Human Enterovirus Diversity by Next-Generation Sequencing Analysis in Urban Sewage Samples From Buenos Aires Metropolitan Area, Argentina: A Retrospective Study.

Human Enteroviruses (hEVs) are responsible for a wide variety of human diseases. During hEVs infection, virions are excreted in human feces and the fecal-oral route is the primary pathway for person-to-person transmission. Sewage surveillance could help in monitoring hEVs circulation and describing their diversity in a specific population. In this study, sewage samples collected in Buenos Aires Metropolitan Area (Argentina) were retrospectively studied through an amplicon-deep sequencing approach and phylogenetic analyses to characterize hEVs spread. We identified 17 different hEVs types belonging to A, B, and C species. To the best of our knowledge, this is the first report in Buenos Aires for 7 identified hEV-C types. Phylogenetic analyses suggest several introductions of coxsackievirus B4, echovirus 1, and echovirus 9 in the country, along with the national spread reached by some variants. Besides, well-supported monophyletic groups of Argentine, Uruguayan, and Brazilian strains unveiled regional circulation patterns for some variants. These results extend our knowledge about hEVs circulation in Buenos Aires and might exhort authorities to implement more active sewage surveillance in the region.

Predictors and outcomes of disseminated tuberculosis in an intermediate burden setting.

SETTING: University-affiliated hospital located in Porto, North Portugal, an area with a low to intermediate incidence of tuberculosis (TB). OBJECTIVE: To identify predictors and outcomes of disseminated TB (dTB). DESIGN: A cohort of patients diagnosed with TB between 2007 and 2013 was retrospectively analysed. Patients with dTB criteria were characterized and compared to single organ TB cases. Factors independently associated with dTB were determined by multivariate logistic regression analysis. RESULTS: A total of 744 patients were analysed, including 145 with dTB. Independent risk factors for dTB were pharmacological immunosuppression (OR 5.6, 95% CI 2.8-11.3), HIV infection (OR 5.1, 95% CI 3.1-8.3), chronic liver failure or cirrhosis (OR 2.3, 95% CI 1.4-4.1) and duration of symptoms (OR 2.3, 95% CI 1.4-3.8). Compared to single organ TB, the clinical presentation of dTB patients differed by the absence of haemoptysis (OR 3.2, 95% CI 1.3-8.4) and of dyspnoea (OR 1.9, 95% CI 1.2-3.1), presence of weight loss (OR 1.8, 95% CI 1.1-2.9), night sweats (OR 1.7, 95% CI 1.1-2.7) and bilateral lung involvement (OR 4.4, 95% CI 2.8-7.1). Mortality and time until culture conversion were higher for dTB patients, although not reaching statistical significance. CONCLUSION: Immunosuppressive conditions and chronic liver failure or cirrhosis were associated with increased risk of dTB. The haematogenous spread may be dependent on longer symptomatic disease and usually progresses with bilateral lung involvement.

Substance P and Calcitonin gene-related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files.

AIM: To quantify Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament from premolars after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files. METHODOLOGY: A total of 50 human periodontal ligament samples were obtained from healthy mandibular premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 40 of these premolars were equally divided into four groups, and root canals were prepared using four different systems: Reciproc Blue, WaveOne Gold, XP EndoShaper and a hand instrumentation technique. The remaining 10 healthy premolars were extracted without treatment and served as a negative control group. All periodontal ligament samples were processed, and SP and CGRP were measured by radioimmunoassay. The Kruskal-Wallis test was used to establish significant differences between groups and LSD post hoc comparisons were also performed. RESULTS: Greater SP and CGRP values were found in the hand instrumentation group, followed by the XP EndoShaper, WaveOne Gold and the Reciproc groups. The lower SP and CGRP values were for the healthy periodontal ligament group. The Kruskal-Wallis test revealed significant differences between groups (P < 0.05). Post hoc Least Significant Difference (LSD) tests revealed significant differences (P < 0.05) in SP and CGRP expression between all the comparisons except for the Reciproc Blue and WaveOne Gold group (P > 0.05). CONCLUSION: All the root canal preparation techniques tested increased SP and CGRP expression in human periodontal ligament, with hand files and XP EndoShaper instruments being associated with greater neuropeptide release compared to Reciproc Blue and WaveOne Gold files.

Satellite DNA methylation status and expression of selected genes in Bos indicus blastocysts produced in vivo and in vitro.

Bovine embryos produced in vivo and in vitro differ with respect to molecular profiles, including epigenetic marks and gene expression profiles. This study investigated the CpG methylation status in bovine testis satellite I (BTS) and Bos taurus alpha satellite I (BTαS) DNA sequences, and concomitantly the relative abundance of transcripts, critically involved in DNA methylation (DNMT1 and DNMT3A), growth and development (IGF2R) and pluripotency (POU5F1) in Bos indicus embryos produced in vitro or in vivo. Results revealed that methylation of BTS were higher (P < 0.05) in embryos produced in vitro compared with their in vivo produced counterparts, while the methylation status of BTαS was similar in both groups. There were no significant differences in transcript abundance for DNMT3A, IGF2R and POU5F1 between blastocysts produced in vivo and in vitro. However, a significantly lower amount of DNMT1 transcripts was found in the in vitro cultured embryos (P < 0.05) compared with their in vivo derived counterparts. In conclusion, this study reported only minor changes in the expression of developmentally important genes and satellite DNA methylation related to the in vitro embryo production system.

Biodiesel production from crude Jatropha oil catalyzed by non-commercial immobilized heterologous Rhizopus oryzae and Carica papaya lipases.

The aim of this study was to evaluate the feasibility of biodiesel production by transesterification of Jatropha oil with methanol, catalyzed by non-commercial sn-1,3-regioselective lipases. Using these lipases, fatty acid methyl esters (FAME) and monoacylglycerols are produced, avoiding the formation of glycerol as byproduct. Heterologous Rhizopus oryzae lipase (rROL) immobilized on different synthetic resins and Carica papaya lipase (rCPL) immobilized on Lewatit VP OC 1600 were tested. Reactions were performed at 30°C, with seven stepwise methanol additions. For all biocatalysts, 51-65% FAME (theoretical maximum=67%, w/w) was obtained after 4h transesterification. Stability tests were performed in 8 or 10 successive 4h-batches, either with or without rehydration of the biocatalyst between each two consecutive batches. Activity loss was much faster when biocatalysts were rehydrated. For rROL, half-life times varied from 16 to 579h. rROL on Lewatit VPOC 1600 was more stable than for rCPL on the same support.

Platelet-activating factor induces cell cycle arrest and disrupts the DNA damage response in mast cells.

Platelet-activating factor (PAF) is a potent phospholipid modulator of inflammation that has diverse physiological and pathological functions. Previously, we demonstrated that PAF has an essential role in ultraviolet (UV)-induced immunosuppression and reduces the repair of damaged DNA, suggesting that UV-induced PAF is contributing to skin cancer initiation by inducing immune suppression and also affecting a proper DNA damage response. The exact role of PAF in modulating cell proliferation, differentiation or transformation is unclear. Here, we investigated the mechanism(s) by which PAF affects the cell cycle and impairs early DNA damage response. PAF arrests proliferation in transformed and nontransformed human mast cells by reducing the expression of cyclin-B1 and promoting the expression of p21. PAF-treated cells show a dose-dependent cell cycle arrest mainly at G2-M, and a decrease in the DNA damage response elements MCPH1/BRIT-1 and ataxia telangiectasia and rad related (ATR). In addition, PAF disrupts the localization of p-ataxia telangiectasia mutated (p-ATM), and phosphorylated-ataxia telangiectasia and rad related (p-ATR) at the site of DNA damage. Whereas the potent effect on cell cycle arrest may imply a tumor suppressor activity for PAF, the impairment of proper DNA damage response might implicate PAF as a tumor promoter. The outcome of these diverse effects may be dependent on specific cues in the microenvironment.

Follicular progesterone concentrations and messenger RNA expression of MATER and OCT-4 in immature bovine oocytes as predictors of developmental competence.

The ability of bovine embryos to develop to the blastocyst stage and to implant and generate healthy offspring depends greatly on the competence of the oocyte. Oocyte competence is attributed to its close communication with the follicular environment and to its capacity to synthesize and store substantial amounts of messenger RNA. Higher developmental competence of bovine oocytes has been associated with both the expression of a cohort of developmental genes and the concentration of sex steroids in the follicular fluid. The aim of this study was to identify differences in the expression of FST in cumulus cells and OCT-4 and MATER in oocytes and the influence of the follicular progesterone and follicular estrogen concentration on the competence of bovine oocytes retrieved 30 minutes or 4 hours after slaughter. Cumulus-oocyte complexes (COCs) were left in postmortem ovaries for 30 minutes (group I) or 4 hours (group II) at 30 °C. Aspirated oocytes were then subjected to IVM, IVF, and IVC or were evaluated for MATER and OCT-4 messenger RNA abundance by quantitative real-time polymerase chain reaction. Total RNA was isolated from pools of 100 oocytes for each experimental replicate. Progesterone and estradiol concentration in follicular fluid was evaluated by immunoassay using an IMMULITE 2000 analyzer. Three repeats of in vitro embryo production were performed with a total of 455 (group I) and 470 (group II) COCs. There were no significant differences between the cleavage rates (72 hours postinsemination [hpi]) between both groups (63.5% vs. 69.1%). However, blastocyst (168 hpi) and hatching (216 hpi) rates were higher (P < 0.05) in group II compared with those of group I (21.3% vs. 30.7% and 27.6% vs. 51.5%, respectively). Group II oocytes exhibited the highest MATER and OCT-4 abundance (P < 0.05). Follicular estradiol concentration was not different between both the groups, whereas the progesterone concentration was lower (P ≤ 0.05) in group II follicles. These results indicate that retrieving COCs 4 hours after slaughter could increase bovine in vitro developmental competence, which is linked to higher levels of oocyte MATER and OCT-4 transcripts and lower follicular progesterone concentration. Moreover, the results of the present study contribute to the identification of factors involved in the developmental competence of immature oocytes.

A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining.

Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53(R172P), which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4(-/-)p53(R172P) mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70(-/-) p53(R172P) mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4(-/-)p53(R172P) phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70(-/-)p53(R172P) colonic epithelial cells show nuclear stabilization of ß-catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70(-/-) mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.

Glutathione in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterised mainly as an autoimmune neurodegenerative disorder. Its cause is unknown but multifactorial; however, some studies suggest that oxidative stress may be one of the sources, or a consequence of the disease, from loss of oxidant/antioxidant balance. This review studies glutathione, one of the most important agents of the endogenous antioxidant defence system, protecting cells from damage caused by oxidative stress. It evaluates glutathione and the enzymes glutathione peroxidase and glutathione reductase in various forms and stages of the disease. Analysis of a literature search suggests that the scientific community is not unanimous in its views, so more studies are required of patients with different forms of the disease and its manifestations, taking into account that the body functions as a whole and reacts in a compensatory manner. It would seem imperative to achieve a consensus on the pathogenesis responsible for severe disability, and explore sensitive biomarkers of its progression and indicators of oxidative stress. It is also important to promote the development of new therapies, with more studies on other substances such as acrolein, lipoic acid and dimethyl fumarate. Clarification of the mechanisms involved in oxidative stress, in different forms of multiple sclerosis, could result in improvements in the monitoring and prognosis of the disease, with subsequent increases in a patient's quality of life.

Reprogramming mammalian somatic cells.

Somatic cell nuclear transfer (SCNT), the technique commonly known as cloning, permits transformation of a somatic cell into an undifferentiated zygote with the potential to develop into a newborn animal (i.e., a clone). In somatic cells, chromatin is programmed to repress most genes and express some, depending on the tissue. It is evident that the enucleated oocyte provides the environment in which embryonic genes in a somatic cell can be expressed. This process is controlled by a series of epigenetic modifications, generally referred to as "nuclear reprogramming," which are thought to involve the removal of reversible epigenetic changes acquired during cell differentiation. A similar process is thought to occur by overexpression of key transcription factors to generate induced pluripotent stem cells (iPSCs), bypassing the need for SCNT. Despite its obvious scientific and medical importance, and the great number of studies addressing the subject, the molecular basis of reprogramming in both reprogramming strategies is largely unknown. The present review focuses on the cellular and molecular events that occur during nuclear reprogramming in the context of SCNT and the various approaches currently being used to improve nuclear reprogramming. A better understanding of the reprogramming mechanism will have a direct impact on the efficiency of current SCNT procedures, as well as iPSC derivation.

The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

Transcriptome analysis of bull spermatozoa: implications for male fertility.

Spermatozoa deliver more than the paternal genome into the oocyte; they also carry remnant messenger RNA from spermatogenesis. The RNA profiles of spermatozoa from high-fertility and a low-fertility Holstein bulls were analysed using Affymetrix bovine genechips. A total of 415 transcripts out of approximately 24,000 were differentially detected in spermatozoa collected from both bulls (fold change > or =2.0; P<0.01). These transcripts were associated with different cellular functions and biological processes. Spermatozoa from high-fertility bulls contained higher concentrations of transcripts for membrane and extracellular space protein locations, while spermatozoa from the low-fertility bulls were deficient of transcripts for transcriptional and translational factors. Quantitative real-time PCR was used on three low-fertility and four high-fertility bulls to validate the microarray data. Two highly represented transcripts in the microarray analysis (protamine 1 and casein beta 2) were validated, as well as a third transcript (thrombospondin receptor CD36 molecule) that showed a lower concentration in low-fertility bulls. This study presents the global analysis of spermatozoa originating from bulls with opposite fertility. These results provide some specific transcripts in spermatozoa that could be associated with bull fertility.

ATM and p53 are essential in the cell-cycle containment of DNA breaks during V(D)J recombination in vivo.

V(D)J recombination is essential for the maturation of lymphocytes. Because of the involvement of cutting and joining DNA double strands, this recombination activity is strictly contained within the noncycling phases of the cell cycle. Such containment is crucial for the maintenance of genomic integrity. The ataxia telangiectasia mutated (ATM) gene is known to have a central role in sensing general DNA damage and mediating cell-cycle checkpoint. In this study, we investigated the role of ATM and its downstream targets in the cell-cycle control of V(D)J recombination in vivo. Our results revealed the persistence of double-strand breaks (DSBs) throughout the cell cycle in ATM(-/-) and p53(-/-) thymocytes, but the cell-cycle regulation of a V(D)J recombinase, Rag-2, was normal. The histone variant H2AX, which is phosphorylated during normal V(D)J recombination, was dispensable for containing DSBs. H2AX was still phosphorylated at V(D)J loci in the absence of ATM. Therefore, V(D)J recombination, a physiological DNA rearrangement process, activates the ATM/p53 pathway to contain DNA breaks within the noncycling cells and surprisingly this pathway is not important for containing Rag-2 activity. This study shows the dynamic multiple functions of ATM in maintaining genomic stability and preventing tumorigenesis in developing lymphocytes.

Neurodevelopmental delay in the Cln3Deltaex7/8 mouse model for Batten disease.

Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is a fatal inherited neurodegenerative disorder. The major clinical features of this disease are vision loss, seizures and progressive cognitive and motor decline starting in childhood. Mutations in CLN3 are known to cause the disease, allowing the generation of mouse models that are powerful tools for JNCL research. In this study, we applied behavioural phenotyping protocols to test for early behavioural alterations in Cln3(Deltaex7/8) knock-in mice, a genetic model that harbours the most common disease-causing CLN3 mutation. We found delayed acquisition of developmental milestones, including negative geotaxis, grasping, wire suspension time and postural reflex in both homozygous and heterozygous Cln3(Deltaex7/8) preweaning pups. To further investigate the consequences of this neurodevelopmental delay, we studied the behaviour of juvenile mice and found that homozygous and heterozygous Cln3(Deltaex7/8) knock-in mice also exhibit deficits in exploratory activity. Moreover, when analysing motor behaviour, we observed severe motor deficits in Cln3(Deltaex7/8) homozygous mice, but only a mild impairment in motor co-ordination and ambulatory gait in Cln3(Deltaex7/8) heterozygous animals. This study reveals previously overlooked behaviour deficits in neonate and young adult Cln3(Deltaex7/8) mice indicating neurodevelopmental delay as a putative novel component of JNCL.

Melatonin increases cleavage rate of porcine preimplantation embryos in vitro.

Melatonin has been used to promote in vitro embryo development in different species. This study determined the effects of melatonin on in vitro porcine embryo development; in particular, cleavage rate, blastocyst rate, and blastocyst cell number. Starting 5 hr after insemination, porcine zygotes were cultured in porcine zygote medium 3 (PZM-3) culture medium supplemented with melatonin at increasing concentrations (10(-12) M, 10(-9) M, 10(-6) M, 10(-3) M). Melatonin at a concentration of 10(-9) M had a positive effect on cleavage rates, while the highest concentration of melatonin (10(-3) M) significantly decreased cleavage rates. Although blastocyst rates were not increased by 10(-9) M melatonin, blastocyst cell numbers were significantly higher for embryos subjected to 10(-9) M melatonin. The expression levels of the pro-apoptotic gene BAX and anti-apoptotic gene BCL2L1 in blastocysts were not affected by the presence of melatonin in the culture medium. To further study the protective properties of 10(-9) M melatonin against stressful conditions, hydrogen peroxide (0.01 mm) and heat (40 degrees C) were used during embryo culture. The addition of melatonin to embryos subjected to 40 degrees C for 3 hr increased cleavage rates, but had no protective effect for embryos subjected to 0.01 mm H(2)O(2), probably because the physiological levels of melatonin could not counteract the pharmacological levels of H(2)O(2). Our data indicate that 10(-9) M melatonin has a positive effect on porcine embryo cleavage rates and blastocyst total cell numbers and it might have a protective effect against heat stress.

2,3,7,8-Tetrachlorodibenzo-p-dioxin elicits aryl hydrocarbon receptor-mediated apoptosis in the avian DT40 pre-B-cell line through activation of caspases 9 and 3.

The halogenated aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to induce immunotoxicity, but relatively little is known regarding its effects on B-lymphocytes, and on avian B-cells in particular. In this study, the avian bursal pre-B-cell line DT40 was exposed to TCDD ranging from 1 to 500 nM for 1 and 6 h. At 100 nM, TCDD caused a significant increase in the number of apoptotic cells, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay, and induced the expression of the chicken cytochrome P450 1A4 (CYP1A4) mRNA, a hallmark of TCDD exposure. TCDD induced transient upregulation of aryl hydrocarbon receptor (AhR) mRNA. At 100 nM, both caspase 3 and caspase 9 were transiently upregulated after 1 h, but returned to normal levels after 6 h of exposure. Challenge with TCDD after AhR blockade with resveratrol, a competitive AhR antagonist, prevented changes in caspases 3 and 9 and in the AhR message itself, suggesting that the effects of TCDD were mediated via the AhR. TCDD did not cause significant changes in the relative gene expression of caspase 8, Bcl-2 and Bcl-xL. We conclude that avian DT40 pre-B-cells exposed to TCDD are susceptible to apoptosis, likely through activation of executioner caspase 3.

FSH- and LH-cells originate as separate cell populations and at different embryonic stages in the chicken embryo.

The histological distribution of gonadotrophs containing either LH or FSH, but not both gonadotropins, has been demonstrated before in the juvenile and adult chicken throughout the caudal and cephalic anterior pituitary lobes. In the present investigation, the distribution of FSH- and/or LH-containing gonadotrophs was further investigated in the chicken embryo by use of the same homologous antibodies as used in our earlier study. Fluorescent dual-labeling immunohistochemistry revealed that during embryogenesis LH and FSH reside exclusively in separate gonadotrophs, as has been described before in the post hatch bird. LH-immunoreactive cells were observed for the first time at day 9 of embryogenesis. This is as much as 4 days earlier than the FSH-immunoreactive cells, which appeared at day 13 of embryogenesis. Our results confirm that FSH- and LH-containing gonadotrophs are distributed throughout both lobes of the anterior pituitary. No conspicuous differences were observed between the sexes in any of the aspects investigated. The described situation is unique in that it seems to imply the existence of separate cell lineages for FSH- and LH-producing cells, as opposed to the single gonadotrope lineage described in all other species studied so far, with the exception of bovine. Our data indeed raise the question as to which signaling and/or transcription factors may cause the unique dichotomy observed in the chicken gonadotrophs.

Three herpes simplex virus type 1 latency-associated transcript mutants with distinct and asymmetric effects on virulence in mice compared with rabbits.

Herpes simplex virus type 1 latency-associated transcript (LAT)-null mutants have decreased reactivation but normal virulence in rabbits and mice. We report here on dLAT1.5, a mutant with LAT nucleotides 76 to 1667 deleted. Following ocular infection of rabbits, dLAT1.5 reactivated at a lower rate than its wild-type parent McKrae (6.1 versus 11.8%; P = 0.0025 [chi-square test]). Reactivation was restored in the marker-rescued virus dLAT1.5R (12.6%; P = 0.53 versus wild type), confirming the importance of the deleted region in spontaneous reactivation. Compared with wild-type or marker-rescued virus, dLAT1.5 had similar or slightly reduced virulence in rabbits (based on survival following ocular infection). In contrast, in mice, dLAT1.5 had increased virulence (P < 0.0001). Thus, deletion of LAT nucleotides 76 to 1667 increased viral virulence in mice but not in rabbits. In contrast, we also report here that LAT2.9A, a LAT mutant that we previously reported to have increased virulence in rabbits (G. C. Perng, S. M. Slanina, A. Yuhkt, B. S. Drolet, W. J. Keleher, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 73:920-929, 1999), had decreased virulence in mice (P = 0.03). In addition, we also found that dLAT371, a LAT mutant that we previously reported to have wild-type virulence in rabbits (G. C. Perng, S. M. Slanina, H. Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 70:2014-2018, 1996), had decreased virulence in mice (P < 0.05). Thus, these three mutants, each of which encodes a different LAT RNA, have different virulence phenotypes. dLAT1.5 had wild-type virulence in rabbits but increased virulence in mice. In contrast, LAT2.9A had increased virulence in rabbits but decreased virulence in mice, and dLAT371 had wild-type virulence in rabbits but decreased virulence in mice. Taken together, these results suggest that (i) the 5' end of LAT and/or a gene that overlaps part of this region is involved in viral virulence, (ii) this virulence appears to have species-specific effects, and (iii) regulation of this virulence may be complex.

Development of multiple warts after skin resurfacing with CO2 laser.

BACKGROUND: Skin resurfacing with CO2 laser is a common surgical procedure to improve photodamaged skin. Many complications may occur after this procedure, however, common warts is relatively rare. OBJECTIVE: To report a case of multiple warts after CO2 laser resurfacing and discuss the complete involution of these lesions. METHODS: A 78-year-old woman with multiple warts after CO2 laser resurfacing is described. RESULTS: The patient developed multiple common warts on the face after resurfacing with CO2 laser. Retinoic acid was introduced and complete involution of the lesions was observed after 5 days with no scars. CONCLUSION: Although emphasis is placed on the hazards of the laser plume to the medical staff, one should be aware of this complication. We believe that the regression of the lesions was spontaneous rather than induced by the retinoic acid.