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At least 991 records · Page 55Linked to original sources
PubMed2003

Robust in vitro replication of Plasmodium falciparum in glycosyl-phosphatidylinositol-anchored membrane glycoprotein-deficient red blood cells.

Red blood cells (RBCs) infected with Plasmodium falciparum are protected from complement-mediated lysis by surface membrane glycosyl-phosphatidylinositol (GPI)-anchored proteins, which include decay accelerating factor (DAF or CD55) and CD59. To determine if P. falciparum avoids or replicates less efficiently in GPI protein-deficient cells at a higher risk for complement-mediated lysis, we compared P. falciparum infectivity among control RBCs with those from subjects with paroxysmal nocturnal hemoglobinuria (PNH), a condition in which RBCs express variable levels of DAF (negative and positive) and CD59 (negative [-], intermediate [I], and high [H]). Co-cultures of 19 matched samples of control and PNH RBCs were infected with P. falciparum to directly compare parasitic invasion. Each PNH RBC sample was then assessed for P. falciparum infectivity across the spectrum of GPI protein deficiency. Identification methods included biotin-streptavidin for RBC populations, fluorescein isothiocyanate-labeled antibodies to DAF and CD59, hydroethidine for parasite DNA, and flow cytometry. The mean +/- SD parasitemias in co-cultured PNH and control RBCs were 24.7 +/- 6.9% versus 21.0 +/- 5.9% (P = 0.12). For individual PNH samples, parasitemias were significantly higher in DAF (-) cells versus DAF (+) cells (25.0 +/- 8.9% versus 19.1 +/- 8.7%; P < 0.001) and in CD59 (-) cells versus I/H cells (22.5 +/- 6.4% versus 17.6 +/- 4.2%; P < 0.0003). Across the CD59 spectrum, mean parasitemias were highest in CD59 (-) cells (24.5 +/- 6.4%), followed by CD59-H cells (19.5 +/- 5.4%), and CD59-I cells (16.4 +/- 4.8%). Expression of DAF in 12 (63%) of 19 infected PNH samples was reduced. Thus, P. falciparum does not selectively avoid RBCs with fewer GPI proteins and parasite replication in PNH cells is at least as robust as in normal RBCs.

Animals↗
PubMed2005

Sexual orientation and personality.

The relation between sexual orientation and personality was examined in a meta-analysis with a total sample of 2,724 heterosexual men, 799 gay men, 157 bisexual men, 5,053 heterosexual women, 697 lesbian women, and 317 bisexual women. Self-ascribed masculinity-femininity (Self-M-F) and gender-related interests showed the largest heterosexual-homosexual differences (respective ds = .60 and 1.28 for men, and -1.28 and -1.46 for women) and the largest sex differences (respective ds = 2.83 and 2.65). Instrumentality and expressiveness showed much smaller heterosexual-homosexual and sex differences. Big Five traits showed a number of small-to-moderate heterosexual-homosexual and sex differences. Bisexual men were much more like gay men than like heterosexual men in their Self-M-F and gender-related interests, whereas bisexual women were intermediate between lesbian and heterosexual women. Homosexual participants were more variable on some gender-related traits than same-sex heterosexuals were. The gender inversion hypothesis-that gay men's traits tend to be somewhat feminized and that lesbians' traits tend to be somewhat masculinized-received considerable support. Results are discussed in terms of biological and psychosocial theories of gender and sexual orientation.

Bisexuality↗
PubMedDate not supplied

[A population analysis of the variability of the hooklets in the cestode Triaenophorus crassus].

The paper presents data on the variability of attachment organs in the cestode Triaenophorus crassus, a parasite of freshwater fishes. The greatest range of variability of all the characters is typical of whitefish, a fish with a long life cycle, while the shortest one is characteristic of vendace and young of trout. It is suggested that the stay of the parasite in fishes, associated with host age, is accompanied by the increase in average sizes of hooks and variability range. Such an approach together with the analysis of hooks variability gives the possibility to estimate the participation of secondary intermediate hosts in the circulation of the parasite in the water body.

Animals↗
PubMed1988

Synthesis and radiopharmaceutical preparation of (ethylenediamine) (1-carbon-11-malonate) platinum(II) for PET studies.

Interest in the distribution, biotransformation, and mechanism of action of anticancer platinum complexes has led to the microscale, semi-automated and remote-controlled synthesis of (ethylenediamine) (1-[11C]malonate) platinum(II) [( 11C]Ptenmal, EDMAL, JM40) from cyclotron-produced [11C]cyanide. Carbon-11 cyanoacetate is produced by reacting [11C]cyanide with bromoacetate. After hydrolysis, the resulting [11C]malonic acid is purified and complexed to (diaquo) (ethylenediamine) platinum(II). Each step of the synthesis was optimized by studying the influence of different variables like reaction time and temperature, pH, necessary purification of intermediates, concentration and ratios of the reactants. Purification of the endproduct is achieved using preparative high performance liquid chromatography. The total incorporation of the [11C]cyanide in the final product was 17-40%. After approximately 1 hr, approximately 40 mCi of [11C]Ptenmal are produced in 10 ml sterile and isotonic dextrose solution ready for i.v. injection. The specific activity is approximately 200 mCi/mumol at EOB.

Carbon Radioisotopes↗
PubMed1978

Hydroxylated metabolies of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) in rats and rabbits.

Two hydroxylated metabolies (M1 and M2) have been isolated from rabbit urine after administration of Ftorafur (FT). The structures of 3'-OH-FT and 4'-OH-FT were assigned to M1 and M2, respectively. A reverse-phase high performance liquid chromatography assay was developed for jeasuring FT, M1, M2, and 5-fluorouracil (FU) plasma levels. M1, M2, and FU were present in rabbit and rat plasma in greatly varying concentrations after FT administration. Pharmacokinetic studies suggest that FU formation proceeds via metabolic intermediate(s) and that the extent of FT activation is variable. A horse liver thymidine phosphorylase ,reparation capable of catalyzing the conversion of beta-ribo-2'-deoxy-5-fluorouracil to FU was inactive against FT and M1. However, 20% of M2 was converted to FU by this enzume, which suggests that the urinary metabolite M2 consisted of a mixture of enantiomers with 20% present in the natural beta-D configuration. The stereochemistry of M1 remains unknown. Hydroxylation of FT to beta-D-4'-OH-FT and subsequent cleavage to FU by thymidine phosphorylase represents one possible activation mechanism of FT to FU. ,owever, lack of correlation between plasma levels of M2 and FU indicates that this mode of metabolic activation may account for only part of the overall activation of FT in vivo.

Animals↗
PubMed1976

Polymorphism of larvae of the genus Aploparaksis Clerc, 1903 (Hymenolepididae).

The larvae of 12 cestode species of the genus Aploparaksis have been studied. In order to confirm the determination, the definitive hosts, birds, were experimentally infected with 5 species and the intermediate hosts, oligochaetes, with 6 species of cestodes. A great variability was observed in the morphology of tail appendix of cysticercoids belonging to five types of larvae. It is assumed that the polymorphism of larvae of the genus Aploparaksis results from the morphological adaptation to the development under arctic conditions.

Animals↗
PubMed2001

Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix.

Unraveling the molecular basis of inherited disorders of epithelial fragility has led to understanding of the complex structure and function of keratin intermediate filaments. Keratins are organized as a central alpha-helical rod domain flanked by nonhelical, variable end domains. Pathogenic mutations in 19 different keratin genes have been identified in sequences corresponding to conserved regions at the beginning and end of the rod. These areas have been recognized as zones of overlap between aligned keratin proteins and are thought to be crucial for proper assembly of keratin intermediate filaments. Consequently, all keratin disorders of skin, hair, nail, and mucous membranes caused by mutations in rod domain sequences are characterized by perinuclear clumping of fragmented keratin intermediate filaments, thus compromising mechanical strength and cell integrity. We report here the first mutation in a keratin gene (KRT1) that affects the variable tail domain (V2) and results in a profoundly different abnormality of the cytoskeletal architecture leading to a severe form of epidermal hyperkeratosis known as ichthyosis hystrix Curth-Macklin. Structural analyses disclosed a failure in keratin intermediate filament bundling, retraction of the cytoskeleton from the nucleus, and failed translocation of loricrin to the desmosomal plaques. These data provide the first in vivo evidence for the crucial role of a keratin tail domain in supramolecular keratin intermediate filament organization and barrier formation.

Amino Acid Sequence↗
PubMed2004

Quantitative histopathological analysis of cervical intra-epithelial neoplasia sections: methodological issues.

OBJECTIVES: As part a Program Project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analysis of biopsies from 1,800 patients. Several methodological issues have arisen with respect to this analysis: (1) Finding the most efficient way to compensate for staining intensity variation with out losing diagnostic information; (2) Assessing the inter- and intra-observer variability of the semi-interactive data collection; and (3) the use of non-overlapping cells from the intermediate layer only. METHODS: Non-overlapping quantitatively stained nuclei were selected from 280 samples with histopathological characteristics of normal (199), koilocytosis (37), CIN 1 (18), CIN 2 (10) and CIN 3 (16). Linear discriminant analysis was used to assess the diagnostic information in three different feature sets to evaluate and compare staining intensity normalization methods. Selected feature values and summary scores were used to evaluate intra- and inter-observer variability. RESULTS: The features normalized by the internal subset of the imaged cells had the same discriminatory power as those normalized by the control cells and by both normalization methods seem to have additional discriminatory power over the set of features which do not require normalization. The use of the internal subset decreased the image acquisition time by approximately 50% at each center, respectively. The intra- and inter-observer variability was of a similar size. Good performance was obtained by measuring the intermediate layer only. CONCLUSION: The use of intensity normalization from a subset of the imaged non-overlapping intermediate layer cells works as well as or better than any of the other methods tested and provides a significant timesaving. Our intra- and inter-observer variability do not seem to affect the diagnostic power of the data. Although this must be tested in a larger data set, the use of intermediate layer cells only may be acceptable when using quantitative histopathology.

Cell Nucleus↗
PubMed1978

Heavy meromyosin labeling of intermediate filaments in cultured connective tissue cells.

Mild treatment with trypsin causes a radical change in the heavy meromyosin (HMM) binding properties of intermediate filaments in glycerinated, myosin-extracted cultured chick embryo connective tissue cells. In non-trypsin-treated cells, HMM labeling of filaments was often indistinct and variable in its distribution. By contrast, in cells treated with trypsin (under conditions which allowed most intermediate filaments to survive), virtually all filaments, including those of intermediate size, decorated with HMM to give distinct arrowhead patterns. We suggest that most intermediate filaments in such cells contain a core of F-actin masked by trypsin-labile accessory proteins.

Actins↗
PubMed1998

Locomotion in alligator mississippiensis: kinematic effects of speed and posture and their relevance to the sprawling-to-erect paradigm

In terms of locomotory posture, amphibians and lizards are considered to be sprawlers, mammals and dinosaurs are considered to be erect, and extant crocodilians are considered to be intermediate because they use the 'high walk', a semi-erect posture where the body is held half-way between the sprawling and erect grades during locomotion. In addition, crocodilians occasionally use a sprawling posture. Extant crocodilians, therefore, provide an interesting model in which to investigate the sprawling-to-erect transition in vertebrate evolution. This study quantifies the sprawl and high walk kinematics of the alligator Alligator mississippiensis moving at different speeds on a treadmill and compares them with kinematic data available for other vertebrates. These data allow us to examine the effects of speed on crocodilian postures and to examine how crocodilian locomotion relates to the sprawling-to-erect paradigm in vertebrate locomotion. Our results show that the crocodilian sprawl is not functionally equivalent to the primitive sprawling behaviors exhibited by salamanders and lizards. In fact, although the high walks and sprawls of alligators exhibit some kinematic differences, they are actually much more similar than expected and, essentially, the crocodilian sprawl is a lower version of a high walk and could be termed a 'low walk'. In terms of the sprawling-to-erect transition, the high walk has knee kinematics intermediate between those of birds and non-archosaurian tetrapods, but alligators increase speed in a way completely different from other terrestrial vertebrates (distal rather than proximal limb elements are used to increase speed). These kinematic data viewed in the light of the fossil and phylogenetic evidence that modern crocodilians evolved from erect ancestors suggest that modern crocodilians have secondarily evolved a variable semi-erect posture and that they are problematic as an intermediate model for the evolutionary transition from sprawling to erect postures in archosaurs.

Journal Article↗
PubMed2003

Highly fluctuating protein structures revealed by variable-pressure nuclear magnetic resonance.

Although our knowledge of basic folded structures of proteins has dramatically improved, the extent of our corresponding knowledge of higher-energy conformers remains extremely slim. The latter information is crucial for advancing our understanding of mechanisms of protein function, folding, and conformational diseases. Direct spectroscopic detection and analysis of structures of higher-energy conformers are limited, particularly under physiological conditions, either because their equilibrium populations are small or because they exist only transiently in the folding process. A new experimental strategy using pressure perturbation in conjunction with multidimensional NMR spectroscopy is being used to overcome this difficulty. A number of rare conformers are detected under pressure for a variety of proteins such as the Ras-binding domain of RalGDS, beta-lactoglobulin, dihydrofolate reductase, ubiquitin, apomyoglobin, p13(MTCP1), and prion, which disclose a rich world of protein structure between basically folded and globally unfolded states. Specific structures suggest that these conformers are designed for function and are closely identical to kinetic intermediates. Detailed structural determination of higher-energy conformers with variable-pressure NMR will extend our knowledge of protein structure and conformational fluctuation over most of the biologically relevant conformational space.

Animals↗
PubMed2000

Variability and noise in continuous force production.

In the present 3 experiments, the authors examined the hypothesis, derived from information theory, that increases in the variability of motor responses result from increases in perceptual-motor noise. Three different groups of participants (Ns = 10, 9, and 10, respectively, in Experiments 1, 2, and 3) produced continuous isometric force under either low, intermediate, or high target force levels. When considered together, the results showed that force variability (SD) increased exponentially as a function of force level. However, an index of information transmission (M/SD), as well as measures of noise in both the time (approximate entropy) and the frequency (power spectrum) domains, changed according to an inverted-U-shaped function over the range of force levels. The findings provide further evidence that increased information transmission is related to increases, and not to decreases, in the noisiness of the structure of force output.

Adolescent↗
PubMed2000

Cell-cell adhesion molecules and signaling intermediates and their role in the invasive potential of prostate cancer cells.

PURPOSE: The highly variable natural history of prostate carcinoma may be reflected in heterogeneity of invasive potential between tumors. MATERIALS AND METHODS: We have examined two prostate cancer cell lines of low invasive potential (CAHPV10 and PZHPV7) and three cell lines of high invasive potential (DU-145, PC-3, LNCapFGC), to determine whether specific adhesion molecule profiles correlated with their invasive behavior. RESULTS: Using an in vitro invasion assay, we demonstrated that DU-145, LNCapFGC and PC-3 cells were highly invasive compared with CA-HPV-10 and PZ-HPV-7 cells. LNCapFGC cells expressed high levels of E-cadherin, alpha-, beta- and gamma-catenin, desmoglein, desmoplakin and GSK3beta using immunoblotting. This was, in general, comparable to immunohistochemical staining. PC-3 cells had no E-cadherin or alpha-catenin, but expressed a high level of the HGF/SF receptor c-Met. In contrast, DU-145 cells were found to express E-cadherin and low levels for all other protein molecules, except c-Met. The DU-145 cell line also lacked alpha-catenin expression. In CA-HPV-10 and PZ-HPV-7 cells, there was no detection of APC, PECAM-1, P-cadherin or Wnt-1. DU-145, LNCapFGC and PC-3 cells formed cell-cell aggregates, which were reduced by inclusion of anti-E-cadherin antibody and the motogen HGF/SF. CONCLUSION: These results show that prostate cancer cells exhibit a diverse expression of cell-cell adhesion molecules and their signaling intermediates. The expression of these adhesion molecules bears an important relationship with the invasive phenotype of these cells.

Adenomatous Polyposis Coli Protein↗
PubMed1990

Cellular migration patterns in the developing mouse cerebral cortex.

The migration patterns of embryonic mouse cortical cells were investigated using a replication-incompetent retrovirus vector (BAG). The lateral ventricles of embryonic day 12 mouse embryos were infected with BAG and brains were harvested 2, 3, 4 and 6 days after infection. The location and morphology of all infected cortical cells were recorded from serial sections of entire brains, which were then reconstructed in three dimensions. Examination of the distribution of labelled cells revealed that there were migration patterns characteristic of each medial-lateral domain of the cortex. In the medial and dorsal areas, migration was often radial, although tangential spread increased with survival time, in large part due to ramification of cells in the intermediate zone. In the dorsolateral and lateral areas of the cortex, radial migration was generally not observed. Rather, variable extents of tangential migration occurred, and often resulted in wide separation of cells in the cortical plate. Almost all of the cellular dispersion occurred in the intermediate zone, although a modest degree of dispersion also occurred within the cortical plate itself. Most dispersion occurred in the mediolateral plane, with relatively little dispersion along the anteroposterior axis. Though characteristic migration patterns could be defined, wide variability in the extents of radial migration and tangential separation of cells was seen. The patterns of migration paralleled the distribution of radial glial fibers in all areas, and are most likely a reflection of the role of this network in supporting the migration of cortical neurons. The extent and variability of cellular dispersion supports a lineage-independent mechanism of cortical column ontogenesis.

Animals↗
PubMed1996

Membrane binding of the colicin E1 channel: activity requires an electrostatic interaction of intermediate magnitude.

In vitro channel activity of the C-terminal colicin E1 channel polypeptide under conditions of variable electrostatic interaction with synthetic lipid membranes showed distinct maxima with respect to pH and membrane surface potential. The membrane binding energy was determined from fluorescence quenching of the intrinsic tryptophans of the channel polypeptide by liposomes containing N-trinitrophenyl-phosphatidylethanolamine. Maximum in vitro colicin channel activity correlated with an intermediate magnitude of the electrostatic interaction. For conditions associated with maximum activity (40% anionic lipid, I = 0.12 M, pH 4.0), the free energy of binding was delta G approximately -9 kcal/mol, with nonelectrostatic and electrostatic components, delta Gnel approximately -5 kcal/mol and delta Gel approximately -4 kcal/mol, and an effective binding charge of +7 at pH 4.0. Binding of the channel polypeptide to negative membranes at pH 8 is minimal, whereas initial binding at pH 4 followed by a shift to pH 8 causes only 3-10% reversal of binding, implying that it is kinetically trapped, probably by a hydrophobic interaction. It was inferred that membrane binding and insertion involves an initial electrostatic interaction responsible for concentration and binding to the membrane surface. This is followed by insertion into the bilayer driven by hydrophobic forces, which are countered in the case of excessive electrostatic binding.

Binding Sites↗
PubMed2003

Structural transformations of oligomeric intermediates in the fibrillation of the immunoglobulin light chain LEN.

LEN is a kappaIV immunoglobulin light chain variable domain from a patient suffering from multiple myeloma but with no evidence of amyloid fibrils. However, fibrils are formed when LEN solutions are agitated under mildly destabilizing conditions. Surprisingly, an inverse concentration dependence was observed on the kinetics of fibril formation because of the formation of off-pathway soluble oligomers at high protein concentration. Despite the fact that most of the protein is present in the off-pathway intermediates at relatively early times of aggregation, eventually all the protein forms fibrils. Thus, a structural rearrangement from the non fibril-prone off-pathway oligomers to a more fibril-prone species must occur. A variety of techniques were used to monitor changes in the size, secondary structure, solvent accessibility, and intrinsic stability of the oligomers, as a function of incubation time. The structural rearrangement was accompanied by a significant increase of disordered secondary structure, an increase in solvent accessibility, and a decrease in intrinsic stability of the soluble oligomeric species. We conclude that fibrils arise from the oligomers containing a less stable conformation of LEN, either directly or via dissociation. This is the first fibrillating system in which soluble off-pathway oligomeric intermediates have been shown to be the major transient species and in which fibrillation occurs from a relatively unfolded conformation present in these intermediates.

Amyloid↗
PubMed1985

Spectral differences between rhodanese catalytic intermediates unrelated to enzyme conformation.

Circular dichroism (CD) spectra and UV absorption spectra of two obligatory intermediates in rhodanese catalysis were compared. A broad CD band between 250 and 287 nm increased in a manner stoichiometrically related to the content of enzyme-bound persulfide. Titration of a sample of sulfur-substituted rhodanese (ES) with either cyanide or sulfite gave a stoichiometry that is consistent with one persulfide/molecule of rhodanese (Mr = 33,000). This result agrees with that determined by x-ray crystallography and a method based on quenching of intrinsic fluorescence. Cyanolysis of the persulfide in ES is accompanied by a decrease of UV absorption in the region between 250 and 300 nm. Cyanide titrations followed by the change in absorbance at 263, 272, and 292 nm gave the expected stoichiometry. The magnitude of the difference between the far UV-CD spectra of E and ES found here is smaller than reported previously. This variability suggests that the differences in the secondary structure of these intermediates may not be obligatorily related to the cyanolysis of the persulfide. This view is compatible with recent evidence which suggested that E and ES may be made different by structural relaxation events that occur outside of the catalytic cycle. Furthermore, the methods developed here will be useful in studies on the stability of the catalytic persulfide that has been suggested to be central in the mechanism of several enzymes important in sulfur metabolism.

Animals↗
PubMed2003

Dermatologist detection and skin self-examination are associated with thinner melanomas: results from a survey of the Italian Multidisciplinary Group on Melanoma.

OBJECTIVE: To investigate patterns of detection and variables associated with early diagnosis of melanoma in a population at intermediate melanoma risk. DESIGN: Survey. SETTING: Hospital and university centers belonging to the Italian Multidisciplinary Group on Melanoma. PATIENTS: Eight hundred sixteen patients who were consecutively diagnosed as having melanoma and treated at 11 participating centers. MAIN OUTCOME MEASURE: Relationship between patterns of detection and patient's and physician's delay with melanoma thickness, assessed by multivariate analysis. RESULTS: A statistically significant association with early diagnosis was found for female sex (odds ratio [OR] for a lesion >1 mm in thickness, 0.70; 95% confidence interval [CI], 0.50-0.97), higher educational level (OR, 0.44; 95% CI, 0.24-0.79), residence in northern and central Italy (compared with southern Italy) (OR, 0.44; 95% CI, 0.30-0.65 and OR, 0.24; 95% CI, 0.15-0.37, respectively), and the habit of performing a skin self-examination (OR, 0.65; 95% CI, 0.45-0.93). When adjusted for all the previously mentioned variables, only melanoma detection made by a dermatologist, maybe incidentally, was associated with a statistically significant additional effect on early diagnosis (OR, 0.45; 95% CI, 0.28-0.73). No significant effect of anatomical site (trunk compared with other sites: OR, 0.83; 95% CI, 0.59-1.17), presence of atypical nevi (OR, 0.78; 95% CI, 0.52-1.17), and patient's delay (>3 months compared with < or =3 months: OR, 1.12; 95% CI, 0.78-1.60) was found. CONCLUSION: Future melanoma early diagnosis strategies should adequately stress the role of skin self-examination among the adult population, and should recommend that dermatologists perform a total skin examination to identify suspect lesions (such an examination should also be performed during consultations for other reasons).

Adult↗