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Biomedical subjects

T Hideshima

Publications and source records attributed to T Hideshima.

At least 55 records · Page 3Linked to original sources

Nonlinear oscillatory reaction of catalase induced by gradual entry of substrate.

Characteristic oscillatory reactions were observed when hydrogen peroxide migrated through semipermeable membrane into a solution of catalase. Measurements were made with DO and an mV meter. Oscillation clearly occurred in the range between 25 degrees C and 37 degrees C and between pH 6.0 and pH 7.6. It was also shown that a driving force for the permeation of H2O2, which was the cause of the oscillations, was a deviation from its equilibrium concentration. We made simulations for oscillatory reactions on the basis of these findings. The result indicated that considering the evaporation of O2 was necessary in order to interpret the oscillatory reactions of catalase in addition to the slow entry of substrate caused by deviation from the equilibrium concentration. The fact that oscillations arise by using this method may provide an important insight into the study of enzyme reactions mediated by membranes in living systems, because many enzyme reactions take place with the mediation of a biomembrane.

Journal Article↗

Medroxyprogesterone acetate treatment reduces serum interleukin-6 levels in patients with metastatic breast carcinoma.

BACKGROUND: The serum interleukin (IL)-6 concentration was very low in patients with metastatic breast carcinoma who had received oral medroxyprogesterone acetate (MPA) treatment as compared with those who had not. Accordingly, the authors conducted a prospective study to determine whether MPA treatment reduces the serum level of IL-6 in patients with this disease. METHODS: In 21 consecutive Japanese patients who were scheduled to receive oral MPA treatment at doses of 600, 800 or 1200 mg/day, serum concentrations of IL-6 were determined with a sensitive enzyme-immunoassay prior to the administration of MPA and again at 4 weeks after the treatment was started. In addition, plasma levels of MPA were determined by high-performance liquid chromatography (HPLC). RESULTS: Four weeks after the oral MPA therapy was started, serum IL-6 levels decreased in all 21 patients regardless of whether or not they responded to the treatment. Although the extent of decrease in the serum IL-6 (delta IL-6) did not correlate with the daily dose of MPA, it correlated closely with the plasma MPA level in these patients. Subjective improvement in appetite and weight gain were more frequent in the delta IL-6 > 3 pg/mL group compared with the delta IL-6 < or = 3 pg/mL group (80% vs. 45% and 70% vs. 45%, respectively). Similar results were obtained for improvement in patients' sense of well-being (100% vs. 55%). CONCLUSIONS: Oral MPA treatment reduces serum IL-6 concentration in patients with metastatic breast carcinoma, but the decrease is not associated with response to MPA. This observation may indicate a potential of this agent for producing subjective improvement.

Administration, Oral↗

The induction of cytotoxicity by a bispecific antibody against CEA positive cell line, in vitro.

A mouse anti-human carcinoembryonic antigen (CEA) x anti-human CD3 bispecific antibody, AB5C10*UCHT1, was developed. This antibody-heteroconjugate was chemically prepared by cross-linking the AB5C10 monoclonal antibody reactive with human CEA with the monoclonal antibody, UCHT1, which binds to CD3 on human T-lymphocytes. The AB5C10*UCHT1 recognized both CEA expressed on the KATOIII cell line and CD3 expressed on T-lymphocytes, as determined using flowcytometry. Next, AB5C10*UCHT1-mediated cytolysis was analyzed by 51Cr-release assay. When 51Cr-labeled target KATOIII cells were incubated for 6 h with effector cells that had been pretreated with AB5C10*UCHT1 for 60 min at 4 degrees C, the percentage specific lysis was significantly increased compared to that of untreated effector cells. Using peripheral blood mononuclear cells (PBMC) and lymphokine-activated killer (LAK) cells pretreated with AB5C10*UCHT1 for effector cells, the percentage specific lysis was determined to be 16.3% and 57.4% at effector: target (E:T) ratios of 100:1 and 12.5:1, respectively. On the other hand, the percentage specific lysis of untreated PBMC and LAK cells determined to be 3.0% and 35.8% at E:T ratios of 100:1 and 12.5:1, respectively. The minimum effective dose of AB5C10*UCHT1 required for antibody-mediated cytotoxicity was 0.1 mu g/ml. The results of this study suggest that AB5C10*UCHT1 could be useful for augmenting the cytotoxicity of CD3-positive T-cells against CEA-positive target cells in vitro.

Animals↗

The unusual presentation of mucinous carcinoma in the colon making preoperative diagnosis difficult: report of a case.

A 51-year-old man was admitted to our hospital for investigation of fever, lower abdominal pain, and pain on micturition. Barium enema and endoscopic findings revealed an extracanal large cavity of the rectosigmoid colon, which suggested an abscess caused by penetration. Histological examination of the endoscopic biopsy specimen demonstrated no malignancy. A preoperative diagnosis of malignant lymphoma was strongly suspected from the imaging findings; however, intraoperative inspection revealed a large tumor invading the urinary bladder. An intraoperative incisional biopsy was performed and histological examination demonstrated mucinous carcinoma. The patient subsequently underwent pelvic exenteration about 1 week later followed by adjuvant chemotherapy and radiotherapy.

Adenocarcinoma, Mucinous↗

Postoperative chylothorax following partial resection of mediastinal lymphangioma: report of a case.

We report herein the rare case of a 20-year-old man in whom a mediastinal lymphangioma was incidentally detected by a chest roentgenogram taken during a routine health examination. Both computed tomography and magnetic resonance imaging confirmed a mass measuring 3 x 7 cm in diameter in the left anterior mediastinum. A thoracoscopic exploration was done, which confirmed a diagnosis of mediastinal lymphangioma, and 3 days later a sternotomy was performed. However, the tumor could not be completely extirpated due to partial invasion. Following the thoracoscopic procedure, a chylous discharge developed which was difficult to treat conservatively and he continued to drain 700-1,000 ml of chyle daily 2 weeks following the tumor extirpation. Therefore, a right thoracotomy with ligation of the thoracic duct was performed which resolved the chylothorax. The patient remains well without any regrowth of the regional tumor 9 months after his operation.

Adult↗

Functional activity of an HIV-1 neutralizing IgG human monoclonal antibody: ADCC and complement-mediated lysis.

The IgG1 kappa, human monoclonal antibody (HMAb), F105, was studied for functional activity in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on the surfaces of infected cells and neutralizes diverse viral strains at antibody concentrations readily achievable in humans. Neither F105 nor serum (diluted 1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate ADCC against the SF2 strain. Normal human serum reduced spontaneous lysis of SF2 by peripheral blood monocytes (PBM). Although mixing of F105 with normal human serum reduced the lysis observed (36 +/- 8 vs. 42 +/- 8%), this still was significantly greater than lysis in media (30 +/- 5%) or normal human serum (23 +/- 6%) (p less than .05). A murine antibody to CD16 significantly reduced spontaneous lysis observed with media (30 +/- 5 vs. 18 +/- 3%) while normal mouse serum had no effect (31 +/- 7%). ADCC mediated by F105 is completely abrogated by the anti-CD16 antibody (42 +/- 8 vs. 22 +/- 4%), while only a fraction of ADCC mediated by HIV sera is inhibited by anti-CD16 (60 +/- 9 vs. 46 +/- 6%), suggesting that several populations of effector cells function in ADCC mediated by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC through a CD16+ PBM population.

Acquired Immunodeficiency Syndrome↗

An IgG human monoclonal antibody that reacts with HIV-1/GP120, inhibits virus binding to cells, and neutralizes infection.

A human mAb (HmAb) termed F105 was obtained by fusion of antibody-producing EBV-transformed cells with the HMMA2.11TG/O cell line. F105 is an IgG1 kappa antibody that binds to the surfaces of cells infected with all HIV-1 strains tested: MN, RF, IIIB, and SF2, but not uninfected cells. The HmAb immunoprecipitates GP120 from all four strains. F105 does not react with denatured GP120 on Western blots, but does react with viral lysates and purified GP120 dotted onto nitrocellulose filter paper under nondenaturing conditions. rGP120 from SF2 and soluble rCD4 inhibit antibody binding to infected cells in a dose-dependent manner. F105 inhibits the binding of free, infectious virions to uninfected HT-H9 cells with 50% of maximal (100%) inhibition at approximately 1 microgram/ml. F105 inhibits infection of HT-H9 cells by 100 tissue culture infective dose 50% units of MN and IIIB strains with 50% inhibition at concentrations of HmAb readily achievable in man. It appears that the F105 HmAb reacts with a conformationally defined epitope on HIV-1/GP120 that is exposed on the free virion and is important for binding to the cell surface by the virion. The epitope, which is immunogenic in humans, appears to be within, or topographically near, the CD4-binding site. F105 and the F105 epitope are potentially useful in therapy and in the design of peptide or anti-Id based vaccines; monitoring of the expression of the Id may prove useful in evaluating immune responses in infected individuals or vaccinated volunteers.

Antibodies, Monoclonal↗

Simulation of an oscillatory reaction of alcohol dehydrogenase in an oil/water system.

With numerical analysis of the enzyme-catalyzed reaction in the so called 'ordered bi-bi' mechanism and the model presented by Theorell and Chance (Acta Chem. Scand. 5 (1951) 1127) for alcohol dehydrogenase, oscillations of the concentrations of coenzyme and intermediate complex were obtained on gradual entry of substrate. Neither autocatalysis nor allostery was included in the reaction mechanism. The features of the reaction were that the oscillations did not occur in a limit cycle and the interval became longer with time. In addition, it was found that the oscillations with an upwardly directed peak occurred at very low concentrations of enzyme in the model of Theorell and Chance. The results were consistent with the experimentally determined data reported previously.

Journal Article↗

HRF20, a membrane inhibitor of complement attack, does not protect cells from the cytotoxic reaction by lymphokine activated killer cells.

HRF20, a 20 kDa homologous restriction factor, is a membrane glycoprotein anchored via galactosyl phosphatidyl inositol. Its function is to protect cells from attack by homologous complement. Adsorption of purified HRF20 to Raji cells which have little, if any, of this factor increased their resistance to cytolysis by homologous complement. However, the same cells treated with HRF20 remained sensitive to cytotoxic attack by IL-2 activated lymphocytes (lymphokine activated killer cells; LAK cells). Since LAK cells are effector cells which release perforin, HRF20 does not appear to protect cells from the damage caused by perforin.

Antibodies, Monoclonal↗

Oscillatory reaction of alcohol dehydrogenase in an oil/water system.

With the use of an oil/water system, oscillatory reactions of an enzyme have been demonstrated. This reaction system has been conceived as an example of the metabolic oscillations of living cells. When a substrate (ethanol) in the oil phase of toluene or chloroform slowly migrated into the aqueous phase containing alcohol dehydrogenase and NAD+, oscillations were observed in the concentration of NADH produced. The gradual entry of substrate into the aqueous phase was essential for the oscillatory reactions to occur. A possible mechanism to account for the appearance of oscillatory reactions of enzymes is proposed, which differs from that presented previously.

Alcohol Dehydrogenase↗

Expression of HRF20, a regulatory molecule of complement activation, on peripheral blood mononuclear cells.

HRF20 is a homologous restriction factor of 20,000 MW that prevents cells from membrane attack by homologous complement. HRF20 has been identified by a monoclonal antibody (mAb), 1F5, and is one of the phosphatidylinositol(PI)-anchored cell-surface glycoproteins. We analysed the distribution of HRF20 expressed on subsets of peripheral blood lymphocytes using 1F5. HRF20 is expressed in relatively large amounts on T cells. In contrast, adherent cells possess smaller amounts of HRF20 while having large quantities of decay-accelerating factor (DAF). Although DAF was shown to be deficient or present at rather low levels on NK cells, HRF20 was detected in 95% of large granular lymphocytes (LGL), as described by FACS analysis. We also determined the effect of 1F5 on both mononuclear leucocytes and T cells in terms of their growth response. The results show that 1F5 induces T-cell proliferation when cells are stimulated with interleukin-2 (IL-2). In addition, induction of proliferation is facilitated by cross-linking 1F5 with a second antibody. These results suggest that HRF20 expressed on T cells not only protects them from cytotoxic attack by homologous complement, but also may initiate intracellular signals leading to cell activation when they happen to be cross-linked.

Antibodies, Monoclonal↗

20 KDa homologous restriction factor of complement resembles T cell activating protein.

We previously identified a 20KDa membrane glycoprotein 1F5 antigen which inhibits the assembly of homologous complement membrane attack complexes and we designate it as HRF20 standing for 20KDa homologous restriction factor. The amino acid sequence deduced from its coding base sequence resembles that of T cell activating protein, most conspicuously in cysteine residues, 10 out of 11 of which occupy identical positions in an overall sequence homology of 24.8%. Furthermore, proliferation of human T cells was stimulated by monoclonal antibody to HRF20.

Amino Acid Sequence↗

[Effect of splenectomy in gastric carcinoma surgery on cell-mediated immunity; evaluation with alteration of peripheral blood lymphocyte subsets].

Peripheral blood lymphocyte subsets were studied in 70 patients who underwent gastrectomy for gastric carcinoma. Lymphocyte subsets were analysed before and after gastrectomy by use of monoclonal antibody for cell membrane markers. There were significant differences in the gastrectomized patients with splenectomy compared to the patients without splenectomy in postoperative changes of lymphocyte subsets as follows. Decrease of OKT4 and increase of OKT8. Temporary decrease of B-1. Continuous increase of Leu-7. These results suggest that gastrectomized patients with splenectomy show a decrease in helper activity, an increase of suppressor activity of T lymphocytes and a compensatory increase of population of natural killer cells in association with suppression of natural killer activity.

Female↗

Kinetics of permeation of nucleotide through oil/water interface in the interaction of nucleotide with octadecylamine and dodecyl guanidine.

The transports of tritiated ATP, ADP and AMP from the aqueous to scintillator phase with and without octadecylamine (or dodecyl guanidine) have been studied by the layered scintillation method and a theory suitable for an explanation of the results has been presented. (1) Transport processes were all expressed by the first order kinetics. (2) For the simple partitioning of ATP, the reciprocal of the rate constant of the backward permeation was linear with respect to the square of the partition coefficient. (3) For the transport of nucleotide with chemical reaction, the reciprocal of the rate constant of the backward permeation was linear against the overall partition coefficient of nucleotide. (4) A theory was presented on the basis of a general diffusion equation by assuming the two-film model with potential energy near the interface. (5) The theory could explain the dependences of the permeation rates on the partition coefficients. (6) From the finding that the ratio of the apparent diffusion coefficient in aqueous to scintillator phase was much smaller than unity, the occurrence of an energy barrier at interface was suggested. For the simple partitioning of ATP, the energy barrier was not significant.

Adenine Nucleotides↗

Potentiation of cytotoxicity against a CEA positive cell line by the bispecific antibody OH1 using LAK cells from cancer-bearing patients.

Bispecific antibody, OH1 was developed, which simultaneously recognizes CD3 on T cells and carcinoembryonic antigen (CEA) on tumor cells. Although there was not significant difference, PBMCs pretreated with OH1 showed tendency to prolong survival of KATO III-injected SCID mice compared with control groups. although cytotoxicity of LAK cells from cancer-bearing patients was suppressed compared with that of cells of healthy donors, LAK cells from the patients pretreated with OH1 showed significantly increased cytotoxicity against KATO III cells. These results suggest that OH1 could be useful in immunotherapy with LAK cells for carcinomas that express CEA on the membrane.

Adult↗

Benign epithelial cyst of the spleen with a high production of carbohydrate antigen 19-9.

A rare case of an epithelial splenic cyst showing a high production of the carbohydrate antigen 19-9 (CA19-9) is presented. A 19-year-old female with high fever and loss of appetite was diagnosed as having a splenic cyst. Laboratory data revealed unusually elevated serum levels of both CA19-9 and CA125. The histological diagnosis was an epithelial splenic cyst, and immunohistochemically the wall of the splenic cyst was strongly positive for CA19-9 and slightly positive for both CA125 and CEA. Fluid in the splenic cyst contained quite high levels of CA19-9, CA125 and CEA. After splenectomy, the serum levels of CA19-9 and CA125 gradually decreased. These findings suggested that the splenic cyst produced CA19-9, CA125 and CEA. And with very high levels of CA19-9 and CA1 25 in the cyst, some had entered into systemic circulation.

Adult↗