The Smads are the signaling mediators of the TGFb superfamily. In the present study, we examined Smad expression in mouse epidermis and chemically-induced skin tumors. Mutations in Smad2 and -4 genes were also screened. Transcripts of Smad1 through -5 were constantly expressed in the epidermis regardless of changes in TGFb signaling, state of dierentiation and stages of carcinogenesis. Smad7 transcripts were barely detectable in keratinocytes, but were induced by TGFb1 treatment and in chemically-induced skin tumors. At the protein level, Smad1 was detected throughout the epidermis, whereas Smad2 through -5 exhibited greater levels in suprabasal layers than basal keratinocytes. In cultured keratinocytes, Smad2, -3 and -4 underwent nuclear translocation upon TGFb1 treatment. Furthermore, nuclear translocation of Smads correlated with decreased BrdU labeling in proliferative keratinocytes. Although no mutations were detected in the Smad2 and -4 genes in tumors, proteins of Smad1 through -5 were partially or completely lost in carcinomas. These data document that Smads are expressed at high levels in the epidermis and mediate signaling of the TGFb superfamily. During skin carcinogenesis, loss of Smad1 through -5 and overexpression of Smad7 may contribute to the loss of growth inhibition mediated by TGFb superfamily members, thus resulting in tumor progression. Oncogene (2001) 20, 471 ± 483.
Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and in vitro-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping. Dengue is a mosquito-borne viral infection in humans that is of global importance. An estimated 390 million infections occur each year, of which 96 million result in clinically apparent infections, and in some epidemics the mortality rate may reach 5% (1, 2). Dengue viruses (DENVs) are members of the family Flaviviridae and consist of four antigenically distinct serotypes which exhibit 65% to 70% sequence homology (3). Disease manifestations range from mild undifferentiated acute dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (4, 5). After an incubation period of 2 to 10 days, a primary infection presents with the acute onset of high fever (Ն40°C), accompanied by headache, retroorbital pain, generalized myalgias, arthralgias, and malaise. The early phase of DHF or DSS has similar clinical features; however, after defervescence, new abdominal pain, nausea, and vomiting, followed by thrombocytopenia and a rise in hematocrit, may progress to shock leading to multiorgan dysfunction, life-threatening hemorrhage, and death. DF symptoms may be clinically indistinguishable from acute febrile illness due to other infectious diseases such as influenza, malaria, measles, and chikungunya virus (CHIKV) infections. CHIKVs are alphaviruses belonging to the ...
Abstract. Chikungunya virus (CHIKV) spread rapidly throughout the Caribbean region in 2014, and the first serologically confirmed case was seen in Grenada in July. This study investigated the outbreak of CHIKV in Grenada to identify the distinguishing clinical manifestations and the symptoms that corresponded the closest with serological test results. Sera were tested by IgM enzyme-linked immunosorbent assay and polymerase chain reaction to distinguish between cases positive or negative for CHIKV. Of 493 cases, 426 (86%) tested positive for CHIKV. The diagnostic decision rule, "Define as CHIKV positive a patient presenting with joint pain and any combination of fever, body pain, or rash," produced the closest agreement (85%) with the serological test results (Cohen's kappa, k = 0.289, P value < 0.001). When laboratory facilities are not available for diagnostic confirmation, syndromic surveillance using these four symptoms could be useful to define cases during a CHIKV outbreak when CHIKV is the predominant circulating arbovirus.Arthropod-borne viruses (arboviruses) comprise many of the most important emerging pathogens due to their geographic expansion and their increasing impact on vulnerable populations.
The typical clinical presentation of several spotted fever group Rickettsia infections includes eschars. Clinical diagnosis of the condition is usually made by analysis of blood samples. We describe a more sensitive, noninvasive means of obtaining a sample for diagnosis by using an eschar swab specimen from patients infected with Rickettsia parkeri.
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