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Biomedical subjects

J Abe

Publications and source records attributed to J Abe.

At least 73 records · Page 4Linked to original sources
PubMed1997

Angiotensin II stimulates p90rsk in vascular smooth muscle cells. A potential Na(+)-H+ exchanger kinase.

Angiotensin II is a multifunctional agonist for vascular smooth muscle cells (VSMCs), stimulating increases in signal events, cell growth, and ion flux. We previously defined protein kinase C (PKC)-dependent and -independent mechanisms by which angiotensin II stimulated activity of the Na(+)-H+ exchanger isoform-1 (NHE-1) and identified a 90-kD kinase that exhibited increased activity in VSMCs isolated from genetically hypertensive rats. To determine whether this 90-kD kinase was p90rsk (RSK), VSMCs were stimulated with 100 nmol/L angiotensin II, and NHE-1 kinase activity was measured by phosphorylation of recombinant NHE-1 (a glutathione S-transferase fusion protein containing amino acids 516 to 815 of the cytoplasmic carboxyl tail) in vitro. NHE-1 kinase (90 kD) activity was markedly decreased by immunodepletion of RSK. Characterization of RSK activation by angiotensin II revealed many similarities to the 90-kD NHE-1 kinase, including time course and NHE-1 domain phosphorylation, as well as regulation by extracellular signal-regulated kinases (ERK1/2), intracellular Ca2+, and PKC. Specifically, angiotensin II stimulated a rapid and transient (peak, 5 minutes) increase in RSK activity. Analysis of several NHE-1 fusion proteins revealed that only proteins containing amino acids 670 to 714 were phosphorylated by RSK. Inhibiting ERK1/2 (30 mumol/L PD098059 for 30 minutes) or chelating intracellular Ca2+ prevented RSK activation. In contrast, downregulating PKC (1 mumol/L phorbol dibutyrate for 24 hours) had little effect. These findings establish RSK as a putative NHE-1 kinase and potential mediator of increased Na(+)-H+ exchange in hypertension.

Amino Acid Sequence↗
PubMed1997

Intraalveolar expression of tumor necrosis factor-alpha gene during conventional and high-frequency ventilation.

The effects of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFO) on intraalveolar expression of the tumor necrosis factor-alpha (TNF-alpha) gene were studied in surfactant-depleted rabbits. After lung lavage with saline, 13 rabbits were administered either CMV (n = 6) or HFO (n = 7) for 1 h at an FiO2 of 1.0 and a mean airway pressure of 13 cm H2O. Lung lavage was then repeated. The rabbits' RNA was extracted from the lavage cells, and mRNA for TNF-alpha was quantitated by reverse-transcription polymerase chain reaction using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal standard. At 1 h of ventilation, PaO2 was slightly lower with CMV than HFO, while lavage cell counts and cytology were similar between the two groups. The ratio of TNF-alpha mRNA to GAPDH mRNA increased with CMV (control, 0.48 +/- 0.04 [SE] versus 1 h, 1.02 +/- 0.14, p < 0.01) but did not change with HFO (0.55 +/- 0.07 versus 0.73 +/- 0.09). In a separate series of experiments, ten surfactant-depleted rabbits continued to be ventilated for 4 h either by CMV (n = 5) or HFO (n = 5). Conventional mechanical ventilation resulted in a progressive hypoxemia, decreased lung compliance, increased number of neutrophils in lung lavage fluid, and substantial morphological changes including hyaline membrane formation and neutrophil accumulation, whereas HFO was associated with minimal changes in such physiological and pathological abnormalities. These results suggest that activation of alveolar macrophages and production of proinflammatory cytokines may play a pivotal role in the early stage of ventilator-induced lung injury, and that ventilator mode (CMV or HFO) substantially modulates macrophage activation and hence the degree of lung injury.

Animals↗
PubMed1997

[Self-evaluation on the ability to retrieve Kanji words: a comparison between an aphasiac and normal subjects].

The present study investigated the accuracy of an aphasiac's self-evaluation on his ability to retrieve words. The aphasiac and six normal subjects were shown a list of words and that of drawings. The words were written in Kanji and the drawings could be translated into the Kanji words. For each word, the subjects rated the likelihood that they could write it, and for each drawing, they rated the likelihood that they could translate it into the Kanji word. A week later, they were asked to translate drawings into Kanji words, and the performance and self-ratings were compared. Although the aphasiac could write far less Kanji words than the normals, his self-rating was as high as the normals. It was suggested that metamnemonic judgments are based on the indirect inferential processes, not on the direct access to the memory-traces. In other words, the aphasiac might raise his rating scores when Kanji words or drawings seemed easy to understand.

Adult↗
PubMed1996

Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase.

Mitogen-activated protein (MAP) kinases are a multigene family activated by many extracellular stimuli. There are three groups of MAP kinases based on their dual phosphorylation motifs, TEY, TPY, and TGY, which are termed extracellular signal-regulated protein kinases (ERK1/2), c-Jun N-terminal kinases, and p38, respectively. A new MAP kinase family member termed Big MAP kinase 1 (BMK1) or ERK5 was recently cloned. BMK1 has a TEY sequence similar to ERK1/2 but has unique COOH-terminal and loop-12 domains. To define BMK1 regulation, its activation in cultured rat vascular smooth muscle cells was characterized. Angiotensin II, phorbol ester, platelet-derived growth factor, and tumor necrosis factor-alpha were the strongest stimuli for ERK1/2 but were weak activators of BMK1. In contrast, H2O2 caused concentration-dependent activation of BMK1 but not ERK1/2. Sorbitol activated both BMK1 and ERK1/2. BMK1 activation by H2O2 was calcium-dependent and appeared ubiquitous as shown by stimulation in human skin fibroblasts, human vascular smooth muscle cells, and human umbilical vein endothelial cells. These findings demonstrate that activation of BMK1 is different from ERK1/2 and suggest an important role for BMK1 as a redox-sensitive kinase.

Amino Acid Sequence↗
PubMed1996

Dual recognition of a human cytotoxic T-cell clone for melanoma antigens.

It is well known that tumor-specific CTLs have a crucial role in the elimination of tumors and that different CTL populations recognize tumor antigens in MHC-restricted and MHC-unrestricted manners. We have established two alpha beta CTL clones that recognize melanoma antigens in both human lymphocyte antigen (HLA)-A2-restricted and HLA-unrestricted manners. Flow cytometry analysis showed that these CTL clones carry CD3, CD8, and alpha beta T-cell receptor (TCR) and express low levels of CD56. In contrast, these CTL clones do not express CD16, indicating that they do not contain natural killer cells. TCR analysis of these CTL clones using an anchored PCR method revealed that each clone carries a single alpha beta TCR. Both CTL clones contained the same Valpha and Vbeta gene segments although they carried different Jalpha and Jbeta gene segments. Taken together, these results confirm that CTL clones that carry a single alpha beta TCR recognize melanoma antigens in both HLA-A2-restricted and HLA-unrestricted manners. It is strongly suggested that the dual recognition of these CTL clones for the melanoma antigens is mediated by TCRs. The novel mechanism for antitumor immunity by these CTLs may be important in the effective elimination of tumors in vivo.

Amino Acid Sequence↗
PubMed1996

Intensified antitumor immunity by a cancer vaccine that produces granulocyte-macrophage colony-stimulating factor plus interleukin 4.

Vaccination with irradiated tumor cells genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF tumor vaccine) induces a potent systemic antitumor immunity. To develop a protocol for cancer therapy to further augment the host immune response, we examined the effects of the GM-CSF tumor vaccines simultaneously producing additional cytokines. We prepared cancer vaccines expressing double cytokines by sequential recombinant retrovirus-mediated genetic transductions. We then used a murine intracerebral tumor model in which the GM-CSF tumor vaccine was less effective in immunopotentiation and evaluated tumor vaccines producing various cytokines in conjunction with GM-CSF. The cytokine combination of GM-CSF and interleukin 4 induced more potent antitumor immunity than GM-CSF alone. An in vivo depletion test showed that CD4+, CD8+, and asialoGM1+ cells were required for the optimum function of the GM-CSF plus interleukin 4 tumor vaccine. Histological examinations revealed infiltration of inflammatory cells at the site of tumor cell challenge as well as at the site of vaccination, indicating the induction of a systemic antitumor immune response which reached the central nervous system. Our findings suggest the feasibility of applying the intensified vaccination strategy to treat human cancers including malignant brain tumors.

3T3 Cells↗
PubMed1996

In vivo antitumor effect of cytotoxic T lymphocytes engineered to produce interferon-gamma by adenovirus-mediated genetic transduction.

Immunotherapy with adoptive transfer of genetically-modified cytotoxic T lymphocytes (CTL) is a promising approach for cancer gene therapy. We developed an adoptive therapy model with murine tumor-specific CTL, to which very efficient (up to 100%) gene introduction was achieved by using recombinant adenoviral vectors. Through a comparative study on the antitumor effects of CTL genetically modified with cytokine genes, transduction with interferon-gamma gene resulted in a prominent increase in therapeutic efficacy of CTL in both metastatic and subcutaneous tumor models. Further additive effect was obtained by the adoptive cellular therapy in combination with vaccination of cytokine gene-modified tumor cells. Our findings provide a hopeful strategy of adoptive immunotherapy for human cancers.

Adenoviridae↗
PubMed1996

Thrombotic occlusion of the coronary artery associated with accidental detachment of undeployed Palmaz-Schatz stent.

We describe a case of coronary stenting in which accidental detachment of the Palmaz-Schatz stent induced thrombotic occlusion of the coronary artery. This case suggests that careful consideration of the risk involving coronary occlusion is mandatory on deciding the therapeutic strategy of the cases in which the unexpanded coronary stent cannot be retrieved following successful deployment.

Adult↗
PubMed1996

Candida albicans induces selective expansion of human T lymphocytes expressing the T-cell receptor variable region V beta 5.1.

Candida albicans is a common pathogen which can present major problems as an opportunistic skin pathogen in patients with immunodeficiency. The exact nature of the T cell responses to C. albicans is poorly understood. The purpose of this study was to determine whether C. albicans could stimulate the selective expansion of T lymphocytes expressing particular V beta gene segments. Human T lymphocytes stimulated in vitro with an extract of C. albicans were analyzed for T cell receptor V beta gene expression by using a quantitative PCR technique. We found that stimulation of peripheral blood mononuclear cells (PBMC) produced a selective increase in the expression of V beta 5.1 and 5.2 gene transcripts. Using cytofluorographic analysis with available anti-V beta monoclonal antibodies, we verified that there was a significant selective expansion (P = 0.035) of V beta 5.1 positive T lymphocytes in PBMC from six subjects stimulated in vitro with C. albicans. PCR analysis of V beta 5.1 expansion in 10 subjects showed increases in V beta 5.1 gene transcripts in 7/10 subjects. More importantly, analysis of the T cell infiltrate 48 h after intradermal injections with C. albicans also showed significant expression of V beta 5.1 in the infiltrates, along with the infiltration of V beta 8.1 + T cells. The selective expansion of V beta 5.1 bearing T lymphocytes in PBMC stimulated with C. albicans and in skin test reactions to C. albicans suggests that a restricted population of T cells react to C. albicans. Furthermore, our present data raise the provocative possibility that one or more antigens in C. albicans can act as a superantigen, producing selective expansion of a population of T lymphocytes bearing a particular V beta specificity.

Antibodies, Monoclonal↗
PubMed1996

Growth suppression in children receiving acetazolamide with antiepileptic drugs.

To clarify the effect of the clinical dosage of acetazolamide on growth in children with epilepsy or febrile convulsion, the standard scores of height and weight in 17 subjects receiving acetazolamide as an adjunct to unchanged monotherapy of antiepileptic drug were compared longitudinally through four phases: before antiepileptic drug administration, with monotherapy of antiepileptic drug, with acetazolamide in addition to monotherapy, and after acetazolamide discontinuation. The standard scores of both height and weight in the subjects were significantly reduced during the phase of acetazolamide administration. During this period, serum concentrations of potassium and total CO2 decreased while that of chloride increased, suggesting the existence of metabolic acidosis in the subjects. For both height and weight, there was no correlation between the degree of standard score reduction during acetazolamide administration and age at the time of acetazolamide initiation, duration of acetazolamide administration, dosages of acetazolamide, and variety of antiepileptic drugs concomitantly administered with acetazolamide. We speculate that metabolic acidosis induced by acetazolamide suppressed the growth of the subjects and that there were large individual differences in the susceptibility to acetazolamide for growth suppression among patients receiving acetazolamide.

Acetazolamide↗
PubMed1996

Primary cytotoxicity of SEB-activated human PBMC and separated CD8+ and CD4+ T lymphocytes elicited by two different stimulation protocols.

The primary cytotoxicity of Staphylococcal enterotoxin B (SEB)-stimulated PBMC and separated CD8+ and CD4+ T cells against Burkitt's lymphoma target cells has been characterized by applying two stimulation protocols. In the bulk protocol, the PBMC were stimulated with 100 ng/mL SEB for 3 days before separation to CD4+ and CD8+ T subsets. In the direct protocol, the separated CD4+ and CD8+ T cells were stimulated with 100 ng SEB preabsorbed to mitomycin C (MMC)-treated APC. Comparison of the results of the two different protocols revealed the following differences: (i) PBMC in the direct protocol provided greater cytolytic activity than in the bulk protocol; and (ii) the CD4+ T cells acquired cytotoxicity only in the direct protocol. Unexpectedly, the superantigen-dependent cellular cytotoxicity (SDCC) of SEB-stimulated cells was not dominant compared with the basal cytotoxicity. The classical NK target, K-562 was also sensitive to SEB-augmented cytotoxicity. The parallel stimulation with IL-2 and SEB caused a similar extent of cytotoxicity enhancement against both types of target cells. However, the cyclosporin A (CSA) inhibited only the SEB-induced cytotoxicity. The results suggest that SEB-induced PBMC acquire mainly a LAK-like cytotoxicity, as a consequence of newly produced lymphokines. This observation might propose a different approach in pathological studies.

Antigen-Presenting Cells↗
PubMed1996

Cervical myelopathy in elderly patients: clinical results and MRI findings before and after decompression surgery.

We examined 173 patients with cervical myelopathy of various causes. Seventy-seven patients underwent anterior decompression and fusion at not more than two levels, while 96 underwent posterior decompression by an expansive laminoplasty. Patients were followed up for between one and 4 1/2 years and the outcome was assessed both from a functional and a radiological point of view. The functional assessment used was according to the Japanese Orthopaedic Association (JOA) score (the higher the better), and the imaging outcome was assessed by a midline sagittal MRI assigned to three categories either for restoration of cord morphology, improvement or unchanged. Patients were divided into two groups: those 65 years old and older (50 patients), and those younger than 65 years old (123 patients). The data allowed the following conclusions to be reached: Older patients were likely to have more levels, and higher levels affected, and as a result were more likely to require a posterior operation. The recovery rate after an anterior operation was the same as that after a posterior operation. The pre- and post-operative JOA scores were higher in younger patients who tended to have milder disease with fewer levels affected. Younger patients had better morphological restoration. The recovery was likely to be better if the postoperative morphology was better. The morphology postoperatively was likely to be better if there had been less compression preoperatively. If the morphology was restored the disease duration was likely to have been less. The patients did better if the cord morphology was restored to normal, and this was easier to achieve in younger patients who had fewer levels involved and had less cord distortion preoperatively.

Adult↗
PubMed1995

Sequence analysis of the gene for a novel superantigen produced by Yersinia pseudotuberculosis and expression of the recombinant protein.

We previously reported that the Gram-negative bacterium Yersinia pseudotuberculosis produces a superantigen (YPM, Y. pseudotuberculosis-derived mitogen) that expands T cells bearing V betas 3, 9, 13.1, and 13.2 in an MHC class II-dependent manner. Based on the previously determined N-terminal 23 amino acids of YPM (T-D-Y-D-N-T-L-N-S-I-P-S-L-R-I-P-N-I-A-T-Y-T-G- (one-letter code)), we cloned the ypm gene and analyzed the nucleotide sequence. The gene encodes a 151-amino acid protein with a 20-amino acid signal peptide at its N terminus. The recombinant YPM expressed by the cloned gene exerted a mitogenic activity on human PBMC at a concentration of approximately 1 pg/ml. T cells bearing V beta 13.3 were preferentially expanded as well as T cells bearing the same V beta repertoires stimulated by native YPM. T cells were stimulated by the recombinant YPM in the presence of either fixed or unfixed HLA class II-transfected mouse fibroblasts. Furthermore, sequence diversity in the junctional region of the TCR beta-chain containing the V beta 3 element could be observed after stimulation by the recombinant YPM. These results indicate that YPM belongs to the category of superantigens and should be included as a novel member. The amino acid sequence of the mature protein showed no significant homology to other superantigens derived from Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes. This observation, together with the substantially smaller m.w. suggest that ypm must have evolved from a different ancestral gene.

Amino Acid Sequence↗
PubMed1995

Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction.

Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus- or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene delivery and a high-level expression of the GM-CSF gene were achieved. Unexpectedly, animal vaccination studies showed that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.

Adenoviridae↗
PubMed1995

Cytokine-gene-modified tumor vaccination intensified by a streptococcal preparation OK-432.

Vaccinations with tumor cells engineered to express certain cytokines have been demonstrated to induce potent and specific antitumor immunity. In our previous report, we carried out a comparative study on the ability of cytokine-gene-modified tumor vaccines to induce host immune responses, and found that irradiated tumor cells, genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine), were the most potent stimulators of systemic antitumor immunity. In this report, using the experimental tumor models in which the GM-CSF tumor vaccine was less effective in immunopotentiation, we found that the combined use of a biological response modifier (BRM) OK-432 remarkably enhanced the antitumor activity induced by the GM-CSF tumor vaccine. These data indicate the possible role of a BRM such as OK-432 to intensify further the specific tumor vaccination therapy.

Animals↗
PubMed1995

Chronic active hepatitis and liver cirrhosis in association with combined tamoxifen/tegafur adjuvant therapy.

Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five years, respectively, after the cessation of the treatment, the results of liver tests were normal and distinct histological improvement was observed in both patients. Because these patients had no viral and immunoserological markers nor any history of alcohol abuse, this study suggested that the tamoxifen and tegafur regimen induced reversible chronic active liver disease.

Adult↗