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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 631 records · Page 35Linked to original sources
PubMed1983

Activation of adenylate cyclase by forskolin in rat brain and testis.

Detergent-dispersed adenylate cyclase from rat cerebrum was detected in two components, one sensitive to Ca2+ and calmodulin and another sensitive to fluoride or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The enzyme activity of both components was markedly augmented by forskolin assayed in the presence or absence of other enzyme activators (e.g., NaF, Gpp(NH)p, calmodulin). The catalytic subunit fraction in which G/F protein was totally lacking was also activated by forskolin. During 1-35 days of postnatal development, the basal adenylate cyclase activities in either cerebrum and cerebellum particulate preparations progressively increased. While the fluoride sensitivity of the cerebrum and cerebellum enzyme increased during postnatal development, the responsiveness to forskolin remained unaltered. There was no enhancement of soluble adenylate cyclase (from rat testis) by forskolin under the assay conditions in which there was a marked stimulatory action on the particulate enzyme. The results seen with the solubilized enzyme, with either Lubrol PX or cholate, indicate that the effects of forskolin on the cyclase do not require either G/F protein or calmodulin and the results of our study of brain enzymes support this view. Data on soluble testis cyclase (a poor or absent response to forskolin by this enzyme) imply that it lacks a protein (other than the catalytic unit) which could confer greater stimulation. The present results do not rule out an alternative explanation that forskolin stimulates adenylate cyclase by a direct interaction with the catalytic subunit, if the catalytic proteins do differ widely in various species of cells and their response to this diterpene.

Adenylyl Cyclases↗
PubMed1983

Effects of OKT3+, OKT4+ and OKT8+ T cell subsets on steady-state granulopoiesis in vitro.

The present study was undertaken to elucidate the role of T cell subsets in regulating the in vitro growth of human granulopoietic progenitor cells (CFU-C). Prior to CFU-C assay, mononuclear cells obtained from bone marrow and cord blood were depleted of T cells or functionally distinct T cell subsets by the method of complement-mediated cytolysis with the use of monoclonal antibodies, OKT3, OKT4 and OKT8. The depletion of any T cell subset of OKT3+, OKT4+ or OKT8+ cells from bone marrow and cord blood cells showed no significant alterations in the generation of CFU-C. The supplementation to the in vitro culture system of OKT4+ or OKT8+ cells, which had been negatively selected by complement-mediated cytolysis using the mutually exclusive monoclonal OKT8 or OKT4 antibody, respectively, did not alter the growth of CFU-C-derived colonies without mitogenic stimulation. In contrast, the production of colony-stimulating activity (CSA) in peripheral blood mononuclear cells was significantly reduced by removing not only OKT3+ cells but also OKT4+ or OKT8+ cell subsets. There were no significant differences in the degree of reduction between the different procedures. These results suggested that T cell subsets played an important role in the regulation of steady-state granulopoiesis through the stimulation of CSA production. The presence of a specific subset of T cells in CSA production was not demonstrated.

Antibodies, Monoclonal↗
PubMed1983

Growth inhibition of transplantable murine colon adenocarcinoma 38 by indomethacin.

The anti-inflammatory drug indomethacin was tested for antitumor activity against transplantable mouse colon adenocarcinoma 38 (colon 38). Groups of BDF1 mice (C57BL/6 X DBA/2) were given intraperitoneal injections of this drug beginning on the 6th day after subcutaneous implantation of the tumor and continued for 4 to 8 days. In other groups of mice, identical treatment was delayed until the 16th day after implantation of the tumor. The higher antitumor activity against colon 38 was obtained with earlier initiation of treatment, indicated by decreased growth of the tumor and increased life span of the host. The later initiation of the treatment produced less antitumor activity. The antitumor activity was, however, less than that of 5-fluorouracil, which was used as a positive control drug. The two drugs in combination produced few advantages over 5-fluorouracil alone using the dose schedule designed in the present experiment. Indomethacin treatment significantly reduced prostaglandin E and F levels in the tumor tissue, but 5-fluorouracil did not. It seems likely that the inhibition of prostaglandin biosynthesis by indomethacin underlies the antitumor effect of this drug on colon 38.

Adenocarcinoma↗
PubMed1983

Immunohistochemical localization of calmodulin in mouse brain.

Calmodulin is a well-known calcium-binding protein which is ubiquitous in the plant and animal kingdoms and regulates many cellular processes. In this paper, the distribution of calmodulin in mouse brain was studied immunohistochemically using specific anti-calmodulin IgG which was raised in the rabbit by immunization with native calmodulin. Immunoreactive staining was observed in the cells in almost all areas of the brain, but its intensity varied. Some areas were stained heavily even in the presence of high concentration of NaCl. These differed from those stained immunohistochemically with antibody against other calcium-binding proteins, parvalbumin or vitamin D-dependent calcium-binding protein.

Animals↗
PubMed1983

Relationship between cholecystectomy and colonic cancer in low-risk Japanese population. A preliminary study.

The relationship between colonic cancer and previous cholecystectomy was investigated in 90 Japanese patients treated surgically for colonic cancer during the period of 1971 to 1980. The patients were in an area where the inhabitants are considered to be at low risk for colonic cancer. The patients were matched for sex and age with other patients having gastric cancer or other digestive organ diseases. The results showed that previous cholecystectomy was prevalent, but the difference was not statistically significant, in the group of colonic cancer patients, compared with the groups of rectal cancer patients and matched controls. A positive association between the proximal colonic cancer and previous cholecystectomy, and between distal colonic cancer and asymptomatic gallstones found concomitantly with the cancer, was noted in the present study. To clarify the relationship between colonic cancer, and cholecystectomy and gallstones, further study of a large number of colonic cancer patients and a prospective study of the incidence of colonic cancer after cholecystectomy are proposed.

Aged↗
PubMed1983

Behavior of fluorescent granular perithelium (FGP) in cerebral cortex of SHR-SP rats under some conditions.

The fluorescent granular perithelial cells (FGP) in control and experimental specimens of SHR-SP rats were studied with light and electron microscopes. The results obtained are as follows. The FGP in SHR-SP rats are localized along small cerebral vessels and provided with many irregularly shaped inclusion bodies. Their matrices are homogenous and relatively less dense. Sometimes, the FGP fall into degeneration and their cytoplasm shrinks and fills with small dense granules. Concomitantly, collagen fibers appear surrounding them. After feeding rats a fat-rich chow, lipoidal substances appear in intracellular granules of FGP at the light microscopical level. Electron microscopically, the FGP are swollen and their inclusion bodies vary in shape and content. Large inclusion bodies are composed of several middle-sized inclusion bodies with heterogenous matrices. Frequently, pale inclusion bodies are provided with intensely stained limiting membranes. These facts suggest an incorporation of fat into the FGP. With the administration of elastase, intracellular lipid decreases moderately and the FGP scarcely swell. The cytoplasm of FGP and the contents of inclusion bodies become defined and contrasty. From this evidence, elastase seems to facilitate a fat metabolism in FGP. Morphological and functional differences between FGP and other perivascular cells including pericytes, microglia, and mast cells are briefly discussed.

Animals↗
PubMed1983

Ontogeny of calmodulin and calmodulin-dependent adenylate cyclase in rat brain.

The development of calmodulin, calmodulin-dependent adenylate cyclase and beta-adrenergic receptors was studied in the rat brain. Membrane-bound calmodulin detected was approximately 40-50% of the total calmodulin throughout the postnatal development of either in the cerebrum or cerebellum. No significant difference was found between the quantitative patterns of the membrane-bound and cytosolic calmodulin during the entire period of postnatal development in either of these tissues. Both the cytosolic and membrane-bound calmodulin were present in low concentrations in the immature brain after birth. Their contents rapidly increased during the second postnatal week. Subsequently, the cytosolic calmodulin content remained constant, but showed a considerable decrease in the particulate fraction after day 14. Basal adenylate cyclase activity in the rat cerebrum slowly increased up to the second postnatal week and decreased after day 14. The responsiveness to calmodulin of this enzyme remained unaltered during postnatal development, whereas fluoride and guanine nucleotide sensitivities increased in the same period. The maximum number of (-)-[3H]dihydroalprenolol binding site sharply increased during day 9-14 in the rat cerebrum, although the dissociation constant Kd of the binding site was not affected by age. The results in the latter study suggest that calmodulin-dependent adenylate cyclase may be already present in the earlier postnatal ages of the rat brain, while the beta-adrenergic receptor and guanine nucleotide regulatory unit, both of which are required for a hormone-sensitive adenylate cyclase, may sharply increase in the second postnatal week.

Adenylyl Cyclases↗
PubMed1983

Inhibition of initiation and promotion by N-methylnitrosourea-induced colon carcinogenesis in rats by non-steroid anti-inflammatory agent indomethacin.

The non-steroid anti-inflammatory drug indomethacin, a prostaglandin synthesis inhibitor, may play a role to prevent the chemically induced colon cancer development in rats. CD-Fischer rats were given 3 intrarectal doses of 4 mg N-methyl-N-nitrosourea in week 1 as an initiation procedure to induce colon cancer. The experimental groups received a 0.001% water solution of indomethacin freely as drinking water at various times either during the initiation stage or the subsequent promotion stage. At autopsy in week 31, the treatment reduced the colon cancer development in the group of rats treated for week 1 (initiation stage), and for week 2-30 (early and late promotion stages) and for week 11-30 (late promotion stage), compared with untreated controls. However, removal of the treatment after effective treatment in promotion stage permitted the cancer development, and it suggests that the initiated cells are surviving during the treatment in promotion stage. It is concluded that indomethacin may inhibit methylnitrosourea-induced initiation and regulate promotion in colon carcinogenesis, presumably correlated with an inhibition of prostaglandin synthesis in the colon by indomethacin.

Adenocarcinoma↗
PubMed1983

Production of antibodies to calmodulin in rabbits and enzyme immunoassays for calmodulin and anti-calmodulin.

The production of anti-calmodulin antibodies in rabbit was examined with the use of performic acid-oxidized calmodulin from bovine brain or an emulsion of native calmodulin and methylated bovine serum albumin as the antigen. The antibodies in rabbit sera were determined serially by means of a sensitive enzyme immunoassay method that uses a mini-column of goat (anti-rabbit IgG) IgG-coupled Sepharose 4B for separation. The antibodies could be produced in rabbits with either antigen. Although the native calmodulin with methylated bovine serum albumin seemed to be a better antigen, the titer of antiserum was not raised to levels detectable in the double immunodiffusion test. Monospecific antibodies were purified from the antiserum, and a competitive enzyme immunoassay method for the assay of calmodulin was developed with the use of the column-separation technique employed in the assay of anti-calmodulin. The method could determine from 10 ng to 10 micrograms (0.6 pmol to 0.6 nmol) of rat calmodulin and gave no cross-reaction with S-100 protein. Calmodulin contents in rat brain determined by the present method were consistent with those measured by the bioassay using calmodulin-deficient phosphodiesterase.

Animals↗
PubMed1983

Increased susceptibility to Escherichia coli infection in mice pretreated with Corynebacterium parvum.

The contribution of activated macrophages to protection against Escherichia coli was studied in mice treated intravenously with Corynebacterium parvum 7 days before infection. C. parvum-treated mice showed increased phagocytic activity and enhanced resistance to Listeria infection. In contrast, these mice showed increased susceptibility to a subsequent challenge with E. coli that correlated closely with a reduction in the LD50 of lipopolysaccharide (LPS) in these mice. The peritoneal macrophages obtained from C. parvum-treated mice had a strong ability to phagocytize and kill E. coli in in vitro experiments. A rapid decline in the number of bacteria in the liver of C. parvum-treated mice was observed in the early period of infection. However, the number of bacteria in liver and spleen increased progressively to a lethal dose from 6 hr after infection. At this time, a significant increase in beta-glucuronidase, a lysosomal acid hydrolase, was found in the serum of these mice. In vitro experiments revealed that the peritoneal macrophages from C. parvum-treated mice were highly susceptible to the cytotoxic effect of LPS after 6 hr of incubation with LPS. It is suggested that the hypersensitivity of activated macrophages to the cytotoxic effect of endotoxin derived from E. coli may be partly responsible for the increased susceptibility of C. parvum-treated mice to E. coli infection.

Animals↗
PubMed1983

Intellectual assessment of young adult chronic patients.

At Rockland Psychiatric Center 60 newly admitted (and readmitted) young adult chronic patients were given tests of intellectual functioning and academic achievement three weeks after admission. The majority of these patients (83 percent) had below-normal IQs and more than half were found to be functionally illiterate. The authors point out that such patients require intensive socialization training and remedial education if they are to survive in the community.

Achievement↗
PubMed1983

Role of the ovary in sexual differentiation of lactotrophs and somatotrophs in the mouse adenohypophysis: a stereological morphometric study by electron microscopy.

To study the effect of the ovary on sexual differentiation of somatotrophs and lactotrophs, the anterior pituitary glands of castrated adult male mice which had received an ovarian transplant during postnatal development were studied using a stereological morphometric technique with an electron microscope. In adult male mice which were castrated neonatally and given ovarian transplants at the age of puberty (NCT-males), the ovaries contained follicles and corpora lutea. The percentages (approximately 40) and numbers (approximately 2 x 10(5)) of lactotrophs were similar in normal dioestrous females and NCT-males, but were higher than the percentage (9.3) and number (4.6 x 10(4)) in normal males. Ovarian grafts in adult male mice which were simultaneously castrated and given an ovarian transplant just before puberty (PCT-males) contained numerous follicles of various sizes but no corpora lutea. The percentage (46.8) and number (3.9 x 10(5)) of lactotrophs were greater in these mice than in dioestrous females. The percentage of somatotrophs in NCT-males (34.7) was less than in normal males (52.6), but was similar to that in dioestrous female mice (37.4). The percentage of somatotrophs in PCT-males (27.4) was less than in normal male and dioestrous female mice. These data indicate that lactotrophs and somatotrophs differentiate to the female phenotype when a cyclically functional ovary is present after puberty.

Animals↗
PubMed1983

[Plasma bradykinin concentration in patients with cardiovascular diseases].

The present study was undertaken to quantify the circulating kinins in patients with various cardiovascular diseases using a newly developed radioimmunoassay technique and to evaluate this method in terms of its clinical application. For the determination of bradykinin (BK), this assay uses a rabbit anti-serum which has been injected with kallidin. This assay shows good specific activity, recovery and reproducibility. In order to avoid the formation of kinin as well as to block its inactivation, human blood samples were collected with a polypropylene syringe containing an inhibitor mixture (EDTA, trasylol, 1-10-phenanthroline, soybean trypsin inhibitor, polybrene). 1) The plasma BK concentration in normal human subjects, in patients with essential hypertension, effort angina and other cardiac diseases were 12.2, 9.2, 8.0 and 14.0 pg/ml, respectively. 2) Thirty min after captopril (12.5 mg, p.o.) administration, blood pressure and pulmonary wedge pressures decreased, and cardiac output increased accompanied with increases in plasma renin activity, plasma BK concentration and plasma norepinephrine concentration. 3) During the cold pressor test, both plasma BK concentration and blood pressure increased in the normal human subjects, whereas plasma BK levels decreased and blood pressure increased in the patients with hypertension. This radioimmunoassay for plasma BK determination makes it possible to measure plasma BK concentration in patients with various cardiac diseases.

Adult↗