Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: The role of primary infection

Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during 1981-1983 had active infection with Epstein-Barr virus (EBV)of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions. © 1985 by The University of Chicago

A fluorescence approach to investigate repartitioning of coalescing agents in acrylic polymer emulsions

Repartitioning of co-solvents between particles of latex emulsions was investigated by means of a fluorescence method based on the detection of the amount of co-solvent via the solvatochromic shift of the emission maximum of a fluorescent probe, copolymerized at a low concentration. Complete repartitioning of co-solvents between particles of latex materials with a low Tg (ca. 25 °C) occurred within minutes. For a hydrophilic latex with a Tg of 68 °C, equilibration was achieved within an hour. Repartitioning was faster for more hydrophobic co-solvents. For a hydrophobic latex of similar Tg, co-solvent repartitioning took place on the same time scale, but complete equilibration was not reached. Possibly, there is an additional slow component in the repartitioning, or the prolonged presence of co-solvent causes a structural change in the latex particles that affects the outcome of the experiment

Seroprevalence of malaria in inhabitants of the urban zone of Antananarivo, Madagascar

BACKGROUND: Antananarivo, the capital of Madagascar, is located at an altitude of over 1,200 m. The environment at this altitude is not particularly favourable to malaria transmission, but malaria nonetheless remains a major public health problem. The aim of this study was to evaluate exposure to malaria in the urban population of Antananarivo, by measuring the specific seroprevalence of Plasmodium falciparum. METHODS: Serological studies specific for P. falciparum were carried out with an indirect fluorescent antibody test (IFAT). In a representative population of Antananarivo, 1,059 healthy volunteers were interviewed and serum samples were taken. RESULTS: The seroprevalence of IgG+IgA+IgM was 56.1% and that of IgM was 5.9%. The major risk factor associated with a positive IgG+IgA+IgM IFAT was travel outside Antananarivo, whether in the central highlands or on the coast. The abundance of rice fields in certain urban districts was not associated with a higher seroprevalence. CONCLUSION: Malaria transmission levels are low in Antananarivo, but seroprevalence is high. Humans come into contact with the parasite primarily when travelling outside the city. Further studies are required to identify indigenous risk factors and intra-city variations more clearly

Functional Interchangeability of Late Domains, Late Domain Cofactors and Ubiquitin in Viral Budding

The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L-) domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1). It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV), where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed

The expansion field: The value of H_0

Any calibration of the present value of the Hubble constant requires recession velocities and distances of galaxies. While the conversion of observed velocities into true recession velocities has only a small effect on the result, the derivation of unbiased distances which rest on a solid zero point and cover a useful range of about 4-30 Mpc is crucial. A list of 279 such galaxy distances within v<2000 km/s is given which are derived from the tip of the red-giant branch (TRGB), from Cepheids, and from supernovae of type Ia (SNe Ia). Their random errors are not more than 0.15 mag as shown by intercomparison. They trace a linear expansion field within narrow margins from v=250 to at least 2000 km/s. Additional 62 distant SNe Ia confirm the linearity to at least 20,000 km/s. The dispersion about the Hubble line is dominated by random peculiar velocities, amounting locally to <100 km/s but increasing outwards. Due to the linearity of the expansion field the Hubble constant H_0 can be found at any distance >4.5 Mpc. RR Lyr star-calibrated TRGB distances of 78 galaxies above this limit give H_0=63.0+/-1.6 at an effective distance of 6 Mpc. They compensate the effect of peculiar motions by their large number. Support for this result comes from 28 independently calibrated Cepheids that give H_0=63.4+/-1.7 at 15 Mpc. This agrees also with the large-scale value of H_0=61.2+/-0.5 from the distant, Cepheid-calibrated SNe Ia. A mean value of H_0=62.3+/-1.3 is adopted. Because the value depends on two independent zero points of the distance scale its systematic error is estimated to be 6%. Typical errors of H_0 come from the use of a universal, yet unjustified P-L relation of Cepheids, the neglect of selection bias in magnitude-limited samples, or they are inherent to the adopted models.Comment: 44 pages, 4 figures, 6 tables, accepted for publication in the Astronony and Astrophysics Review 15

NaV1.7 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders.

Contains fulltext : 70933.pdf (publisher's version ) (Open Access)Gain-of-function mutations of Na(V)1.7 have been shown to produce two distinct disorders: Na(V)1.7 mutations that enhance activation produce inherited erythromelalgia (IEM), characterized by burning pain in the extremities; Na(V)1.7 mutations that impair inactivation produce a different, nonoverlapping syndrome, paroxysmal extreme pain disorder (PEPD), characterized by rectal, periocular, and perimandibular pain. Here we report a novel Na(V)1.7 mutation associated with a mixed clinical phenotype with characteristics of IEM and PEPD, with an alanine 1632 substitution by glutamate (A1632E) in domain IV S4-S5 linker. Patch-clamp analysis shows that A1632E produces changes in channel function seen in both IEM and PEPD mutations: A1632E hyperpolarizes (-7 mV) the voltage dependence of activation, slows deactivation, and enhances ramp responses, as observed in Na(V)1.7 mutations that produce IEM. A1632E depolarizes (+17mV) the voltage dependence of fast inactivation, slows fast inactivation, and prevents full inactivation, resulting in persistent inward currents similar to PEPD mutations. Using current clamp, we show that A1632E renders dorsal root ganglion (DRG) and trigeminal ganglion neurons hyperexcitable. These results demonstrate a Na(V)1.7 mutant with biophysical characteristics common to PEPD (impaired fast inactivation) and IEM (hyperpolarized activation, slow deactivation, and enhanced ramp currents) associated with a clinical phenotype with characteristics of both IEM and PEPD and show that this mutation renders DRG and trigeminal ganglion neurons hyperexcitable. These observations indicate that IEM and PEPD mutants are part of a physiological continuum that can produce a continuum of clinical phenotypes