Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma.

DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy.

Structure-function of the channel-forming colicins.

The channel-forming colicins are plasmid-encoded bacteriocins that kill E. coli and related cells and whose mode of action is of interest in related problems of protein import and toxicology. Colicins parasitize metabolite receptors in the outer membrane and translocate across the periplasm with the aid of the Tol or Ton protein systems.

Antiretroviral therapy is associated with a decrease in unintegrated HIV-1 DNA in pediatric patients.

Good markers for monitoring the efficacy of antiretroviral therapy in children do not currently exist. This study examined the effect of antiretroviral therapy on human immunodeficiency virus (HIV-1) unintegrated DNA (uDNA), integrated DNA (iDNA), percent uDNA, immune complex dissociated (ICD) p24 antigenemia, and plasma viral titer. Seven children were followed at therapy initiation and at approximately 3- and 10-month intervals.

GRAFTER: a computational aid for the design of novel proteins.

The GRAFTER suite of programs provides geometric search and evaluation functions that simplify and automate the process of identifying the best scaffolds for a particular structural motif. Three application of the GRAFTER suite are presented. Potential grafts between lambda repressor and 434 repressor were identified that should change the DNA binding specificity of these repressors.

Contrast-enhanced magnetic resonance imaging estimation of altered capillary permeability in experimental mammary carcinomas after X-irradiation.

Rationale And Objectives: Dynamic magnetic resonance imaging (MRI) enhanced with a macromolecular contrast medium, albumin-(Gd-DTPA)35, was used to detect changes in microvascular characteristics in R3230 mammary adenocarcinomas induced by x-irradiation.

Methods: Tumors were implanted in either flank in nine rats. One of the tumors was exposed to single-dose x-irradiation (30 Gy) 3 days before MRI.

The environment and cancer in New Jersey.

Tumorigenesis involves a complex series of steps. These steps are influenced by genetic predisposition and by lifestyle, tobacco and alcohol use, diet, and occupation. The way a person chooses to or is forced to live will influence the risk of developing cancer.

Characterization of a Plasmodium vivax cysteine proteinase gene identifies uniquely conserved amino acids that may mediate the substrate specificity of malarial hemoglobinases.

The gene encoding a cysteine proteinase of the human malaria parasite Plasmodium vivax has been identified and characterized. The sequence predicted by the proteinase gene shares several unique features with the sequences of two recently characterized cysteine proteinases of other malarial species. These features include the conservation of a number of amino acids that are predicted, based on a recently devised model for the related Plasmodium falciparum cystine proteinase, to be located near the enzyme's active site.

The origins of protein secondary structure. Effects of packing density and hydrogen bonding studied by a fast conformational search.

Globular proteins fold to create compact structures rich in alpha-helices and beta-sheets. While studies of cubic lattice models of simplified polypeptide chains have concluded that secondary structure is a necessary consequence of chain compactness, different conclusions have been reached from studies of off-lattice models of simplified chains. In an attempt to resolve this controversy, we study an all-atom off-lattice model of a protein subject to a variety of simplified energy functions.

Conformation of CD4-derived cyclic hexapeptides by NMR and molecular dynamics.

Two cyclic hexapeptides, cyclo[Ala1-D-Ala2-Ser3-Phe4-Gly5-Ser6] and cyclo[Ala1-Gly2-Ser3-Phe4-Gly5-Ser6], derived from the loop portion of the C'C" ridge of CD4, were characterized by high-resolution nmr spectroscopy and simulated annealing studies. In DMSO-d6 both of these peptides display a single conformer on the nmr time scale with two intramolecular H-bond (1<--4) stabilized beta-turns at positions 2-3 and 5-6. The nmr derived distance constraints were used in simulated annealing calculations to generate the solution structures.

Proposed three-dimensional structure for the cellular prion protein.

Prion diseases are a group of neurodegenerative disorders in humans and animals that seem to result from a conformational change in the prion protein (PrP). Utilizing data obtained by circular dichroism and infrared spectroscopy, computational studies predicted the three-dimensional structure of the cellular form of PrP (PrPc). A heuristic approach consisting of the prediction of secondary structures and of an evaluation of the packing of secondary elements was used to search for plausible tertiary structures.

Research on families and pediatric human immunodeficiency virus disease: a review and needed directions.

Human immunodeficiency virus (HIV) disease in children has important and longlasting effects on families. Although aspects of other childhood illnesses can be applied to the study of pediatric HIV disease, the total constellation of symptoms and effects makes HIV disease unique. Further, the majority of families affected by HIV disease are minority and disadvantaged.

Spectroscopic characterization of conformational differences between PrPC and PrPSc: an alpha-helix to beta-sheet transition.

Although no chemical modifications have been found to distinguish the cellular prion protein PrPC from its infectious analogue PrPSc, spectroscopic methods such as Fourier transform infrared (FTIR) spectroscopy reveal a major conformational difference. PrPC is rich in alpha-helix but is devoid of beta-sheet, whereas PrPSc is high in beta-sheet. N-terminal truncation of PrPSc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the FTIR absorption to lower frequencies, typical of the cross beta-pleated sheets of amyloids.

Four helix bundle diversity in globular proteins.

Four helix bundles are a common structural motif that can be observed both independently and as components of larger folding units. We examined 221 globular proteins of known structure for possible four helix bundles. Previous computational studies of four helix bundles have placed arbitrary restrictions on interhelical packing angles.

Structure from function: screening structural models with functional data.

Structural constraints derived from different antibody epitopes on human growth hormone (hGH) were used to screen three-dimensional models of hGH that were generated by computer algorithms. Previously, alanine-scanning mutagenesis defined the residues that modulate binding to 21 different monoclonal antibodies to hGH. These functional epitopes were composed of 4-14 side chains whose alpha-carbons clustered within 4-23 A.

Foster care of HIV-positive children in the United States.

A national study regarding the foster care of children identified as human immunodeficiency virus-positive (HIV-positive) was conducted in 1991. A survey form was sent to the administrators of the State agency responsible for foster care in each State, the District of Columbia, and U.S.

Computer-assisted drug discovery--a review.

A structure-based approach to new drug development is an attractive alternative to the traditional paradigm of drug discovery through screening. The elements of this approach are reviewed, with emphasis on the use of homology-built model structures. Two examples, proteases from the organisms that cause malaria and schistosomiasis, illustrate both the model-building process and the feasibility of using such models to computationally screen and identify compounds that inhibit their targets in the low micromolar range.

Origins of structural diversity within sequentially identical hexapeptides.

Efforts to predict protein secondary structure have been hampered by the apparent structural plasticity of local amino acid sequences. Kabsch and Sander (1984, Proc. Natl.

Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.

The 17-juxtamembrane cytoplasmic residues of the polymeric immunoglobulin receptor contain an autonomous basolateral targeting signal that does not mediate rapid endocytosis (Casanova, J. E., G.

Influenza virus hemagglutinin-induced cell-planar bilayer fusion: quantitative dissection of fusion pore kinetics into stages.

Cells expressing the influenza virus hemagglutinin (HA) fuse to planar bilayer membranes under acidic conditions. After an electrically quiescent perfusion stage (Q), a fusion pore forms that enlarges in three subsequent stages. A repetitively flickering pore stage (R) develops into a securely open stage (S) that exhibits conductances ranging from a few to tens of nS.

Influenza hemagglutinin-mediated fusion pores connecting cells to planar membranes: flickering to final expansion.

We have studied the fusion between voltage-clamped planar lipid bilayers and influenza virus infected MDCK cells, adhered to one side of the bilayer, using measurements of electrical admittance and fluorescence. The changes in currents in-phase and 90 degrees out-of-phase with respect to the applied sinusoidal voltage were used to monitor the addition of the cell membrane capacitance to that of the lipid bilayer through a fusion pore connecting the two membranes. When ethidium bromide was included in the solution of the cell-free side of the bilayer, increases in cell fluorescence accompanied tee admittance changes, independently confirming that these changes were due to formation of a fusion pore.

Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.

Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each.

Immunologic changes occurring at kindergarten entry predict respiratory illnesses after the Loma Prieta earthquake.

Previous studies in adult populations have demonstrated alterations in immune function after psychologically stressful events, and pediatric research has shown significant associations between stress and various childhood morbidities. However, no previous work has examined stress-related immune changes in children and subsequent illness experience. Twenty children were enrolled in a study on immunologic changes after kindergarten entry and their prospective relationship to respiratory illness (RI) experience.