Structure and physiological activity of conidial polysaccharides of Mycosphaerella pinodes. I.
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Biomedical subjects
Publications and source records attributed to M Matsubara.
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There has been increasing the evidence on the significances of the measurements of LHRH, one of the hypothalamic hormones, but there are no report on endogenous LHRH levels in patients with internal diseases associated with gonadal dysfunction or intracranial diseases. In this report, the radioimmunoassay of LHRH was established, and plasma LHRH levels in chronic renal failure before and during haemodialysis, and the levels in cerebrospinal fluid (CSF) and plasma in patients with acute intracranial diseases were determined. Plasma levels of immunoreactive LHRH in healthy adults were less than 7 pg/ml for men (n = 17) and less than 8 pg/ml for women (n = 25). The levels were increased in women in menstrual midcycle, postmenopausal period or in patients with hypergonadotropic hypogonadism. CSF LHRH levels were less than 6.1 pg/ml in control subjects, and there were no difference between postmenopausal subjects and the others. The immunoreactivities of CSF and plasma extracts were eluted in identical fractions with synthetic LHRH on Sephadex G-25 chromatography, and these dilutions gave a displacement curve parallel to that with the standard. Plasma LHRH levels were increased in patients with chronic renal failure before haemodialysis (11.1 +/- 1.4 pg/ml, mean +/- SE), and the levels were declined after the dialysis to 4.8 +/- 0.5 pg/ml. These suggest that elevated plasma LHRH reflects the decreased feedback inhibition by primary gonadal failure, and might in turn be responsible at least in part for high concentrations of plasma LH in this condition, and that plasma LHRH is mainly not bound to plasma proteins. LHRH levels of CSF and plasma in patients with acute intracranial diseases, e.g. cerebral bleeding, cerebral thrombosis and meningitis were often elevated abnormally, and these levels were decreased following the abatement of the diseases. These elevations are supposed to be the non-specific changes of this brain peptide suggesting the leakage from the damaged brain, but further studies are needed to clarify these potential significances.
Isopentenyl pyrophosphate isomerase, farnesyl pyrophosphate synthetase, and geranylgeranyl pyrophosphate synthetase were detected in cell-free extracts of Bombyx mori and were partially purified by hydroxyapatite and Sephadex G-100 chromatography. Two forms of farnesyl pyrophosphate synthetase were chromatographically separated. They were designated as farnesyl pyrophosphate synthetases I and II in the order of their elution from hydroxyapatite. Both enzymes catalyzed the exclusive formation of (E,E)-farnesyl pyrophosphate from isopentenyl pyrophosphate and either dimethylallyl pyrophosphate or geranyl pyrophosphate. However, they were not interconvertible, unlike the enzyme from pig liver. These two enzymes resembled each other in pH optima and molecular weights but differed in susceptibility to metal ions. Farnesyl pyrophosphate synthetase II was stimulated by Triton X-100 while synthetase I was inhibited by the same reagent.
Comparative substrate specificities of farnesyl pyrophosphate synthetases I and II purified from larvae of silkworm, Bombyx mori, were studied by use of the possible biosynthetic intermediates of juvenile hormones in the insect. In the presence of Mn2+ ions farnesyl pyrophosphate synthetase II showed higher activity than synthetase I and the corresponding enzyme from pig liver with the following substrate homologues: (Z)-3-methyl-2-pentenyl-, 3-ethyl-3-butenyl-, (2E,6Z)-3,7-dimethyl-2,6-nonadienyl-, and (2E,6Z)-3-ethyl-7-methyl-2,6-nonadienyl pyrophosphate. When (Z)-3-methyl-2-pentenyl-, 3-ethyl-3-butenyl-, and isopentenyl pyrophosphate were mixed and incubated with farnesyl pyrophosphate synthetase II, (2E,6E,10Z)-3,11-dimethyl-7-ethyl-2,6,10-tridecatrienyl-, (2E,6E,10Z)-3,7,11-trimethyl-2,6,10-tridecatrienyl, and a trace amount of (2E,6E,10Z)-3,7-diethyl-11-methyl-2,6,10-tridecatrienyl pyrophosphate, whose carbon skeletons were the same as those of juvenile hormone I, II, and O, respectively, were formed. (Z)-3-Methyl-2-pentenyl pyrophosphate was produced from 3-ethyl-3-butenyl pyrophosphate as a single product by the action of silkworm isopentenyl pyrophosphate isomerase, though the enzyme activity was much lower with this substrate than with the usual substrate, isopentenyl pyrophosphate.
The effect of dexamethasone on the GH response to GH-releasing hormone (GHRH) was studied in vivo in six patients with acromegaly as well as in vitro in monolayer cultures of GH-secreting pituitary tumor cells obtained from three of these patients. Oral administration of 9 mg/day dexamethasone for 2 days decreased plasma GH responses to iv injection of 100 micrograms GHRH-(1-44 amide) in all six patients. Blood glucose levels were significantly increased, while plasma somatomedin-C levels were significantly decreased by this regimen of dexamethasone treatment. On the other hand, 2-day pretreatment with 50 nM dexamethasone of monolayer cultures of pituitary adenoma cells potentiated GH release basally and/or in response to 100 pM to 1 nM GHRH in vitro. These results indicate that the potentiating action of 2-day treatment of dexamethasone in vitro is overwhelmed in vivo by some extra-pituitary action, probably on the central nervous system, of glucocorticoids in patients with acromegaly.
ACTH response in vivo and in vitro to synthetic ovine corticotropin-releasing factor (o-CRF) was examined in a bronchial carcinoid from a patient with ectopic ACTH syndrome. o-CRF, 1 microgram/kg iv bolus, scarcely increased plasma ACTH or cortisol on one occasion, but they showed a low response on retesting. On the other hand, 10(-8) and 10(-7) M of o-CRF significantly stimulated ACTH release in cultured bronchial carcinoid cells.
The effect of dexamethasone on the release of ACTH, GH, PRL, LH and TSH was studied in monolayer cultures of rat pituitary cells in 4-hour incubation. With or without the addition of rat hypothalamic extract, the release of GH was significantly inhibited by dexamethasone at concentrations higher than 10(-9) M, although less remarkably than that of ACTH. Intracellular ACTH and GH were unchanged. PRL, LH and TSH were not affected. These results indicate that dexamethasone, when exerted for 4 hours, suppressed the release of GH as well as ACTH, at least in part, at the pituitary level.
The responses of pituitary and adrenomedullary hormones to insulin-induced hypoglycemia were studied in 10 patients with anorexia nervosa and 7 control females of comparable age. The increases in plasma GH and PRL were significantly smaller in the patients, while the responses of GH to arginine and of PRL to TRH were indistinguishable. Plasma cortisol attained similar peak levels in both groups with higher basal levels and smaller increments in the patients. The response of plasma epinephrine was markedly lower in the patients, although urinary epinephrine showed similar increase in both groups. These results suggest the possibility that the process by which hypoglycemic stimulus causes pituitary and adrenomedullary hormone secretion is deranged in patients with anorexia nervosa.
To examine the sensitivity to epinephrine in patients with anorexia nervosa, 20-60 micrograms/kg body weight/min of epinephrine was infused for 30 min each in 5 patients and 5 controls. The increase in pulse rate and the decrease in diastolic blood pressure were significantly smaller in the patient group. Elevated plasma GH levels in the patients were markedly suppressed by epinephrine infusion. These results indicate the beta-adrenergic function is decreased at least in the cardiovascular system in patients with anorexia nervosa.
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Persistent bullous keratopathy was produced in one eye of a rabbit by anterior chamber irrigation with benzalkonium chloride solution (BAK). Corneal grafts were made from both eyes of another rabbit and they were transplanted to the eye with bullous keratopathy and the normal fellow eye, which served as the control. Subsequently, at intervals flat preparations of the endothelium of both eyes stained with silver nitrate were made. On panoramic photographs of the endothelium along one meridian of the cornea, the endothelial cell sizes were determined on both sides of the host-graft junction and at every 1 mm from the junction. In the control eyes the cell sizes increased, in the early postoperative period, near the host-graft junction both in the graft and in the host, and this increase gradually diminished by the end of the 6-month observation period. However, even after 6 months the mean cell size in both graft and host was slightly larger than the normal cell size. In the eye with bullous keratopathy, the cell size in the graft center increased rapidly and progressively. After 3 months the endothelial cells were seen in the host cornea and the cell sizes were considerably larger than those in the control cornea. After 6 months the cells were seen even in the periphery of the host cornea. In three sets of experiments, bullous keratopathy was produced in one eye of a male rabbit and the graft from a female rabbit was transplanted. Four months later, the detection frequency of the sex chromatin stained with acetic orcein was similar between the cells in the graft and in the host bullous cornea, indicating that the cells in the host had migrated from the graft.
The authors have been analyzed the results from 19 patients who underwent transsphenoidal microsurgery for their pituitary adenomas. All of the patients showed some degree of clinical improvement after surgery. Surgical complications seemed to be negligible except one patient who had suffered from persistent diabetes insipidus postoperatively. The results in terms of postoperative GH levels were almost good in 17 patients in whom preoperative GH levels had been below 100 ng/ml. There was no relationship between postoperative GH values and tumor grades or types (in Hardy's classification) in this group of patients. In 12 of them, postoperative GH values fell and remained below 5 ng/ml, although abnormal GH responses to dynamic testing were still noted. On the other hand, the results were particularly poor in the remaining 2 patients in whom preoperative GH levels had been higher than 100 ng/ml. Postsurgical radiation therapy was applied to 5 cases. Postirradiation GH values decreased in all 5 cases, but did not reach to the normal level (below 5 ng/ml) in 3 of them.
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Two tRNA precursors were isolated from 32P-labeled or unlabeled HeLa cells by two dimensional polyacrylamide gel electrophoresis, and were sequenced. These were the precursors of tRNAMet and tRNALeu, and both contained four extra nucleotides including 5'-triphosphates at their 5'-end and nine extra nucleotides including oligo U at their 3'-end. These RNAs are the first naturally occurring tRNA precursors from higher eukaryotes whose sequences have been determined. In these molecules, several modified nucleosides such as m2G, t6A and ac4C in mature tRNAs were undermodified. Two additional hydrogen bonds were formed in the clover leaf structures of these tRNA precursors. These extra hydrogen bonds may be responsible for the stabilities of these tRNA precursors.