Isotope fractionation in silicate melts by thermal diffusion.

The phenomenon of thermal diffusion (mass diffusion driven by a temperature gradient, known as the Ludwig-Soret effect) has been investigated for over 150 years, but an understanding of its underlying physical basis remains elusive. A significant hurdle in studying thermal diffusion has been the difficulty of characterizing it. Extensive experiments over the past century have established that the Soret coefficient, S(T) (a single parameter that describes the steady-state result of thermal diffusion), is highly sensitive to many factors. This sensitivity makes it very difficult to obtain a robust characterization of thermal diffusion, even for a single material. Here we show that for thermal diffusion experiments that span a wide range in composition and temperature, the difference in S(T) between isotopes of diffusing elements that are network modifiers (iron, calcium and magnesium) is independent of the composition and temperature. On the basis of this finding, we propose an additive decomposition for the functional form of S(T) and argue that a theoretical approach based on local thermodynamic equilibrium holds promise for describing thermal diffusion in silicate melts and other complex solutions. Our results lead to a simple and robust framework for characterizing isotope fractionation by thermal diffusion in natural and synthetic systems.

Poststreptococcal dystonia with bilateral striatal enlargement: MR imaging and spectroscopic findings.

Isolated bilateral striatal necrosis is an abnormality of the basal ganglia associated with acute dystonia in children. This report describes the development of dystonic movements in a 7-year-old male patient 2 weeks after streptococcal pharyngitis.

A pediatric case of low-grade lymphomatoid granulomatosis presenting with a cerebellar mass.

Lymphomatoid granulomatosis (LA) is a rare angiocentric lymphoreticular proliferative disease that primarily involves the lungs but may also involve extrapulmonary sites including the central nervous system, skin, and kidneys. It is rare for this condition to affect children, and presentation as a cerebellar mass is unusual. In this report, we describe a 10-year-old girl with biopsy-proved cerebellar LA.

Metachronous, multicentric giant cell tumor of the sphenoid bone with histologic, CT, MR imaging, and positron-emission tomography/CT correlation.

Giant cell tumor (GCT) of the sphenoid bone is a relatively rare entity and metachronous multicentric GCT of the sphenoid is even rarer; we are aware of only 3 previous cases in the literature. We describe here a tumor of the sphenoid bone that was identified 15 years after multiple resections of a GCT of the left inferior pubic ramus. Correlation is made between the histopathologic findings, MR imaging of the brain, CT of the head, and fusion positron-emission tomography (PET)/CT scan performed with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). This report is the first to describe the appearance of a GCT of the sphenoid bone on a fusion PET/CT examination. High metabolic activity in the base of the skull adjacent to the middle cranial fossa was demonstrated in a fashion similar to that of the known pelvic lesion. This case also demonstrates that the increased metabolic activity seen in a GCT of the sphenoid bone may be partially obscured by the adjacent physiologic high metabolic activity of the brain.

Cassini observes the active south pole of Enceladus.

Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain of folded ridges and troughs at approximately 55 degrees S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.

Medical genetics and patient use of the Internet.

Clinical experience suggests that the Internet is increasingly becoming a resource for patients seen in medical genetics. A prospective analysis was performed exploring patient use of the Internet prior to attending a medical genetics appointment. We administered 200 questionnaires assessing: 1) the frequency of patient use of the Internet for genetic information, 2) factors associated with Internet use, 3) patient assessment of the value of the information, and 4) patient views of the responsibility of medical genetics professionals to be familiar with Internet information. Results show that 77% (153/200) of patients have access to the Internet of which 29% (44/153) report searching the Internet for genetic information. A correlation was found between patient use of the Internet and reason for referral (p<0.001), presence of a specific diagnosis (p<0.001), and frequency of Internet use (p<0.05). Overall, 80% (33/41) of patients found Internet information useful. Seventy-four percent (115/155) believed that medical genetics professionals have a responsibility to review relevant Internet sites for accuracy and 80% (123/153) felt that professionals should provide their patients with appropriate and useful Internet sites. These results suggest that the role of medical genetics professionals is changing as a result of the development of the Internet.

The phagosome proteome: insight into phagosome functions.

Phagosomes are key organelles for the innate ability of macrophages to participate in tissue remodeling, clear apoptotic cells, and restrict the spread of intracellular pathogens. To understand the functions of phagosomes, we initiated the systematic identification of their proteins. Using a proteomic approach, we identified >140 proteins associated with latex bead-containing phagosomes. Among these were hydrolases, proton pump ATPase subunits, and proteins of the fusion machinery, validating our approach. A series of unexpected proteins not previously described along the endocytic/phagocytic pathways were also identified, including the apoptotic proteins galectin3, Alix, and TRAIL, the anti-apoptotic protein 14-3-3, the lipid raft-enriched flotillin-1, the anti-microbial molecule lactadherin, and the small GTPase rab14. In addition, 24 spots from which the peptide masses could not be matched to entries in any database potentially represent new phagosomal proteins. The elaboration of a two-dimensional gel database of >160 identified spots allowed us to analyze how phagosome composition is modulated during phagolysosome biogenesis. Remarkably, during this process, hydrolases are not delivered in bulk to phagosomes, but are instead acquired sequentially. The systematic characterization of phagosome proteins provided new insights into phagosome functions and the protein or groups of proteins involved in and regulating these functions.

TIMP-1/MMP-9 imbalance in an EBV-immortalized B lymphocyte cellular model: evidence for TIMP-1 multifunctional properties.

Tissue inhibitors of metalloproteinases (TIMPs) were initially described as agents controlling metalloproteinase activity. The purpose of this study was to investigate the expression and the roles of TIMP-1 secreted by Epstein-Barr-virus (EBV)-immortalized B lymphocytes. TIMP-1 was isolated from conditioned medium of interleukin (IL)-1beta stimulated EBV-B lymphocytes; purified TIMP-1 was identified by mass spectrometry and immunochemistry. TIMP-1-free MMP-9 was quantified after purification by zymography and enzyme-linked immunosorbent assay. EBV-B lymphocyte-secreted TIMP-1 inhibited MMP-9 gelatinolytic activity resulting in decreased B-cell transmigration as measured in vitro. The release of huge amounts of TIMP-1 in proportion to MMP-9 from B lymphocytes after EBV transformation was shown to be correlated with secretion of IL-10 and dependent on culture time. In contrast, there was little TIMP-1 and almost no IL-10 released from native B cells, suggesting a possible IL-10 mediated autocrine regulation mechanism of TIMP-1 synthesis. The MMP-9/TIMP-1 imbalance observed in the culture medium of EBV-B lymphocytes (TIMP-1>MMP-9) and of native B cells (MMP-9>TIMP-1) is suggestive of a new function for TIMP-1. We propose that TIMP-1 acts as a survival factor controlling B-cell growth and apoptosis through an autocrine regulation process involving IL-10 secreted by EBV-B lymphocytes.

Evolution of diagnostic neuroradiology from 1904 to 1999.

Neuroradiology began in the early 1900s soon after Roentgen discovered x rays, with the use of skull radiographs to evaluate brain tumors. This was followed by the development of ventriculography in 1918, pneumoencephalography in 1919, and arteriography in 1927. In the beginning, air studies were the primary modality, but this technique was supplanted by angiography in the 1950s and 1960s. The first full-time neuroradiologist in the United States was Cornelius G. Dyke at the New York Neurological Institute in 1930. Neuroradiology took a firm hold as a specialty in the early 1960s when Dr Juan M. Taveras brought together fourteen neuroradiologists from the United States and Canada to establish the nucleus of what was to become the American Society of Neuroradiology, or ASNR. This society's initial goals were to perform research and to advance knowledge within the specialty. Neuroradiologists initially were able to diagnose vascular disease, infections, tumors, trauma, and alterations in cerebrospinal fluid flow, because the brain structure was invisible. Neuroradiology was forever changed with computed tomography (CT) because the brain structure became visible. Soon thereafter, magnetic resonance (MR) imaging was developed, and it not only provided anatomic but also made possible vascular and physiologic functional imaging.

Membrane proteomics: use of additive main effects with multiplicative interaction model to classify plasma membrane proteins according to their solubility and electrophoretic properties.

Recent efforts at the proteomic level were employed to describe the protein equipment of the plasma membrane of the model plant Arabidopsis thaliana. These studies had revealed that the plasma membrane is rich in extrinsic proteins but came up against two major problems: (i) few hydrophobic proteins were recovered in two-dimensional electrophoresis gels, and (ii) many plasma membrane proteins had no known function or were unknown in the database despite extensive sequencing of the Arabidopsis genome. In this paper, several methods expected to enrich a membrane sample in hydrophobic proteins were compared. The optimization of solubilization procedures revealed that the detergent to be used depends on the lipid content of the sample. The corresponding proteomes were compared with the statistical model AMMI (additive main effects with multiplicative interaction) that aimed at regrouping proteins according to their solubility and electrophoretic properties. Distinct groups emerged from this analysis and the identification of proteins in each group allowed us to assign specific features to several of them. For instance, two of these groups regrouped very hydrophobic proteins, one group contained V-ATPase subunits, another group contained proteins with one transmembrane domain as well as proteins known to interact with membrane proteins. This study provides methodological tools to study particular classes of plasma membrane proteins and should be applicable to other cellular membranes.

Towards a human repertoire of monocytic lysosomal proteins.

The lysosomal compartment of human monocytic cells has never been investigated by a proteomic approach. By a combination of one-dimensional (1-D) and two-dimensional (2-D) gel electrophoresis, protein identification by N-terminal sequencing, matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS) peptide mass fingerprinting and tandem mass spectrometry (MS/MS) peptide sequence analysis, we initiated an exhaustive study of the human lyososomal proteome, which aims at establishing a 2-D reference map of human soluble lyososomal proteins. Human monocytic U937 cells were induced to secrete lysosomal soluble hydrolases by addition of NH4Cl in the culture medium. Since lysosomal soluble proteins are characterized by the presence of mannose-6-phosphate, they were purified on an affinity support bearing mannose-6-phosphate receptor. Analysis of the purified fraction led to the preliminary identification of fifteen proteins, among which twelve are well-known lysosomal hydrolases, one is assumed to be lysosomal on the basis of sequence homology to cysteine proteinases of the papain family, and two (leukocystatin and the human cellular repressor of E1A-stimulated genes) are described here for the first time as mannose-6-phosphate-containing proteins.

Two distinct regions of the yeast mitochondrial ADP/ATP carrier are photolabeled by a new ADP analogue: 2-azido-3'-O-naphthoyl-[beta-32P]ADP. Identification of the binding segments by mass spectrometry.

A novel photoactivatable radioactive ADP derivative, namely, 2-azido-3'-O-naphthoyl-[beta-(32)P]ADP (2-azido-N-[(32)P]ADP), was synthesized with the aim at mapping the substrate binding site(s) of the yeast mitochondrial ADP/ATP carrier. It was used with mitochondria isolated from genetically modified strains of Saccharomyces cerevisiae, producing the native or the His-tagged Anc2p isoform of the carrier. In darkness, 2-azido-N-[(32)P]ADP was reversibly bound to the carrier in mitochondria, without being transported. Upon photoirradiation, only the ADP/ATP carrier was covalently radiolabeled among all mitochondrial proteins. Specificity of labeling was demonstrated since carboxyatractyloside (CATR), a potent inhibitor of ADP/ATP transport, totally prevented the incorporation of the photoprobe. To localize the radioactive region(s), the purified photolabeled carrier was submitted to CNBr or hydroxylamine cleavage. The resulting fragments were characterized and identified by SDS-PAGE, Western blotting, amino acid sequencing, and MALDI-MS and ESI-MS analyses. Two short photolabeled distinct segments, eight and nine residues long, were identified: S183-R191, located in the central part of the ADP/ATP carrier; and I311-K318, belonging to its C-terminal end. Plausible models of organization of the nucleotide binding site(s) of the carrier involving the two regions specifically labeled by 2-azido-N-[(32)P]ADP are proposed.

Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse.

The enamel knot (EK), located in the center of cap-stage tooth germs, is a transitory cluster of non-dividing epithelial cells, eventually linked to the outer dental epithelium by the enamel septum (ES). It might act as a signaling center providing positional information for tooth morphogenesis and could regulate the growth of tooth cusps through the induction of secondary signaling EKs. The EK undergoes apoptosis, which could constitute a mechanism whereby the signaling functions of this structure are terminated. Recently, we demonstrated the segregation of 5-bromo-2'-deoxyuridine (BrdU) negative inner dental epithelial (IDE) cells of the EK into as many individual groups of cells as cusps will form and suggested a morphogenetic role for these particular IDE cells. Using Z-VAD-fmk, a specific caspase inhibitor, apoptosis in the primary EK of first mouse lower cap-staged molars and lower incisors cultured in vitro was abrogated. No obvious histological alterations were observed in the incisors, whereas a prominent EK and an ES connecting the outer dental epithelium (ODE) and the BrdU negative IDE cells capping cusp L2 were observed in the molars. EK specific transcription (Shh, Msx-2, Bmp-2, Bmp-4) was down-regulated in the body of these structures with the exception of the associated IDE cells. In these experimental conditions, segregation of non-dividing transcriptionally active IDE cells occurred and a normal cusp pattern was expressed.

A close-up look at Io from Galileo's near-infrared mapping spectrometer.

Infrared spectral images of Jupiter's volcanic moon Io, acquired during the October and November 1999 and February 2000 flybys of the Galileo spacecraft, were used to study the thermal structure and sulfur dioxide distribution of active volcanoes. Loki Patera, the solar system's most powerful known volcano, exhibits large expanses of dark, cooling lava on its caldera floor. Prometheus, the site of long-lived plume activity, has two major areas of thermal emission, which support ideas of plume migration. Sulfur dioxide deposits were mapped at local scales and show a more complex relationship to surface colors than previously thought, indicating the presence of other sulfur compounds.

Prometheus: Io's wandering plume.

Unlike any volcanic behavior ever observed on Earth, the plume from Prometheus on Io has wandered 75 to 95 kilometers west over the last 20 years since it was first discovered by Voyager and more recently observed by Galileo. Despite the source motion, the geometric and optical properties of the plume have remained constant. We propose that this can be explained by vaporization of a sulfur dioxide and/or sulfur "snowfield" over which a lava flow is moving. Eruption of a boundary-layer slurry through a rootless conduit with sonic conditions at the intake of the melted snow can account for the constancy of plume properties.

Anticipated versus actual emotional reactions to disclosure of results of genetic tests for cancer susceptibility: findings from p53 and BRCA1 testing programs.

PURPOSE: We examined the ability of individuals undergoing genetic testing for cancer susceptibility in two structured research protocols to accurately anticipate emotional reactions to disclosure of their test result. We explored whether accuracy of emotional anticipation was associated with postdisclosure psychologic adjustment. METHODS: Data from 65 individuals were analyzed; 24 members of Li-Fraumeni cancer syndrome families were tested for p53 mutations (all 24 were unaffected), and 41 subjects with hereditary breast-ovarian cancer susceptibility were tested for BRCA1 mutations (34 were unaffected and seven were affected). Subjects were from families in which a germline mutation had been previously identified. At the pretest session, subjects rated the extent to which they anticipated feeling each of six emotional states (relief, happiness, sadness, guilt, anger, and worry) after disclosure that they did or did not carry the familial mutation. After receiving their test result, they rated their feelings on the same scale of emotions for the appropriate condition. Extent of accuracy and association with psychologic distress at 6 months, as assessed with standardized measures, were evaluated. RESULTS: Overall, mean levels of emotional reactions after receiving test results were not different from those anticipated before result disclosure. However, affected BRCA1 carriers experienced higher levels of anger and worry than they had anticipated. Underestimation of subsequent distress emotions related to test result was associated with a significant increase in general psychologic distress at 6 months. CONCLUSION: Unaffected individuals in cancer-predisposition testing programs are generally accurate in anticipating emotional reactions to test results. However, cancer patients may underestimate their distress after disclosure of positive results and could benefit from intervention strategies.

Identification of amylase crystalloids in cystic lesions of the parotid gland.

OBJECTIVE: To identify alpha-amylase crystalloid formations in parotid specimens obtained by fine needle aspiration. STUDY DESIGN: The study concerned three cases of sialadenitis with crystalloid formation observed between 1993 and 1998. In one of these cases, transmission electron microscopy, mass spectrometry and measurement of amylase activity were used to characterize the nature of the crystalloids. RESULTS: Light microscopy revealed the same crystalloid structure in all three cases. In one case, where the material was saved, a biochemical method made it possible to reveal high amylase activity, while protein electrophoresis and mass spectrometry were used to identify salivary alpha-amylase. CONCLUSION: Crystalloids of salivary alpha-amylase can be identified by May-Grünwald-Giemsa and Papanicolaou stain and can be rapidly confirmed through determination of amylase activity.

BRCA1 testing and informed consent in a woman with mild retardation.

Cancer predisposition testing can pose complex genetic counseling issues. This case report discusses whether it is appropriate to provide BRCA1 testing to a woman with limited intellectual capacity and documented psychological distress. This case is one of several cancer counseling cases presented to our Genetic Counseling Supervision Group over the past three and a half years. The Supervision Group provided valuable feedback and support to proceed with this challenging case.

Morphogenesis of the lower incisor in the mouse from the bud to early bell stage.

The development of the lower incisor in the mouse was investigated from histological sections using computer-aided 3D reconstructions. At ED 13.0, the incisor was still at the bud stage. At ED 13.5, the initial cap was delimited by a short cervical loop, the development of which proceeded on the labial side, but was largely retarded on the medial side. This difference was maintained up to ED 15.0. From ED 16.0, the bell stage was achieved. Metaphases had a ubiquitous distribution both in the enamel organ and in the dental papilla from the bud to early bell stage. Apoptosis gradually increased in the mesenchyme posteriorly to the labial cervical loop from ED 13.5 to 14.0 and then disappeared; this apoptosis was not related to the posterior growth of the incisor. From ED 13.5, a high apoptotic activity was observed in the stalk. A focal area of apoptosis was observed at ED 13.5 in the enamel organ, approaching the epithelio-mesenchymal junction at the future tip of the incisor. There, the inner dental epithelium formed a bulbous protrusion towards dental papilla, reminiscent of the secondary enamel knot of mouse molars. This epithelial protrusion was still maintained at the bell stage. The enamel knot in the incisor demonstrated specific features, different from those characterizing the enamel knot in the molar: the concentric arrangement of epithelial cells was much less prominent and the occurrence of apoptosis was very transitory in the incisor at ED 13.5. The disappearance of the enamel knot despite a low apoptotic activity and the maintenance of the protrusion suggested a histological reorganization specific for rodent incisor.