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Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I.

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Development↗

Dissociation of selective renal venous plasma endothelin-1 activity and corresponding plasma renin activity in a patient with hypertension, severe stenosis of unilateral renal artery and ipsilaterally decreased renal function.

Plasma endothelin-1 (ET-1)-like immunoreactivity in selective renal venous blood and peripheral venous blood was measured and compared with plasma renin activity and aldosterone level in a 26-year-old woman with suspected renovascular hypertension due to stenosis of the left renal artery. Although there was no significant step-up in plasma renin activity between the right and the left renal vein, left/right ratio of plasma ET-1 in the renal vein was 2.18. This case suggests that ET-1 may be one of the hypertensive mechanisms of suspected renovascular hypertension in addition to the renin-angiotensin system.

Adult↗

Effect of interferon on plasma lipoproteins and on the activity of postheparin plasma lipases.

The effect of interferon administration on the concentration of plasma lipoproteins and on the activity of postheparin plasma lipoprotein lipase and hepatic lipase was studied in six healthy men. Daily injection of human leukocyte interferon for 1 week lowered the plasma level of total cholesterol, very low density lipoprotein + low density lipoprotein cholesterol, high density lipoprotein cholesterol, and apolipoprotein A-1 in all subjects. Simultaneously, the activity of postheparin plasma hepatic lipase and lipoprotein lipase decreased by 20% to 50%. These observations may be of importance in the interpretation of lipoprotein changes seen in acute and chronic infections and should be borne in mind when prolonged treatment with interferon is considered.

Adult↗

The effects of des-Asp1-angiotensin II on blood pressure, plasma aldosterone concentration, and plasma renin activity in the rabbit.

To examine the hypothesis that des-Asp-1-angiotensin II (angiotensin III) may be an important mediator of various responses to angiotensin II, both peptides were given sequentially at 25 ng/kg per min by systemic infusion to conscious rabbits, and the effects on blood pressure, plasma aldosterone concentration, and plasma renin activity were compared. The mean arterial pressure increased with angiotensin II infusion an average of 18.2 mm Hg, and with angiotensin III infusion only 3.2 mm Hg. Both peptides, however, produced a six- to sevenfold increase in plasma aldosterone concentration, and a threefold decrease in plasma renin activity. Renal clearance data suggest that the suppression of renin activity was not a consequence of renal hemodynamic change or altered sodium transport, but of direct inhibition through a receptor mediating a short feedback loop. These data in the intact rabbit, taken together with in vitro studies by others, suggest that the responses of these three organ systems to angiotensin peptides are mediated by receptors of varied specificity: those mediating vasoconstriction exhibit a greater response to angiotensin II than to angiotensin III; those mediating the secretion of aldosterone exhibit a lesser response to angiotensin II than to angiotensin III; and those mediating the suppression of renin release do not appear to discriminate between the two peptides.

Aldosterone↗

Arterial and venous angiotensin II in normal subjects. Relation to plasma renin activity and plasma aldosterone concentration, and response to posture and volume changes.

Plasma renin activity, arterial and venous angiotensin II (A II) concentrations, and plasma aldosterone concentration were measured in 16 normal subjects (mean age = 34 years) after 8 hours of recumbency, following 2 hours of ambulation, and again 30 minutes after administration of furosemide intravenously. Measurements were obtained during periods of sodium restriction and again during sodium surfeit. Both arterial and venous A II exhibited a 3-fold increase from low values of 8.8 +/- 2.5 and 8.6 +/- 2.5 pg/ml of plasma, respectively, during recumbency on high sodium intake to values of 23.9 +/- 4.1 and 26.5 +/- 6.2 pg/ml, respectively, following intravenous furosemide during sodium restriction. Corresponding values for aldosterone exhibited a 5-fold rise from 5.6 ng/100 ml to 32.0 ng/100 ml, whereas plasma renin activity (PRA) measured by an in vitro assay exhibited a 20-fold rise from 0.6 +/- 0.2 ng of angiotensin I (AI) generated per ml per hour to 13.1 ng/ml per hour. Despite the disparity in the magnitude of these increases, significant correlations were identified between all four of the measured parameters, indicating a major role of the renin-angiotensin system in regulating aldosterone output in response to volume and posture-related stimuli. Values of arterial and venous immunoreactive A II were closely correlated ( r = +0.72, P less than 0.005), but significant differences were demonstrated between low and high salt periods, suggesting that changes in metabolism of A II in the peripheral circulation may occur during sodium restriction.

Adult↗

Plasma lithography--thin-film patterning of polymeric biomaterials by RF plasma polymerization I: Surface preparation and analysis.

Plasma lithography, combining plasma deposition with photolithography, is described as a versatile method to manufacture all-polymeric substrates with thin-film patterns for applications in biomedical engineering. Patterns of a hydrophobic fluorocarbon plasma polymer with feature sizes between 5 and 100 microm were deposited on a base substrate in a lift-off process: an intermediate tetraglyme plasma polymer layer provides non-fouling properties to the base substrate. Careful analysis of critical process parameters identified the narrow window of process conditions that led to the formation of functional surface patterns. High pattern fidelity, aspect ratios, and resolution of the patterns are demonstrated by atomic force microscopy. Electron spectroscopy for chemical analysis (ESCA) and secondary ion mass spectroscopy (SIMS) were used to characterize the surfaces, showing good retention of the original chemical structure of the pattern components throughout the process. SIMS imaging was used for specific chemical imaging of the components. Potential applications for the patterned polymer films, e.g., for studying cell behavior in vitro in dependence of shape and size of adhering cells, are discussed.

Biocompatible Materials↗

Regulation of factor Xa in vitro in human and mouse plasma and in vivo in mouse. Role of the endothelium and plasma proteinase inhibitors.

The regulation of human Factor Xa was studied in vitro in human and mouse plasma, and in vivo in mouse. In human plasma, 125I-Factor Xa bound to alpha 1-proteinase inhibitor, antithrombin III, and alpha 2-macroglobulin in a ratio of 4.9:1.9:1 as determined by gel electrophoresis and by adsorption to IgG-(antiproteinase inhibitor)-Sepharose beads. The distribution of Factor Xa in mouse plasma was similar. The clearance of Factor Xa in mice was rapid (50% clearance in 3 min) and biphasic. alpha 1-Proteinase inhibitor-trypsin, even at a 2,000-fold molar excess, failed to inhibit the clearance of Factor Xa, while alpha 2-macroglobulin-trypsin inhibited only the later phase of clearance. The plasma clearance of diisopropylphosphoryl-Factor Xa was more rapid than native Factor Xa (50% clearance in 2.5 min), and the clearance was blocked by diisopropylphosphoryl-thrombin. Electrophoresis experiments confirmed that by 2 min after injection into the murine circulation, 90% of the bound Factor Xa was on alpha 2-macroglobulin, in marked contrast to the in vitro results. Organ distribution studies at 3 and 15 min with 125I-Factor Xa demonstrated that the majority of radioactivity was in the liver, with significant radioactivity also present in lung and kidney. Autopsies performed 30 s after injection of 125I-Factor Xa also demonstrated significant binding to the aorta and vena cava. These studies indicate that Factor Xa binds to specific thrombin-binding sites on endothelial cells, and that this binding alters its proteinase inhibitor specificity. Factor Xa binds to alpha 2-macroglobulin in vivo, whereas the predominant in vitro inhibitor of Factor Xa is alpha 1-proteinase inhibitor.

Animals↗

Plasma CD14 decreases monocyte responses to LPS by transferring cell-bound LPS to plasma lipoproteins.

CD14, a myeloid cell-surface receptor and soluble plasma protein, binds LPS and other microbial molecules and initiates the innate immune response to bacterial invasion. The blood concentration of soluble CD14 (sCD14) increases during the systemic response to infection. Although high sCD14 blood levels have correlated with increased risk of dying from severe sepsis, sCD14 can diminish cell responses to LPS. We show here that in human serum, sCD14 increases the rate at which cell-bound LPS is released from the monocyte surface and binds to plasma lipoproteins. This enhanced rate of LPS efflux is associated with a significant reduction in the ability of monocytes to produce cytokines in response to LPS. Serum from septic patients reduced the LPS-monocyte interaction by as much as tenfold, and depletion of sCD14 from the serum restored LPS-monocyte binding and release kinetics to near normal levels. In serum from septic patients, monocyte-bound LPS also moved more rapidly into lipoproteins, which completely neutralized the biologic activity of the LPS that bound to them. In human plasma, sCD14 thus diminishes monocyte responses to LPS by transferring cell-bound LPS to lipoproteins. Stress-related increases in plasma sCD14 levels may help prevent inflammatory responses within the blood.

Bacterial Infections↗

High-dose statin treatment does not alter plasma marker for brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels.

Statins inhibit endogenous cholesterol synthesis, up-regulate low-density lipoprotein (LDL) receptor expression in mammalian liver cells, and thus decrease circulating LDL-cholesterol concentrations. As cholesterol seems to play a role in the development of neurodegenerative diseases, it is of interest to evaluate the effect of high dosages of statins (eg, atorvastatin or simvastatin) on brain cholesterol metabolism. Plasma samples from 44 participants (aged 30-69 years, 16 men and 18 women) of an earlier randomized, placebo-controlled, double-blind trial, who took 40 mg atorvastatin or 80 mg simvastatin daily for 2 months, were used to analyze total cholesterol, its precursor lathosterol, and its metabolites 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Despite a significant decrease in absolute plasma concentrations of oxysterols, total cholesterol, and its endogenous synthesis rate, indicated by a decreased ratio of lathosterol to cholesterol, the plasma 24(S)-hydroxycholesterol to cholesterol ratio, a surrogate marker of brain cholesterol homeostasis, remained unchanged. Short-term high-dose atorvastatin and simvastatin treatment does not seem to influence brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels.

Adult↗

Nyctohemeral rhythm of plasma renin activity and plasma aldosterone in children.

Circadian rhythms of plasma renin activity (PRA) and plasma aldosterone (PA) were studied in eight healthy children, 7 to 15 years old. Blood samples were obtained at 7:00 AM, 10:00 AM, 1:00 PM, 4:00 PM, 5:00 PM, 8.00 PM, and midnight on day 1 and 4:00 AM and 7:00 AM on day 2. Children had normal activity during this test. Intra- and interindividual changes were noted in PRA in plasma taken in the upright position. Mean PRA values for samples taken in the upright position were maximal at 1:00 PM (7 ng/ml/hr) and minimal at 5:00 PM (4.1 ng/ml/hr). Mean PRA in the supine position was maximal at 4:00 AM on day 2 (5.6 ng/ml/hr), and its rise was statistically significant compared with the mean PRA at 7:00 AM on the same day (3.9 ng/ml/hr). Plasma aldosterone varied without any definite pattern. No correlation was found between PRA and PA and 24-hr urinary sodium excretion.

Adolescent↗

Somatomedin peptide distribution and somatomedin-binding protein content in cord plasma: comparison to normal and hypopituitary plasma.

To characterize the macromolecular forms of somatomedin (SM) in human newborn plasma, we have studied the molecular weight distribution of endogenous SM peptides as well as the content and distribution of the acid-stable and the unsaturated SM-binding proteins (SMBP) in cord blood from 13 normal term infants. The radioreceptor assayable SM peptide content was significantly reduced in newborns compared with that in normal adults. Furthermore, 50% of the SM content of newborns circulated as part of a 50,000 mol wt complex, in contrast to adult plasma where the majority of SM peptide content is found in the 150,000 mol wt range. Unsaturated SMBP was strikingly elevated in newborns (mean +/- SRM, 2.75 +/- 1.73 U/ml) compared to adult values of 0.63 +/- 0.24. Sephacryl-200 chromatography demonstrated that the unsaturated SMBP is found in the 40,000-50,000 mol wt region in newborns, adults, and GH-deficient children, although adults appear to have a secondary peak of unsaturated SMBP in the 150,000 mol wt region. Assay of the acid-stable SMBP indicated similar levels in newborns (1.15 +/- 0.26 U/ml) and adults (1.18 +/- 0.47) and strikingly lower values in GH-deficient subjects. The molecular weight of the acid-stable SMBP of newborns, adults, and hypopituitary dwarfs appeared to be similar, measuring approximately 60,000. We conclude that despite low levels of SM peptides, human cord plasma contains normal levels of the acid-stable SMBP and elevated of the unsaturated SMBP. The role of these binding proteins in cord plasma remains uncertain, but suggests that other SM peptides may be important in fetal growth.

Adult↗

Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract.

A means of estimating human enteroglucagon (glucagon-like immunoreactivity of intestinal origin) in tissues and plasma is described, based on the subtraction of RIA values obtained with the C-terminal-directed glucagon antiserum RCS5 from the total glucagon-like immunoreactivity determined with the N-terminal- to midmolecule-directed glucagon antiserum R59. Gel filtration on Sephadex G-50 of human plasma and extracts of normal human intestine separated the R59 immunoreactivity into three peaks: a small peak of void volume material, a major peak coeluting with porcine glicentin, and a smaller peak coeluting with pancreatic glucagon. No RCS5 immunoreactivity was detected in the human gut, except for a small amount constituting less than 2% of the total glucagon-like immunoreactivity in the ileum and rectum only. In extracts of human pancreas, the chromatographic profiles obtained with RCS5 and R59 assays differed from the intestinal patterns, but were identical to each other, giving no evidence of a significant amount of pancreatic R59 immunoreactivity that was not also reactive with RCS5. Chromatography of plasmas from healthy subjects and patients with dumping syndrome, active coeliac disease, and tropical sprue showed that only the second major peak of R59 immunoreactivity reflected the basal or postnutrient increases in the plasma enteroglucagon concentration. In patients with exaggerated enteroglucagon release, the rise was again found to be entirely due to an increase in this peak of immunoreactivity. This major molecular form of human enteroglucagon, similar in size to porcine glicentin, is, thus, the form most likely to be of physiological and pathophysiological significance.

Adult↗

No change in plasma free testosterone ratio and plasma sex hormone-binding globulin concentration during hCG stimulation.

Plasma sex hormone-binding globulin (SHBG) levels and free testosterone ratios were determined independently after administration of hCG for 4 consecutive days to eight normal men. Correcting for nonspecific dihydrotestosterone binding, no changes in plasma SHBG were found. The free testosterone ratio, measured by equilibrium dialysis, did not change despite doubling of total plasma testosterone. The increase in plasma testosterone after hCG stimulation was due to increased production only, with equivalent changes in free testosterone concentration, and was not a result of changes in SHBG concentration.

Chorionic Gonadotropin↗

Purification and characterization of PK-120, a novel substrate for plasma kallikrein, from guinea pig plasma.

PK-120 is a novel substrate of plasma kallikrein isolated from human plasma. Western blotting using anti-human PK-120 polyclonal antibodies demonstrated the presence of a PK-120-like protein in guinea pig, rat and mouse plasma. We purified the immunoreactive-120 kDa protein from guinea pig plasma by polyethylene glycol fractionation followed by ion-exchange chromatography using Q-Sepharose, heparin-Sepharose, Mono-Q and gel filtration with TSK G3000. The 120 kDa protein thus isolated was similar to human PK-120 with respect to limited proteolysis by kallikrein, amino acid composition, and the N-terminal amino acid sequence, indicating that the immunoreactive 120 kDa protein was guinea pig PK-120.

Amino Acid Sequence↗

The distribution of plasma norepinephrine concentration and the relation of plasma norepinephrine concentration to pulmonary arterial pressure in heart disease.

Plasma norepinephrine (NE) concentration was measured in blood samples from the pulmonary artery (PA), the superior vena cava (SVC), the inferior vena cava (IVC) and the femoral artery (FA) in 34 patients undergoing diagnostic cardiac catheterization. In patients with pulmonary hypertension, the mean plasma NE concentrations in PA, SVC and FA were significantly higher than that of IVC, but no such difference was found in patients without such hypertension. Except in IVC, the plasma NE concentration in patients with pulmonary hypertension was significantly higher than in others. Furthermore, the plasma NE concentration was positively correlated with the mean pulmonary arterial pressure and inversely related to pulmonary arterial oxygen saturation in patients without a shunt. These results suggest the possibility that vasoconstriction by the sympathetic nervous system may contribute to the development of pulmonary hypertension in patients without the shunt.

Adolescent↗

Utilization of plasma and urine methadone concentration measurements to limit narcotics use in methadone maintenance patients: II. Generation of plasma concentration response curves.

Controversy exists still concerning the proper daily dose of methadone required to eliminate illicit narcotics use. To address this, urine methadone and opioid concentrations were measured prospectively (150 maintenance patients, 18 month period, 9250 urine samples) using fluorescence polarization immunoassay. Results demonstrate that current thresholds (EMIT uses 300 micrograms/L) defining opiate positive urines are overly high (FPIA can go as low as 25 micrograms/L), causing severe underestimation of opioid use in the typical clinic. Using this data, plasma methadone concentration and dose response probability curves were generated for illicit opiate use. Results demonstrate a S-shaped, 24 hr trough plasma methadone concentration response curve with effective concentrations, EC90 = 80 micrograms/L, EC98 = 600 micrograms/L. Plotting mean plasma methadone concentration versus dose gives a monotonically increasing function: Conc = 5.367*dose0.858, raw R-squared = 0.967, corrected R-squared = 0.802. Unfortunately, coefficients of variation for plasma concentrations at each prescribed dose are unacceptably large, explaining poor dose response relationships for some patients.

Adult↗

Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma.

Some non-Hodgkin lymphomas show marked plasmacytic differentiation. In such cases, it may be difficult to differentiate these lymphoma from plasmacytoma or myeloma, especially with limited diagnostic material. However, there may be immunophenotypic differences in the plasma cells in these disorders that distinguish them. This study characterizes the immunophenotypes of neoplastic plasma cells in 41 cases of B-lineage non-Hodgkin lymphoma and compares them with those in plasma cell myeloma. We found that plasma cells in lymphoma were significantly more likely to express CD19, CD45, and surface immunoglobulin and less likely to express CD56 than those in myeloma. We further show that CD 19 and CD56 expression can be used reliably to distinguish these entities. Myeloma-associated osseous lesions and solitary plasmacytoma of bone showed myeloma-like immunophenotypes. However, some extramedullary plasmacytomas showed lymphoma-like phenotypes, suggesting that, in reality, they may represent non-Hodgkin lymphomas with extensive plasmacytic differentiation.

ADP-ribosyl Cyclase 1↗

Hsp30, the integral plasma membrane heat shock protein of Saccharomyces cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase.

Saccharomyces cerevisiae has a single integral plasma membrane heat shock protein (Hsp). This Hsp30 is induced by several stresses, including heat shock, ethanol exposure, severe osmostress, weak organic acid exposure and glucose limitation. Plasma membrane H(+)-ATPase activities of heat shocked and weak acid-adapted, hsp30 mutant and wild-type cells, revealed that Hsp30 induction leads to a downregulation of the stress-stimulation of this H(+)-ATPase. Plasma membrane H(+)-ATPase activity consumes a substantial fraction of the ATP generated by the cell, a usage that will be increased by the H(+)-ATPase stimulation occurring with several Hsp30-inducing stresses. Hsp30 might therefore provide an energy conservation role, limiting excessive ATP consumption by plasma membrane H(+)-ATPase during prolonged stress exposure or glucose limitation. Consistent with the role of Hsp30 being energy conservation, Hsp30 null cultures give lower final biomass yields. They also have lower ATP levels, consistent with higher H(+)-ATPase activity, at the glucose exhaustion stage of batch fermentations (diauxic lag), when Hsp30 is normally induced. Loss of Hsp30 does not affect several stress tolerances but it extends the time needed for cells to adapt to growth under several stressful conditions where the maintenance of homeostasis will demand an unusually high usage of energy, hsp30 is the first yeast gene identified as both weak organic acid-inducible and assisting the adaptation to growth in the presence of these acids.

Adenosine Triphosphate↗