Europa's differentiated internal structure: inferences from four Galileo encounters

Radio Doppler data from four encounters of the Galileo spacecraft with the jovian moon Europa have been used to refine models of Europa's interior. Europa is most likely differentiated into a metallic core surrounded by a rock mantle and a water ice-liquid outer shell, but the data cannot eliminate the possibility of a uniform mixture of dense silicate and metal beneath the water ice-liquid shell. The size of a metallic core is uncertain because of its unknown composition, but it could be as large as about 50 percent of Europa's radius. The thickness of Europa's outer shell of water ice-liquid must lie in the range of about 80 to 170 kilometers.     

Lack of effect of olanzapine on the pharmacokinetics of a single aminophylline dose in healthy men

STUDY OBJECTIVE: To test whether olanzapine, an atypical antipsychotic, is an inhibitor of cytochrome P450 (CYP) 1A2 activity, we conducted a drug interaction study with theophylline, a known CYP1A2 substrate. DESIGN: Two-way, randomized, crossover study. SETTING: Clinical research laboratory. SUBJECTS: Nineteen healthy males (16 smokers, 3 nonsmokers). INTERVENTIONS: Because the a priori expectation was no effect of olanzapine on theophylline pharmacokinetics, a parallel study using cimetidine was included as a positive control. In group 1, 12 healthy subjects received a 30-minute intravenous infusion of aminophylline 350 mg after 9 consecutive days of either olanzapine or placebo. In group 2, seven healthy subjects received a similar aminophylline infusion after 9 consecutive days of either cimetidine or placebo. MEASUREMENTS AND MAIN RESULTS: Concentrations of theophylline and its metabolites in serum and urine were measured for 24 and 72 hours, respectively. Plasma concentrations of olanzapine and its metabolites were measured for 24 hours after the next to last dose and 168 hours after the last olanzapine dose. Olanzapine did not affect theophylline pharmacokinetics. However, cimetidine significantly decreased theophylline clearance and the corresponding formation of its metabolites. Urinary excretion of theophylline and its metabolites was unaffected by olanzapine but was reduced significantly by cimetidine. Steady-state concentrations of olanzapine (15.3 ng/ml), 10-N-glucuronide (4.9 ng/ml), and 4'-N-desmethyl olanzapine (2.5 ng/ml) were observed after olanzapine 10 mg once/day and were unaffected by coadministration of theophylline. CONCLUSION: As predicted by in vitro studies, steady-state concentrations of olanzapine and its metabolites did not affect theophylline pharmacokinetics and should not affect the pharmacokinetics of other agents metabolized by the CYP1A2 isozyme.     

Mechanisms of anterior cruciate ligament neovascularization and ligamentization

Columbia-Rambouillet cross-bred sheep were used to study the revascularization and ligamentization process of anterior cruciate ligament (ACL) reconstruction over a 6-month period using basic histology, immunohistochemistry, and electron microscopy. The reconstruction technique studied was a quadruple-hamstring, interference screw fixation technique. Further, these specimens, after retrieval at 6, 12, and 26 weeks, were compared with human arthroscopic 'second looks' and with 10 en bloc specimens obtained when a cruciate-sacrificing total knee replacement was performed. The study showed that, with this reconstruction technique, Sharpey's fibers were seen at 6 weeks in both sheep and human specimens. The intratunnel specimens showed proliferative chondrification, then ossification of the matrix. Intra-articular neovascularization, ligamentization, and junction ossification occurred. Myoblasts or smooth muscle cells appear to mediate the ligamentization as evidenced in electron microscopy by proliferate collagen manufacture. These myoblasts were seen in both the healing sheep and human second looks, but not seen in mature ACL grafts or in normal ACLs. At 6 months postoperatively, the sheep ACL reconstruction appeared clinically, histologically, and immunohistochemically indistinguishable from the normal sheep ACL. A correlation of this work with published animal studies in which biomechanical testing was performed and with human 'second looks' would imply that an ACL reconstruction may be vulnerable during this period of neovascularization and ligamentization.     

The conducting form of gramicidin A is a right-handed double-stranded double helix

The linear pentadecapeptide antibiotic, gramicidin D, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The x-ray crystal structures of the right-handed double-stranded double-helical dimers (DSDH) reported here agree with 15N-NMR and CD data on the functional gramicidin D channel in lipid bilayers. These structures demonstrate single-file ion transfer through the channels. The results also indicate that previous crystal structure reports of a left-handed double-stranded double-helical dimer in complex with Cs+ and K+ salts may be in error and that our evidence points to the DSDH as the major conformer responsible for ion transport in membranes.     

Choice maintained by cocaine or food in monkeys: effects of varying probability of reinforcement

BACKGROUND: Tracheal aspirate Gram's stains are used to guide antibiotic selection in empiric pneumonia treatment in the surgical intensive care unit (SICU). We questioned whether Gram's stains predict the organism cultured. METHODS: A retrospective review of prospectively collected data. RESULTS: Gram's stains correlated with the cultured organism in 284 of 543 (52%) SICU cultures and in 226 of 403 (56%) trauma intensive care unit (TICU) cultures. Gram-negative rod (GNR) stains yielded GNR organisms in 182 of 205 (89%) SICU cultures and in 160 of 176 (91%) TICU cultures. Gram-positive coccus (GPC) stains yielded GPC organisms in 75 of 228 (33%) SICU cultures and in 52 of 149 (35%) TICU cultures. Noncorrelates in the GPC group were predominantly GNRs (185 of 250 (74%)). CONCLUSION: When the clinical decision has been made that empiric antibiotic coverage is necessary, GNR coverage should be instituted regardless of Gram's stain result. The decision to institute GPC coverage needs to be supported by clinical data other than the Gram's stain.     

Measurement of genetic variation within and between Japanese quail lines using DNA fingerprinting

The objective of the present experiment was to study genetic variation within and among well-defined Japanese quail lines by DNA fingerprinting. The Japanese quail lines included a randombred control line (R1) and lines developed from R1 by divergent selection over 30 generations for 4-wk BW (HW, LW) and total plasma phosphorus (TPP) (HP, LP), a measure of yolk precursor in the blood. In addition, two sublines (HW-HP, HW-LP) of HW, developed in the ninth generation, were included in the analysis. Males of the sublines were selected for increased 4-wk BW whereas females were selected for increased (HW-HP) or decreased (HW-LP) TPP. Sixteen individual DNA samples per line were digested with HaeIII restriction enzyme and hybridized with Jeffreys' 33.6 probe. The DNA fingerprints were analyzed with computer programs designed to measure band sharing (BS). Within lines, BS ranged from 0.384 to 0.525. The BS within the R1 line was less than that of all selected lines, except for the HP and LP lines, indicating that, in general, selection had increased genetic homogeneity within the selected lines. Between lines, BS was less than within lines and the R1 line had the highest average level of BS (0.278) with the other lines. The BS between lines for the selected lines ranged from 0.230 to 0.308 with an average of 0.265. In the comparison of the R1 line with the selected lines, it appeared that selection for increased TPP or decreased BW may have influenced BS levels. The relationships of the HW line with its sublines (HW-HP and HW-LP) were not accurately predicted by the DNA fingerprinting technique used. All lines were separated, as indicated by the genetic distance between lines.     

Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea

Elevated nocturnal melatonin is found in women with idiopathic hypogonadotropic hypogonadism (IHH), but it is not known whether this is implicated in the etiology of their GnRH deficiency. It is unlikely that nocturnal melatonin can be implicated in the etiology of the GnRH deficiency of Kallmann's syndrome (KS), because this condition is caused by defective neuronal migration in embryonic life. We therefore measured nocturnal melatonin in women with IHH and KS to determine whether it was elevated in one or both conditions and thereby to determine whether it was implicated as cause or consequence of GnRH deficiency. Four women with IHH, 3 women with KS, and 7 individually matched (age and body size) controls were recruited. Frequent day- and nighttime samples were taken for LH pulsatility studies. All patients showed absent or diminished LH pulsatility, compared with their respective controls. Samples were also taken over 24 h for melatonin and 6-sulphatoxymelatonin (the principle metabolite of melatonin and an independent marker of its secretion). Melatonin and 6-sulphatoxymelatonin levels were elevated in 6 of 7 patients (compared with their matched controls) and were significantly elevated in the KS group (compared with their controls). The finding of elevated nocturnal melatonin (and its metabolite) in GnRH-deficient women with KS (as well as IHH) suggests that nocturnal melatonin is elevated as a consequence of GnRH deficiency, irrespective of its etiology.     

Dying dogma: the pathological diagnosis of epidermotropic metastatic malignant melanoma

Distinguishing primary cancer from a metastasis is a fundamental task in surgical pathology that has crucial therapeutic and prognostic implications. When metastatic melanoma involves the skin and extends into the epidermis (epidermotropic), differentiating it from primary cutaneous melanoma may be particularly difficult. Early investigators dismissed this issue as a nonproblem and dogmatically declared that junctional change was requisite for the diagnosis of primary cutaneous melanoma. Epidermotropic metastases of malignant melanoma (EMMM) are now recognized to have many features in common with primary melanoma, which can include involvement of the dermal-epidermal junction, extension of the intraepidermal component beyond the dermal component, and even an epidermal-only pattern. This article traces the evolution in criteria used to diagnose EMMM and highlights why much of the original thinking is no longer accepted. Current concepts in EMMM morphology are elaborated and illustrated. The role of immunomicroscopy and molecular pathology in the detection of EMMM is also discussed.     

Why nobody has P450scc (20,22 desmoslase) deficiency

Human pregnancy is associated with profound changes in the mother's steroid hormone milieu because of steroids produced by the corpus luteum of pregnancy and by the fetoplacental unit. The precise roles of these hormones in the maintenance of pregnancy, in fetal development, and in parturition have been controversial, but recent developments have clarified many of these areas.