Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor

Recent evidence suggests that primary patient isolates of T-cell-tropic human immunodeficiency virus type 1 (HIV-1 ) have lower affinities for CD4 than their laboratory-adapted derivatives, that this may partly result from tighter gp120-gp41 bonds that constrain the CD4 binding sites of the primary viruses, and that selection for increased CD4 affinity may be the principal factor in laboratory adaptation of HIV-1 (S. L. Kozak, E. J. Platt, N. Madani, F. E. Ferro, Jr., K. Peden, and D. Kabat, J. Virol. 71:873-882, 1997). These conclusions were based on studies with a panel of HeLa-CD4 cell clones that differ in CD4 levels over a broad range, with laboratory-adapted viruses infecting all clones with equal efficiencies and primary T-cell-tropic viruses infecting the clones in proportion to cellular CD4 levels. Additionally, all of the primary and laboratory-adapted T-cell-tropic viruses efficiently used CXCR-4 (fusin) as a coreceptor. To test these conclusions by an independent approach, we studied mutations in the laboratory-adapted virus LAV/IIIB that alter the CD)4 binding region of gp120 and specifically reduce CD4 affinities of free gp 120 by 85 to 98% (U. Olshevsky et al., J. Virol. 64:5701-5707, 1990). These mutations reduced virus titers to widely varying extents that ranged from severalfold to several orders of magnitude and converted infectivities on the HeLa-CD4 panel from CD4 independency to a high degree of CD4 dependency that resembled the behavior of primary patient viruses. The relative infectivities of the mutants correlated closely with their sensitivities to inactivation by soluble CD4 but did not correlate with the relative CD4 affinities of their free gp120s. Most of the mutations did not substantially alter envelope glycoprotein synthesis, processing, expression on cell surfaces, incorporation into virions, or rates of gp120 shedding from virions. However, one mutation (D457R) caused a decrease in gp160 processing by approximately 80%. The fact that several mutations increased rates of spontaneous viral inactivation (especially D368P) suggests that HIV-1 life spans may be determined by structural stabilities of viral envelope glycoproteins. All of the wild-type and mutant viruses were only slowly and inefficiently adsorbed onto cultured CD4-positive cells at 37 degrees C, and the gradual declines in viral titers in the media were caused almost exclusively by spontaneous inactivation rather than by adsorption. The extreme inefficiency with which infectious HIV-1 is able to infect cultured susceptible CD4-positive cells in standard assay conditions casts doubt on previous inferences that the vast majority of retrovirions produced in cultures are noninfectious. Apparent infectivity of T-cell-tropic HIV-1 in culture is limited by productive associations with CD4 and is influenced in an interdependent manner by CD4 affinities of viral gp120-gp41 complexes and quantities of cell surface CD4.     

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.     

High resolution glass capillary columns with chemically bonded stationary phases: application to the gas chromatographic analysis of sterols and steroids in biological extracts

A new approach has been developed for the preparation of highly stable glass capillary columns using irreversible bonding of polysiloxane polymers to the glass surface. The general procedure involves (a) synthesis of reactive linear polysiloxanes from variously (alkyl, aryl) substituted dichlorosilanes through homologous or heterologous polymerization under alcaline aqueous conditions, and (b) covalent condensation of the polymers to a properly prepared glass capillary surface at high temperature. The principle has been first applied to the successful preparation of apolar gas chromatographic systems (methylpolysiloxanes), then extended to the obtention of polar systems (methyl phenyl polysiloxanes). The flexibility of the approach is demonstrated by the possibility of obtaining stationary phases of various and controlled polarity (i.e., extent of phenyl substitution), tailor-made to a given analytical problem. These gas Chromatographic systems appear to be remarkably stable both with time and temperature up to 300 C and compare favorably to existing systems for their high resolution properties. These columns have been satisfactorily used in the last years for the analysis of sterols and steroids of biological origin and most extensively in the study of urinary steroid metabolite in humans under pathological conditions.     

Nail surgery

Nail deformities may present as wither medical or cosmetic problems, often requiring surgical intervention. These deformities have a number of etiologic factors including infections, inflammatory disease processes, congenital abnormalities, trauma, tumors, and systemic diseases. This article discusses several nail problems and surgery techniques.     

Aureole nanofibers by electrospinning of PAMAM‐PEO solution

Poly(amido amine) (PAMAM) dendrimer‐polyethylene oxide (PEO) nanofibers as dendrimeric‐polymeric composite nanofibers were prepared via electrospinning of PEO solution containing PAMAM dendrimer. The resultant fibers were characterized by means of transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The morphology and thermal properties of PEO nanofibers with and without PAMAM dendrimer were compared and the effect of PAMAM concentration on morphology and thermal properties of the resultant fibers was studied. The fibers had a size range of about 400–1300 nanometer in diameter with aureole morphology in most regions. The phase change temperature, phase transition heat, and the crystallinity of the produced composite fibers were determined by DSC analyses. TGA was also used to confirm the presence of PAMAM and to determine the amount of it within the fibers. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

New methods for enhancing fine acquisition in dual folding algorithm of long pseudo noise codes

Long code Direct Sequence Spread Spectrum is a good choice for applications where security and antispoofing ability of a spread spectrum connection is concerned. Due to long period of spreading code, acquisition is a challenge for these systems because a trade‐off between detection probability and acquisition time must be made. For confronting this challenge, various algorithms were proposed in the literature but almost all of them focus on expediting the coarse acquisition. In this paper, we consider the efficient dual folding algorithm for coarse acquisition level and propose 3 methods for enhancing the fine acquisition level leading to faster execution of overall acquisition algorithm. The methods are based on estimations from coarse acquisition level that are not used in conventional algorithms for fine acquisition, ie, zero padding. Theoretical expressions of 2 main comparison criteria in acquisition algorithms, ie, detection probability and mean acquisition time, are derived for conventional zero padding and each of the proposed method. Besides, a coarse estimate of resource consumption is provided by the number of floating point operations for each algorithm to make a useful comparison. Considering these 3 parameters, in comparison, the proposed methods surpass zero padding in 1, 2, or all of the 3 aspects. Simulation agrees well with analytical results.     

Random Crystal Field in a Mixed Spin <Emphasis Type="Italic">S</Emphasis> = 1/2 and <Emphasis Type="Italic">S</Emphasis> = 3/2 Ising Model by Renormalization Group Theory

In this work, we study the Ising model with mixed spins S = ?1/2 and S = ?3/2 on the hypercubic lattice and the random crystal field at the sublattice with S =?3/2 described by a two peaks law. To achieve this, we use an approximation of position space renormalization group (PSRG) namely Migdal-Kadanoff in which we use both the free energy derivative and the flow in the parameter space of the Hamiltonian. For all values of the random probability, the critical behavior is determined via the critical exponents at the second-order fixed points while at low temperatures; the discontinuities of the of the free energy derivative provide the positions of the first-order transitions. The introduction of a minimal amount of disorder causes a change in the phase diagram showing the relevance of disorder for d =?2 and d =?3. The second-order transition remains always with the same critical exponents as those of the pure model, and a new first-order transition appears at very low temperature. Also, a comparison with other similar works is given.