Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 649 records · Page 36Linked to original sources

PubMed1989

[Antigen presentation in pulmonary tuberculosis].

Antigen presenting capacity (APCC) by monocytes (Mono) and alveolar macrophages (AM), using PPD as the antigen, was determined in 15 patients with pulmonary tuberculosis and 9 healthy controls who all showed positive PPD skin tests. Results were as follows: 1) Mono from both healthy controls and tuberculosis showed APCC to autologous peripheral T lymphocytes, and no significant difference was observed between the two groups. 2) AM from tuberculosis showed APCC to autologous peripheral T lymphocytes, however AM from healthy controls did not. 3) APCC by autologous Mono or AM to lung T-lymphocytes was lower than that to peripheral T-lymphocytes, but the difference was not significant. 4) In tuberculosis, APCC, observed before chemotherapy, was remarkably weakened during the first two months of therapy, and almost recovered to the previous level thereafter. 5) The mechanism which enhances APCC by AM in tuberculosis is uncertain. But neither increased DR antigen expression on AM nor release of IL-1 from AM suggested to be be responsible for the enhanced APCC in tuberculosis.

Adult↗

PubMed1988

Regulation of proliferation by the cholera toxin B subunit in FRTL-5 cells may involve a mechanism independent from the modulation of membrane receptor function.

In quiescent rat thyroid (FRTL-5) cells, the B subunit of cholera toxin, which binds to cell surface ganglioside GM1 specifically, alone induced DNA synthesis and markedly enhanced that induced by insulin in serum-free medium. On the other hand, the B subunit inhibited DNA synthesis induced by thyrotropin (TSH). The B subunit did not activate adenylate cyclase and had no effect on the TSH-induced cyclic adenosine 3',5'-monophosphate (cAMP) production. Moreover, the B subunit inhibited DNA synthesis induced by dibutyryl cAMP (Bt2cAMP) or phorbol-12-myristate-13-acetate (PMA). These data demonstrate that the B subunit has both stimulatory and inhibitory effects on DNA synthesis in FRTL-5 cells depending on the presence of other growth factors and that these effects on cell proliferation by the interaction of the B subunit, possibly with cell surface ganglioside GM1, may involve a mechanism independent from the modulation of membrane receptor function through interaction with growth factor receptor.

Animals↗

PubMed1988

Enhancement of antitumor effects of 1-hexylcarbamoyl-5-fluorouracil combined with hyperthermia on Ehrlich ascites tumor in vivo and Nakahara-Fukuoka sarcoma cell in vitro.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) was found to be hydrolyzed to 5-fluorouracil (5-FU) depending on temperature. In this study, the antitumor effects of HCFU with hyperthermia were studied on Ehrlich ascites in tumor-bearing CD-1 mice and Nakahara-Fukuoka sarcoma cells. Concurrently, the change of 5-FU concentration in the Ehrlich tumor was also observed. In vivo, Ehrlich cells were transplanted in the foot pads of mice. HCFU (80 mg/kg) and 5-FU (40 mg/kg) (same molarity) were administered orally on the 3rd, 6th, and 9th days after transplantation and simultaneously hyperthermia (43.5 degrees C, 45 min) was induced. The antitumor effect was evaluated by the tumor volume. On the 9th day after transplantation, HCFU (150 mg/kg) and 5-FU (75 mg/kg) were administered with or without hyperthermia (43.5 degrees C, 45 min) and the tumor tissues were taken for 5-FU concentration analysis. In addition, Nakahara-Fukuoka sarcoma cells were incubated (42 degrees C various times) with our without HCFU and 5-FU (both 1 x 10(-4) M) in vitro. The cytotoxicity was evaluated by colony forming assay. The most effective condition was found to be the combination of HCFU with hyperthermia in vitro and in vivo. The highest 5-FU concentration was observed by the treatment of HCFU combined with hyperthermia in vivo. Hence, HCFU could be clinically useful in thermochemotherapy.

Animals↗

PubMed1988

Phorbol esters have a dual action through protein kinase C in regulation of proliferation of FRTL-5 cells.

In quiescent rat thyroid (FRTL-5) cells, phorbol-12-myristate-13-acetate (PMA) inhibited DNA synthesis induced by a combination of insulin and thyrotropin (TSH) or dibutyryl cyclic AMP (Bt2cAMP). This inhibitory effect of PMA was observed even when PMA was added after addition of these growth factors, and was maximal when PMA was added 2-4 h after the growth factors (late in the G1-phase of the cell cycle). On the other hand, PMA alone induced DNA synthesis and also enhanced that induced by Bt2cAMP or insulin in these quiescent cells. 1-Oleoyl-2-acetylglycerol mimicked these effects of PMA, but 4 alpha-phorbol-12,13-didecanoate had no effect. These data demonstrate that in FRTL-5 cells protein kinase C has a stimulatory effect on the G0 to G1 transition and an inhibitory effect on the G1 to S transition in the cell cycle.

Animals↗

PubMed1988

Three Epstein-Barr virus (EBV)-determined nuclear antigens induced by the BamHI E region of EBV DNA.

In our previous study (Takada et al., 1986a), we showed that the BamHI E fragment of Epstein-Barr virus (EBV) DNA induces a nuclear antigen that is detected by human antisera against EBV-determined nuclear antigen (EBNA), when transfected into baby hamster kidney (BHK) cells. The present study shows that the sub-fragment containing the central open reading frame BERF2b of the BamHI E fragment (Baer et al., 1984) is responsible for nuclear antigen induction. In addition, 2 fragments corresponding to 2 other open reading frames of the BamHI E, BERFI and BERF4 also induce nuclear antigens upon transfection into BHK cells. These 3 antigens, designated RF2b, RFI and RF4 antigens, were serologically classified as EBNA and antigenically distinct. In immunoblotting analysis of latently EBV-infected BJ-B95-8 cells, 3 high-molecular-weight polypeptides (136, 142 and 147 kDa) were identified by anti-EBNA sera. Immunoblotting analysis of transfected BHK cells indicated that the RF2b antigen is 145 kDa in its native form and antigenically related to the 147-kDa protein of BJ-B95-8 cells. Although RFI and RF4 antigens were not detected by immunoblotting, reactivities of sera with RFI and RF4 antigens in the immunofluorescence test were correlated with those of sera with the 136- and 142-kDa polypeptides of BJ-B95-8 cells, respectively. The results suggest that 3 high-molecular-weight proteins of latently EBV-infected cells are encoded by 3 open reading frames of the BamHI E DNA fragment.

Animals↗

PubMed1988

Alteration of cholesterol biosynthetic pathways in the skin of mice administered polycyclic aromatic hydrocarbons.

When polycyclic aromatic hydrocarbons were applied solely or together with a tumor promoter (12-O-tetradecanoylphorbol-13-acetate) to the skin of mice, a marked decrease in the level of lathosterol was observed, reflecting a significant change in the metabolism of sterols. Yet the total amount of cholesterol was not changed. When diazacholesterol (a metabolic inhibitor) was administered to mice, both desmosterol and 5 alpha-cholesta-7,24-dien-3 beta-ol accumulated in the skin, whereas the level of lathosterol decreased. These results seem to suggest that a significant portion of lathosterol is formed via 5 alpha-cholesta-7,24-dien-3 beta-ol in addition to the pathway through methostenol. When polycyclic aromatic hydrocarbon was applied to the skin of the mouse treated with diazacholesterol, a significant increase of desmosterol and a marked drop of the level of 5 alpha-cholesta-7,24-dien-3 beta-ol were observed. These results strongly suggest that polycyclic aromatic hydrocarbons perturb the metabolism of sterol in the skin of mice while keeping the total amount of cholesterol unchanged. A similar metabolism also seems to be operating in tumor tissue itself.

Animals↗

PubMed1988

Intestinal absorption enhanced by unsaturated fatty acids: inhibitory effect of sulfhydryl modifiers.

In vitro absorption of carboxyfluorescein was performed with everted colonic segments of rats. Oleic acid solubilized by a nonionic surfactant HCO-60, but not HCO-60 alone, markedly enhanced the permeation of the otherwise poorly permeant carboxyfluorescein through the colonic mucosa. The effect produced by oleic acid was reduced to different extents by pretreating the mucosa with several SH reagents, with N-ethyl-maleimide being the most effective. The inhibitory effect of N-ethylmaleimide was concentration dependent, with more than 5 mM completely blocking the enhancement of transmucosal permeability by oleic acid. The in vitro effect of N-ethylmaleimide in the absorption experiments was also observed in situ. The inhibitory effects of HgCl2 and iodoacetamide were comparable to that of N-ethylmaleimide, whereas PCMPS, an impermeant SH blocker, had no effect on the enhanced permeation. Various other amino-group modifiers had also no effect on the enhancement. On the other hand, the inhibition was accompanied by a significant reduction in the level of non-protein thiols as well as protein SH groups. Diethyl maleate, which reduced only the non-protein SH level, had no pronounced effect on the oleic acid-induced permeability change. These results suggest that the intact SH group of membrane-associated protein is necessary for the enhanced permeation of carboxyfluorescein elicited by oleic acid.

Animals↗

PubMed1988

Highly sensitive peptide-4-methylcoumaryl-7-amide substrates for blood-clotting proteases and trypsin.

Seventy-four peptide amides of 7-amino-4-methylcoumarin (Mec) of the type Boc-Xaa-Yaa-Arg-NH-Mec were newly synthesized and tested to find specific substrates for blood-clotting proteases and trypsin. The Xaa and Yaa residues of these substrates have been replaced by 12 and 15 different amino acids, respectively. Among these peptides, the followings were found to be most sensitive substrates for individual enzymes: Boc-Asp(OBzl)-Pro-Arg-NH-Mec (kcat = 160 s-1, Km = 11 microM, kcat/Km = 15,000,000 M-1 s-1) for human alpha-thrombin, Z-less than Glu-Gly-Arg-NH-Mec (kcat = 19 s-1, Km = 59 microM, kcat/Km = 320,000 M-1 s-1) for bovine factor Xa, Boc-Gln-Gly-Arg-NH-Mec (kcat = 5.8 s-1, Km = 140 microM, kcat/Km = 42,000) for bovine factor XIIa, Boc-Asp(OBzl)-Ala-Arg-NH-Mec (kcat = 9.2 s-1, Km = 120 microM, kcat/Km = 77,000 M-1 s-1) for bovine activated protein C, and Boc-Gly-Phe-Arg-NH-Mec (kcat = 29 s-1, Km = 230 microM, kcat/Km = 130,000 M-1 s-1) for bovine plasma kallikrein. Moreover, Boc-Glu(OBzl)-Ala-Arg-NH-Mec (kcat = 46 s-1, Km = 370 microM, kcat/Km = 120,000 M-1 s-1) was newly found as a good substrate for human factor XIa. Bovine trypsin effectively hydrolyzed peptide-NH-Mec substrates containing Ala and Pro at the P2 site. The most reactive substrate was Boc-Gln-Ala-Arg-NH-Mec (kcat = 120 s-1, Km = 6.0 microM, kcat/Km = 20,000,000 M-1 s-1).

Amino Acids↗

PubMed1988

Detection of impaired left ventricular function in coronary artery disease with acceleration index in the first derivative of the transthoracic impedance change.

In order to detect impaired left ventricular (LV) function in coronary artery disease (CAD) patients using acceleration index (Ac) of impedance cardiography (ICG), exercise ICG was performed in 29 patients with chest pain but without CAD (Group 1) and 21 patients with CAD (Group 2), and their resting values were compared with 30 healthy controls (Group 3). The acceleration index, which reflects indirectly aortic blood flow acceleration, was calculated as the ratio of dZ/dtmax to its accelerating time (AT). At rest, the values for Ac in Groups 1, 2, and 3 were 23 +/- 10, 15 +/- 6, and 36 +/- 13 omega/s2, respectively. There were significant differences between Group 1 versus 3, 2 versus 3, and 1 versus 2 (all p less than 0.001). At maximal exercise, Ac showed the largest percent change among the various indices used in this study. An increase of 198% for Group 2 was markedly lower than that of 250% in Group 1 (40 +/- 14 vs. 68 +/- 24 omega/s2, p less than 0.001). With a value of less than or equal to 40 omega/s2, Ac can detect the CAD patients, with a sensitivity of 62% and specificity of 90%, superior to stress ECG using CM5 lead. It is concluded that: (1) Ac is the sole index capable of distinguishing not only between the normals and diseased groups, but also between CAD patients and suspected CAD cases at rest. (2) Ac is a remarkably sensitive index for detecting impaired LV function at maximal exercise. (3) Exercise ICG is useful for predicting CAD from the population predisposing to CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Comparative studies on nephrotoxic effects of tris (2,3-dibromopropyl) phosphate and bis (2,3-dibromopropyl) phosphate on rat urinary metabolites.

The mechanism of Tris-BP or Bis-BP (a metabolite of Tris-BP) induced nephrotoxicity was investigated by determining urinary excretion of enzymes and selected metabolites. Rats received single oral doses of 0, 71.7, 143.4 and 286.8 mumol/kg tris (2,3-dibromopropyl) phosphate (Tris-BP) or bis (2,3-dibromopropyl) phosphate (Bis-BP). Urine was collected over a 24 h period and subjected to biochemical examinations. Comparative studies on Tris-BP- and Bis-BP-induced nephrotoxicities were carried out for abnormal patterns of urinary excretion. The urinary excretion of glucose was higher in Bis-BP than Tris-BP at a dose of 143.4 mumol/kg, but this pattern reversed at a dose of 286.8 mumol/kg. Peak lactate excretion occurred later than peak glucose excretion with 143.4 and 286.8 mumol/kg Tris BP and 143.4 mumol/kg Bis-BP. Bis-BP 286.8 mumol/kg caused a transient urinary elevation of lactate on Day 2. Uric acid was excreted at higher levels for Bis-BP than Tris-BP on day 2 of urine collection. Activities of urinary enzymes including alkaline phosphatase, aspartate aminotransferase and gamma-glutamyltransferase, were different on the first day of post-treatment for Tris-BP and Bis-BP. Leucine aminopeptidase and lactate dehydrogenase levels differed on the second day. Activities of the former enzymes on the day 2 urine suggested a transformation of Tris-BP to Bis-BP. Urinary patterns of lactate dehydrogenase isoenzymes (LDH-1-LDH-5) were different between Tris-BP and Bis-BP when rats were treated with the dose of 286.8 mumol/kg: Tris-BP caused a higher excretion of LDH-4 and LDH-5 in urine on day 1 and all five isoenzymes into the day 2 urine. Bis-BP caused slightly higher excretion of LDH-5 and LDH-4 into the day 1 and 3 urine, respectively. Bis-BP but not Tris-BP caused abnormally urinary excretion of sodium ion. Histopathologically, the nephrotoxic effect of Tris-BP appeared one day later and was more obvious than that of Bis-BP in rats after single oral administration.

Animals↗

PubMed1988

Tris (2,3-dibromopropyl) phosphate nephrotoxicity in the rat: histological and biochemical changes in renal components by 13C-NMR spectra.

Rats receiving a single oral dose of 286.8 mumol/kg tris(2,3-dibromopropyl)phosphate (Tris-BP) showed pyknosis of the renal tubular epithelial cells on Day 1, necrosis on Day 2, regeneration from Day 3 and large nuclei formation from Day 4. 13C-NMR spectra were applied to clarify changes of the renal low-molecular-weight components in the kidney injured by Tris-BP, and sialic acid and inositol were found as the desired marker components. The lesions produced by Tris-BP were characterized by changes in the renal components and enzyme activities. Increases in sialic acid content of the kidney were observed both on Day 1, suggesting destruction of the epithelial cell membrane, and on Day 5, suggesting regeneration accompanied by an increase of inositol content on Days 7 and 10. Renal activity of cytoplasmic enzyme, alanine aminopeptidase, was decreased on Days 1 and 5 and elevated on Days 7 and 10. Lactate dehydrogenase activity showed a tendency to decrease in the kidneys on Day 1 and to increase significantly on Days 2, 5, 6 and 7.

Animals↗

PubMed1988

Neuropathological study on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine of the crab-eating monkey.

Experimental parkinsonism was induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the crab-eating monkey (Macaca fascicularis). In the acute stage, the substantia nigra showed necrotic nerve cells, extracellular release of pigment granules and histiocytic infiltration. The nerve cells underwent vacuolation of the cytoplasm with chromatin clumping of the nucleus and disintegration of the nucleolus. The striking feature was the presence of variously-shaped inclusion bodies within abnormal mitochondria which sometimes disclosed a distortion of the cristae. Golgi apparatus and endoplasmic reticulum were also dilated. In the locus ceruleus swollen nerve cells were observed with vacuolated cytoplasm and pyknotic nucleus where expanded mitochondria also contained the inclusions. Some of the inclusion bodies are probably insoluble precipitations due to inhibition of mitochondrial oxidation by a certain metabolite of MPTP. In the protracted stage the substantia nigra revealed a considerable loss of the nerve cells associated with melanophagia and astrocytic proliferation. A few surviving nerve cells showed an increased number of Golgi apparatus and rough endoplasmic reticula, and the presence of autophagosomes, dense bodies and intra-mitochondrial inclusion. These changes are interpreted as being a part of the reparative process from the cellular damage.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1988

Cortical dysplasia in Fukuyama congenital muscular dystrophy (FCMD): a Golgi and angioarchitectonic analysis.

The Golgi and vascular impregnation methods were applied to the abnormal cerebral cortex in Fukuyama congenital muscular dystrophy (FCMD). The cortical dysplasia in FCMD has been categorized into three patterns by the degrees of cytoarchitectural abnormalities. Cortical dysplasia type 1 is characterized by the presence of verrucose nodules in the otherwise normally stratified cortex. By the Golgi method, many neurons at the top of the verrucose nodules showed abnormal morphology and dendritic orientation, while the rest of pyramidal neurons appeared relatively normal. A single 'central blood vessel' often penetrated vertically at the axis of the verrucose nodules, so that it was suggested that such nodules were formed around the long perforating blood vessels. In type 2 dysplasia, or unlayered micropolygyria, individual cells showed relative paucity of lateral dendritic arborization. Despite mutual parallel alignment, neurons were often tilted in varying degrees. Concentration of relatively large blood vessels was seen at the microsulci. In the severest dysplastic pattern, or type 3 dysplasia, in addition to highly distorted cellular alignment, dendritic arborization of individual neurons were very poor. The cortical vasculature in type 3 consisted of two heterogeneous patterns; an extreme vascular distortion in the upper layer and a relatively well-preserved radial pattern in the deep layer. The upper layer is supposed to represent the extra-cortical gliomesenchymal layer intermixed with neuronal clusters seen in the 23-week FCMD fetus we reported previously. By that fetal case analysis, we had hypothesized that cortical dysplasia in FCMD has resulted from superficial heterotopia of migrating neurons related to diffuse proliferation of the extra-cortical gliomesenchymal tissue and focal or extensive defects of glia limitans. The abnormalities in cellular morphology, cellular alignment, and cortical vascular patterns shown in the present study seem to be compatible with our hypothesis.

Cerebral Cortex↗

PubMed1988

Malignant tumor cell lines produce interleukin-1-like factor.

Sixty-four malignant cell lines were examined for interleukin-1 (IL-1) activities in their conditioned medium using thymocyte and fibroblast proliferation assays. Sixteen cell lines showed high IL-1 activity. Comparison of these activities with human IL-1 showed similarity between some biological properties. However there was no correlation between cell origin and IL-1 activity. These results suggest the possibility that most malignant cells may produce an IL-1-like factor.

Epidermal Growth Factor↗

PubMed1988

Diagnostic evaluation of hepatobiliary scintigraphy using 99mTc-N-pyridoxyl-5-methyltryptophan in acute cholecystitis.

Hepatobiliary scintigraphy using 99mTc-N-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) was carried out in 80 patients with benign biliary diseases, excluding cholecystectomized patients, for the diagnosis of acute cholecystitis. Using the conventional diagnostic criteria based on nonvisualization of the gallbladder in acute cholecystitis, the specificity, efficiency and positive predictability test results were 63%, 72% and 45%, respectively. When delayed intestinal transit of radioactive material was added to this criteria, the diagnostic value was significantly improved (p less than 0.01); the specificity, efficiency and positive predictability test results were 97%, 97% and 90%, respectively. Delayed intestinal transit of radioactive material should be considered in the diagnosis of acute cholecystitis.

Acute Disease↗

PubMed1988

Discriminative stimulus effects of intravenous nicotine in squirrel monkeys.

Three squirrel monkeys were trained to emit one response after IV administration of nicotine (0.1 or 0.18 mg/kg depending on the subject) and a different response after IV administration of saline. Subjects emitted nicotine-appropriate responses with substitutions of higher doses, but only emitted saline-appropriate responses after substitutions of lower doses. Discrimination performance was then maintained at 0.1 mg/kg of nicotine in all subjects. Neither morphine nor cocaine substituted for the effects of nicotine in any subjects across a range of doses up to those that suppressed responding. Ethyl-beta-carboline-3-carboxylate, an inverse agonist at the benzodiazepine receptor, substituted or partially substituted for nicotine in both subjects in which it was studied.

Animals↗

PubMed1988

A case of late variant form of infantile Krabbe disease with a partial deficiency of galactocerebrosidase.

A female was diagnosed as a late variant form of infantile Krabbe disease at 1 year and 3 months because of the late onset of regressive clinical course, decreased motor nerve conduction velocities, high cerebrospinal protein concentration and partial deficiency of galactocerebrosidase (15.6%) in the cultured skin fibroblasts. She showed normal development until 8 months when she lost her ability of sitting alone after febrile infection, and died accidentally at 2 years and 4 months. A considerable residual enzyme activity may correlate to the milder clinical course of this case.

Cells, Cultured↗

PubMed1988

Effects of fluocinolone acetonide on mouse skin sterol metabolism and two-stage carcinogenesis.

Fluocinolone acetonide (FA) is one of the most potent synthetic glucocorticoids and is known to possess an anti-tumor promoting activity. An attempt was made to evaluate this activity by estimating tumor promoting activity. Unexpectedly, when 10 micrograms of FA was applied alone or after a single application of a subcarcinogenic dose of 3-methylcholanthrene to mouse skin, results suggested that FA itself may be a tumor promoter or a complete carcinogen. Other glucocorticoids tested, e.g. dexamethasone, hydrocortisone and prednisolone, also revealed similar effects but were less potent than FA. To verify the possibility that glucocorticoid is a complete carcinogen or a tumor promoter, a tumor incidence experiment was performed for 24 weeks. As a result it was found that FA possesses a tumor promoting activity at some dose levels but no tumor initiating activity.

Animals↗