Evidence for functional subsets of CD4+ and CD8+ T cells in human disease: lymphokine patterns in leprosy.
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Animals↗
Biomedical subjects
M Yamamura
Publications and source records attributed to M Yamamura.
A new proteinase degrading type IV collagen.
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Carcinoma↗
Microcalorimetric measurements of heat production in isolated rat brown adipocytes.
Heat production, oxygen consumption, and lipolysis in isolated interscapular brown adipocytes from the rat were investigated. Epinephrine, norepinephrine, and isoproterenol increased heat production in a concentration-dependent manner, showing, about 6-, 4-, and 5-fold higher effects than controls, respectively. The concentration of isoproterenol for threshold heat production and glycerol release were 10(-10) M and 10(-9) M, respectively. The fact that 10(-9) M isoproterenol increased heat production by about 3-fold while glycerol release had no effect at all indicates that calorimetry is more appropriate for investigation of brown adipocytes. At least the method is more sensitive than that of measuring glycerol release.
Adipose Tissue↗
Defining protective responses to pathogens: cytokine profiles in leprosy lesions.
The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.
Base Sequence↗
[A case of ulcerative colitis showing anti-Rh (e)autoantibody associated with autoimmune hemolytic anemia].
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Adult↗
Plasminogen activators in human gastric cancers: correlation with DNA ploidy and immunohistochemical staining.
Plasminogen activator activity was investigated in extracts of 42 surgically removed gastric carcinomas. The mean levels of total plasminogen activator (total-PA) and urokinase-type plasminogen activator (u-PA) activities in the gastric carcinomas were significantly higher than those in the background normal tissues (p less than 0.001). On electrophoresis, gastric cancers were found to contain u-PA as the predominant PA, this being confirmed using zymography by direct inhibition with anti-urokinase antibody. Assessment of the relationship between PA activity and biological behavior of gastric cancer revealed total-PA and u-PA levels to be significantly higher in differentiated than in undifferentiated tumors (p less than 0.001), and in aneuploid than in diploid ones (p less than 0.01). Immunohistochemical staining showed that the proportion of u-PA-positive cancer cells in the carcinoma tissues also correlated with activity as measured by the azocaseinolytic method. These findings suggest that the study of PA contents in gastric cancer, combined with a nuclear DNA ploidy and immunohistochemical analysis, might be useful for understanding the biological characteristics of the tumor.
Adult↗
Expression of HLA-DR and secretory component antigens and lymphocyte infiltration in human gastric nonmalignant and malignant tissues: an immunohistochemical study.
The relation between HLA-DR and secretory component (SC) expression and the degree of lymphocyte infiltration was immunohistochemically examined in human gastric mucosa with or without intestinal metaplasia and gastric carcinoma tissues. Gastric mucosa without obvious inflammation showed neither expression of HLA-DR or SC nor remarkable lymphoid infiltration. In contrast, gastric mucosa with chronic inflammation, tissues with incomplete type of intestinal metaplasia, and carcinoma demonstrated both HLA-DR and SC in almost the same area and also prominent lymphoid infiltration in the surrounding stroma. This simultaneous expression of HLA-DR and SC was not observed in complete type of intestinal metaplasia. The results indicate a close relationship between expression of HLA-DR and SC and the presence of lymphocyte infiltration in gastric mucosa, areas of incomplete type of intestinal metaplasia and in gastric carcinomas.
Adenocarcinoma↗
Immunohistochemical analysis of plasminogen activator expression in human colorectal carcinomas: correlation with CEA distribution and tumor cell kinetics.
Fifty cases of colorectal adenocarcinoma were immunohistochemically examined for the relationship between distribution of plasminogen activators (PAs) and the degree of differentiation of cancer cells as reflected by carcinoembryonic antigen (CEA) expression as well as tumor cell kinetics. The A chain of urokinase-type PA (u-PA-A) was mainly observed in the apical portions of highly differentiated cancer cells. Increased expression and change in localization to the cytoplasm were found with progressive dedifferentiation. The numbers of DNA polymerase alpha (pol. alpha) positive cancer cells also increased in line with u-PA-A expression. The B chain of u-PA (u-PA-B), and the A and B chains of tissue-type PA (t-PA-A and -B) did not show similar alteration. The present findings suggest that the distribution of u-PA-A in colorectal carcinoma tissues, the degree of tumor differentiation, and the proliferation kinetics of cancer cells are closely related.
Adenocarcinoma↗
Quantitative analysis of the Epstein-Barr virus-inducing properties of short-chain fatty acids present in the culture fluids of oral bacteria.
The culture fluids of various anaerobic bacteria induced the synthesis of early antigens (EA) in Epstein-Barr virus (EBV) carrying lymphoblastoid cells. The culture fluids of Corynebacterium butyricum and Fusobacterium nucleatum were the effective inducer on EA. The inducing activity was, to some extent, dependent on their n-butyric acid content, but appeared to be regulated by yet unidentified materials.
Antigens, Viral↗
Change in the acid protease activity in plasma of patients with disseminated intravascular coagulation.
Lysosomal protease was determined in the serum of patients with disseminated intravascular coagulation (DIC) to clarify whether the platelet count is an appropriate diagnostic index which allows the early initiation of treatment. The platelet count and the serum level of cathepsin D, a lysosomal protease, were determined in 60 patients diagnosed to have DIC. The cathepsin D activity could not be detected in the sera of healthy individuals with a platelet count of 100,000 or above, but was detectable in the serum of DIC patients with a platelet count of 100,000, and this activity increased as the platelet count decreased to 70,000 and 50,000, and was about 5 times higher at a platelet count of 30,000 than at 70,000. In DIC patients, the decrease in the platelet count was correlated with the increase in the serum lysosomal protease activity. The appearance of cathepsin D activity in the serum of DIC patients is considered to reflect the release of lysosomal enzyme activities from damaged organs, and the treatment for DIC must be initiated before the platelet count decrease below 100,000, and cathepsin D activity then appears in the serum. At a platelet count of 30,000 or less, DIC becomes established, and no therapeutic effects can be expected because of the associated multiple organ failure.
Cathepsin D↗
Inhibition by selenium of intrahepatic cholangiocarcinoma induction in Syrian golden hamsters by N'-nitrosobis(2-oxopropyl)amine.
The effects of selenium supplementation on induction of cholangiocarcinomas and related precancerous lesions in female Syrian Golden hamsters by N'-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Four-week-old animals were divided into two groups according to the selenium level contained in the drinking water (0.1 ppm or 4.0 ppm) and fed a purified diet containing less than 0.05 ppm of the trace element. Starting at Week 4 of the experiment, hamsters were administered 10 weekly injections of BOP (10 mg/kg body wt) and then killed 18 weeks after the last carcinogen administration. Animals receiving physiological saline alone served as controls. Cholangiocellular carcinomas tended to be reduced, and putative preneoplastic lesions of cholangiofibrosis were significantly decreased in the high-as opposed to the low-selenium groups in terms of both incidence rate and number per effective animal. The respective high and low selenium values for incidence and number were 24/38% and 0.34/0.66, respectively, for cholangiocarcinomas and 50/89% and 1.21/8.44, respectively, for cholangiofibroses. Proliferation of intrahepatic bile ducts was also significantly inhibited in the high-selenium group along with cyst formation. Biochemical investigation revealed both selenium level and glutathione peroxidase activity to be significantly greater in the high-than in the low-selenium group livers. The results thus suggest that selenium may inhibit BOP-induction of bile duct lesions, possibly via glutathione peroxidase-mediated alteration of carcinogenesis.
Adenoma, Bile Duct↗
Penetration of lysophosphatidylcholine into the dermis.
The ability of Lysophosphatidylcholine (LPC) to penetrate into the dermis and its degradation were investigated in vivo using hairless rats. Phosphatidylcholine (PC) was used as a control. Radioactively labelled LPC and PC were applied on the surface of skin, and the radioactivities of the epidermis and dermis were measured at 8, 24, and 48 hours. The recoveries of radioactive materials of LPC and PC within the area of epidermis and dermis at 8 hours were 0.21% and 0.25%; at 24 hours, 0.68% and 0.31%; and at 48 hours, 0.42% and 0.92%. No radioactivity was detected in serum. The radioactive substances which had penetrated were identified as LPC, PC, diglycerides, and free fatty acids. It was also found that topical application of LPC did not change the structure of skin as seen by microscopical examination. These findings indicate that a small amount of LPC can penetrate without the damaging skin structure and is enzymatically degraded into several lipids. Since LPC has bactericidal and antiviral activity, this substance could be an useful agent for dermatological use.
Animals↗
Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (IV): Effects on experimental memory impairment in mice and rats.
The effects of a new TRH analog, TA-0910, orally administered, on experimental memory impairments for the one-trial passive avoidance response in anoxic mice (light-dark box), active avoidance response in basal forebrain (BF)-lesioned rats (shuttle box), and delayed alternation task in scopolamine-treated rats (T-maze) were studied. In mice, TA-0910 (3-30 mg) administered 60 min before the retention trial dose-dependently prolonged the passive avoidance response latency reduced by CO2-exposure that was given immediately after the acquisition trial, but not when it was given 60 min before the acquisition or just after the anoxic treatment. In rats, TA-0910 (0.3-3 mg/kg) administered 40-60 min before the test trial, dose-dependently prevented the reduction in mean avoidance rate caused by BF-lesioning and elevated the scopolamine (0.1 mg/kg, i.p.)-induced reduction in percent correct choice level in the alternation task. TRH (30-300 mg/kg), on the other hand, produced no improvements in any of the above tests. These results suggest that TA-0910 improves impaired memory by correcting the retrieval process of memory.
Administration, Oral↗
Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (II): Involvement of the DA system in the locomotor stimulating action of TA-0910.
The mechanism of the locomotor stimulating action of a new thyrotropin-releasing hormone (TRH) analog, TA-0910, was studied in rats. The locomotor stimulating action of TA-0910 (3 mg/kg) was inhibited by haloperidol or alpha-methyl-p-tyrosine (alpha-MT); slightly inhibited by phenoxybenzamine, prazosin, clonidine, or naloxone; not affected by propranolol, metergoline, or a low dose of scopolamine; and was enhanced by a high dose of scopolamine. The locomotor activity was increased by TA-0910 (0.3 mg/kg) in combination with methamphetamine, apomorphine, or L-DOPA under pretreatment with pargyline. A low dose of apomorphine inhibited the increase in locomotor activity induced by TA-0910 (3 mg/kg). The increase in locomotion was most notable and dose-dependent with the injection of 20 ng or more in the nucleus accumbens. The intravenous administration of TA-0910 produced dose-dependent and significant hyperlocomotion at 1 mg/kg or more. In the rats lesioned unilaterally in the nigrostriatal dopamine (DA) pathway by 6-hydroxydopamine, TA-0910 induced ipsilateral circling behavior at 3 mg/kg or more. This circling behavior was inhibited by haloperidol or alpha-MT. These results suggest that the locomotor stimulating action of TA-0910 is mediated primarily via the dopaminergic neuron, especially the nucleus accumbens of the mesolimbic DA system. Other possible mechanisms are also discussed.
Animals↗
Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (III): Inhibition of pentobarbital anesthesia.
Sites and mechanisms of the antagonistic action of TA-0910, a new thyrotropin-releasing hormone (TRH) analog, on pentobarbital anesthesia were studied in rats. Intravenous administration of TA-0910 dose-dependently shortened the duration of pentobarbital anesthesia at 30 micrograms/kg or more. The anti-anesthetic action of TA-0910 after intracerebral injection was in the following order of effectiveness: the posterior lateral hypothalamic area greater than midbrain reticular formation greater than raphe nuclei = locus ceruleus greater than anterior lateral hypothalamic area = ventral globus pallidus = hippocampus. TA-0910 injected into the nucleus accumbens, medial septal nucleus, parietal cortex or striatum had no effect, even at high doses. The anti-anesthetic action of TA-0910 (0.1 mg/kg, i.v.) was inhibited by a low dose of scopolamine or mecamylamine and by a high dose of haloperidol, phenoxybenzamine or metergoline. However, physostigmine and oxotremorine showed no anti-anesthetic action alone or in combination with TA-0910 (0.01 mg/kg, i.v.). Pentobarbital anesthesia was not inhibited by carbachol injected into various sites of the brain. These results suggest that the inhibitory effect of TA-0910 on pentobarbital anesthesia is mainly produced by activation of the posterior lateral hypothalamic area and the midbrain reticular formation, and that the involvements of not only acetylcholine but also other neurotransmitters such as dopamine, serotonin, and noradrenaline should be examined for their anti-anesthetic action.
Animals↗
Effects of Eicosapentaenoic Acid on Lipid Metabolism in Obesity Treatment.
In this study, we investigated the hypolipidemic action of eicosapentaenoic acid (EPA) and its mechanism. Three types of 5% fat diets (stearic acid, linoleic acid, and EPA) were prepared in our laboratory. Rats that weighed 170-190 g were fed one of these diets for 20 weeks at an equivalent calorie value (groups S, L, and E). Weight gain occurred in the following order: group E < group S < group L. Serum levels of total cholesterol, triglycerides, phospholipids and total lipids were significantly lower in group E than in the other groups. Analysis of the fatty acid composition of adipose tissue showed that the level of C18:1 was significantly higher in group S, that of C18:2 was significantly higher in group L, and that of C16:0 was significantly higher in group E than in the other groups. These results indicated that EPA had a hypolipidemic action, higher ketogenicity, and lower lipogenicity than the other fatty acids. Inclusion of EPA in the diet of hyperlipidemic subjects may thus help in the primary prevention of hyperlipidemia and, in turn, morbid obesity.
Journal Article↗
Preparation of alkyl-substituted pyrrolidone derivatives and their evaluation as transdermal penetration enhancers.
The preparation of novel transdermal penetration enhancers derived from 2-pyrrolidone were carried out, and the enhancing activities of drug permeation through the skin were evaluated by means of in vitro experiment. All the enhancers contain a short alkyl group, such as methyl, ethyl, propyl or butyl group, at 1-position and a dodecyl group at 3-position of 2-pyrrolidone ring. The enhancing activities were considerably influenced by the length of the short alkyl group at 1-position. 1-Propyl and 1-butyl-3-dodecyl-2-pyrrolidone showed the effective enhancement of penetration of indomethacin through the skin in 60 wt% ethanolic aqueous solution. Moreover, the similar enhancing activities of these compounds were also observed even in ethanolic vehicle.
Administration, Cutaneous↗
Preparations of phosphonate, phosphoramidate and phosphate derivatives and their evaluation as transdermal penetration enhancers.
Phosphonate, phosphoramidate and phosphate derivatives containing long alkyl groups were prepared, and their activities enhancing drug penetration through the skin were evaluated by means of in vitro experiments. The effect of chemical structure of these compounds on enhancing activity was investigated. Among the phosphonate and phosphoramidate derivatives, compounds having a hexadecyl group showed the most effective enhancement of transdermal penetration of indomethacin. For the phosphate derivatives, the enhancing activities were almost equal in the compounds containing dodecyl, tetradecyl and hexadecyl group. All the compounds having an octyl group were not effective in penetration enhancement. Diethyl hexadecylphosphonate and diethyl hexadecylphosphoramidate brought about the highest enhancing activities among these compounds, and the permeability coefficient of indomethacin was about 10-fold as much as that without enhancer. The relationship between the enhancing activities and the lipophilicities of these compounds was discussed.
Administration, Cutaneous↗