Biomedical subjects

K Yagawa

Publications and source records attributed to K Yagawa.

At least 55 records · Page 3Linked to original sources

PubMed1988

Distribution of hematoporphyrin derivative in normal and malignant tissue.

The distribution of [14C]hematoporphyrin derivative (HpD) has been studied in mice bearing human lung tumor and in guinea pig bearing Line 10 tumor. The amount of [14C]HpD in the transplanted tumor tissue of mice at various times following drug administration (20 mg/kg) was higher than in skin or muscle tissue but was less than in liver, kidney, spleen, lung and heart tissue. The distribution pattern of [14C]HpD in guinea pig at 2 days following injection was also similar to that in mice. Our data were different from those that suggested the selectivity of uptake and retention of HpD by malignant tissues, using fluorometric techniques.

Animals↗

PubMed1988

[Hyperfunctioning follicular carcinoma of the thyroid. A case report].

A 76-year-old female patient with a large neck lump of 15-year duration, was accompanied by palpitation and tremor. The lump was 9 x 5cm in size and the lower half of it was not palpable because the lower pole was located in the mediastinum. Physical examination revealed two enlarged lymph nodes in the right supraclavicular area. Chest X-ray film showed a coin lesion in the right lung that seemed to be a metastasis. The patient was apparently thyrotoxic with elevated serum concentrations of 15.7 micrograms/dl thyroxin and 359 ng/dl triiodothyronine. A neck scintigraphy using 123Iodine showed a thyroid hot nodule in accordance with this lesion. A total thyroidectomy with a modified neck dissection was carried out. This was followed by 131Iodine therapy. Specimen of the primary lesion weighed 147 g. Pathology of this tumor was follicular carcinoma of the thyroid. The patient was doing well 14 months after surgery. In the literature, three cases of similar hyperfunctioning thyroid carcinoma have been reported, all of which had a large primary lesion. The histological features proved to be of follicular or papillofollicular type. The treatment in these cases was administration of an antithyroid drug followed by surgical removal.

Adenocarcinoma↗

PubMed1987

Restoration of Fc receptor-mediated desensitization of superoxide generation in human PMN by PMA.

The superoxide (O2-) generating activity of human polymorphonuclear leukocytes (PMN) was suppressed more than 50% compared with control cells by preincubation of the cells with soluble immune complexes (Fc receptor-mediated desensitization). The suppression was observed when wheat germ agglutinin (WGA) or N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP) was used as stimuli for O2- generation. However, the desensitized cells could produce as much O2- as control cells when they were stimulated with phorbol myristate acetate (PMA). The desensitized cells were pre-exposed to a small dose of PMA for a short period (2-3 min). By this procedure, the activity of the cells for WGA or fMLP induced O2- generation was almost completely restored. Similarly, the inhibitory effect of 3'-deazaadenosing on WGA, fMLP or immune complexes (IC) induced O2- generation was abolished by the short-term pre-exposure of the cells to a small dose of PMA.

Antigen-Antibody Complex↗

PubMed1987

Structural requirements of muramylpeptides for induction of necrosis at sites primed with Mycobacterium tuberculosis in guinea pigs.

Intracutaneous injection of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in guinea pigs caused an extensive necrotic reaction in footpads prepared by injection of heat-killed Mycobacterium tuberculosis in water-in-mineral-oil emulsion. We examined a variety of analogs and derivatives of muramylpeptides for their ability to provoke this reaction. A maximum and a minimum structure responsible for the necrotic reaction were found to be N-acetylglycosaminyl-beta(1-4)-N-acetylmuramyl-tripeptide (GlcNAc-MurNAc-L-Ala-D-isoGln-meso-A2pm) and MDP, respectively. An unexpected finding was that GlcNAc-MurNAc-tetrapeptides having L-amino acids at their C termini, unlike comparable compounds having C-terminal D-amino acids, exhibited definite necrosis-inducing activity, probably due to their tendency to undergo in vivo degradation to GlcNAc-MurNAc-tripeptide. Introduction of some acyl groups, especially the stearoyl group, to the 6-O position of the muramic acid or the peptide moiety of muramylpeptides increased the necrosis-inducing activity of the parent molecules. However, this was not observed with 1-thio-muramic acid analogs of MDP. Modification of the alpha- or gamma-carboxyl groups of the glutamic acid residues of muramylpeptides tended to decrease their necrosis-inducing ability. Analogs and derivatives of muramylpeptides which are capable of inducing necrosis at a primed site, with few exceptions, exhibited powerful adjuvanticity against ovalbumin in guinea pigs. However, the reverse was not necessarily true.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1987

Superoxide (O2-) assay monocyte adherence test for the detection of cell-mediated immunity in cancer patients.

The reactivity of mononuclear cells from patients with breast cancer to the 3 M KCl extract of breast tumor was tested using the superoxide (O2-) assay monocyte adherence test. The mononuclear cells were incubated with the 3 M KCl extract of breast tumor or normal breast tissues in a microcell for spectrophotometer analysis. After 2 h incubation, the nonadherent cells were removed, and the O2- generated from the monocytes adherent to the intersurface of the microcell was assayed. Thirty of 36 patients with breast cancer before treatment reacted to the extract of breast tumor. Sixteen patients showed adherence inhibition and 14 adherence stimulation. None of 8 patients with breast cancer reacted to the extract of lung tumor. Of 31 control donors (19 healthy volunteers and 12 patients with cancer of other organs), only 3 reacted to the extract of breast tumor.

Humans↗

PubMed1987

Accumulation of inosine 5'-monophosphate in human erythrocytes incubated with inosine.

The changes in inosine 5'-monophosphate (IMP) and adenine nucleotides were studied in human erythrocytes incubated with glucose alone, or with glucose plus inosine in the presence or absence of monoiodoacetate, a strong inhibitor of the glycolytic pathways of the cells. HPLC was useful in analyzing the changes in these nucleotides. When the cells were incubated with glucose and inosine for several hours at pH 7.0, 37 degrees C, they produced much IMP, while the cells incubated with glucose and monoiodoacetate accumulated AMP rapidly within 2 hours, accompanied with the decomposition of ADP and ATP; but IMP was not accumulated. When the cells were incubated with glucose and inosine in the presence of monoiodoacetate, AMP increased more rapidly to about 1400 mu mols/ml of cells within 1 hour and then gradually decreased. ATP was consumed completely and ADP decreased correspondingly. However, IMP was produced in this case, though its accumulation was not so high as in the case with glucose plus inosine without monoiodoacetate. The production of IMP depended on the pH of the cell suspension, i.e., more IMP was produced at higher pHs.

Adenine Nucleotides↗

PubMed1986

Influence of chemotherapy on superoxide anion-generating activity of polymorphonuclear leukocytes in patients with lung cancer.

The superoxide anion (O2-) generating activity of polymorphonuclear leukocytes (PMN) in peripheral venous blood obtained from 15 patients with lung cancer was measured weekly after drug treatment. The amount of O2- generated by the cells before chemotherapy was 5.74 +/- 0.42 nmol/minute/10(6) cells (mean +/- SE). The value decreased gradually and reached a nadir of 1.98 +/- 0.24 at 2 weeks after chemotherapy, at which time PMN count also reached a nadir of 1359 +/- 251/microliters (mean +/- SE). The decreased O2- generating activity of the PMN recovered gradually thereafter and reached the level seen before the chemotherapy at 4 weeks. Expression of Fc receptors on the plasma membrane in PMN was measured after chemotherapy by the binding of iodine 125 (125I)-immune complexes to the cells. Almost 40% decrease of the binding was observed in the cells obtained at 2 weeks after chemotherapy, compared with that in the cells before chemotherapy. These results indicate that PMN present in peripheral blood at 2 weeks after chemotherapy are not fully matured, in terms of O2- generating activity and the expression of Fc receptors.

Adenocarcinoma↗

PubMed1986

Abolishment of inhibitory effects of 3'-deazaadenosine on superoxide generation of guinea pig phagocytes by pre-exposure to phorbol myristate acetate.

Superoxide generation by guinea pig macrophages and polymorphonuclear leukocytes induced by wheat germ agglutinin, immune complexes or formyl-methionyl-leucyl-phenylalanine was inhibited considerably by 3'-deazaadenosine. The pre-exposure of the 3'-dezazaadenosine-treated cells to a small amount of phorbol myristate acetate abolished the inhibitory effect of 3'-deazaadenosine on the generation of superoxide.

Animals↗

PubMed1986

Monoclonal antibody to Streptococcus mutans type e cell wall polysaccharide antigen.

A monoclonal antibody against the polysaccharide antigen of Streptococcus mutans serotype e was prepared. It was found that beta-methyl-D-glucopyranoside and cellobiose markedly inhibited the precipitin reaction, whereas maltose showed no inhibition. The beta-glucosyl moiety of the type e polysaccharide seems to be the predominant antigenic determinant of the antigen.

Animals↗

PubMed1985

Superoxide anion generation by polymorphonuclear leukocytes enhanced in a patient with colony-stimulating activity-producing lung cancer.

We examined superoxide (O-2)-generating activity of polymorphonuclear leukocytes (PMN) from a patient with lung cancer in whom there was a marked granulocytosis. There was a high level of colony-stimulating activity (CSA) in both the serum and the supernatant of the culture of the primary tumor. The PMN from the patient produced almost three times more O-2 than did the PMN from healthy donors and other patients with lung cancers but with no granulocytosis. The binding of wheat germ agglutinin (WGA), used as a stimulus for O-2 generation, to the surface membrane of cells and the protein content in the cells were about double that noted in the case of healthy donors. Following total extirpation of the tumor, the level of CSA in the serum decreased, as did activity of PMN for O-2 generation, and the binding of WGA to the cells reverted to normal levels.

Blood Proteins↗

PubMed1985

Down-regulation of Fc receptor expression in guinea pig peritoneal exudate macrophages by muramyl dipeptide or lipopolysaccharide.

Expression of Fc receptors on the plasma membrane of guinea pig peritoneal exudate macrophages (PEM) was suppressed to almost one-half of that of the controls by long-term exposure to lipopolysaccharide (LPS) or muramyl dipeptide (MDP) in culture. The effect of the reagents was dose and time dependent, and as little as 0.5 ng/ml LPS or 5 ng/ml MDP was effective for the suppression. The expression of the Fc receptors decreased to 60 to 70% of the control level at 48 hr and to 45 to 50% at 72 hr after incubation of the cells in the presence of LPS or MDP. A Scatchard plot of the binding of 125I-soluble immune complexes (I.C.) to the cells revealed that the decrease in the binding of 125I-I.C. is due to a reduction in the number of Fc receptors on the cell membrane and not to a decreased affinity of the receptors. The membrane protein was radio-labeled with 125I, and the Fc receptors were purified by being bound to insoluble I.C. The specific binding of the 125I-labeled Fc receptors, from the LPS-treated macrophages, to the insoluble I.C. was almost one-half of that from the untreated control cells. SDS-PAGE analysis of the purified 125I-labeled Fc receptors revealed that the major peak of the m.w. 44,000 molecule in the LPS-treated cells was almost one-half of that of the control. Contrary to the effect of LPS or MDP, 72-hr incubation of macrophages with MIF-rich supernatant, cultured from lymph node cells, enhanced the expression of Fc receptors. Macrophages were treated with I.C. for 4 hr at 37 degrees C to remove the Fc receptors from the surface membrane. The reappearance of the receptors on the plasma membrane of the cells was significantly suppressed by LPS and MDP. The effect of LPS on the binding of five murine monoclonal antibodies (Ab) raised against PEM to the macrophage membrane and also that of 125I-wheat germ agglutinin (WGA) or 125I-insulin was studied. The monoclonal Ab were selected for their activity to induce superoxide anion generation in the macrophages, as do I.C., although the binding sites for the monoclonal Ab were not related to Fc receptors. The bindings of the five monoclonal Ab were not affected by exposure of the cells to LPS or MDP. Macrophages treated with the reagents bound as much 125I-insulin or WGA as did the untreated control cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1985

Characterization of three monoclonal antibodies which induce and modulate superoxide anion generation in guinea pig macrophages.

Three monoclonal antibodies (Ab), termed KY 12, KY 22, and KY 25 and raised against guinea pig macrophages, induced superoxide anion (O2-) generation in the cells. Although each monoclonal Ab bound to macrophages, each had a different pattern of binding to other cell types. In response to each of the Ab, the amount of O2- generated by 5 X 10(5) macrophages was between 0.5 and 0.7 nmol/min and was augmented threefold to fivefold by the addition of F(ab')2 fragments of rabbit Abs to mouse Ig. When macrophages were pretreated with soluble immune complexes (I.C.) prior to stimulation by the monoclonal Ab, the O2- generation stimulated by KY 12 or KY 22 was reduced by more than 70%. In contrast, pretreatment of macrophages with I.C. did not reduce O2- generation in response to KY 25. KY 12 and KY 22 stimulated adenyl cyclase activity in macrophages, but KY 25 did not. Pretreatment of the cells with soluble I.C. did not interfere with the enhancing effect of the monoclonal Ab on adenyl cyclase activity. Pretreatment of macrophages with KY 12 reduced by over 60% of subsequent generation of O2- in response to wheat germ agglutinin, I.C., formyl-methionyl-leucyl-phenylalanine, phorbol myristate acetate, KY 22, or KY 25. KY 22 or KY 25 did not suppress the generation of O2- in response to other stimuli. These results suggest that KY 22 and KY 25 activate O2- generation in a manner that differs from that of KY 12. These monoclonal Ab should prove useful in examining the regulation of O2- production.

Adenylyl Cyclases↗

PubMed1985

Fc receptor-mediated desensitization of superoxide (O2-) generation response of guinea-pig macrophages and polymorphonuclear leucocytes.

Guinea-pig macrophages were pretreated with soluble immune complexes (1 hr, at 37 degrees). By this procedure, the capacity of the cells to produce superoxide anions (O2-) upon stimulation with wheatgerm agglutinin (WGA) was inhibited by as much as 80% (desensitization). However, the receptors for WGA were still available on the cell surfaces as determined by the binding of 125I-labelled WGA to both the pretreated and control cells. This inhibition of O2- generation was also observed when opsonized zymosan (Op-zymosan) was used as the stimulus for O2- generation. In contrast, the inhibition by soluble immune complexes was less than 25% of the control levels when the desensitized cells were stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol myristate acetate (PMA). The same procedure was also used to desensitize guinea-pig polymorphonuclear leucocytes (PMN). In this case, the O2- generation of the PMN was suppressed to 50-55% of the control level when WGA or fMLP was used as stimulus. However, the PMA-induced O2- generation was far less affected by this treatment, as was the case with the macrophages. The activity of the desensitized macrophages for O2- generation recovered gradually to a normal level 24 hr after removal of the immune complexes from the medium. These results suggest that (i) some regulatory mechanisms which suppress the activation of NADPH oxidase are accentuated by prolonged exposure of guinea-pig macrophages and PMN with soluble immune complexes; (ii) the mechanism for O2- generation mediated by WGA or Op-zymosan may be different from that for O2- generation mediated by PMA, and (iii) the mechanism for O2- generation mediated by fMLP differs between macrophages and PMN.

Animals↗

PubMed1985

Immune reactivity to Thomsen-Friedenreich antigen in patients with lung cancer detected by superoxide assay-leukocyte adherence inhibition test.

The immune reactivity to partially purified Thomsen-Friedenreich antigen was investigated in patients with lung cancer. The modified method of original leukocyte adherence inhibition test, termed superoxide assay-leukocyte adherence inhibition test, was used to detect the reactivity. The coded peripheral mononuclear cells from 34 of 50 (68%) patients with lung cancer showed a positive response to the antigen whereas in only 3 of 19 (16%) patients with benign pulmonary disease was there a reaction to the antigen. The same experiments were performed using the 3 m KCl extract of lung tumors as an antigen. In this case in 39 of 50 (78%) patients with lung cancer but in only 4 of 24 (17%) with benign pulmonary disease and in none of the breast cancer patients (0 of 17) was there a reaction to the antigen. These results strongly suggest that patients with lung cancer are sensitized to both Thomsen-Friedenreich antigen and tumor-associated antigens expressed in cancer cells of lung tissue origin.

Adult↗

PubMed1985

[A case of multiple cavernous hemangiomas of the lung].

A case of multiple cavernous hemangiomas of the lung is presented. A 61-year-old woman was suffering from mitral stenosis and insufficiency. On the chest roentgenogram, multiple tumor shadows were revealed at all the lobes of the lung. She had been followed up for about 10 years under the diagnosis of the metastatic carcinoma of the lung. But no tumor lesion had been found at any other organs. Throughout this period, the tumor shadows had not changed in size or number. She died of congestive heart failure, and an autopsy was performed. Histologically, the tumors were diagnosed as cavernous hemangiomas and differentiated from arteriovenous fistula or sclerosing hemangioma.

Female↗

PubMed1984

Biphasic effects of muramyl dipeptide or lipopolysaccharide on superoxide anion-generating activities of macrophages.

The superoxide anion (O2-)-generating activity of guinea pig macrophages stimulated by wheat germ agglutinin (WGA), immune complexes, or phorbol myristate acetate (PMA) was studied after short- and long-term exposures of the cells to muramyl dipeptide (MDP) or lipopolysaccharide (LPS). Neither MDP nor LPS alone induced O2- release in macrophages. Short-term (30 min) exposure to these agents caused the enhanced release of O2- in response to WGA or immune complexes, though the PMA-induced O2- generation was not affected. On the other hand, long-term exposure (more than 24 h) to MDP or LPS progressively enhanced O2- generation of the cells induced by WGA, immune complexes, or even PMA. These results suggest that the mechanism for O2- generation of macrophages stimulated by WGA or immune complexes differs from that stimulated by PMA and that the differences also exist between short- and long-term exposure to MDP or LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1984

Phorbol myristate acetate-induced modulation of antibody-dependent cellular cytotoxicity by human polymorphonuclear leukocytes.

The effect of phorbol myristate acetate (PMA) on the antibody-dependent cellular cytotoxicity (ADCC) of human polymorphonuclear leukocytes (PMNs) against human erythroleukemic K562 cells was studied by the use of a 3-h 51Cr-release assay. Pretreatment of PMNs with PMA (10 ng/ml) for 60 min resulted in inhibition of subsequent ADCC. This inhibition was dependent on doses of PMA. The effect of pretreatment of PMNs with PMA on O2- generation of the cells was also studied. The ability of the cells to generate O2- was not suppressed, and the expression of Fc receptors on the cell membrane was well preserved. In contrast, the addition of PMA to the ongoing ADCC (5 to 30 min after the start of the ADCC assay) enhanced the activity of the cells for ADCC. This augmentation was abolished by catalase, whereas ADCC itself was not affected by the agent. These results imply divalent effects of PMA on the ADCC of PMNs. The suppression of ADCC activity of PMNs by pretreatment with PMA is not due to inhibition of the reactive oxygen burst of the cells. The augmentation of ongoing ADCC by the addition of PMA is due to secretion of hydrogen peroxide from the cells induced by PMA, and this augmentation occurs only when the interaction between effector and target cells exists through Fc receptor.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1984

Synthesis of adult-type hemoglobin in human erythremia cell line.

KMOE -2/05 cells, derived from a patient with acute erythremia, became benzidine-positive after the addition of cytosine arabinoside (CA). Radioimmunoassays using antihuman hemoglobin antibodies revealed an elevated amount of hemoglobin in the CA-exposed cells over that in the control cells (without CA). Isoelectric focusing of the CA-exposed cell lysate formed benzidine-positive foci in the positions of human adult Hb (HbA) and human fetal Hb (HbF). To determine the types of globin synthesized in the CA-exposed cells, globin chains internally labeled with [3H] leucine were purified by carboxy-methyl (CM)-Sephadex column chromatography, immunoadsorption by Sepharose-coupled antihuman Hb antibodies and Sephadex G-100. The labeled globin chains were finally separated by CM-cellulose chromatography in urea. Two distinct peaks of radioactivity were shown in exactly the same fractions as carrier human globin alpha- and beta-chains. These observations indicate that these KMOE -2/05 cells synthesize HbA.

Cell Line↗