PubMed Health⌕ Search

Biomedical subjects

K Akimaru

Publications and source records attributed to K Akimaru.

At least 55 records · Page 3Linked to original sources
PubMed1993

A case report of post-thymectomy myasthenia gravis with residual thymoma.

A forty-nine-year-old female patient, complaining of swallowing difficulties and general fatigue, was admitted to the first hospital of Nippon Medical School. At the age of 32, she was operated on for the removal of a well encapsulated non-invasive thymoma. Since then, she had been well till the age of 46, when chest X-ray films showed a recurrent thymoma which was excised together with the complete thymic tissues. One year later, she developed myasthenia gravis (MG) with a ptotic right upper eyelid and general fatigue. Subsequently, she was placed on medication. After 21 months, however, she died of myasthenic crisis in spite of vigorous respiratory and nutritional support. The autopsy revealed a small residual thymoma on the left lung, and systemic atrophy of the skeletal muscles. In this paper, the mechanism of post-thymectomy MG and the recurrence of non-invasive thymoma are discussed.

Female↗
PubMed1992

Role of tyrosyl phosphorylation in neutrophil priming by tumor necrosis factor-alpha and granulocyte colony stimulating factor.

The ability of human tumor necrosis factor-alpha (TNF-alpha) and human granulocyte colony stimulating factor (G-CSF) to induce phosphorylation of protein tyrosyl residues in human peripheral neutrophils (PMN) was investigated by Western blot analysis with antiphosphotyrosine antibody. Both TNF-alpha and G-CSF increased the tyrosyl phosphorylation of various proteins, such as species of 54-, 63-, 72-, 83-, 98-, 108-, and 115-kDa proteins. The ligand-stimulated tyrosyl phosphorylation of the 115-kDa protein was time- and concentration-dependent. When the 115-kDa protein was phosphorylated, it was recovered from membrane fractions. The phosphorylation of the 115-kDa protein was inhibited by genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide (ST 638), inhibitors of tyrosine kinase (TK), and was enhanced by 1-(5-isoquinoline-sulfonyl) methyl-piperazine dihydrochloride (H-7) and staurosporine, inhibitors of Ca(2+)- and phospholipid-dependent protein kinase (PKC). Similar inhibition by the TK inhibitors and stimulation by the PKC inhibitors were also observed with formylmethionyl-leucyl-phenylalanine (FMLP)-induced superoxide (O2.-) generation by TNF-alpha- or G-CSF-primed PMN. Phosphorylation of the 115-kDa protein occurred in parallel with the ligand-dependent generation of O2.-. These and other observations suggested that substrate proteins for tyrosine kinase, such as the 115-kDa protein, might play critical roles in the mechanism for priming of neutrophils. This is the first report describing that tyrosyl phosphorylation is involved in the priming of neutrophils by G-CSF and TNF-alpha.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Stimulus-specific enhancement of luminol chemiluminescence in neutrophils by phosphatidylserine liposomes.

When stimulated with different stimuli, neutrophils generate various active oxygen species. These active oxygen molecules can be analyzed by luminol chemiluminescence (LCL). Phosphatidylserine (PS)-liposomes increased the formylmethionyl-leucyl-phenylalanine-induced LCL of guinea pig peritoneal neutrophils without affecting their oxygen consumption and superoxide (O2.-) generation. Similar effects of PS-liposomes were also observed in LCL of neutrophils stimulated by phorbol myristate acetate or arachidonic acid but not by opsonized zymosan. Kinetic analysis revealed that the PS-liposome-induced increase in LCL depended on extracellulary generated O2.-. Moreover, the stimulatory effect of PS could be seen only when it formed liposomal membranes. The effect of PS-liposomes was also inhibited by superoxide dismutase, catalase, and deferoxamine, an iron chelator, but not by azide, an inhibitor of myeloperoxidase. Similar enhancement of stimulation-dependent LCL response was also observed with Fe3+ and ADP-Fe3+, but the degree of enhancement was much greater with PS-liposomes than with iron and its complex. The increase in hydroxyl radical generation by PS-liposome-treated neutrophils was confirmed by experiments with EPR spectrometry using spin-trapping agents. These results suggested that the interaction of neutrophils with PS-containing membrane surface might generate reactive oxygen species that enhance the stimulus-dependent LCL response of neutrophils.

Animals↗
PubMed1992

Modulation of TNF-alpha-priming and stimulation-dependent superoxide generation in human neutrophils by protein kinase inhibitors.

Human peripheral blood polymorphonuclear leukocytes (HPPMN) from healthy individuals are not primed and, hence, weak stimulation-dependent responses are induced by certain stimuli which bind to membrane receptors. When HPPMN were exposed to recombinant human tumor necrosis factor alpha (rHuTNF-alpha) or recombinant human granulocyte colony stimulating factor (rG-CSF), they underwent priming and the rate of superoxide anion (O.-2) generation was increased by subsequent exposure to formyl-methionyl-leucyl-phenylalanine (FMLP) or opsonized zymosan (OZ). However, the degree of enhancement was very small upon exposure to phorbol myristate acetate (PMA) or dioctanoyl glycerol (DOG). The oxygen burst induced by FMLP or OZ was inhibited by genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamid (ST638), which are inhibitors of tyrosine kinase (TK), and was enhanced by 1-(5-isoquinoline-sulfonyl)-3-methyl-piperazine (H-7) and staurosporine, which are inhibitors of protein kinase C (PKC). Without priming, however, O.-2 generation from HPPMN by high concentrations of FMLP was not inhibited strongly by genistein or ST638. On the contrary, the oxygen burst induced by PMA or DOG was stimulated by genistein or ST638 and was inhibited by H-7 or staurosporine. Furthermore, O.-2 generation by guinea pig peritoneal neutrophils, which are already primed in vivo, was induced markedly by FMLP by a mechanism which was stimulated by a low concentration of genistein or ST638. Thus, FMLP-mediated O.-2-generation of HPPMN is coupled with rHuTNF-alpha- or rG-CSF-priming and is inhibited by TK inhibitors, whereas PMA- or DOG-induced O.-2 generation is not coupled with TNF-alpha or G-CSF-priming and is inhibited by PKC inhibitors. These results suggest that both PKC and TK play critical roles in the regulatory mechanism of priming and NADPH-oxidase activation in neutrophils.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Differentiation of HL-60 cells by phorbol ester is correlated with up-regulation of protein kinase C-alpha.

To clarify the mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced macrophage-like differentiation of HL-60 cells, we investigated the correlation between the effects of protein kinase C (PKC) inhibitors on the induction of markers of TPA-induced differentiation and those on suggested critical steps of the differentiation. H-7, sphingosine, and trifluoroperazine significantly suppressed TPA-induced cell adhesion but their effects on the induction of acid phosphatase and nonspecific esterase differed among the inhibitors. The three inhibitors failed to affect on TPA-induced annexin I expression. In contrast, staurosporine markedly suppressed the induction of all these markers. The effects of the inhibitors on some suggested critical steps of the differentiation, a rapid phosphorylation of specific proteins, a rapid membrane association of PKC, and down-regulation of PKC at 18 h after addition of TPA, were not correlated with those on the differentiation marker induction. Only the effect of the inhibitors on up-regulation of PKC-alpha was closely correlated with TPA-induced annexin I expression; staurosporine inhibited up-regulation of PKC-alpha but other inhibitors did not similarly affect the induction of annexin I expression. These results suggest that PKC-alpha is intimately related to macrophage-like differentiation of HL-60 cells by TPA.

Acid Phosphatase↗
PubMed1992

Effect of tumor necrosis factor-alpha on the stimulus-coupled responses of neutrophils and their modulation by various inhibitors.

Preincubation of human peripheral blood polymorphonuclear leukocytes (HPPMN) with recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) enhanced the formylmethionyl-leucylphenylalanine (FMLP)-induced superoxide (O2-.) generation in a concentration- and preincubation time-dependent manner. The enhancement was very high for the FMLP- or opsonized zymosan (OZ)-induced O2-. generation, but was low for arachidonic acid (AA)- and phorbol myristate acetate (PMA)-induced O.2- generation. The rHuTNF-alpha has no effect on the steady state of intracellular calcium ion concentration ([Ca2+]i) nor on the membrane potential of neutrophils. The rHuTNF-alpha-primed FMLP-induced O2-. generation was inhibited by nicotineamide (NA), pertussis toxin (PT), and by the tyrosine kinase (TK) inhibitor, genistein, but was enhanced by the protein kinase C (PKC) inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-3-methyl-piperazine). The inhibitory actions of NA and PT were also observed in in vivo primed guinea pig peritoneal neutrophils (GPtPMN). However, FMLP-induced O2-. generation of GPtPMN was enhanced by genistein, but was inhibited by H-7. These data indicate that TNF-alpha does not induce changes in [Ca2+]i nor in membrane potential of HPPMN, and that TNF-alpha-primed FMLP-induced O.2- generation of HPPMN is coupled with ADP-ribosylation and activation of G-proteins, and that protein kinases, especially TK, seem to exert an important role in the priming action of TNF.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Nonsteroidal antiestrogen suppresses protein kinase C--its inhibitory effect on interaction of substrate protein with membrane.

The mechanism by which nonsteroidal antiestrogen inhibits Ca(2+)- and phospholipid-dependent protein kinase (PKC) activity was investigated. Antiestrogenic agents, clomiphene and tamoxifen, inhibited the PKC-dependent phosphorylation of histone and r-annexin I in a dose-dependent manner. Ki values for the agents were different for two substrate proteins. The inhibitory action of the agents depended on the membrane-substrate protein interaction. Phosphorylation of cytoplasmic proteins obtained from rat uterus and mammary gland, including annexin I, by endogenous PKC was also inhibited by low concentrations of these agents. These results suggest that the inhibitory action of nonsteroidal antiestrogens occurs through their inhibitory effect on the membrane-substrate protein interaction.

Animals↗
PubMed1989

[Partial liver transplantation techniques for future clinical application].

Using grafts from brain-dead donors for liver transplantation is a very controversial subject in Japan and those candidates for transplantation who have received livers outside of Japan have been harshly criticized. Under these circumstances, a partial liver transplantation is an attractive method in terms of preserving the donor's life, freshness of the graft and easier donor availability. In other words, for adults with non-cancerous incurable liver disease the donor's left lobe can be transplanted after the recipient has had a left lobectomy, and for children with biliary atresia the whole liver and vena cava can be replaced with a parent's left lobe and iliac vein. Our report concerns the procedures of orthotopic partial liver transplantation for canines and humans.

Animals↗
PubMed1988

Peritoneovenous shunting for intractable cirrhotic and cancerous ascites using different types of shunting tubes.

A total of twenty six peritoneovenous shuntings were performed in our department between 1978 and 1984, on twelve cirrhotic and ten cancerous patients with intractable ascites, using Pudenz, LeVeen or Denver type shunting tubes. Reduced ascites was noted postoperatively with statistical significance in both the cirrhotic group (p less than 0.05) and the cancerous group (p less than 0.01), of whom eight cirrhotic and seven cancerous patients exhibited an abdominal girth reduced by 9.7 cm (a 10.9 per cent reduction) in two weeks. A larger urinary output was noted in 13 patients, with a mean increase of 587 ml/day compared with the pre-shunting output. These patients lost a mean weight of 6.13 kg in two weeks, while the nonreduced ascites group gained weight. The post-shunting serum albumin level was higher in the reduced ascites group. The mean functioning periods of the shunts were 5.1 and 2 months, respectively for the cirrhotic and cancerous patients whose shunts were patent. The patients' outcome was shown to depend on the disease itself, with the exception of one patient who died of disseminated intravascular coagulopathy following shunting. In comparing several types of shunting systems, the Denver-type was proven as being the most unlikely to plug or malfunction because of its simpler structure.

Adult↗
PubMed1986

DNA amplification of the c-myc and c-erbB-1 genes in a human stomach cancer.

High-molecular-weight DNAs from 43 human primary tumor tissues were examined by Southern blot hybridization for possible rearrangement and/or amplification of the following protooncogenes: the c-myc, c-erbB-1, N-myc, c-mos and c-fos genes. In an adenosquamous cell carcinoma of the stomach, the c-myc and c-erbB-1 genes were found to be simultaneously amplified 5- and 30-fold, respectively. Cooperative expression of the amplified c-myc and c-erbB-1 genes might be involved in the genesis or progression of the gastric cancer.

DNA, Neoplasm↗
PubMed1984

[In vivo evaluation of cellular immunity in melanoma patients against melanoma].

Evaluation of cellular immunity against human melanoma was performed in an in vivo model using Balb/c nude mice bearing the human melanoma. Intraperitoneal injection of 1 X 10(7) melanoma cells produced peritonitis carcinomatosa which lead to death of the mice at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from healthy donors and the melanoma cells cultured on the back of the nude mouse were given to nude mice intraperitoneally, and survival times of 22.0 +/- 2.3 days were observed (N = 8). PBL from four of the five healthy donors which have been presensitized on monolayers of the melanoma tissue culture cells in flask failed to prolong host survival times. In contrast, PBL from 15 of 20 melanoma patients were found to prolong the survival of the tumor bearing nude mice. Of these 15 patients, 8 were treated with specific active immunotherapy, but 7 had not been sensitized except by the disease process. The ability of PBL from patients to prolong survival of the melanoma bearing nude mice did not seem to correlate with either the stage of the disease or the clinical course. The possible mechanisms for the prolonged survival and the usefulness of this in vivo model were discussed.

Animals↗
PubMed1981

In vivo evaluation of cell mediated immunity against human melanoma.

Evaluation of cell mediated immunity against human melanoma target cells was performed in an in vivo model using human tumor xenografts growing in Balb/c athymic mice. Intraperitoneal inoculation of 1 x 10(7) human melanoma cells produced carcinomatosis which lead to death of the animals at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from normal donors were administered to tumor bearing mice, and survival times of 22.0 +/- 2.3 days were observed (N = 8). Peripheral blood lymphocytes from the four of five normal donors which had been presensitized on monolayers of melanoma tissue culture cells in vitro failed to prolong host survival times. In contrast, PBL obtained from 15 or 20 melanoma patients were found to prolong survival of the tumor bearing nude mice. Of these 15 patients, 8 were undergoing specific active immunotherapy, while 7 had not been sensitized except by the disease process. The ability of PBL obtained from patients to prolong survival of tumor bearing animals did not appear to correlate with either the stage of the disease or the patient's clinical course. The possible mechanisms for the prolonged survival and usefulness of this model are discussed.

Animals↗
PubMed1981

Human melanoma growth in the peritoneal cavity of the athymic mouse--a model for in vivo study of cell-mediated immunity.

Intraperitoneal injections of 2 X 10(7) SH-Me cells (human metastatic melanoma cells)( to 20 Balb/c nu/nu mice (Group A) and 1 X 10(7) cells to 20 mice (Group B) were performed. All animals were studied clinicopathologically. Five animals in Group A were sacrificed serially, revealing marked tumor growth of the melanoma within the peritoneal cavity. These tumors grew in multiple nodular configurations and tumor ascites was present by the third week. The remaining 15 animals in Group A were allowed to progress and seven subsequently died with mouse viral hepatitis (MVH). These animals had suppressed tumor growth. The remaining eight animals died of peritoneal carcinomatosis with survival time of 24.1 +/- 5.0 days. Eight of the animals in Group B died of mouse viral hepatitis while the remainder died of peritoneal tumor without distant metastasis. Survival time in these animals was 23.8 +/- 2.6 days. Both 2 X 10(7) and 1 X 10(7) tumor cells injected intraperitoneally will constantly produce tumor nodules in non-MHV-infected nude mice with similar survival. This experimental model has proven useful for in vivo study to assess the immunoreactivity of melanoma patient cells reactive against target tumor cells.

Animals↗