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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

31P NMR spectroscopy, 1H magnetic resonance (MR) imaging, and 23Na MR imaging were used to study the biochemical difference between nine hormone-sensitive and six hormone-resistant rat prostate cancers and to follow bioenergetic and morphologic changes subsequent to androgen deprivation in the hormone-sensitive model. Neither 1H nor 23Na MR image characteristics were useful in distinguishing androgen-sensitive from androgen-resistant prostate cancer nor in identifying androgen deprivation. 31P NMR spectroscopy did detect bioenergetic differences between the hormone-sensitive and hormone-resistant tumors. Baseline spectra showed a significantly higher PCr/ATP ratio (mean 0.86 +/- 0.09 SEM) for hormone-sensitive tumors than for hormone-resistant tumors (mean 0.26 +/- 0.07 SEM). By 3 days after androgen deprivation (orchiectomy (castration], PCr/ATP ratios had decreased noticeably; by 1 week, the decrease was statistically significant and remained so for the rest of the study (3 weeks). It appears that 31P NMR spectroscopy is useful in detecting androgen sensitivity of prostatic carcinoma.
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PMID:Androgen sensitivity of rat prostate carcinoma studied by 31P NMR spectroscopy, 1H MR imaging, and 23Na MR imaging. 277 8

The influence of exercise intensity on the accumulation of inosine monophosphate (IMP) in human skeletal muscle has been investigated. Ten men cycled at workloads corresponding to 40%, 75% and 100% of their maximal oxygen uptake (VO2 max). Muscle IMP was below the detection limit (less than 0.01 mmol kg-1 dry wt) at rest and after exercise at 40% of VO2 max, but increased to 0.26 +/- 0.06 (mean +/- SEM) and 3.50 +/- 0.51 mmol kg-1 dry wt after exercise at 75% and 100% of VO2 max respectively. Accumulation of IMP corresponded to a similar decrease in the total adenine nucleotide content. The muscle content of IMP was positively related to lactate and negatively related to phosphocreatine (PCr). IMP was formed in both fibre types, but the IMP content at fatigue was about twice as high in type II fibres as in type I fibres. It was concluded that the IMP content of human skeletal muscle is very low at rest and after low-intensity exercise, but increases after moderate and high-intensity exercise. In contrast to rat muscle, where deamination of AMP predominantly occurs in the fast-twitch muscle fibres, IMP is formed during exercise in both fibre types in human muscle. Accumulation of IMP appears to reflect an imbalance between the rate of utilization and the rate of regeneration of ATP.
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PMID:Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise. 278 92

The tolerance against two different levels of enzymatically generated oxygen radicals was studied in isolated Langendorff-perfused hearts from selenium (Se)-deficient and control rats. The glutathione peroxidase activity of the Se-deficient hearts was less than 5% of that of the controls. Examination of the ultrastructure was made after random sampling using morphometric methods. Selenium-deficient hearts demonstrated some areas with myocytes with intracellular oedema. Oxygen radicals (hydrogen peroxide and superoxide) were generated by adding xanthine oxidase for 12 min (high dose: 25 U/l; low dose: 12.5 U/l) and hypoxanthine to the buffer of isolated Langendorff-perfused rat hearts. Left ventricle-developed pressure (LVDP) and high-energy phosphates (ATP and CP) were measured. After the low dose of oxygen radicals, LVDP was reduced to 32.7 +/- 6.5% (mean +/- SEM) of initial values in the Se-deficient group, but only to 58.3 +/- 8.4% in the control group (p less than 0.05). After the high dose, LVDP decreased abruptly to zero in both groups. However, ATP content was significantly (p less than 0.05) lower in Se-deficient than in control hearts. Perfusion with oxygen radicals (low dose) resulted in the appearance of mitochondrial damage in both groups, but intracellular oedema was still present only in the Se-deficient hearts. It is concluded that protection against oxygen radicals was reduced in Se-deficient hearts. This was probably due to loss of myocardial glutathione peroxidase activity.
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PMID:The selenium-deficient rat heart with special reference to tolerance against enzymatically generated oxygen radicals. 283 46

Sarcoplasmic reticulum membrane vesicles isolated from frog skeletal muscle display high conductance calcium channels when fused into phospholipid bilayers. The channels are selective for calcium and barium over Tris. The fractional open time was voltage-independent (-40 to +25 mV), but was steeply dependent on the free cis [Ca2+] (P0 = 0.02 at 10 microM cis Ca2+ and 0.77 at 150 microM Ca2+; estimated Hill coefficient: 1.6). Addition of ATP (1 mM; cis) further increased P0 from 0.77 to 0.94. Calcium activation was reversed by addition of EGTA to the cis compartment. Magnesium (2 mM) increased the frequency of rapid closures and 8 mM magnesium decreased the current amplitude from 3.4 to 1.2 pA at 0 mV, suggesting a reversible fast blockade. Addition of increasing concentrations of inositol (1, 4, 5)-triphosphate (cis), increased P0 from 0.10 +/- 0.01 (mean +/- SEM) in the control to 0.85 +/- 0.02 at 50 microM in an approximately sigmoidal fashion, with an apparent half-maximal activation at 15 microM inositol (1, 4, 5)-trisphosphate in the presence of 40 microM cis Ca2+. Lower concentrations of this agonist were required to produce a significant increase in P0 when 10 microM or less cis Ca2+ were used. The channel was blocked by the addition to the cis compartment of either 0.5 mM lanthanum, 0.5 microM ruthenium red, or 200 nM ryanodine, all known inhibitors of Ca2+ release from sarcoplasmic reticulum vesicles. These results demonstrate the presence of calcium channels in the sarcoplasmic reticulum from frog skeletal muscle with a pharmacological profile consistent with a role in excitation contraction coupling and with the hypothesis that inositol ( 1,4,5)-trisphosphate is a physiological agonist in this process.
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PMID:Inositol (1,4,5)-trisphosphate activates a calcium channel in isolated sarcoplasmic reticulum membranes. 285 37

To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n = 19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates. Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n = 19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5 +/- 7.5 mm Hg vs. 262.6 +/- 3.4 mm Hg in controls, mean +/- SEM (p less than 0.01) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2 +/- 0.2 to 5.6 +/- 0.3 mumol/gww (p less than 0.01). ATP was reduced from 4.8 +/- 0.2 to 3.9 +/- 0.3 mumol/gww (p less than 0.01). Phosphocreatine was elevated to 7.0 +/- 0.6 mumol/gww, x +/- SEM (p less than 0.01). Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions - in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content.
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PMID:High-energy phosphates, myocardial contractile function and material properties after short periods of oxygen deficiency. 292 9

Idiopathic hypercalciuria is a common disorder whose inheritance suggests an enzyme abnormality in calcium transport. We measured calcium-magnesium-ATPase activity in erythrocytes from 38 patients (mean age [+/- SEM], 40 +/- 2.1 years) with idiopathic hypercalciuria (24-hour urinary calcium excretion greater than or equal to 0.1 mmol per kilogram of body weight) and a history of multiple calcium oxalate kidney stones. As compared with 41 healthy controls, the patients with hypercalciuria had increased erythrocyte-membrane calcium-magnesium-ATPase activity (64.2 +/- 2.19 vs. 51.6 +/- 1.91 nmol of ATP split per milligram per minute; P less than 0.01) and increased sodium-potassium pump activity (6866 +/- 233 vs. 6096 +/- 228 mumol of sodium per liter of red cells per hour; P less than 0.05). No significant difference between the two groups was found in erythrocyte sodium-potassium cotransport, sodium-lithium countertransport, or potassium content. In 66 patients with kidney stones (38 with hypercalciuria and 28 with normal calcium excretion), 24-hour urinary calcium excretion correlated with calcium-magnesium-ATPase activity (r = 0.46, P less than 0.001). Erythrocyte calcium-magnesium-ATPase activity remained unchanged in eight subjects studied after four months on a low-calcium diet. A study of 30 healthy families found significant correlations between mean values in parents and those in offspring for calcium-magnesium-ATPase (r = 0.68, P less than 0.001) and urinary calcium excretion (r = 0.45, P less than 0.02), with no significant correlations between parents with respect to these measures (r = 0.27 and r = 0.08, respectively). We conclude that abnormalities in erythrocyte calcium-magnesium-ATPase activity may represent an inherited defect in calcium transport related to the cause of idiopathic hypercalciuria.
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PMID:Abnormal red-cell calcium pump in patients with idiopathic hypercalciuria. 297 Nov 39

Effects of purine nucleosides and asthma mediators on airway tone have been examined in the guinea-pig isolated perfused lung preparation. Acetylcholine (10 pmol-0.3 nmol), histamine (1-10 nmol), adenosine (10 nmol-0.3 mumol), ATP (10 nmol-0.3 mumol) and inosine (10 mumol-0.1 mmol) all produced a dose dependent increase in lung resistance (RL) and a decrease in dynamic compliance (CDYN). ATP was equipotent with adenosine whereas inosine was about 500 times less potent. The adenosine-induced bronchoconstriction was affected neither by disodium cromoglycate (150 microM) nor by the histamine H1-receptor antagonist, mepyramine (1 microM) suggesting that histamine is not involved in this response. Furthermore, it was studied whether the xanthines theophylline and enprofylline specifically interacted with the adenosine induced bronchoconstriction. Theophylline significantly (P less than 0.01-0.001) and concentration dependently prevented both acetylcholine and adenosine-induced increase in RL. The response to 0.1 nmol acetylcholine was reduced by 32.8 +/- 8.4% (mean +/- SEM) and 58.1 +/- 4.0%, respectively, by 75 and 150 microM theophylline. Theophylline, 75 and 150 microM, also inhibited the increase in RL caused by 0.1 mumol of adenosine by 61.4 +/- 9.6% and 83.4 +/- 5.2%, respectively. Theophylline, was significantly (P less than 0.05-0.01) more potent in preventing the RL increase produced by adenosine than that by acetylcholine. Enprofylline, 30 microM, equally well as 75 microM theophylline reduced the acetylcholine-induced bronchoconstriction by 41.8 +/- 7.6% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine-induced bronchoconstriction in the guinea-pig isolated lung: interaction with theophylline and enprofylline. 298 Feb 92

Thyrotropin (TSH), stimulators of guanyl nucleotide regulatory protein, (sodium fluoride and guanyl-5'-yl-imido-diphosphate [Gpp(NH)p]) and a stimulator of the catalytic unit of adenylate cyclase (AC) (forskolin) were used to probe the TSH receptor-guanyl nucleotide regulatory protein-cyclase unit in normal and neoplastic thyroid tissue from 17 patients. Eleven of these patients had benign follicular adenomas and six patients had differentiated thyroid carcinomas. An 8000 X g particulate fraction that is rich in thyroid plasma membranes was prepared, and the activity of AC was determined by the conversion of alpha-32P-ATP to P32-cAMP. Thyroid neoplasms had a greater AC response to TSH than did normal thyroid tissue removed from the same patients (p less than 0.001). The AC response to NaF and Gpp(NH)p was greater in the neoplastic thyroid tissue, although in these experiments the increase was not significant. In contrast, the AC response to forskolin was comparable in normal (573 +/- 129) and neoplastic (526 +/- 132) thyroid tissue (mean +/- SEM). The effects of NaF, Gpp(NH)p, and forskolin on AC activity were additive with TSH when used at concentrations for optimal AC activity. Low concentrations of NaF and Gpp(NH)p stimulated AC activity whereas high concentrations of NaF and Gpp(NH)p assayed either together or separately inhibited AC activity. When forskolin and NaF were assayed together there was a greater than additive effect or potentiated effect on activity. Basal AC activity was increased in the presence of manganese (Mn+2) (2 mM) over magnesium (Mg+2) (2 mM) (p less than 0.001), whereas TSH-stimulated (p less than 0.01) and Gpp(NH)p-stimulated AC activity (p less than 0.05) were lower in the presence of Mn+2 than Mg+2. There was an excellent correlation between basal AC activity and AC activity in response to forskolin in both normal and neoplastic thyroid tissue, whereas there was no correlation between basal AC activity and TSH-stimulated AC activity in the thyroid neoplasms. These data suggest that the abnormality responsible for the greater AC response to TSH in neoplastic thyroid tissue is proximal to the catalytic unit of AC and most probably is due to an alteration in the guanyl nucleotide regulatory protein or in the coupling of the guanyl nucleotide regulatory protein to either the receptor or the catalytic unit of AC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms. 298 5

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.
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PMID:Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats. 298 35

To characterize the insulin-like growth factor I (IGF-I) receptor on human erythrocytes, cells were purified from peripheral blood by Ficoll-Hypaque gradient centrifugation and incubated with [125I]IGF-I. Specific binding was maximal at pH 8.0 after 24 h at 4 C and increased linearly with cell number to 3.9 +/- 0.2% (+/- SEM) for 3.0 X 10(9) cells/ml. The Scatchard plot of the binding data was linear, with 7 fmol [125I]IGF-I bound/10(9) cells and an affinity constant (K) of 1.8 X 10(9) M-1. Unlabeled IGF-I inhibited tracer binding half-maximally at 6 ng/ml. Multiplication-stimulating activity (or rat IGF-II) was 40% as potent (ED50, 15 ng/ml), whereas insulin and proinsulin were 30- to 500-fold less potent. A monoclonal antibody to the IGF-I receptor (alpha IR-3) inhibited IGF-I binding by 50% at a 1:1000 dilution and by 80% at a 1:250 dilution. Insulin binding was unaffected by the same dilutions. IGF-I receptor phosphorylation was studied in erythrocyte ghosts prepared by hypotonic lysis and solubilized in 1% Triton. The extract was preincubated with and without 100 ng/ml IGF-I or porcine insulin and incubated with [gamma-32P]ATP in the presence of Mn2+, and the receptor was identified by immunoprecipitation with alpha IR-3 antibody and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IGF-I stimulated 4-fold the incorporation of 32P into a protein of 95,000 mol wt, which was immunoprecipitated by alpha IR-3; insulin produced a 2-fold stimulation of this protein. This protein corresponds to the beta-subunit of the IGF-I receptor. These data demonstrate that human erythrocytes have specific receptors for IGF-I, and that this IGF-I receptor, like the insulin receptor, undergoes ligand-stimulated autophosphorylation. Thus, analysis of erythrocyte IGF-I binding and receptor phosphorylation may be useful tools for the study of patients with a variety of growth disorders.
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PMID:The human erythrocyte insulin-like growth factor I receptor: characterization and demonstration of ligand-stimulated autophosphorylation. 300 55


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