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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 19 recordsLinked to original sources
PubMed1992

Tumor-associated M(r) 34,000 and M(r) 32,000 membrane glycoproteins that are serine phosphorylated specifically in bovine leukemia virus-induced lymphosarcoma cells.

Tumor-associated antigens that are expressed in tumor cells of cattle with enzootic bovine leukosis (EBL) were analyzed previously by use of 13 monoclonal antibodies. We biochemically identified one of the tumor-associated antigens, which is recognized by the c143 monoclonal antibody, as two glycoproteins, each having an apparent molecular weight of 32,000 or 34,000. These glycoproteins were found in the plasma membrane of peripheral blood lymphocytes of both bovine leukemia virus (BLV)-free normal and BLV-infected cattle. With the progression of EBL, the proportion and the absolute number of cells positive for the tumor-associated antigen increased. Moreover, the level of the M(r) 34,000 component, which was susceptible to cell-surface labeling, increased over the level of the M(r) 32,000 component. Partial proteolytic peptide mapping with V8 protease and deglycosylation analysis revealed that the two glycoproteins most likely have an identical M(r) 30,000 polypeptide portion but have different N-linked oligosaccharide portions. Both glycoproteins were found to be phosphorylated at serine residue(s) in EBL-derived B-lymphoid cell lines and in tumor cells and peripheral blood lymphocytes from cattle with EBL, but not in peripheral blood lymphocytes from BLV-free normal cattle and BLV-infected cattle without any evidence of tumor, suggesting that the phosphorylation of these glycoproteins is related to the transformed state of the BLV-infected B-lymphoid cells.

Animals↗
PubMed1992

Tissue-type plasminogen activator, type 1 plasminogen activator inhibitor and their complex in plasma with disseminated intravascular coagulation.

The levels of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and t-PA/PAI-1 complex antigens were analyzed in the plasma of disseminated intravascular coagulation (DIC) patients and healthy controls. Other fibrinolytic parameters such as the levels of plasminogen, alpha 2-antiplasmin (alpha 2-AP), plasmin/alpha 2-AP (PAP), and D-dimer were also estimated to clarify the fibrinolytic states in these plasmas. The antigens of t-PA, PAI-1, and t-PA/PAI-1 complex were found to increase from 8.5 +/- 4.3, 54.4 +/- 21.2, and 8.6 +/- 3.5 ng/ml in normal plasma to 36.4 +/- 25.1, 106.8 +/- 54.7, and 46.6 +/- 34.5 ng/ml in DIC plasma, respectively. The molar ratio of total t-PA to total PAI-1 was 1:6 and 1:3 in normal plasma and DIC plasma, respectively, indicating an enhanced fibrinolytic state in the DIC plasma. The DIC plasma revealed a significant consumption of plasminogen (62.1 +/- 27.8%), and alpha 2-AP (63.7 +/- 25.3%) and an increase in PAP (2.6 +/- 2.7 micrograms/ml) and D-dimer (3.9 +/- 10.7 micrograms/ml). These results suggest that the production and secretion of t-PA and PAI-1 from endothelial cells were enhanced in DIC, resulting in an increased t-PA/PAI-1 complex with dominant fibrinolytic activity.

Disseminated Intravascular Coagulation↗
PubMed1992

Analysis of binding protein for tissue-type plasminogen activator in human endothelial cells.

The specific binding sites for tissue-type plasminogen activator (t-PA) were investigated in human umbilical vein endothelial cells. After adding 125I-t-PA (M.W. 70 kDa) to endothelial cells in suspension culture, the ligand was recovered from the cell extract after disuccinimidyl suberate treatment as a high molecular complex with M.W. of 90 kDa on SDS-PAGE. The complex reacted to only anti-t-PA IgG but not to anti-PAI-1 IgG immunoblot analysis, indicating a t-PA specific binding protein. 125I-t-PA ligand blotting of the cell extract revealed that the binding protein had M.W. 20 kDa. The binding of 125I-t-PA to endothelial cells was reduced in the presence of an excess amount of t-PA, plasminogen and 6-aminohexanoic acid, indicating that the binding sites were also recognized by plasminogen, and that t-PA and plasminogen were bound via lysine binding sites in the molecule. These findings suggest that human endothelial cells have specific t-PA binding molecules which may be expressed on the cell surface as t-PA receptors.

Aminocaproic Acid↗
PubMed1992

Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice.

Topoisomerase (topo) I and II are nuclear enzymes which are novel targets of cancer chemotherapy. A new camptothecin (CPT) analog, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyl-oxy-CPT (CPT-11), is a topo-I inhibitor with a higher activity and less toxicity than CPT. To investigate topo-I and -II-targeting chemotherapy in an in vivo model, we studied the effect of sequential or co-treatment using CPT-11 and adriamycin (ADR) a topo-II inhibitor, in 6 human tumor xenografts (2 esophageal, 2 gastric and 2 colon tumor lines). In sequential treatment, adriamycin was administered i.v. 24 hr after CPT-11 treatment, and no antagonistic effect of this treatment schedule was observed. ADR cytotoxicity was potentiated significantly by CPT-11 pretreatment in the case of 2 esophageal and 2 gastric tumor lines and 1 colon tumor line. On the other hand, co-treatment abolished the sensitivity to CPT-11 and ADR in all 6 tumor lines. Moreover, CPT-11 did not significantly enhance the cytotoxicity of other agents tested, including mitomycin C (MMC) and cisplatin (CDDP). Flow cytometry and dot-blot analyses showed that CPT-11 pretreatment induced an increase in the S-phase cell population with an increase of topo-II mRNA expression after 24 and 48 hr, respectively, in the esophageal and colon tumor lines. These results suggest that CPT-11 can modulate topo-11 levels to enhance the effect of topo-II inhibitors in some human tumors, and this suggests a new clinical method of topo-I and -II targeting chemotherapy for human solid tumors.

Animals↗
PubMed1992

Tissue-type plasminogen activator and its inhibitor in human glomerulonephritis.

We carried out an immunohistochemical study of tissue-type plasminogen activator (PA) and urokinase-type PA, and their inhibitors, PA inhibitor-1 and PA inhibitor-2, using renal biopsy specimens obtained from 86 patients with various forms of glomerulonephritis. The controls were four normal renal tissue specimens. On immunofluorescent observation, granular staining for tissue-type PA was found to be distributed along the glomerular capillary walls. The fluorescence was weak in the normal renal tissue and occasionally intense in the tissues of patients with IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA inhibitor-1 was abundant in the glomerular epithelial cells and scarce in the mesangial area and glomerular capillary lumens of the normal renal tissues. This was confirmed by immunoelectron microscopy using gold staining. The fluorescence of PA inhibitor-1 was weaker in some specimens of nephritic tissues than in the normal renal tissues. Urokinase-type PA and PA inhibitor-2 were negative within the glomeruli in all the specimens. In the glomerulonephritic tissues which were fibrin deposition-positive, tissue-type PA expression in the glomeruli tended to be strong. An association between fibrin deposition and PA inhibitor-1 staining was not clear. These data suggest that expression of tissue-type PA in the glomeruli increases in association with fibrin deposition.

Fibrin↗
PubMed1992

Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma.

A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%.

Aged↗
PubMed1992

The inflammatory cytokines in measles: correlation between serum interferon-gamma levels and lymphocyte subpopulations.

Interleukin-1 (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) were measured in serum from children with measles using an immunoradiometric assay. The IFN-gamma level was increased in 52 out of 54 patients in the acute phase of measles (less than 7 days of illness), and then declined to an undetectable level in the convalescent phase. Neither IL-1 nor TNF could be detected during the course of the illness. The mean serum IFN-gamma level was at its peak on day 4 and could be detected over a 7-day period after the onset of fever, coinciding with the febrile period (6.9 +/- 1.5 days). In the acute phase, the phytohaemagglutinin responses, absolute number of platelets, total lymphocyte counts, CD3+, CD4+, CD8+ cell counts and the CD4/8 ratio were depressed, while stab cell number and lactate dehydrogenase levels were higher than those in the convalescent phase. Using Spearman rank sum test, the IFN-gamma level was correlated negatively with the peripheral lymphocyte (P less than 0.01), CD3+ (P less than 0.05), CD4+ (P less than 0.05) cell counts and the CD4/8 ratio (P less than 0.05) and correlated positively with the stab cell count (P less than 0.01) but not with any other parameter. When the acute phase findings were compared between 28 complicated and 40 uncomplicated patients, the former were younger (P less than 0.01) and had higher maximum body temperature during the illness (P less than 0.05) than the latter, there was no difference in their IFN-gamma levels. These results show that endogenous IFN-gamma appears in the circulation during the acute febrile phase of measles, but does not contribute directly to any complication of the disease.

Acute Disease↗
PubMed1992

A monoclonal antibody (1G10) recognizes a novel human mesangial antigen.

We have identified a unique mesangial matrix protein of the human glomerulus by using a monoclonal antibody, 1G10, generated against culture human glomerular cells. By immunofluorescence, the antigen recognized by 1G10 (1G10 antigen) is present in mesangium and smooth muscle tissue and cannot be detected in any other tissue examined. Immunoelectron microscopy of glomeruli indicated that 1G10 antigen is present exclusively in the mesangial matrix at the endothelial-mesangial interface. The 1G10 antigen is also expressed by cultured mesangial cells, but not by cultured glomerular epithelial cells, umbilical endothelial cells or fibroblasts. 1G10 did not react with the mesangial matrix proteins [fibronectin (FN), laminin (LAM), collagen types I, III, IV, V, and VI (Col I, III, IV, V, VI), heparin sulfate proteoglycan (HSPG), or thrombospondin (TS)] present under normal and diseased states or smooth muscle antigens (myosin, actin), but did react with a 4 M urea extract of renal cortex and a 0.3% deoxycholate extract of isolated glomeruli. Two dimensional immunoblot analysis using the urea extract demonstrated the binding of 1G10 to an approximately 200 KDa polypeptide with pI 6.0. On one dimensional immunoblot this band did not show cross react with polyclonal antisera to FN, LAM, Col IV, V, VI, HSPG or TS. This mesangial matrix component is trypsin and periodate sensitive, suggesting that it has the character of glycoprotein. In renal biopsy specimens from patients with mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN, the expression of the 1G10 antigen increased along with mesangial hypercellularity or increased accumulation of mesangial matrix, but decreased in completely sclerosed glomeruli. No significant changes in 1G10 antigen expression was observed in membranous GN or minimal change nephrosis compared to normal glomeruli. This study suggests that the 1G10 antigen may not only be a useful marker for the clinical assessment of GN, but may also serve as a potential tool for the study of the pathogenesis of glomerular diseases characterized by cellular proliferation and mesangial matrix expansion.

Animals↗
PubMed1992

Augmentation of bovine leukemia virus (BLV)-specific lymphocyte proliferation responses in ruminants by inoculation with BLV env-recombinant vaccinia virus: their role in the suppression of BLV replication.

Lymphocyte proliferation responses were investigated in sheep and cattle, in which the replication of bovine leukemia virus (BLV) had been known to be suppressed by inoculation with recombinant vaccinia virus (rVV) expressing BLV envelope glycoprotein (gp60). Enhanced lymphocyte proliferation responses were observed in animals inoculated with rVV, regardless of whether they were naive or BLV carriers. These responses were roughly inversely correlated to the growth of BLV in the peripheral blood leukocytes. In contrast, there was no apparent correlation between humoral immune response and BLV growth. Based on these results, it was suggested that rVV rendered its suppressive effect of BLV replication primarily via augmentation of cell-mediated immunity.

Animals↗
PubMed1992

The measles outbreak in Chikuhou District, Fukuoka, Japan, 1990: correlation between herd immunity level and outbreak size.

A measles outbreak occurred in the Chikuhou district of Fukuoka, Japan from May to October 1990, during which 71 patients were cared for at the Itoda Public Hospital. Hospital records revealed a large outbreak in the adjacent town of Kanada. In order to characterize the outbreak, questionnaires were sent to all preschool-age children in Itoda (73% effective response) and in Kanada (76% effective response) requesting information about their vaccination and/or history of measles. The number of patients was 22 (4%) in Itoda and 63 (14%) in Kanada, most of these being preschoolers, while the vaccination rate was 61% and 44%, respectively. The herd immunity levels in age-specific groups were compared between the two towns. Before the epidemic, the immunity level of 1 year old children in Kanada, who showed the higher attack rate, was lower (18%) than that in Itoda (39%), while after the epidemic it rose above 60% in both towns. When we studied the correlation between the attack rate and the vaccination rate, or the number of children susceptible to measles (susceptibility rate) in each preschool, the attack rate correlated negatively with the vaccination rate (correlation coefficient [CC] = -0.818; P less than 0.01), and positively with the susceptibility rate (CC 0.860; P less than 0.01). The regressed equation on the correlation indicated that the immunity level should be more than 70% to keep the attack rate under 5% in preschools. After the epidemic, the immunity levels of all preschoolers reached above 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Cellular mechanisms of vasopressin and endothelin to mobilize [Mg2+]i in vascular smooth muscle cells.

The present study was undertaken to examine the effects of arginine vasopressin (AVP) and endothelin-1 (ET-1) on cytosolic free Mg2+ ([Mg2+]i) in cultured rat vascular smooth muscle cells (VSMC). [Mg2+]i was measured using the fluorescence indicator dye mag-fura-2. AVP and ET-1 at a concentration of 1 x 10(-9) M or higher induced the mobilization of [Mg2+]i and cytosolic free Ca2+ ([Ca2+]i) in a dose-dependent manner in rat VSMC. Atrial natriuretic peptide and sodium nitroprusside producing cellular guanosine 3',5'-cyclic monophosphate did not affect [Mg2+]i and [Ca2+]i. A diterpene activator of adenylate cyclase, forskolin, also did not alter [Mg2+]i and [Ca2+]i. The removal of extracellular Mg2+ enhanced the AVP-mobilized [Ca2+]i and did not change the AVP-mobilized [Mg2+]i. The Ca(2+)-free and nominally Mg2+/Ca(2+)-free states decreased the AVP-mobilized [Mg2+]i and [Ca2+]i. The Na(+)-free state enhanced the sustained, but not peak, level of the AVP-mobilized [Mg2+]i. These results indicate that AVP and ET-1 mobilize [Mg2+]i mediated through their intracellular second messenger [Ca2+]i and independent of extracellular Mg2+. Also, an increase in [Mg2+]i is indicated to stimulate the Na(+)-Mg2+ exchange to increase cellular Mg2+ efflux.

Animals↗
PubMed1992

pH dependence of the action of arginine vasopressin in renal collecting tubule.

We determined whether extracellular pH (pHe) and intracellular pH (pHi) modulate the cellular actions of arginine vasopressin (AVP) in rat renal papillary collecting tubule cells in culture. AVP significantly increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) production and cellular free calcium concentration ([Ca2+]i). pHe ranging from 6.8 to 8.0 distributed the pHi between 6.94 and 7.27. The acidified pHe reduced the AVP- and forskolin-induced cAMP production, the AVP-mobilized [Ca2+]i, and [3H]AVP receptor binding, and the alkalinized pHe enhanced the AVP- and forskolin-produced cAMP. Intracellular acidification occurred under three different conditions as follows: using carbonyl cyanide-m-chlorophenylhydrazone (CCCP), acetate buffer, and bicarbonate buffer with a reduced concentration of bicarbonate. Intracellular acidification significantly diminished both the AVP- and forskolin-induced increases in cAMP production and the AVP-mobilized [Ca2+]i but did not alter [3H]AVP receptor binding. Intracellular alkalinization by NH4Cl or chloride-free bicarbonate buffer, in contrast, augmented them. These results indicate that alterations in pHi modulate the cellular action of AVP to produce cAMP and mobilize [Ca2+]i in renal papillary collecting tubule cells. Also, reduced receptor binding of AVP is involved in the mechanism of the effects of low pHe.

Ammonium Chloride↗
PubMed1992

pH dependence of inhibition of arginine vasopressin-induced adenosine 3',5'-monophosphate production by cellular sodium depletion in rat renal inner medullary collecting duct cells in culture.

The present study was undertaken to determine whether the change in cellular Na+ concentration ( [Na+]i) or cellular pH (pHi) is essential for the modulation by Na+/H+ antiporter of the cellular action of arginine vasopressin (AVP) in renal inner medullary collecting duct cells in culture. Extracellular Na+ depletion promptly decreased [Na+]i from 15.8 to 5.4 mM (P less than 0.01), which was closely related to the decrease in pHi (7.19 to 6.97; P less than 0.01). In the presence of 0.5 mM 3-isobutyl-1-methylxanthine, AVP increased cellular cAMP production in a dose-dependent manner. This was significantly blunted in the Na(+)-depleted cells (1 nM AVP; 481.9 vs. 341.0 fmol/micrograms protein; P less than 0.01). When cells were incubated with the Na(+)-depleted medium containing 25 mM NaHCO3, [Na+]i decreased promptly, but the pHi remained unchanged. Under this condition, the AVP-induced increase in cellular cAMP production was not altered (1 nM AVP; 390.9 vs. 334.8 fmol/micrograms protein). Also, after the Na(+)-depleted cells were incubated in 20 mM NH4Cl, which promptly normalized pHi despite the decreased [Na+]i, the response of cAMP production to AVP was restored. Amiloride (1 x 10(-5)-1 x 10(-3) M), which blocks the Na+/H+ exchange, decreased pHi and AVP- and forskolin-induced cAMP production in a dose-dependent manner. These results indicate that the decrease in [Na+]i promptly inhibits AVP-induced cAMP production mediated through the reduction in pHi in renal inner medullary collecting duct cells.

Amiloride↗
PubMed1992

Properties of agents that effectively entrap liquid lipids.

A droplet of an oil-in-water emulsion of methyl linoleate in a saccharide or protein solution that contained with a surfactant, a stabilizer, or both was dehydrated by drying equipment for a single droplet that resembled a spray drier. The lipid exposed on the surface of dehydated samples was extracted and measured by gas chromatography. Gum arabic or gelatin without additives resulted in little lipid being exposed; they were good entrapping agents. Little lipid was exposed with a pullulan solution containing lecithin, sugar ester, carboxymethylcellulose, or sodium caseinate but much was exposed with a maltodextrin solution containing any of the surfactants tested. When both the surfactant lecithin and the stabilizer xanthan gum were added to the emulsion prepared in a maltodextrin solution, lipid was not detected. The results suggested that effective entrapping agents of liquid lipids cause much emulsification, stabilize the emulsion (that is, they cause the continuous phase to be very viscous), and create a dehydrated matrix of fine, dense network layers.

Chemical Phenomena↗
PubMed1992

[Esophago-bronchial fistula caused by chemotherapy with bronchial artery infusion for pulmonary metastases from urinary tract cancer].

We treated a patient who had had postchemotherapeutic pulmonary metastases from urinary tract cancer by bronchial artery infusion (BAI) chemotherapy. Pulmonary lesions showed a 33.0% reduction after the treatment. However, esophago-bronchial fistula (EBF) occurred after the second BAI. The patient died of recurrent aspiration pneumonia and sepsis in the sequelae of the repair surgery. The fistula was considered to have resulted from an increase in the blood flow to the esophageal branch originating from the bronchial artery after the first BAI, which had consequently damaged the local tissue due to accumulation of anti-cancer drugs. In order to avoid these complications, the secondary change of blood flow should be examined precisely by preceding angiographical mapping, and the concentration and the infusion speed of the cytotoxic drugs, should be under adequate control.

Adult↗
PubMed1992

Clinical features of patients suffering from Streptococcus milleri infections--a retrospective analysis.

We examined the clinical records of patients from whom S. milleri was isolated at Kyushu University Hospital from January 1987 through December 1988. Sixty-one patients were treated in 64 episodes with drainage or antibiotics. Oral and nasopharyngeal infections were observed in 27 cases, intrathoracic infections in 13, urogenital infections in 8, intraabdominal infections in 6 and skin and subcutaneous infections in 6. Except for acute bronchitis and urogenital infections, all of them were suppurative. As to underlying diseases, 21 patients had malignancies and 6 had diabetes mellitus. Leukocytopenia was not observed in any of the patients. S. milleri can be eradicated by treatment but it is sometimes replaced by other organisms. However, considering its tendency to cause suppurative infections, its pathogenic significance should be taken into account and patients should undergo surgical drainage combined with antibiotic therapy.

Humans↗