Evidence for non-synchronous rotation of Europa. Galileo Imaging Team

Non-synchronous rotation of Europa was predicted on theoretical grounds, by considering the orbitally averaged torque exerted by Jupiter on the satellite's tidal bulges. If Europa's orbit were circular, or the satellite were comprised of a frictionless fluid without tidal dissipation, this torque would average to zero. However, Europa has a small forced eccentricity e approximately 0.01 , generated by its dynamical interaction with Io and Ganymede, which should cause the equilibrium spin rate of the satellite to be slightly faster than synchronous. Recent gravity data suggest that there may be a permanent asymmetry in Europa's interior mass distribution which is large enough to offset the tidal torque; hence, if non-synchronous rotation is observed, the surface is probably decoupled from the interior by a subsurface layer of liquid or ductile ice. Non-synchronous rotation was invoked to explain Europa's global system of lineaments and an equatorial region of rifting seen in Voyager images. Here we report an analysis of the orientation and distribution of these surface features, based on initial observations made by the Galileo spacecraft. We find evidence that Europa spins faster than the synchronous rate (or did so in the past), consistent with the possibility of a global subsurface ocean.     

Adjustment of magnesium sulfate infusion rate in patients with preterm labor

OBJECTIVE: Our purpose was to investigate factors that might influence serum magnesium levels during intravenous magnesium sulfate tocolytic therapy. STUDY DESIGN: Thirty-three women receiving magnesium sulfate for preterm labor participated in this prospective, observational study. Gestational ages were 24 to 34 weeks. Four groups of women were identified according to the maintenance magnesium infusion rate required for arresting preterm labor after 5 g of therapy induction: 1.5, 2, 2.5, and 3 g/h. Serum magnesium samples were drawn after a predefined period of at least 18 hours of arrested preterm labor, at a minimum of every 6 hours. Variables examined included serum albumin; serum protein; serum ionized calcium; serum creatinine; creatinine clearance; 24-hour urine output; maternal height, weight, body surface area; and body mass index. RESULTS: By use of a multivariate stepwise regression model we identified four variables that independently and significantly contributed to the model: magnesium infusion rate (P < .001); total serum protein level (P < .001); serum creatinine level (P = .009); and maternal weight squared (P = .026). Seventy-two percent of the variance was accounted for by use of these parameters. A predictive linear model, developed to relate these factors, produced the following formula: Suggested magnesium infusion rate = 0.89 x Serum magnesium concentration (mg/dL) - 3.16 x Serum creatinine (mg/dL) - 0.66 x Serum total proteins (g/dL) + 0.0001 x (maternal weight)2 (kg) + 2.30. CONCLUSIONS: Serum creatinine, serum protein, and maternal weight can be used to adjust the dose of magnesium sulfate in patients with premature labor to achieve therapeutic serum levels of magnesium more rapidly and safely.     

Regional activation of L-type voltage-sensitive calcium channels in experimental thiamine deficiency

At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in the mammalian genome has provided promising new tools for use in identifying carcinogens and characterizing their (qualitative) risk. Several transgenic mouse lines are currently under study to test their possible use in short-term carcinogenicity testing. One such candidate alternative transgenic model is the XPA knock-out mouse. These mice have an almost complete deficiency in DNA nucleotide excision repair (NER). Nevertheless, XPA-deficient mice are viable and have a background of a low incidence of spontaneous development of cancers. Approximately 15% of the mice develop hepatocellular adenomas (only after 1.5 yr). After treatment with ultraviolet-B radiation or 7,12-dimethylbenz(a)anthracene, the XPA-deficient mice developed squamous cell carcinomas and papillomas, respectively, on their skin. Oral treatment of XPA-deficient mice with benzo[a]pyrene (B[a]P), 2-acetylaminofluorene (2-AAF), and 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP) resulted in lymphomas (B[a]P), liver and bladder tumors (2-AAF), and intestinal adenomas plus lymphomas (PhIP). These results look encouraging, but it should be noted that the compounds and agents tested thus far have all been substrate for nucleotide excision repair. Animal studies with different genotoxic or nongenotoxic compounds, as organized for instance within the framework of the International Life Sciences Institute/Health and Environmental Sciences Institute program, are needed to further evaluate the suitability of the XPA model for short-term carcinogenicity testing.     

Structure-activity relationships of astemizole derivatives for inhibition of store operated Ca2+ channels and exocytosis

The effects of a series of analogues of the antiallergic drug astemizole on the exocytosis of the enzyme beta-hexosaminidase were studied in a mast cell model, the rat basophilic leukemia (RBL-2H3) cell. Besides differences in the effects on Fc epsilonRI receptor-stimulated exocytosis, changes were also observed in Ca2+ influx and in the perturbation of the cell membrane. A strong correlation was found between the effects on antigen- and thapsigargin-stimulated 45Ca2+ influx. Furthermore, the inhibition of 45Ca2+ influx was correlated with the inhibition of beta-hexosaminidase release and membrane stabilization. It is concluded that the astemizole analogues are capable of inhibiting mast cell beta-hexosaminidase release through inhibition of Ca2+-store-operated Ca2+ channels (SOC). Compounds with high lipophilicity also released Ca2+ from intracellular stores. Lowering of the hydrophobicity by introduction of nitrogens or truncation at different sites in the astemizole structure decreased inhibitory activity on SOC channels. The inhibition of SOC channels cannot completely be ascribed to non-specific membrane effects. The piperidinyl-benzimidazole moiety was found to be important for inhibition of SOC channels. The observed differences in activity possibly depend on the way the compounds penetrate the membrane bilayer. Astemizole is an interesting new tool to study SOC channels and can be a lead for the design of mast cell-stabilizing antiallergic drugs.     

1997 American Urological Association Gallup survey: Changes in diagnosis and management of prostate cancer and benign prostatic hyperplasia, and other practice trends from 1994 to 1997

PURPOSE: The American Urological Association first commissioned the Gallup Organization to conduct a study to assess urologist practice patterns in 1992. We present the results of the 1997 survey, the sixth consecutive Gallup survey performed for the Association. MATERIALS AND METHODS: A random sample of 502 American urologists who had completed urological residency and practiced at least 20 hours weekly in 1996 was interviewed by telephone in February and March 1997. RESULTS: Emerging trends showed significant changes since 1994 in how urologists diagnosed and treated prostate cancer. The survey revealed a significant change in the tests routinely ordered to stage newly diagnosed prostate cancer and for diagnostic evaluation of patients with benign prostatic hyperplasia. CONCLUSIONS: Urologists are becoming more cost conscious and effective in ordering pretreatment testing. Urologists are becoming more oriented toward medical treatment for the management of benign prostatic hyperplasia, and less laser surgery is being performed.     

Differential inducibility of specific mRNA corresponding to five CYP3A isoforms in female rat liver by RU486 and food deprivation: comparison with protein abundance and enzymic activities

Cranial neural fold fusion in the chick embryo is known to commence in the midbrain region before progressing cranially and caudally to involve the fore- and hindbrain regions, respectively. The two epithelial layers at the tips of the neural folds that participate in fusion are the surface ectoderm and the neuroepithelium. We have examined and compared cranial neural fold fusion in both layers, and our results show that fusion of the neuroepithelial component of the neural folds, unlike that of the surface ectoderm, starts in the caudal portion of the forebrain. Second, contrary to the widely accepted opinion, we have demonstrated that in the hindbrain region, fusion of the neuroepithelial component of the neural folds does not occur. Soon after neural fold apposition, a neuroepithelial eminence appears in rhombomeres 1 and 2, and this, together with other neuroepithelial cells in the dorsal midline of the hindbrain, undergoes massive apoptosis. The absence of neuroepithelial fusion in the hindbrain may be due to the presence of massive apoptosis among neuroepithelial cells that should have participated in the fusion process. The events described above may predispose the hindbrain to the development of neural tube defects. The appearance of cranial neural crest cells in the midline during their migration may enhance the fusion of the surface ectodermal portion of the neural folds.     

Mental disorders in elderly suicide

The purpose of this study was to investigate the prevalence and comorbidity of current mental disorders defined by DSM-III-R among elderly suicide victims and to compare them with the mental disorders among younger victims. Using a psychological autopsy method, we collected comprehensive data on all suicides in Finland during 1 year. Retrospective Axis I-III consensus diagnoses were assigned to a random sample consisting of 43 victims aged 60 years or over and 186 victims aged under 60 from the nationwide suicide population. At least one Axis I diagnosis was made for 91% of the elderly victims. Major depression as the principal diagnosis was more common among the elderly victims. Almost all elderly female victims were major depressives. Psychiatric comorbidity was more common among elderly male than among elderly female victims. More of the elderly victims (88%) than the younger (36%) received Axis III diagnoses. Suicide among the elderly without a diagnosable mental disorder and somatopsychiatric comorbidity seems to be rare.     

Mode matches in hydrophobic free energy eigenfunctions predict peptide-protein interactions

OBJECTIVE: To find out whether concentrations of albumin (reflecting nutritional state), C-reactive protein (reflecting an acute phase reaction) or plasma protease inhibitors (reflecting ongoing proteolysis) are good predictors of postoperative complications, and whether other biochemical tests may improve diagnostic accuracy. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 260 patients undergoing elective surgery for malignant (n = 149) or benign (n = 111) disease. MAIN OUTCOME MEASURES: Preoperative biochemical plasma measurements and postoperative complications. RESULTS: 192 patients recovered uneventfully and 35 had minor and 33 major postoperative complications. An increased plasma C-reactive protein concentration preoperatively, as well as a reduced albumin concentration, predicted the risk of developing major postoperative complications. Measurement of plasma protease inhibitors (C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III), specific biochemical studies of microheterogeneity, or comparison of quantitative and functional concentrations of the inhibitors gave no additional information. CONCLUSION: One measurement of the C-reactive protein and albumin concentrations preoperatively will identify patients at risk of developing severe postoperative complications.     

Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation

Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. We compared the isometric contractile and fatigue properties of 1) control CK-sufficient (Ctl), 2) M-CK-deficient (M-CK[-/-]), and 3) combined M-CK/ScCKmit-deficient null mutant (CK[-/-]) diaphragm (Dia) to determine the effect of the absence of M-CK activity on Dia performance in vitro. Baseline contractile properties were comparable across groups except for specific force, which was approximately 16% lower in CK[-/-] Dia compared with M-CK[-/-] and Ctl Dia. During repetitive activation (40 Hz, (1)/(3) duty cycle), force declined in all three groups. This decline was significantly greater in CK[-/-] Dia compared with Ctl and M-CK[-/-] Dia. The pattern of force decline did not differ between M-CK[-/-] and Ctl Dia. We conclude that Dia isometric muscle function is not absolutely dependent on the presence of M-CK, whereas the complete absence of CK acutely impairs isometric force generation during repetitive activation.