Search PubMed⌕ Search

Biomedical subjects

S Takano

Publications and source records attributed to S Takano.

At least 235 records · Page 13Linked to original sources

Purification and characterization of cytotoxic factors in the venom of the Okinawa habu (Trimeresurus flavoviridis).

Two cytotoxic factors in the venom of Okinawa habu (Trimeresurus flavoviridis), a crotalid, have been purified and characterized. They had cell monolayer-disrupting activity against cells cultivated in vitro, but no proteolytic, hemorrhagic or direct hemolytic activity nor lethal toxicity. They were heat labile acidic proteins (isoelectric points 5.2 and 5.4) having similar molecular weights (approx. 14,000) and amino acid compositions. They were indistinguishable immunologically.

Amino Acids↗

Low molecular weight immunosuppressive factors found in elevated amounts in cancer ascitic fluids of mice. 1. Isolation, identification and immunosuppressive effects of uric acid and uracil.

A definite increase in two low molecular weight factors, G10-2 and G10-3 was found in Ehrlich ascitic fluids, parallel to tumor growth. The isolation and identification of the two factors were attempted through gel filtration and reversed phase column chromatography, using ascitic fluids obtained 13 days after intraperitoneal implantation of Ehrlich tumor cells. As a result, two highly purified factors were observed upon examination by high performance liquid chromatography. Additional analytical data, collected by UV spectrum, NMR spectrum and mass analysis, allowed us to identify G10-2 as uric acid and G10-3 as uracil. Detailed immunological analysis of uric acid and uracil revealed that the augmenting activities of mouse and human NK cells by mouse IFN alpha/beta or human rIFN alpha A/D were impaired in the presence of either compound at concentrations of 0.07 mM, the concentration detectable in the ascitic fluid of tumor bearing mice.

Animals↗

Low molecular weight immunosuppressive factors found in elevated amounts in cancer ascitic fluids of mice. 2. 1-Methyladenosine isolated from cancer ascitic fluids enhances Listeria infection in mice.

The low molecular weight fraction (mol wt less than 1,000) of Ehrlich cancer ascitic fluid has been known to enhance Listeria infection in mice. Chemical characterization of the entities in this fraction revealed four purine and pyrimidine analogues, i.e. uric acid, uracil, pseudouridine and 1-methyladenosine (m1Ado). When the effect of each of these components was studied on Listeria infection in mice, only m1Ado markedly enhanced the infection and killed the mice within a short period. The optimal enhancement was obtained when m1Ado was given intravenously to mice 3-6 days before the infection at a concentration of between 1 and 100 micrograms/mouse. On the other hand, uric acid, uracil and pseudouridine failed to show such an enhancing effect. m1Ado inhibited macrophage accumulation in the peritoneal cavity of mice after an intraperitoneal injection of phytohemagglutinin. Although m1Ado did not show any inhibitory effect on the phagocytic and bactericidal activities of macrophages in vitro, peritoneal macrophages obtained from mice which received m1Ado 3 days ahead revealed impaired bactericidal activity, suggesting the migration of different cell populations from the bone marrow of m1Ado-receiving mice. The results may suggest that m1Ado is a major factor in tumor ascites causing, in small doses, an impairment of macrophage functioning as can be detected in tumor-bearing hosts.

Adenosine↗

Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (SS554), in mice.

The antitumor effect on Meth-A fibrosarcoma in BALB/c mice of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha,alpha-trehalose (designated as SS554), was examined. Only intratumoral injection had a curative effect; subcutaneous, per oral, or intravenous routes had no such effect. The co-presence of an oily vehicle has been shown to be necessary for antitumor activity of a natural cord factor. When SS554 was examined in suspensions of sesame oil, squalane, squalene or sesame oil and water emulsion, a 60% cure rate was achieved. However, no such effect was obtained with a suspension in Tween-PBS or a solution. It should also be noted that sequential but independent administrations of SS554 and oil were found to be as effective as the simultaneous administration of oil and SS554 in emulsion form. In the case of the emulsion, the amount of sesame oil necessary was over 10%, or 0.01 ml in absolute terms. Cures were obtained in a dose-dependent manner by injection of SS554 in amounts in excess of 1 mg. The effect of the time of administration was also examined; the best result was obtained when intratumoral injection was done on day 3 after tumor implantation. Mice cured by SS554 exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific; it did not extend to a rechallenge with RLmale-1 leukemia cells.

Animals↗

[Antitumor effect of a synthetic cord factor, 6,6'-di-O-decanoyl-alpha, alpha-trehalose (SS 554) in mice].

The antitumor effect of a synthetic cord factor (6, 6'-Di-O-decanoyl-alpha, alpha-trehalose) (SS 554) on the growth of Meth-A fibrosarcoma in BALB/c mice was examined. With regard to administration routes, only intratumoral (i.t.) injection showed a curative effect; subcutaneous (s.c.), per oral (p.o.) or intravenous (i.v.) routes has no such effect. To show the antitumor effect of known natural and synthetic cord factors, the co-presence of oily vehicles has been shown to be necessary. Accordingly, compound SS 554 examined in suspensions of sesame oil, squalane (SQA), squalene (SQE) or sesame oil and water emulsion had a curative effect with a 60% survival rate. However, no such effect was obtained with a suspension in PBS or in HCO-60 solution. In this regard, it should be noted that sequential but independent administration of SS 554 and oil was found to be equally as effective as simultaneous administration of oil with SS 554. Thus the effect of the oil should be reconsidered through an examination of the sequential appearance of effector cells. In the case of sesame oil, the amount of oil necessary was over 10%, or 0.01 mg absolutely. When the dose effect of SS 554 was examined in the presence of 10% sesame oil, doses over 1 mg exhibited a dose dependent curative effect. In tumor-bearing mice, the effect of the time of administration was also examined; the best result was obtained when intratumor injection was performed on day 3 after tumor implantation. Mice that recovered after SS 554 treatment exhibited growth inhibition and rejection of rechallenged Meth-A cells. However, this immunity was specific as it did not extend to a rechallenge with RL male-1 leukemia cells.

Animals↗

Hyperglycemia induces intestinal sucrase activity in subtotally pancreatectomized rats.

The effects of experimental diabetes, hypertonic glucose infusion, and subsequent insulin administration on the sucrase activity of the small intestine were studied using intestinal segments completely excluded from luminal continuity by construction of Thiry-Vella fistulas in rats. Eight weeks after subtotal pancreatectomy, the rats contracted insulin-deficient diabetes mellitus, and sucrase activity was enhanced in both the Thiry-Vella loop and in the proximal jejunum in continuity. Subcutaneous injections of insulin during the last 4 weeks maintained the enzyme activity in the control range in both segments. There was a positive correlation between sucrase activity and blood glucose level in the pancreatectomized rats. Hyperglycemia in normal rats induced by intravenous infusion of 30% glucose solution over 48 hours enhanced the sucrase activity in the jejunum. Furthermore, insulin administration with a glucose solution inhibited the enhancement of enzyme activity. These findings suggest that hyperglycemia itself might play an important role in the diabetic increment of sucrase activity.

Animals↗

A comparison of two exponential models of the time constant during left ventricular isovolumic pressure decay in coronary artery disease.

To make a comparison of two exponential models of the time constant (Tw: Weiss's method, Tc: exponential analysis with a variable asymptote) during left ventricular (LV) isovolumic relaxation, we assessed LV pressure decay in 104 patients with coronary artery disease (CADpts) and 21 normal subjects at rest and after pacing, and investigated the hemodynamic determinants of these two models using forward-backward stepwise multiple regression analysis. At rest, Tw was prolonged as the left ventricular minimal pressure (LVPmin), the left ventricular end-diastolic pressure (LVEDP) and the end-systolic volume (ESV) increased (multiple regression coefficient: R = 0.87), whereas Tc was prolonged as ESV and regional wall motion abnormality (RWMA) increased (R = 0.72). Pacing-induced changes in Tw were augmented as LVPmin and RWMA increased (R = 0.75), whereas changes in Tc were augmented as RWMA increased (R = 0.63). Thus, the changes in Tw may be due to an increase in LVPmin rather than to any direct effect of ischemia on the relaxation rate. The relaxation rate can be evaluated more reliably by Tc than by Tw, irrespective of associated pressure changes during ischemia in CADpts.

Adult↗

Study on the mitral valve prolapse. I. Incidence in Kobe University students. II. Follow up study.

Incidence of mitral valve prolapse (MVP) in 4517 students of Kobe University, and clinical features in cases with MVP were studied. MVP was detected in 42 cases by two-dimensional echocardiography, and the prevalence of MVP was 0.93 percent (42 of 4517 cases). Among 42 cases with MVP, apparent mitral regurgitation (MR) was noted in one case with severe MVP, ventricular tachycardia was detected in one and ST-T wave abnormalities were detected in 10 respectively. In another follow up study of our hospital, 14 of 85 patients followed more than one year were noted to be deterioration in echocardiographic parameters. Eight of 14 patients had severe prolapse with severe MR, but remaining 6 had mild or moderate prolapse with mild or absent of MR. However, ST-T wave abnormalities, serious arrhythmias, and low response of %FS increase on exercise were found in high incidence in 6 of mild or moderate prolapse as well as in severe prolapse. So these follow up results suggested that not only students with severe MVP but also students with mild or moderate MVP with ST-T wave changes or VPC found in university medical examination must be followed up carefully.

Adolescent↗

Inhibition of phospholipase A2 by tiaramide in rabbit platelets.

The mechanism by which tiaramide inhibited platelet aggregation was investigated using phospholipid labelling techniques by 14C-arachidonic acid (AA) and thin-layer chromatography. Tiaramide did not affect cyclo-oxygenase nor thromboxane synthetase, because TXB2 was detected in tiaramide-treated platelets, unlike aspirin-treated ones, and PGE2 and PGD2 did not increase, unlike in platelets treated with OKY-1581 (an inhibitor of thromboxane synthetase). Total phospholipid radioactivity was 82.5% of radioactivity recovered before aggregation, and this decreased to 49.0% (n = 5, P less than 0.05) after aggregation by collagen (30 micrograms/ml). AA radioactivity was 9.6% before aggregation and 40.0% after. Tiaramide (100 microM) restored total phospholipid and AA levels to those before aggregation. Tiaramide decreased the amount of AA liberated from 2-(3H-arachidonyl)phosphatidylcholine by whole platelet phospholipase A2 (PLA2). Tiaramide at 10 microM inhibited collagen-induced aggregation, but not that by AA. Tiaramide did not affect 45Ca-uptake by itself nor collagen-induced 45Ca-uptake from the external medium. Tiaramide did not inhibit intracellular Ca mobilization, and it did not affect the calmodulin-dependent cyclic nucleotide phosphodiesterase of rabbit brain. These facts suggest that tiaramide inhibits platelet PLA2 through mechanisms other than the blockade of Ca-influx and intracellular Ca mobilization or antagonism to calmodulin.

Animals↗

Relationships between red cell cation contents and blood pressure level.

Red cell sodium (R-Na), potassium (R-K) and sodium to potassium ratio (R-Na/K) were studied in 2,542 adults participating in periodic medical examinations. The mean values of R-Na and R-Na/K in untreated borderline (n = 406) and definite hypertensives (n = 485) were higher than those in normotensives (n = 1,651), but that of R-K was not different among the groups. The increased R-Na and R-Na/K in the hypertensives were observed only in those under 50 years, but not in those 50 years and over. In the normotensive subjects, age and sex affected the intraerythrocyte cation contents, but a positive family history of hypertension did not. Although a few characteristics correlated with both R-Na and mean blood pressure, and with both R-Na/K and mean blood pressure, multiple regression analyses revealed that R-Na and R-Na/K independently and significantly contributed to the variation in mean blood pressure. It was also indicated that these relations of R-Na and R-Na/K to mean blood pressure were significant in those under 50 years, but not in those 50 years and over. While several characteristics confound the relationships between red cell cation contents and blood pressure, these results suggest that the contributions of R-Na and R-Na/K to the mechanisms of human hypertension still persist in young to middle-aged people.

Adult↗

Differentiation in mouse leukemia cells mediated by an immune interferon preparation.

Antiviral and cell-differentiating (CD) activities of immune interferon (IFN-gamma) preparation were investigated. Male STD-ddY mice were sensitized with BCG. Three weeks later, they were challenged with BCG or purified protein derivative (PPD), and exsanguinated at intervals. The sera were assayed for antiviral and CD activities. The CD activity appeared and reached the maximum earlier than the antiviral activity. The CD activity was thermostable, whereas the antiviral activity was thermolabile. By dialysis at pH 2 for 24 h, the CD activity was reduced to 15%, while the antiviral titer was completely lost. Lipopolysaccharide (LPS) given 24 h before the challenge has markedly suppressed the appearance of antiviral activity following the challenge, but did not so much affect the CD activity. The challenge with PPD stimulated greater antiviral activity and poorer CD activity than the challenge with BCG did. These findings suggest that IFN-gamma preparations contain a CD factor(s) besides IFN.

Animals↗

Disappearance of terminal deoxynucleotidyltransferase in human malignant T-lymphoblasts treated with a human alpha interferon preparation.

Human T-lymphoblastoid cell lines RPMI 8402, MOLT-3, and CCRF-CEM were treated with interferon (IFN) to determine if the treatment would result in the disappearance of cellular terminaldeoxynucleotidyltransferase (TdT), a possible differentiation marker for T-lymphocytes. Incubation of RPMI 8402 cells in the presence of IFN preparation caused a decrease in the number of TdT-positive cells and in TdT activity of the cell extract. The inhibition of cell multiplication was dose dependent. The anticellular effect of IFN preparation was cytostatic, not cytocidal. The IFN preparation modified neither the TdT content nor proliferation of MOLT-3 and CCRF-CEM cell lines. The effects of IFN preparation thus varied with the cell line.

Cell Division↗

A new antitumor antibiotic, kazusamycin.

A new antibiotic kazusamycin, was isolated from the culture broth of Streptomyces sp. No. 81-484, which shows antitumor activity against experimental murine tumors. This antibiotic did not possess antibacterial activity against Gram-positive and Gram-negative bacteria, but showed strong cytotoxic activity against HeLa cells in vitro. The chemical and physico-chemical properties of kazusamycin suggest that the molecular formula of this antibiotic is C33H48O7 (MW 556).

Animals↗