[Potassium-losing nephropathy].
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Humans↗
Biomedical subjects
T Terano
Publications and source records attributed to T Terano.
Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-beta activation.
To elucidate the atherogenicity of lipoprotein(a) (Lp(a)), we examined its growth-stimulating activity in rat resident peritoneal macrophages. When macrophages were incubated with Lp(a), cell numbers were increased 1.5-fold as compared with control macrophages. Furthermore, apolipoprotein(a) (apo(a)), a plasminogen-like glycoprotein which is covalently attached to a low density lipoprotein-like particle (Lp(a)), also induced macrophage growth, while the growth-stimulating effect of Lp(a-) was negligible. These results suggest that apo(a) plays an active role in the mitogenic activity of Lp(a). Lp(a)-induced macrophage growth was inhibited by exogenously added active transforming growth factor-beta (TGF-beta) dose-dependently, and also by the addition of plasmin, which converts latent TGF-beta to an active form. Moreover, the amounts of endogenous active TGF-beta in the medium were significantly reduced by the incubation with Lp(a). It is evident from these results that Lp(a) induces macrophage growth by inhibiting TGF-beta activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be novel atherogenic function of Lp(a).
Animals↗
Eicosapentaenoic acid suppressed the proliferation of vascular smooth muscle cells through modulation of various steps of growth signals.
Among fatty acids, only n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibited the proliferation of vascular smooth muscle cells. DHA was less effective than EPA. To clarify the anti-proliferative effect of n-3 polyunsaturated fatty acid, we have explored the effect of EPA on the signal transduction pathway of platelet derived growth factor (PDGF). EPA inhibited PDGF binding on its receptor and activation of protein kinase C. EPA also suppressed c-fos mRNA expression, one of immediate early genes, through partly inhibiting c-fos transcription. These data revealed that EPA could inhibit vascular smooth muscle cell proliferation through modulating various steps of the signal transduction by PDGF.
Animals↗
Characteristics of the pituitary gland in elderly subjects from magnetic resonance images: relationship to pituitary hormone secretion.
OBJECTIVE: Physiological changes in the pituitary gland with age have not been fully evaluated. The aim of this study was to clarify the morphological characteristics of the pituitary gland by magnetic resonance imaging(MRI) in elderly subjects and to relate them to pituitary hormone secretion. DESIGN AND PATIENTS: We investigated the pituitary MRI in 59 elderly (15 males, 44 females; median 82 years) and 41 young (13 males, 28 females; median 34 years) healthy subjects. RESULTS: Pituitary height, width and volume in the elderly subjects were less than those in the young subjects. Empty sella was more frequently observed in the elderly subjects (19%), especially women, than in the young ones. However, no relation was observed between the pituitary size or volume and basal levels of anterior pituitary hormones. Posterior pituitary bright signal(PBS) on T1-weighted MRI, which is thought to reflect its storage of the neurophysin-peptide complex, was not detected in 29% of the elderly subjects while it could be detected in all the young subjects. None of the elderly subjects showed clinical signs or symptoms of diabetes insipidus. Fasting plasma osmolarity and AVP in the elderly subjects were significantly higher than in the young subjects. Moreover, plasma AVP was significantly higher in the elderly subjects without the PBS than in those with the PBS. CONCLUSIONS: It is suggested that the excessive release of AVP from the posterior pituitary as a result of persistently raised plasma osmolality in the elderly subjects may lead to depletion of the neurosecretory granules in the posterior pituitary gland and may result in disappearance of the posterior pituitary bright signal on T1-weighted MRI. As these morphological changes might relate to the normal physiological occurrence of ageing, we should be cautious in evaluating MRI of the pituitary gland in elderly subjects.
Adrenocorticotropic Hormone↗
Thyrotropin induces G1 cyclin expression and accelerates G1 phase after insulin-like growth factor I stimulation in FRTL-5 cells.
We have investigated the mechanism by which TSH pretreatment potentiates insulin-like growth factor I (IGF-I)-induced DNA synthesis in FRTL-5 cells. As previously described, pretreatment with TSH increased IGF-I-induced DNA synthesis, suggesting that the effect of TSH is mediated through the cAMP pathway. TSH and A kinase activators required at least 12 h to precondition cells to respond to IGF-I stimulation. The presence of cycloheximide abolished the effect of TSH to increase IGF-I-induced DNA synthesis. When the time course of thymidine uptake after IGF-I addition was studied, TSH pretreatment increased the maximum DNA incorporation and shortened the G1 phase interval. These results indicated that some proteins induced by TSH are required for the effect of TSH on IGF-I activity, and the proteins are important for cell cycle progression. Cyclins are key regulators of the cell cycle; therefore, we investigated the expression of cyclins D1 and E after TSH stimulation. TSH- and A kinase-activating agents increased the expression of cyclins D1 and E after 24 h. The same amounts of cyclins D1 and E induced by IGF-I were increased after TSH pretreatment. TSH pretreatment induced the expression of G1 cyclin in FRTL-5 cells, and IGF-I caused the accumulation of enough G1 cyclins to drive the cell cycle from G1 to S phase in a short time, which accounts for the effect of TSH on IGF-I induced DNA synthesis.
Animals↗
Quantitative analyses of lesion areas of coronary atherosclerosis in cholesterol-fed rabbits.
A simple method to quantitatively evaluate atherosclerosis in the rabbit coronary arteries by measuring macroscopic lesion areas (%) was attempted in the present study. Sixteen rabbits were fed a 0.5% cholesterol diet for 15 weeks and then 9 rabbits were sacrificed whereas the remaining 7 rabbits were maintained for further 9 weeks on a normal chow (at week 24). The left circumflex coronary arteries (LCX) were excised from the rabbit hearts under stereoscopic observation. The prepared arterial strips of LCX were 38.7 +/- 7.1 mm long and all of them reached the cardiac apex from the orifice. At week 15, the lesion area in LCX was negligible (3.2 +/- 0.4%) whereas the aortic lesions significantly developed (50.0 +/- 7.6%). At week 24, atherosclerotic lesions in both LCX and aortas increased to 32.8 +/- 9.2% and 85.9 +/- 5.6%, respectively. This is the first report that determined the luminal surface areas of atherosclerotic lesions in rabbit coronary arteries. This method may be more practical and useful for quantitative evaluation of coronary atherosclerosis in a large number of rabbits than histological observations of serial sections of rabbit hearts.
Animals↗
Serum levels of dehydroepiandrosterone sulfate in patients with asymptomatic cortisol producing adrenal adenoma: comparison with adrenal Cushing's syndrome and non-functional adrenal tumor.
The reported number of adrenal incidentalomas has been increasing because of wider application of imaging techniques. Patients with asymptomatic cortisol producing adrenal adenoma (ASCA) which secretes cortisol without clinical evidence of Cushing's syndrome has been more frequently observed than previously assumed, and they have a risk of adrenal insufficiency after adrenalectomy. Therefore patients with incidentalomas should be screened for cortisol overproduction. The aim of this study is to discover an easy screening test to uncover ASCA. We investigated the hormone profiles of 4 patients with ASCA in comparison with 11 patients with non-functional adrenal tumor and 10 patients with adrenal Cushing's syndrome. We also investigated the expression of dehydroepiandrosterone sulfotransferase (DHEA-ST) in surgically removed attached non-neoplastic adrenal tissues by immunostaining, which was considered to represent the degree of suppression of the hypothalamo-pituitary-adrenal axis. Serum dehydroepiandrosterone sulfate (DHEA-S) levels of all the patients with ASCA and adrenal Cushing's syndrome were lower than those of healthy subjects of corresponding age, but they were within the normal range in the patients with non-functional adrenal tumors. The serum DHEA-S level reflects the degree of suppression of the normal adrenal gland by cortisol hypersecretion from adrenal tumors. But the serum level of DHEA-S decreases with age, and because the normal range of serum DHEA-S is low in elderly subjects, we should be careful to evaluate the level of DHEA-S in elderly patients with adrenal Cushing's syndrome or ASCA. The immunohistochemical study showed DHEA-ST expression was noticeably suppressed in the adjacent adrenal cortex in ASCA and adrenal Cushing's syndrome. The decreased expression of DHEA-ST may reflect autonomous neoplastic cortisol secretion and subsequent ACTH suppression in ASCA and adrenal Cushing's syndrome. A single measurement of plasma ACTH or measurement of ACTH response to corticotropin-releasing hormone was not enough to screen for ASCA because of the wide variation among the cases. Dexamethasone suppression test is essential in identifying ASCA and also a single determination of serum DHEA-S is easy and may be useful for the screening of ASCA in adrenal incidentalomas in young and middle aged subjects, and is especially useful for outpatients.
Adenoma↗
[Cardiovascular changes in Cushing's syndrome and primary aldosteronism].
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Cardiovascular System↗
Comparison of monoclonal and polyclonal enzyme-linked immunoabsorbent (ELISA) assays for serum Lp(a) and differences in reactivities to Lp(a) phenotypes.
We have prepared a monoclonal antibody to Lipoprotein(a)[Lp(a)] and have used it to develop an ELISA test for assaying Lp(a) in serum. The monoclonal antibody employed in the assay system reacts uniformly with S1, S2, S3 and B phenotypes of isoforms, and no cross-reaction with plasminogen at a concentration of 100 mg/dL was observed. Results of the monoclonal ELISA assay were similar to those obtained with a polyclonal antibody ELISA method and demonstrated a correlation coefficient, r = 0.99 with the equation for the regression line: Y(proposed) = 1.06 x (polyclonal antibody reference ELISA test) = 0.36 (N = 51). Inter- and intra-assay precision(CVs) of the monoclonal ELISA assay were between 2.2-3.6% at a mean Lp(a) concentration range of 19.1-68.2 mg/dL,(N = 12). Assay results of various standards were compared by both monoclonal and polyclonal antibody ELISA tests. We observed some discrepancies between expected concentrations and the polyclonal antibody ELISA assay results, which is thought to be more uniformly reactive to the various Lp(a) phenotypes. The monoclonal antibody employed in our proposed method reacts uniformly with Lp(a) phenotypes, and the assay exhibits excellent sensitivity, specificity, and accuracy and is well suited for clinical use.
Adult↗
Measurement of Lp(a) with a two-step monoclonal competitive sandwich ELISA method.
OBJECTIVE: To evaluate the results of Lipoprotein (a)[Lp(a)] measurements by a competitive two-step monoclonal enzyme-linked immuno sorbent assay method comparing them with those by a conventional ELISA. METHODS: Serum having various isoforms of Lp(a) and purified Lp(a) were assayed using the method described here and commercially available kits. The reference range was determined with the use of 324 normal subjects by means of calculation from Lp(a) results of logarithmic transformation. RESULTS: Our method takes advantage of a competitive reaction between fixed antibody and free antibody to Lp(a), having the detection range up to 1000 mg/L with the lowest detection limit of 2 mg/L. The anti-Lp(a) monoclonal antibody employed in the assay system reacts uniformly with all phenotypes of Lp(a) but showing very low cross-reactivity for plasminogen and LDL. Within-run and between-run precisions were excellent, giving CVs of 2.9 and 4.0% with mean values of 145 and 635 mg/L, respectively. In comparison of the results by our method with those by a polyclonal method (Biopool) or a monoclonal antibody method (Terumo), they correlated well; Y (our method) = 0.99 x (polyclonal method, Biopool) - 1.9, r = 0.994 (n = 60), and Y = 0.94 X(monoclonal method, Terumo) -9.8, r = 0.97 (n = 60), respectively. The reference range was 105.9 +/- 25.4 mg/L, the difference between the sexes was not significant. CONCLUSION: Our method has proven highly accurate and specific. It is applicable with auto analyzer because it does not require such a pre-dilution step as is necessary for Lp(a) determination by conventional ELISA assay. Accordingly, we can conclude that our test method is workable for both clinical laboratories and mass screening.
Antibodies, Monoclonal↗
Intravenous injection of rabbit apolipoprotein A-I inhibits the progression of atherosclerosis in cholesterol-fed rabbits.
The effects of intravenous injection of purified rabbit apoA-I on the progression of aortic atherosclerosis in cholesterol-fed rabbits were examined. In experiment 1, 28 rabbits were equally divided into groups A and B and fed a 0.5% cholesterol diet for 90 days. For the last 30 days, group B received 40 mg apoA-I every week. The fatty streak lesions in group B (23.9 +/- 15.6%) were significantly suppressed compared with those in group A (46.0 +/- 24.9%) (P < .05). In experiment 2, 33 rabbits were divided into four groups (8 or 9 rabbits per group) and fed a 0.5% cholesterol diet. Group A was killed on day 105, while groups B, C, and D were maintained for an additional 60 days on a normal diet, during which time groups C and D received 1 mg apoA-I every other day or 40 mg apoA-I every week, respectively. The lesions in group C (70.2 +/- 15.4%) and group D (65.7 +/- 20.0%) were significantly suppressed compared with those in group B (86.2 +/- 13.7%) (P < .05) but were not reduced to the level of group A (50.0 +/- 22.9%). Although apparent regression was not observed under these conditions, the present study provided the first evidence for the antiatherogenic effect of homologous and apoA-I on the progression of atherosclerosis in cholesterol-fed rabbits.
Animals↗
[Vasopressin (anti-diuretic hormone: ADH)].
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Humans↗
[Corticotropin-releasing hormone (CRH)].
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Corticotropin-Releasing Hormone↗
The capacity of dog lung to release prostaglandin I2 as a biochemical parameter for evaluating lung damage during preservation.
The release of prostaglandin I2 (PGI2) from the vasculature is thought to reflect damage to the vessels. Basal and bradykinin (BK)-stimulated release of PGI2 from isolated dog lungs after 6-hr preservation were investigated to evaluate lung damage after preservation. Maximal PGI2 release induced by BK decreased significantly after preservation at 24 degrees C (room temperature), but not after hypothermic preservation at 4 degrees C, although basal PGI2 release without BK stimulation did not change in either group of lungs after preservation. The function of allotransplanted lungs assessed by arterial oxygen tension was impaired by preservation at room temperature but not by hypothermic preservation. No differences were observed by light microscopy in either group in the pulmonary tissues, including the pulmonary artery, after preservation. In summary, damage to the lung after preservation may be reflected by the maximal PGI2 release from the lung after BK infusion. Therefore the maximal PGI2 releasing capacity induced by BK may be a useful biochemical parameter for estimating the viability of preserved lungs.
Animals↗
[Changes in fatty acid composition, platelet aggregability and RBC function in elderly subjects with administration of low-dose fish oil concentrate and comparison with younger subjects].
Anti-thrombotic and anti-atherogenic effects of eicosapentaenoic acid (EPA) through the modulation of various cell functions related to thrombogenesis have been reported recently. We previously reported that the administration of EPA at low doses could more effectively elevate the plasma EPA concentration in elderly subjects than in younger ones. Magnetic resonance imaging examination of the brain often reveals lacunar lesions in elderly subjects without any signs or symptoms of cerebrovascular diseases. In this study we clarified the effect of administration of low doses of fish oil concentrate on platelet and RBC function in elderly subjects, compared with younger subjects. Thirty six elderly subjects (mean age 78) without any signs or symptoms of cerebrovascular diseases, all receiving the same diet in the same lodging house for the aged, were divided into 3 groups. Different amounts of fish oil concentrate (0.25-0.5 g/day of EPA) were administered to the 3 groups, daily for more than 1 month. Changes of plasma fatty acid composition, platelet aggregability, whole blood viscosity and RBC deformability was examined before and after EPA administration. One month after EPA treatment, the plasma EPA content had increased dose dependently, with suppression of platelet aggregation and improvement of RBC function. In younger subjects receiving the same amount of EPA, the elevation of plasma EPA was less than that observed in the elderly. In summary, low dose EPA administration can improve the function of platelet and RBC to an anti-thrombotic state and would be useful to prevent the occurrence of cerebrovascular diseases in elderly subjects without any side effects.
Adult↗
[Diet, drugs and blood platelet function].
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Arachidonic Acid↗