed1994

Antitumor effect of intratumoral administration of biological response modifiers: induction of immunosuppressive acidic protein, a type of alpha 1-acid glycoprotein, in mice.

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model, the "double grafted tumor system" were analyzed. Male BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on the right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into the right tumor on days 3, 4 and 5. PSK (a protein-bound polysaccharide preparation), interleukin-1 (IL-1) and cepharanthin (CR) cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG and tumor necrosis factor (TNF) cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) and IL-6 inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, CR, OK-432 and TNF in BALB/c mice. Lentinan, however, did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. The biochemical difference between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed affinity immunoelectrophoresis with concanavalin A. IAP of murine serum was separated into 4 peaks. IAP in normal mouse was rich in high-mannose type sugar chain (Peak 3) and contained no hybrid-type sugar chain (Peak 4), which was present in inflammatory and tumor-induced IAP. Inflammatory IAP was rich in biantennary sugar chain (Peak 2) and tumor-induced IAP was rich in tri-tetraantennary sugar chain (Peak 1).

Animals↗
PubMed1994

[Antitumor effect of intratumoral administration of a Coriolus preparation, PSK: inhibition of tumor invasion in vitro].

The antitumor effects of biological response modifiers (BRM) in an experimental mouse model, the "double grafted tumor system," were analysed. Intratumoral administration of PSK (polysaccharide Kureha), a Coriolus preparation into primary tumor induced a cure of not only the primary solid tumor but also the metastatic, distant tumor. The effect of PSK on in vitro invasion by murine RL male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton Dickinson Labware). We determined the ability of tumor cells to penetrate matrigel-coated filters in the presence or absence of PSK. PSK (100 micrograms/ml) reduced to half the number of invasive tumor cells for 3 hr incubation. PSK inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent manner. Matrigel includes laminin, collagen, fibronectin and heparan sulfate proteoglycan. It is possible, therefore, that PSK may inhibit enzymes which digest the components of basement membranes, extra cellular matrices (ECM). This phenomenon suggests that PSK also inhibits metastatic activity of tumor cells in vivo.

Animals↗
PubMed1993

Closure of ventricular septal rupture caused by acute myocardial infarction using a transaortic balloon catheter.

We report a case of successful transaortic closure of a postinfarction ventricular septal rupture using a Swan-Ganz catheter. The method markedly reduced a left-to-right shunt and the improved hemodynamic condition of the patient, an 81-year-old woman, was maintained for about a week before surgical treatment. Inflation of the balloon with water made the balloon visible via echocardiography and was effective in maintaining inflation and echocardiographic follow-up.

Aged↗
PubMed1993

Oral passive immunization effect of anti-human rotavirus IgY and its behavior against proteolytic enzymes.

The neutralization titer of anti-human rotavirus (HRV) IgY was completely inactivated by pepsin at pH 2.0. However, it was not significantly affected by trypsin or chymotrypsin under certain conditions. The immunological activity of the IgY was observed in the intestine of suckling mice for 2 h after oral administration and the activity rapidly decreased thereafter. The effects of oral supply of IgY were thus estimated for HRV-induced diarrhea in suckling mice and it was found that a previous supply of the IgY (1 h before HRV infection) completely prevented the HRV-induced diarrhea. The preventive effect was decreased as the time gap between IgY administration and HRV infection was longer. However, the oral supply of the IgY within 24 h after HRV infection was still effective and decreased the incidence of HRV diarrhea in suckling mice.

Administration, Oral↗
PubMed1993

[Differences in antitumor effect of various BRMs by intratumoral administration: induction of immunosuppressive acidic protein].

The antitumor effects of biological response modifiers (BRM) in a new experimental mouse model, the "double grafted tumor system", were analysed. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into right tumor on day 3, 4 and 5. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. PSK (a protein-bound polysaccharide preparation), IL-1 and Cepharanthin, cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, OK-432 and TNF in BALB/c mice. But Lentinan did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. At 21 days after tumor inoculation, IAP in serum reached a maximum level (300 micrograms/ml). The serum IAP level of Meth-A-bearing mice as well as that of normal mice increased after the intratumoral injection of PSK. At 21 days after tumor inoculation, IAP in PSK-treated mice returned to normal level. The biochemical differences between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed immunoaffino electrophoresis (CIAE). Inflammatory IAP was rich in biantennary sugar chain, and tumor-induced IAP was rich in tri-tetraantennary sugar chain.

Animals↗
PubMed1992

Passive immunizations of suckling mice and infants with bovine colostrum containing antibodies to human rotavirus.

After immunizing 8-month pregnant Holstein cows with the human rotavirus MO strain, cow colostrum containing neutralizing antibody to four different serotypes of human rotavirus, designated Rota colostrum, was obtained. Oral inoculation of human rotavirus MO strain into 5-day-old BALB/c mice causes gastroenteritis characterized by diarrhea. Using this small animal model, passive protection of suckling mice against human rotavirus infection was achieved with the use of Rota colostrum. Rota colostrum completely protected against rotavirus infection, but purified IgG and IgA obtained from Rota colostrum were unable to protect against infection. After grouping randomly 20 infants from a baby care center, 10 infants received 20 ml of Rota colostrum per day for 2 weeks and 10 control infants did not. Rotavirus-associated diarrhea developed in 7 of 10 infants in the control group. None of the three infants in the every day recipient group of Rota colostrum had such symptoms, and one of three infants in the every other day recipient group developed rotavirus-induced diarrhea. All four infants who received Rota colostrum after symptoms appeared developed diarrhea. Oral administration of Rota colostrum seems to be an effective and safe means of preventing diarrhea caused by human rotavirus infection.

Age Factors↗
PubMed1992

Antitumor effect of a Coliolus preparation, PSK: induction of macrophage chemotactic factor (MCF) in spleens of tumor bearing mice.

The effect of administration of PSK (Polysaccharide Kureha), a Coliolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK-treated tumor bearing mice were examined for induction of macrophage chemotatic factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or concanavalin A (Con A). MCF-producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, interferon and tumor necrosing factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected.

Animals↗
PubMed1992

Antitumor effect of PSK at a distant site: tumor-specific immunity and combination with other chemotherapeutic agents.

The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male-1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti-metabolite, 5-fluorouracil.

Adenocarcinoma↗
PubMed1992

[Differences of antitumor effect of various BRMs by intratumoral administration].

The antitumor effects of biological response modifiers (BRM) in a new experimental mouse model, the "double grafted tumor system", were analysed. BALB/c mice received simultaneous inoculations of Meth-A fibrosarcoma cells on right flank (10(6) cells) and left flank (2 x 10(5) cells) on day 0, and BRMs were injected intratumorally into right tumor on day 3, 4 and 5. The growth of the left-flank tumor was the real target for the evaluation of a given drug after 21 days. PSK (a protein-bound polysaccharide preparation), IL-1 and Cepharanthin cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) inhibited neither the right nor the left tumor. Spleen cells from PSK-treated tumor bearing mice produced macrophage chemotactic factor (MCF) after 48 hrs cultivation in the presence of Con A or Meth-A tumor cells. MCF producing cells were indicated to be L3T4 positive cells. On the other hand, PMN activated by PSK treatment produced MCF in the culture supernatant. Therefore, our present and previous studies on the antitumor effect of BRM in the double grafted tumor system show that intratumoral administration of BRM first induces neurophils in the right tumor via an IL-8-like factor and then cytotoxic macrophages are induced by MCF. Then Lyt-1 (L3T4)-positive cells are induced in the right regional lymph nodes and in the spleen, probably via IL-1, which might be produced from macrophages in contact with tumor cells. Subsequently, Lyt-1-positive cells reach the left tumor through the blood stream, come into contact with Meth-A tumors and then produce MCF. Intratumoral administration of PSK in the right tumor thus induces cytotoxic macrophages in the left, non-treated tumor, thereby bringing about the regression of the distant tumor.

Animals↗
PubMed1991

Protease inhibitors prevent the development of human rotavirus-induced diarrhea in suckling mice.

Oral inoculation of human rotavirus MO strain (serotype 3) into 5-day-old BALB/c mice caused gastroenteritis characterized by diarrhea (90% on the average, on day 2). Using this animal model, preventive effect of antiviral agents on the development of rotavirus-induced diarrhea was examined. The infectivity of human rotavirus was enhanced by treatment with protease in vitro. A cysteine protease inhibitor, E-64-c, was given orally at 12 hr and 24 hr after MO infection. Oral administration of 0.3 mg of E-64-c decreased the diarrhea ratio to 17.5% on day 2 and to 10% on day 3. Oral administration of 0.15 mg of cysteine protease inhibitor, ovocystatin, completely prevented the diarrhea on day 2. Serine protease inhibitor, aprotinin (0.15 mg x 2), also prevented the diarrhea on day 2 to 14.3%. These protease inhibitors were nontoxic in vitro and to suckling mice. The histopathological changes in the small intestine due to infection recovered 2 days after MO infection in mice treated with E-64-c and ovocystatin. These results suggest that protease inhibitors are protective agents for human rotavirus infection by inhibiting proteases required for viral replication.

Administration, Oral↗
PubMed1991

Antitumor effector mechanism of interleukin-1 beta at a distant site in the double grafted tumor system.

Recombinant human interleukin-1 beta (IL-1 beta) inhibited the growth of not only the right, but also the left non-treated tumor in a double grafted tumor system. Since the antitumor activity of IL-1 beta against the right and left tumors was not seen in nude mice, lymphocytes have a key role in the antitumor effect of intratumoral administration of IL-1 beta. TIL (tumor-infiltrating leukocytes) obtained from left and right side tumors treated with IL-1 beta were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TIL from the right side clearly inhibited the growth of admixed Meth-A cells, but control TIL did not. Spleen cells and right and left regional lymph node cells prepared from IL-1-treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1-positive lymphocytes increased in the spleen and in the right regional lymph nodes after intratumoral administration of IL-1. Isolated tumor cells obtained from the right tumor treated with IL-1 beta and the left side tumor on day 6 were cultured in RPMI 1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor and macrophage chemotactic factor activities were detected in the culture media from IL-1-treated tumor tissues cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated tumor tissues. These results suggest that intratumoral administration of IL-1 first induces neutrophils and macrophages in the right tumor, then Lyt-1-positive cells in the right regional lymph nodes and in the spleen, and subsequently induces macrophages in the left, non-treated tumor.

Animals↗
PubMed1991

[Antitumor Effector mechanism of plant alkaloid preparation, cepharanthin, by intratumoral administration].

The antitumor effect of biscoclaurine alkaloids, at a distant site was examined in the double grafted tumor system, in which mice received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 x 10(5) cells) flanks and were then injected with 0.5 mg of CR in the right tumor on days 3, 4 and 5. CR inhibited the growth of not only the right but also the left, non-treated tumor. In order to examine the role of lymph nodes in the antitumor activity of CR, regional (axillary and inguinal) lymph nodes were resected. Since in resected mice the antitumor activity of CR against the left tumor was weakened, the regional lymph nodes have a very important role in the antitumor effect of intratumoral administration of CR at a distant site. Spleen cells prepared from CR treated mice were examined for Lyt-1, Lyt-2 and L3T4 phenotypes. The number of Lyt-1 positive lymphocytes increased in the spleen after intratumoral administration of CR. Isolated tumor cells obtained from the right tumor treated with CR and the left side tumor on day 6 were cultured for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophil or macrophage. Significant neutrophil chemotactic factor (NCF) activity was detected in the culture media from CR-treated right tumor tissue, and macrophage chemotactic factor (MCF) activity was detected in the culture media from left tumor tissue. CR-induced NCF was partially neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8 factor. These results suggest that intratumoral administration of CR first induces neutrophils in the right tumor, then Lyt-1 positive cells in the spleen, and subsequently induces cytotoxic macrophages in the left, non-treated tumor, thus bringing about the regression of distant tumors.

Alkaloids↗