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Prediction of biologic behavior in adrenocortical neoplasms is difficult because of the lack of availability of reliable clinical, biochemical, and pathologic prognostic markers. Reliable objective markers predictive of clinical outcome in adrenocortical neoplasms are needed to assign optimal treatment of potentially malignant tumors. In the current article, the authors evaluated a set of molecular markers (topoisomerase II alpha (Topo II alpha), MIB-1, p53, human epithelial cadherin (E-cadherin), retinoblastoma gene protein product, and HER-2/neu) and correlated their expression with histologic diagnosis and clinical outcome. Paraffin-embedded, formalin-fixed tissue blocks from 30 cases of adrenocortical neoplasms (15 benign and 15 malignant) were obtained from the surgical pathology archives at the University of Utah Health Sciences Center (Salt Lake City, UT) and the Medical College of Wisconsin (Milwaukee, WI). Age, gender, recurrence, tumor size and weight, hemorrhage, necrosis, pleomorphism, mitotic count, capsular and lymphovascular invasion, hyaline globules, intranuclear inclusions, and immunohistochemical expression of Topo II alpha, p53, MIB-1, E-cadherin, retinoblastoma gene protein product, and HER-2/neu were studied. Clinical data were obtained from the clinical charts, or communication with the treating physician, or both. Adrenocortical neoplasms with hemorrhage, necrosis, large size (>5 cm), weight more than 100 g, nuclear pleomorphism, lymphovascular invasion, and brisk mitotic rate (more than 5 per 30 high-power fields) were more likely to behave in a malignant fashion (P approximately 0.001-0.009). The difference in proliferation indices in benign and malignant neoplasms was statistically significant (P < 0.001). The difference in p53 staining in benign and malignant neoplasms also was statistically significant (P < 0.001). Higher p53 labeling index (>20%) was present in 73% (11/15) of malignant lesions but was found in only 1 of 15 (6.6%) benign lesions. The difference in retinoblastoma staining between benign and malignant neoplasms was statistically significant (P = 0.004). There was no significant difference in staining pattern of E-cadherin expression between benign and malignant lesions. HER-2/neu overexpression was not observed in any of the benign or malignant adrenocortical neoplasms.
Appl Immunohistochem Mol Morphol 2001 Sep
PMID:Value of topoisomerase II alpha, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu immunohistochemical expression for the prediction of biologic behavior in adrenocortical neoplasms. 1155 48

The effects of an intravenous injection of Interleukin-12 (IL-12) after endotoxin administration and without endotoxin administration on diaphragm muscle were studied using Wistar rats. Three treatment groups, namely a control (Saline+endotoxin) group, an IL-12+endotoxin group and an IL-12 only group were studied. E. coli endotoxin (30 mg/kg) was injected intraperitoneally 5 min after Saline or IL-12 (0.25 microg) injection. In the control group, the force-frequency curves, twitch tension (TT) and slope during contraction time (TT/CT) were significantly lower at 4 h than those at 0 h due to endotoxin (P<0.001, P<0.01 and P<0.01, respectively), and NO production was increased at 4 h as shown by NADPH diaphorase staining. In the IL-12+endotoxin group, the decrement of the force-frequency curves, TT and TT/CT induced by endotoxin at 4 h were significantly prevented compared with those of the control group (P<0.001, P<0.05 and P<0.05, respectively), and NO production was blocked at 4 h. In the IL-12 only group, the force-frequency curves were decreased in the range of high frequency and IL-12 resulted in NO production. Furthermore, the positive muscle fibers detected by NADPH diaphorase staining were classified as type I and IIa muscle fibers by ATPase staining in the control and IL-12 only groups. It is concluded that IL-12 prevents the deterioration of diaphragm muscle contraction induced by endotoxin by reducing NO production in type I and IIa muscle fibers. These results suggest that IL-12 and endotoxin may interfere with each other.
Comp Biochem Physiol A Mol Integr Physiol 2001 Nov
PMID:Interleukin-12 prevents diaphragm muscle deterioration in a septic animal model. 1169 2

The effects of in ovo peptide YY (PYY) or epidermal growth factor (EGF) administration on chick growth, yolk absorption and yolk stalk function in posthatch (0-5 days) meat-type or broiler chicks were determined. At Day 18 of incubation, treated eggs were injected into the air cell with 100 microl of either PYY (Trial 1) or EGF (Trial 2) at a dosage of 600 microg/kg egg weight. Saline-treated control eggs were injected similarly with 0.9% saline. At hatch, 200 microl of (51)Cr-labeled microspheres were injected into chick yolk sacs. Epidermal growth factor increased ileal wet weight adjusted for body weight as well as ileal serosal dry matter. Body weight, feed consumption and excreta weight per bird, and relative weights of the yolk sac, intestine and liver were significantly affected by age of the chick in both trials. Relative radioactivity of the yolk sac, yolk stalk, blood, liver, and kidneys were affected by bird age in Trial 2; however, there were no significant effects due to PYY or EGF treatments on relative radioactivity of the tissues and organs examined. These data suggest that PYY and EGF had no effect on yolk absorption or yolk stalk function through 5 days in the posthatch chick.
Comp Biochem Physiol A Mol Integr Physiol 2001 Nov
PMID:In ovo peptide YY and epidermal growth factor administration and their effects on growth and yolk utilization in neonatal meat-type chickens (Gallus domesticus). 1169 10

Bulk shear viscosities were measured with a cone and plate microviscometer as a function of concentration, shear rate, and temperature for lavaged calf lung surfactant (LS), Exosurf, Infasurf, Survanta, and synthetic lipid mixtures dispersed in normal saline. Viscosity increased with phospholipid concentration for all surfactants, but its magnitude and shear dependence varied widely among the different preparations. Saline dispersions of Exosurf and synthetic phospholipids had low viscosities of only a few centipoise (cp) and exhibited minimal shear dependence. LS, Infasurf, Survanta, and lipid mixtures containing palmitic acid and tripalmitin had larger non-Newtonian viscosities that increased as shear rate decreased. At 35 mg of phospholipid/ml and 37 degrees C, viscosity values were 52.3 cp (Survanta), 31.1 cp (LS), and 25 cp (Infasurf) at a shear rate of 77 s(-1) and 16.9 cp (Survanta), 10.1 cp (LS), and 6.6 cp (Infasurf) at 770 s(-1). At 25 mg of phospholipid/ml and 37 degrees C, viscosity values at 77 s(-1) were 28.8 cp (Survanta), 4.7 cp (LS), and 12.5 cp (Infasurf). At fixed shear rate, viscosity was substantially decreased at 23 degrees C compared with 37 degrees C for LS and Infasurf but was increased for Survanta. Calcium (5 mM) greatly reduced the viscosity of both Survanta and Infasurf at 37 degrees C. Studies on synthetic mixtures indicated that phospholipid/apoprotein interactions were important in the rheology of lung-derived surfactants and that palmitic acid and tripalmitin contributed to the increased viscosity of Survanta. The viscous behavior of clinical exogenous surfactants potentially influences their delivery and distribution in lungs and varies significantly with composition, concentration, temperature, ionic environment, and physical formulation.
Am J Physiol Lung Cell Mol Physiol 2002 Feb
PMID:Bulk shear viscosities of endogenous and exogenous lung surfactants. 1179 32

Domestic pigs, Sus scrofa, build a maternal nest on the day before parturition. A model for nest building has been established in pigs, in which exogenously administered prostaglandin (PG) F(2alpha) may be used to elicit nesting behaviour in cyclic, pseudopregnant and pregnant pigs. The central mechanisms mediating this response are unknown. The present study determined regional brain activity using semi-quantitative analysis of c-fos mRNA, after induction of nest-building behaviour by PGF(2alpha) in Large White pseudopregnant pigs. Oestradiol valerate injections (5 mg/day) were given on days 11-15 of the oestrous cycle to induce pseudopregnancy. The pigs were housed individually in pens (2.8 x 1.7 m) containing straw. On the test day (day 46 or 47 of pseudopregnancy) animals were injected with 3 ml saline (n=5) or 15 mg of PGF(2alpha) (Lutalyse, Upjohn; n=6) intramuscularly. Pigs treated with PGF(2alpha), but not saline, displayed bouts of rooting, pawing and gathering straw, which we interpret as nest building behaviour. The pigs were killed 65 min after treatment, which was 30 min after peak nest building activity, and the brain, uterus and ovaries removed for processing using in situ hybridisation. Saline-treated pigs had elevated levels of c-fos mRNA, compared to background, in the pituitary, corpus luteum and uterus, and a lower, but elevated, level of expression in cerebellum, cortex, hippocampus and olfactory bulb. PGF(2alpha)-treated pigs had significantly higher levels of c-fos mRNA expression than saline-treated pigs in the parvocellular and magnocellular regions of the hypothalamic paraventricular nucleus, the supraoptic nucleus (including the pars dorso-medialis), the neural lobe of the pituitary gland and the cerebellum. PGF(2alpha)-treated pigs also had significantly higher c-fos induction in corpus luteum. These data show that the pattern of c-fos mRNA expression in specific brain areas is different between pigs that show PGF(2alpha)-induced nest building and saline-injected controls.
Brain Res Mol Brain Res 2002 Jul 15
PMID:c-fos mRNA expression associated with PGF(2alpha)-induced nest-building behaviour in female pigs. 1211 48

This paper updates the information on the prevalence of the disorders induced by iodine deficiency (IDD) in Europe. Thirty-two European countries were still affected by mild to severe iodine deficiency in the late 1990s. The most severely affected countries were in Eastern Europe, including Central Asia, but Western Europe was also still affected. National surveys recently conducted in 11 of these countries show that, with the exception of the Netherlands, none has yet reached a state of iodine sufficiency, though very significant improvement in the situation has been evidenced in many of them, e.g. Poland, Bulgaria and Macedonia. The consequences of persisting iodine deficiency are goitre, hyperavidity of the thyroid for iodide (which increases the risk of thyroid irradiation in the event of a nuclear accident) and subclinical hypothyroidism during pregnancy and early infant (with a concomitant risk of minor brain damage and irreversible impairment of the neuropsychointellectual development of offspring). Access to iodised salt at the household level in European countries affected by IDD increased from 5%-10% in 1990 to 28% in 1999. This constitutes encouraging progress. However, in terms of access of iodine-deficient countries to iodised salt, Europe remains the worst region in the world, as shown by the fact that the mean figure worldwide in 1999 was 68%. In Latin America it even reached 90%. Salt iodisation has to be further implemented in Europe. Until that goal is achieved, iodine supplementation in those groups most sensitive to the effects of iodine deficiency (pregnant and lactating women and young infants) will have to be considered in the most severely affected areas.
Eur J Nucl Med Mol Imaging 2002 Aug
PMID:Iodine deficiency in Europe and its consequences: an update. 1219 40

Doxorubicin is a chemotherapeutic agent that can induce cardiotoxicity and congestive heart failure (CHF). In this study we tested whether intracoronary Akt1 gene delivery could inhibit doxorubicin-induced CHF. Saline or a replication defective adenoviral vector expressing constitutively-active Akt1 (myrAkt) or beta-galactosidase (betagal) was delivered to the myocardium of 8 week old rats one day prior to initiating doxorubicin administration. In animals receiving saline or betagal, doxorubicin resulted in significant decreases in cardiac function and retarded post-natal heart growth at the 5 weeks time point. In contrast, transduction of myrAkt protected hearts against doxorubicin-induced decreases in fractional shortening and cardiac index, and improved left ventricular function at 5 weeks time point. Delivery of myrAkt also reversed the doxorubicin-induced reduction in post-natal heart growth and diminished lung edema. These data show that myocardial Akt can inhibit doxorubicin-induced reductions in cardiac function and growth, suggesting that manipulation of this signaling pathway may have utility for the treatment of congestive heart failure.
J Mol Cell Cardiol 2002 Oct
PMID:Elevated myocardial Akt signaling ameliorates doxorubicin-induced congestive heart failure and promotes heart growth. 1239 81

Both rat and human kidney nuclei exhibited time and pH dependent oxalate or histone-oxalate uptake which was inhibited by anion transport inhibitor, 4,4'-dithiocyanostilbene-2,2'-disulphonic acid. Sodium chloride had no effect. Nuclear membrane had oxalate binding at pH 7.4. Extraction of nuclear membrane by Triton-high salt mixture showed maximal oxalate binding activity with nuclear pore complex while nuclear lamin had no oxalate binding. The rat and human kidney nuclear pore complex showed oxalate binding of 144 and 220 pmoles/mg protein respectively. Subsequent purification of the protein on diethyl amino ethyl-Sephadex A 50 column and Sephadex G-200 column yielded 4-fold purification. The protein revealed a molecular weight of 205 kDa on SDS-PAGE. The protein was found to be saturable at 2 microM oxalate and had a Kd of 2.98 pM and a Bmax of 197 pmoles. Antibody for 205 kD was separated from primary biliary cirrhosis serum containing auto antibody against 205 kDa using affinity column chromatography. The oxalate binding activity as well as the nuclear uptake of oxalate or histone-oxalate were inhibited by its antibody.
Mol Cell Biochem 2003 Jan
PMID:Characterisation of nuclear pore complex oxalate binding protein from human kidney. 1261 82

Parallel experimental measurements and theoretical calculations have been used to investigate the energetics of electrostatic interactions in the complex formed between a 22 residue, alpha-helical peptide from the N protein of phage lambda and its cognate 19 nucleotide box B RNA hairpin. Salt-dependent free energies were measured for both peptide folding from coil to helix and peptide binding to RNA, and from these the salt-dependence of binding pre-folded, helical peptide to RNA was determined ( partial differential (DeltaG degrees (dock))/ partial differential log[KCl]=5.98(+/-0.21)kcal/mol). (A folding transition taking place in the RNA hairpin loop was shown to have a negligible dependence on salt concentration.) The non-linear Poisson-Boltzmann equation was used to calculate the same salt dependence of the binding free energy as 5.87(+/-0.22)kcal/mol, in excellent agreement with the measured value. Close agreement between experimental measurements and calculations was also obtained for two variant peptides in which either a basic or acidic residue was replaced with an uncharged residue, and for an RNA variant with a deletion of a single loop nucleotide. The calculations suggest that the strength of electrostatic interactions between a peptide residue and RNA varies considerably with environment, but that all 12 positive and negative N peptide charges contribute significantly to the electrostatic free energy of RNA binding, even at distances up to 11A from backbone phosphate groups. Calculations also show that the net release of ions that accompanies complex formation originates from rearrangements of both peptide and RNA ion atmospheres, and includes accumulation of ions in some regions of the complex as well as displacement of cations and anions from the ion atmospheres of the RNA and peptide, respectively.
J Mol Biol 2003 Aug 01
PMID:Electrostatic interactions in a peptide--RNA complex. 1287 37

Salt-inducible kinase (SIK), expressed in Y1 mouse adrenocortical tumor cells at an early stage of adrenocorticotropic hormone (ACTH)-stimulation, represses the cAMP-responsive element (CRE)-dependent gene expression of CYP11A and StAR by acting on bZIP domain of CRE-binding protein. ACTH induced the SIK's nuclear to cytosolic translocation in a PKA-dependent manner. A mutant SIK in which the PKA-dependently phosphorylatable Ser577 had been replaced with Ala could not move out of the nucleus. The degree of CRE-reporter repression by SIK was strong as long as SIK was present in the nucleus. These indicated that intracellular translocation of SIK might be an important factor to determine the time-dependent change in the level of steroidogenic gene expression in ACTH-stimulated cells. Promoter analyses suggested that SIK repressed gene expressions not only of CYP11A and StAR but also of CYP11B1, CYP11B2 and SIK itself. We propose here that SIK is one of important molecule regulating expression of steroidogenic genes in the early phase of ACTH treatment.
J Steroid Biochem Mol Biol 2003 Jun
PMID:Salt-inducible kinase-mediated regulation of steroidogenesis at the early stage of ACTH-stimulation. 1294 28


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