Cavernous Sinus Vascular Venous Malformation.

Vascular venous malformations of the cavernous sinus have multiple imaging features that can be used to distinguish them from other entities in the region. Accurate identification of these lesions is essential: Vascular venous malformation lesions carry considerable risk of intraoperative hemorrhage, so preoperative recognition of vascular venous malformations can greatly impact the treatment strategies used. Nevertheless, because of their scarcity, many radiologists are unfamiliar with the radiologic and clinical features of cavernous sinus vascular venous malformations. This article will describe a case of an asymptomatic vascular venous malformation; outline its imaging, clinical, and pathologic features; and review the relevant literature regarding this diagnosis.

Association of amyloid angiopathy with microbleeds in logopenic progressive aphasia: an imaging-pathology study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) and superficial siderosis (SS) are frequent neuroimaging findings in patients with logopenic progressive aphasia (LPA), often with frontal lobe predilection. Cerebral amyloid angiopathy (CAA) is hypothesized to be the major pathologic determinant of MB/SS in these patients; however, neuroimaging-pathologic data are limited. METHODS: All patients who had been prospectively recruited by the Neurodegenerative Research Group at the Mayo Clinic (Rochester, MN) between 2010 and 2015 and met the following inclusion criteria were included: (i) received an antemortem LPA diagnosis, (ii) had a gradient-recalled echo T2*-weighted magnetic resonance imaging (MRI) performed, (iii) died and completed a brain autopsy. Demographic, genetic, neuroimaging, and clinical and pathologic characteristics were compared between patients with/without MB/SS. Two-tailed Fisher exact and Wilcoxon rank sum tests were used for comparison of categorical and continuous variables, respectively. RESULTS: Thirteen patients met inclusion criteria, six (46%) had MB/SS on MRI. Moderate/severe CAA was associated with the presence of MB/SS (p = 0.029). As expected, MB/SS most frequently involved the frontal lobes, followed by the parietal lobes. No clear associations were found between regional MB/SS distribution and regional distribution of CAA or hypometabolism on [18 F]-fluorodeoxyglucose-positron emission tomography. There was some evidence for a regional association between MB/SS and uptake on Pittsburgh compound B, although not in all patients. No formal statistical analyses to assess topographic relationships were performed due to the small sample size. CONCLUSIONS: The presence of MB/SS is a strong indicator of underlying moderate/severe CAA in LPA, although the biological mechanisms underlying the topographic distribution of MB/SS remain unclear.

An empirical potential based quasicontinuum theory for structural prediction of water.

An empirical potential based quasicontinuum theory (EQT) is proposed to predict the structure, concentration, and various potential profiles of water in confined environments. EQT seamlessly unifies the continuum theory given by the Nernst-Planck equation and the atomistic theory governed by interatomic potentials. In particular, the interatomic potentials describing various interactions in water are directly incorporated into the Nernst-Planck theory. We introduce a new empirical potential to compute electrostatic interactions in water. The results from the EQT formalism are compared with molecular dynamics simulations and a good match is observed for channels with widths ranging from 2sigma(ow) to 20sigma(ow), where sigma(ow) is the water-oxygen Lennard-Jones distance parameter. While molecular dynamics can be limited to small length scales, EQT can be used at various length scales to effectively and accurately capture both the interfacial structure and bulk properties of water making it a robust and fast method that can predict properties in widths ranging from the macroscale down to the nanoscale.

Interatomic potential-based semiclassical theory for Lennard-Jones fluids.

An interatomic potential based semiclassical theory is proposed to predict the concentration and potential profiles of a Lennard-Jones (LJ) fluid confined in a channel. The inputs to the semiclassical formulation are the LJ parameters of the fluid and the wall, the density of channel wall atoms, and the average concentration of the fluid inside the channel. Using the semiclassical formulation, fluid confinement in channel with widths ranging from 2sigma ff to 100sigma ff, where sigma ff is the fluid-fluid LJ distance parameter, is investigated. The concentration and potential predicted by the semiclassical formulation are found to be in good agreement with those from equilibrium molecular dynamics simulations. While atomistic simulations in large channels are computationally expensive, the proposed semiclassical formulation can rapidly and accurately predict the concentration and potential profiles. The proposed semiclassical theory is thus a robust and fast method to predict the interfacial and "bulk" fluid phenomena in channels with widths ranging from the macroscale down to the scale of a few atomic diameters.

Self-consistent molecular dynamics formulation for electric-field-mediated electrolyte transport through nanochannels.

A self-consistent molecular dynamics (SCMD) formulation is presented for electric-field-mediated transport of water and ions through a nanochannel connected to reservoirs or baths. The SCMD formulation is compared with a uniform field MD approach, where the applied electric field is assumed to be uniform, for 2nm and 3.5nm wide nanochannels immersed in a 0.5M KCl solution. Reservoir ionic concentrations are maintained using the dual-control-volume grand canonical molecular dynamics technique. Simulation results with varying channel height indicate that the SCMD approach calculates the electrostatic potential in the simulation domain more accurately compared to the uniform field approach, with the deviation in results increasing with the channel height. The translocation times and ionic fluxes predicted by uniform field MD can be substantially different from those predicted by the SCMD approach. Our results also indicate that during a 2ns simulation time K+ ions can permeate through a 1nm channel when the applied electric field is computed self-consistently, while the permeation is not observed when the electric field is assumed to be uniform.

Molecular understanding of osmosis in semipermeable membranes.

We investigate single-file osmosis of water through a semipermeable membrane with an uncharged, a positively and a negatively charged nanopore. Molecular dynamics simulations indicate that the osmotic flux through a negatively charged pore (J_) is higher compared to the osmotic flux in a positively charged pore (J+) followed by the osmotic flux in the uncharged pore (J(0)), i.e., J_ > J+ > J(0). The molecular mechanisms governing osmosis, steady state osmosis, and the observed osmotic flux dependence on the nanopore charge are explained by computing all the molecular interactions involved and identifying the molecular interactions that play an important role during and after osmosis. This study helps in a fundamental understanding of osmosis and in the design of advanced nanoporous membranes for various applications of osmosis.

Functional analysis of B144/LST1: a gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells.

B144/LST1 is a gene encoded in the human major histocompatibility complex that produces multiple forms of alternatively spliced mRNA and encodes peptides fewer than 100 amino acids in length. B144/LST1 is strongly expressed in dendritic cells. Transfection of B144/LST1 into a variety of cells induces morphologic changes including the production of long, thin filopodia differing from those seen on transfection of a dominant active CDC42 gene. The structures are dynamically rearranging and sometimes connect one cell with another. The full effect of B144/LST1 protein on cell morphology requires the retention of at least one of the four cysteines of the peptide plus the presence of a hydrophobic segment in the protein, but requires only one of the two coding regions present in the terminal 3' exons.

Rolling circle amplification: a new approach to increase sensitivity for immunohistochemistry and flow cytometry.

Immunohistochemistry is a method that can provide complementary diagnostic and prognostic information to morphological observations and soluble assays. Sensitivity, specificity, or requirements for arduous sample preparation or signal amplification procedures often limit the application of this approach to routine clinical specimens. Rolling circle amplification (RCA) generates a localized signal via an isothermal amplification of an oligonucleotide circle. The application of this approach to immunohistochemistry could extend the utility of these methods to include a more complete set of immunological and molecular probes. RCA-mediated signal amplification was successfully applied to the sensitive and specific detection of a variety of cell surface antigens (CD3, CD20, and epithelial membrane antigen) and intracellular molecules (vimentin and prostate-specific antigen) within a variety of routinely fixed specimens, as well as samples prepared for flow cytometry. RCA technology, which has an intrinsically wide dynamic range, is a robust and simple procedure that can provide a universal platform for the localization of a wide variety of molecules as a function of either antigenicity or nucleic acid sequence. The use of RCA in this way could enhance the use of markers of current interest as well as permit the integration of emerging information from genomics and proteomics into cell- and tissue-based analyses.

Expression and cellular localization of the protein encoded by the 1C7 gene: a recently described component of the MHC.

The major histocompatibility complex (MHC) is located on human Chromosome 6 and includes clusters of class I, class II, and class III genes. Centromeric to the class I region is a cluster of genes designated as MHC class IV encoding genes involved in immunity and inflammation, including the 1C7 gene. The human 1C7 gene has several alternatively spliced forms and potentially codes for proteins with at least three unique carboxy termini. 1C7 mRNA in human (h1C7) is present in spleen, tonsil, B and NK cell lines, and with a different splicing pattern in liver. The 1C7 RNA and protein are present at highest levels in the germinal center of the lymphoid follicles in tonsil. The protein is expressed in NKL cells, tonsil, and unexpectedly in brain. In contrast, the mouse 1C7 gene is transcribed in liver but is predicted to be a pseudogene. However, the 1C7 homologue expressed in rat is predicted to have long stretches of amino acids essentially identical to the human protein.

Synthesis and properties of iron(II) and manganese(II) complexes derived from a topologically constrained pentadentate ligand.

The novel bicyclic pentadentate ligand 5-methyl-1,5,9,24,25-pentaazapentacyclo[7.7.7.5.5]pentacosane11,13,15,18(25),20,22-hexene (L1) has been synthesized. Because of its cross-bridged topology it exhibits a relatively rigid preorganized conformation especially appropriate to complex formation, as shown by the crystal structure of the monoprotonated ligand salt, HL1ClH2O [orthorhombic, P212121, a = 9.4405(5) A, b = 13.3617(5) A, c = 16.710(1) A]. The complexes of L1 with both iron(II) and manganese(II) have been characterized, including the crystal structures of [FeL1CH3CN][FeCL4] and [MnL1Cl][PF6] [monoclinic, P21/n, a = 10.0460(5) A, b = 19.237(9) A, c = 15.6254(8) A, beta = 95.97(2)degrees and a = 7.745(2) A, b = 22.786(4) A, c = 14.639(4) A, beta = 105.074(10)degrees respectively]. The manganese complex is high spin with mueff = 5.96 and theta = 2.5 +/- 0.8 cm(-1), indicating weak ferromagnetic interactions. The reactions of the complexes with tert-butyl hydroperoxide and hydrogen peroxide have been shown by ESR spectroscopy to produce the tert-butyl peroxyl and hydroperoxyl radicals, as evidenced by their spin adducts with the spin traps N,N-dimethyl-1-pyrroline-N-oxide and N-tert-butyl-phenyl-nitrone.

STEP: a family of brain-enriched PTPs. Alternative splicing produces transmembrane, cytosolic and truncated isoforms.

The family of striatal enriched phosphatases (STEPs) consists of protein tyrosine phosphatases (PTPs) that are enriched within the central nervous system. Previous biochemical studies have shown that the STEP family includes transmembrane, as well as soluble, cytosolic proteins. We now extend these findings with the isolation and characterization of a new, truncated member of this family, termed STEP38. The cDNA of STEP38 encodes a protein of 346 amino acids with a predicted mobility of 38 kDa. In contrast to the cytosolic variants, it contains two hydrophobic amino acid sequences at its N-terminus, two sequences enriched in Pro, Glu, Asp, Ser and Thr residues (PEST sequences), and two polyproline domains. We have used differential centrifugation, continuous sucrose gradients, and transfection experiments to clarify the subcellular localization of STEP38 within membrane compartments. These experiments suggest that a pool of STEP38 is targeted to membrane compartments of the endoplasmic reticulum. The STEP38 cDNA contains a stop codon upstream of the catalytic phosphatase domain that is normally present in other STEP variants, and enzymatic assays conform that STEP38 is inactive. Thus, the STEP family consists of cytosolic, transmembrane, and truncated isoforms. These findings are similar to what has been found for some members of the protein tyrosine kinase (PTK) family that uses alternative splicing mechanisms to produce active and inactive variants. By analogy with suggested mechanisms of action for the truncated PTKs, inactive STEP isoforms may participate in signaling events by protecting potential substrates from dephosphorylation by other members of this family.

Transient compartmental expression of a family of protein tyrosine phosphatases in the developing striatum.

The expression of a family of intracellular protein tyrosine phosphatases (STEP) was studied in the striatum of rats during ontogeny. Links between the formation of dopamine islands and STEP immunoreactive patches in the striatum were examined since previous work had suggested that STEP isoforms were selectively expressed in dopaminoceptive brain regions. STEP protein and mRNAs were distributed in a patchy manner during the first postnatal week. By 2 weeks, STEP immunoreactivity was homogeneous, indicating that both patch and matrix neurons express STEP by maturity. Two-color immunofluorescent staining was also performed to compare STEP with specific markers for patch and matrix. Tyrosine hydroxylase immunoreactive fibers from the substantia nigra form distinctive dopamine islands in the striatum during late embryonic development, and occupy the sites of future patches [23,37,38,54]. These fiber islands align with STEP immunoreactive neuronal patches during the first two postnatal weeks, suggesting that STEP is a marker for patch neurons in early postnatal development. When STEP's distribution was compared with other markers for patch (substance P) or matrix (calbindin), STEP co-localized with substance P in most striatal neurons on postnatal days 1 through 7. However, STEP was also expressed within a subset of calbindin-positive neurons in the lateral striatum, but not with these neurons elsewhere in the striatum. By adulthood, STEP colocalized with both markers. These results suggest that STEP is expressed first within patch neurons but not matrix, and subsequently within both. The expression of STEP may be triggered by the arrival of striatal afferents or other regulatory factors.

Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase.

Regional variations in the expression of a striatal enriched protein tyrosine phosphatase called STEP were studied in the adult rat brain by a combination of immunocytochemistry, lesion studies, Western blotting, and in situ hybridization. Monoclonal antibodies generated against STEP identified multiple polypeptides of M(r) 46, 37, 33 and a doublet of M(r) 64-66 kDa on Western blots. Although the three STEP immunoreactive bands with lower molecular weights were enriched in cytosolic fractions, the 64-66 kDa doublet was enriched in membrane fractions. All of the immunoreactive forms were abundant in the caudate-putamen and were present in lower amounts or were undetectable in other brain regions. In substantia nigra, the M(r) 64-66 kDa doublet was not detected but bands with M(r) 46, 37, and 33 kDa were present. Immunocytochemical and lesion experiments demonstrated that the cytosolic STEP isoforms present in the substantia nigra are in presynaptic axons originating from the projection neurons of the caudate putamen, which innervate this structure. Additional in situ hybridization studies showed that STEP mRNA expression patterns correlate with the patterns of immunocytochemical staining. These findings indicate that there are multiple polypeptide isoforms of STEP enriched in the basal ganglia and related structures which differ in terms of their intracellular locations and functional roles.

Differential effects of 15-HPETE and 15-HETE on BHK-21 cell proliferation and macromolecular composition.

Arachidonate and/or linoleate metabolites have been implicated in modulating cell growth, replication and cell transformations. In studies with BHK-21 cells, we found lipoxygenase and cyclooxygenase inhibitors (NDGA and indomethacin, respectively) to be antiproliferative. Studies on the metabolism of arachidonic acid in BHK-21 cells have demonstrated that prostaglandin D2 is the major cyclooxygenase product, and 15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase product. Addition of D2 showed a significant decrease in the BHK-21 cell number showing antiproliferative action. Addition of lipoxygenase products, on the other hand, showed differential effects in that 15-HPETE decreased the cell number while 15-HETE increased. NDGA and 15-HPETE decreased DNA, RNA and protein contents, while 15-HETE significantly increased them. 5-HPETE and 5-HETE also showed similar results but were less potent than 15-H(P)ETEs. The differential effects of 15-HPETE and 15-HETE could be due to the generation of free radicals by the hydroperoxide and mitogenic response by hydroxide.

Influence of media composition on the production of delta-endotoxin by Bacillus thuringiensis var. thuringiensis.

Powders of edible leguminous seeds, greengram (Vigna radiata) or soybean (Glycine max), were used as the major protein source with different combinations of soluble starch and/or cane sugar molasses as the major carbohydrate source for the production of delta-endotoxin by Bacillus thuringiensis var. thuringiensis serotype 1 in submerged fermentation. The primary product (lyophilized with 6 g of lactose) yield was 8.7 to 9.1 g/liter from media with dehusked greengram powder and 9.7 to 10.3 g/liter from media with defatted soybean powder in basal medium. The toxicity of primary products was assayed against fifth-instar Bombyx mori larvae by force-feeding. The primary product from the medium containing defatted soybean powder and soluble starch gave a maximum viable spore count of 91.3 x 10(6)/mg, with a corresponding potency of 35,800 IU/mg, whereas the medium containing dehusked greengram powder and cane sugar molasses gave a spore count of 49.5 x 10(6)/mg, with a highest potency of 38,300 IU/mg. Either legume protein in combination with cane sugar molasses yielded primary product 2.1 to 2.4 times more potent than the U.S. standard. The combined carbohydrate source consisting of soluble starch and cane sugar molasses, irrespective of the source of protein in the media, drastically reduced delta-endotoxin production, thereby reducing the potency of the primary products compared to the U.S. standard.