[Translated article] Spanish Academy of Dermatology and Venereology (AEDV) expert recommendations for the management of sexual transmitted parasitosis. Scabies, and pediculosis pubis.

Sexually transmitted infections are communicable diseases where the pathogen is transmitted through sexual contact. The Sexually Transmitted Infections Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) is engaged in the drafting of documents to guide dermatologists and health care personnel who treat Spanish patients with these infections. This document analyzes the epidemiological, clinical, therapeutic, and control characteristics of 2 sexually transmitted parasitosis: scabies due to Sarcoptes scabiei var. hominis, and pubic pediculosis due to Phthirus pubis. Both parasitoses share a sort of mixed spread through sexual and community transmission regardless of the route through which the infection was initially acquired. This specific feature creates particularities in the management and control of the infestation.

Spanish Academy of Dermatology and Venereology (AEDV) expert recommendations for the management of sexual transmitted parasitosis. Scabies, and pediculosis pubis. / Recomendaciones de expertos de la Academia Española de Dermatología (AEDV) para el manejo de las ectoparasitosis de transmisión sexual. Escabiosis y pediculosis púbica.

Sexually transmitted infections are communicable diseases where the pathogen is transmitted through sexual contact. The Sexually Transmitted Infections Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) is engaged in the drafting of documents to guide dermatologists and health care personnel who treat Spanish patients with these infections. This document analyzes the epidemiological, clinical, therapeutic, and control characteristics of 2 sexually transmitted parasitosis: scabies due to Sarcoptes scabiei var. hominis, and pubic pediculosis due to Phthirus pubis. Both parasitoses share a sort of mixed spread through sexual and community transmission regardless of the route through which the infection was initially acquired. This specific feature creates particularities in the management and control of the infestation.

SARS-CoV-2 systemic infection in a kidney transplant recipient: sequence analysis in clinical specimens.

OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.

[Utility of Pediatric Appendicitis Score and abdominal ultrasound in the diagnostic process of acute appendicitis]. / Utilidad del Pediatric Appendicitis Score y la ecografía abdominal en el proceso diagnóstico de apendicitis aguda.

INTRODUCTION: Pain in the right iliac fossa is a frequent reason for consultation and the diagnosis of appendicitis remains a challenge. The Pediatric Appendicitis Score (PAS) stratifies the risk of suffering appendicitis, and abdominal ultrasound provides information without irradiation. This study aims to correlate the score and the ultrasound with the screening of appendicitis and evaluate its efficiency. PATIENTS AND METHODS: Prospective study of cases and controls, analytical, observational and longitudinal. Patients <15 years of age, treated for suspected appendicitis in the emergency department of a II level center, were evaluated for 6 months. The data were analyzed univariate and bivariate, using nonparametric and parametric tests according to the distribution. RESULTS: 68 patients with pain in the right iliac fossa were included: 26 appendicitis (cases) (38.2%) and 42 (61.7%) other diagnoses (controls). The PAS in appendicitis was 7.5±1.8 and in other diagnoses 5.4±1.8 (p <0.01). At 70.5% with PAS ≥4 an ultrasound was performed (diagnosis of appendicitis 58.1%, discarded 25.6% and inconclusive 16.3%). Sensitivity and specificity were calculated by PAS groups only, and including ultrasound. The best result was for PAS ≥4 with ultrasound with a sensitivity of 96.2%, specificity 94.1%, PPV 96.1% and NPV 94.1%. CONCLUSIONS: PAS is a good screening tool for the diagnosis of appendicitis. Ultrasound presents a high efficiency for the diagnosis of appendicitis. This efficiency improves when performed in the group of patients with PAS ≥4.

INTRODUCCION: El dolor en fosa ilíaca derecha es un motivo frecuente de consulta y el diagnóstico de apendicitis sigue siendo un reto. El Pediatric Appendicitis Score (PAS) estratifica el riesgo de padecer apendicitis, y la ecografía abdominal aporta información sin irradiación. Este estudio pretende correlacionar su puntuación y la ecografía con el despistaje de apendicitis y valorar su rendimiento. MATERIAL Y METODOS: Estudio prospectivo de casos y controles, analítico, observacional y longitudinal. Se evaluó a los pacientes <15 años, atendidos por sospecha de apendicitis en urgencias de un centro de II nivel, durante 6 meses. Se analizaron los datos de forma univariante y bivariante, utilizando pruebas no paramétricas y paramétricas según la distribución. RESULTADOS: Se incluyeron 68 pacientes con dolor en fosa ilíaca derecha: 26 apendicitis (casos) (38,2%) y 42 (61,7%) otros diagnósticos (controles). El PAS en apendicitis fue de 7,5±1,8 y en otros diagnósticos de 5,4±1,8 (p <0,01). Al 70,5% con PAS ≥4 se les realizó una ecografía (diagnósticas de apendicitis 58,1%, descartaron 25,6% y no concluyentes 16,3%). Se calculó la sensibilidad y especificidad por grupos de PAS solamente, e incluyendo la ecografía. El mejor resultado fue para PAS ≥4 con realización de ecografía con una sensibilidad 96,2%, especificidad 94,1%, VPP 96,1% y VPN 94,1%. CONCLUSIONES: El PAS es una buena herramienta de cribado para el diagnóstico de apendicitis. La ecografía presenta un alto rendimiento para el diagnóstico de apendicitis. Este rendimiento mejora al realizarla en el grupo de pacientes con PAS ≥4.

Utilidad del Pediatric Appendicitis Score y la ecografía abdominal en el proceso diagnóstico de apendicitis aguda / Utility of Pediatric Appendicitis Score and abdominal ultrasound in the diagnostic process of acute appendicitis

Introducción: El dolor en fosa ilíaca derecha es un motivo frecuente de consulta y el diagnóstico de apendicitis sigue siendo un reto. El Pediatric Appendicitis Score (PAS) estratifica el riesgo de padecer apendicitis, y la ecografía abdominal aporta información sin irradiación. Este estudio pretende correlacionar su puntuación y la ecografía con el despistaje de apendicitis y valorar su rendimiento. Pacientes y métodos: Estudio prospectivo de casos y controles, analítico, observacional y longitudinal. Se evaluó a los pacientes <15 años, atendidos por sospecha de apendicitis en urgencias de un centro de II nivel, durante 6 meses. Se analizaron los datos de forma univariante y bivariante, utilizando pruebas no paramétricas y paramétricas según la distribución. Resultados: Se incluyeron 68 pacientes con dolor en fosa ilíaca derecha: 26 apendicitis (casos) (38,2%) y 42 (61,7%) otros diagnósticos (controles). El PAS en apendicitis fue de 7,5±1,8 y en otros diagnósticos de 5,4±1,8 (p<0,01). Al 70,5% con PAS ≥4 se les realizó una ecografía (diagnósticas de apendicitis 58,1%, descartaron 25,6% y no concluyentes 16,3%). Se calculó la sensibilidad y especificidad por grupos de PAS solamente, e incluyendo la ecografía. El mejor resultado fue para PAS ≥4 con realización de ecografía con una sensibilidad 96,2%, especificidad 94,1%, VPP 96,1% y VPN 94,1%. Conclusiones: El PAS es una buena herramienta de cribado para el diagnóstico de apendicitis. La ecografía presenta un alto rendimiento para el diagnóstico de apendicitis. Este rendimiento mejora al realizarla en el grupo de pacientes con PAS ≥4

Introduction: Pain in the right iliac fossa is a frequent reason for consultation and the diagnosis of appendicitis remains a challenge. The Pediatric Appendicitis Score (PAS) stratifies the risk of suffering appendicitis, and abdominal ultrasound provides information without irradiation. This study aims to correlate the score and the ultrasound with the screening of appendicitis and evaluate its efficiency. Patients and methods: Prospective study of cases and controls, analytical, observational and longitudinal. Patients <15 years of age, treated for suspected appendicitis in the emergency department of a II level center, were evaluated for 6 months. The data were analyzed univariate and bivariate, using nonparametric and parametric tests according to the distribution. Results: 68 patients with pain in the right iliac fossa were included: 26 appendicitis (cases) (38.2%) and 42 (61.7%) other diagnoses (controls). The PAS in appendicitis was 7.5±1.8 and in other diagnoses 5.4±1.8 (p <0.01). At 70.5% with PAS ≥4 an ultrasound was performed (diagnosis of appendicitis 58.1%, discarded 25.6% and inconclusive 16.3%). Sensitivity and specificity were calculated by PAS groups only, and including ultrasound. The best result was for PAS ≥4 with ultrasound with a sensitivity of 96.2%, specificity 94.1%, PPV 96.1% and NPV 94.1%. Conclusions: PAS is a good screening tool for the diagnosis of appendicitis. Ultrasound presents a high efficiency for the diagnosis of appendicitis. This efficiency improves when performed in the group of patients with PAS ≥4

The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane.

Hepatitis B x antigen up-regulates the liver expression of URG7 that contributes to sustain chronic virus infection and to increase the risk for hepatocellular carcinoma by its anti-apoptotic activity. We have investigated the subcellular localization of URG7 expressed in HepG2 cells and determined its membrane topology by glycosylation mapping in vitro. The results demonstrate that URG7 is N-glycosylated and located to the endoplasmic reticulum membrane with an Nlumen-Ccytosol orientation. The results imply that the anti-apoptotic effect of URG7 could arise from the C-terminal cytosolic tail binding a pro-apoptotic signaling factor and retaining it to the endoplasmic reticulum membrane.

Genetic analysis of the 2q33 region containing CD28-CTLA4-ICOS genes: association with non-Hodgkin's lymphoma.

There is strong evidence that altered immunological function entails an increased risk of lymphoma, although the current knowledge of aetiological factors for lymphomas is limited. The CTLA4 gene encodes a receptor that provides a negative signal to the T-cell once an immune response is initiated and completed. We analysed the 2q33 chromosomal region harbouring CD28, CTLA4 and ICOS genes, which are closely linked and have related functions in immune regulation, for association in 100 non-Hodgkin's lymphoma (NHL) patients and in 128 healthy controls; both groups originated from Sardinia. There was a strong association of the CTLA4 49A and the 3'-untranslated region (AT)(82) alleles with NHL [odds ratio (OR) = 2, 95% confidence interval (CI) = 1.2-3.2, and OR = 1.6, 95% CI = 1.1-2.4 respectively]. CTLA4-318C:49A:(AT)(82) was the most represented haplotype in the studied population and was associated with NHL (P = 0.0029, OR = 1.76, 95% CI = 1.2-2.5). Strong linkage disequilibrium was detected between CD28, CTLA4 and ICOS and a 'common' haplotype was found very frequently among NHLs. However, no independent association between CD28, ICOS, D2S72 markers and NHL was observed. Our findings enable CTLA4 from adjacent functionally related genes as the true causative risk gene for NHL susceptibility at least in Sardinian patients.

Formation of helical hairpins during membrane protein integration into the endoplasmic reticulum membrane. Role of the N and C-terminal flanking regions.

The helical hairpin, two closely spaced transmembrane helices separated by a short turn, is a common structural element in integral membrane proteins. Previous studies on the sequence determinants of helical hairpin formation have focussed on the role of polar and charged residues placed centrally in a long stretch of hydrophobic residues, and have yielded a "propensity scale" for the relative efficiency with which different residues promote the formation of helical hairpins. In this study, we shift our attention to the role of charged residues flanking the hydrophobic stretch. Clusters of charged residues are known to hinder membrane translocation, and thus flanking charged residues may conceivably force a long hydrophobic segment to form a helical hairpin even if there are no or only weakly turn-promoting residues in the hydrophobic stretch. We indeed find that Lys and, more surprisingly, Asp residues strongly affect helical hairpin formation when placed next to a poly-Leu-based transmembrane segment. We also find that a cluster of four consecutive Lys residues can affect the efficiency of helical hairpin formation even when placed approximately 30 residues downstream of the hydrophobic stretch. These observations have interesting implications for the way we picture membrane protein topogenesis within the context of the endoplasmic reticulum (ER) translocon.

Effects of 'hydrophobic mismatch' on the location of transmembrane helices in the ER membrane.

We have studied the effects of 'hydrophobic mismatch' between a poly-Leu transmembrane helix (TMH) and the ER membrane using a glycosylation mapping approach. The simplest interpretation of our results is that the lumenal end of the TMH is located deeper in the membrane for both short (negative mismatch) and long (positive mismatch) TMHs than for poly-Leu segments of intermediate length. We further find that the position-specific effect of Lys residues on the location of short TMHs in the membrane varies with an apparent helical periodicity when the Lys residue is moved along the poly-Leu stretch. We discuss these findings in the context of models for peptide-lipid interactions during hydrophobic mismatch.

[Episiotomy and puerperium at home]. / Episiotomía y puerperio domiciliario.

This article reports on an observational and prospective study by means of a telephone questionnaire carried out between three and six months after childbirth via vaginal delivery among 100 women; its purpose was to discover the differences among episiotomies, large, small and with tears, and their effects during puerperium, in order to make professionals aware of the importance of pain and the consequences of a episiotomy. 82% of the women contacted by telephone responded to this questionnaire. 74.4% of these patients had undergone a right mediolateral episiotomy; 12.2% of these patients had undergone a left mediolateral episiotomy. The delay in starting to have sexual relations was significant among those women who underwent a large episiotomy (> 4 cm) p < 0.001. Another finding was that the duration of dyspareunia increased significantly in relation to the size of the episiotomy, p < 0.0059; as well as the difference in hemoglobin before or intra-birth and postbirth, p < 0.0153 in the skin and 0.026 in the vagina. The relationship among pain, analgesia and size was significant in the skin readings, p < 0.007.

Turns in transmembrane helices: determination of the minimal length of a "helical hairpin" and derivation of a fine-grained turn propensity scale.

We have recently reported a first experimental turn propensity scale for transmembrane helices. This scale was derived from measurements of how efficiently a given residue placed in the middle of a 40 residue poly(Leu) stretch induces the formation of a "helical hairpin" with two rather than one transmembrane segment. We have now extended these studies, and have determined the minimum length of a poly(Leu) stretch compatible with the formation of a helical hairpin. We have also derived a more fine-grained turn propensity scale by (i) introducing each of the 20 amino acid residues into the middle of the shortest poly(Leu) stretch compatible with helical hairpin formation, and (ii) introducing pairs of residues in the middle of the 40 residue poly(Leu) stretch. The new turn propensities are consistent with the amino acid frequencies found in short hairpin loops in membrane proteins of known 3D structure.

N-tail translocation in a eukaryotic polytopic membrane protein: synergy between neighboring transmembrane segments.

We have used the natural N-glycosylation site in the N-tail of cig30, a eukaryotic polytopic membrane protein, as a marker for N-tail translocation across the microsomal membrane. Analysis of C-terminally truncated cig30 constructs reveals that the first transmembrane segment is sufficient for translocation of the wild-type N-tail; in contrast, in a mutant with four arginines introduced into the N-tail the second transmembrane segment is also required for efficient N-tail translocation. Our observations imply a non-sequential assembly mechanism in which the ultimate location of the N-tail relative to the membrane may depend on more than one transmembrane segment.

A turn propensity scale for transmembrane helices.

Using a model protein with a 40 residue hydrophobic transmembrane segment, we have measured the ability of all the 20 naturally occurring amino acids to form a tight turn when placed in the middle of the hydrophobic segment. Turn propensities in a transmembrane helix are found to be markedly different from those of globular proteins, and in most cases correlate closely with the hydrophobicity of the residue. The turn propensity scale may be used to improve current methods for membrane protein topology prediction.

Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helix.

We have studied the effects of single charged residues on the position of a model transmembrane helix in the endoplasmic reticulum membrane using the glycosylation mapping technique. Asp and Glu residues cause a re-positioning of the C-terminal end of the transmembrane helix when placed in the one to two C-terminal turns but not when placed more centrally. Arg and Lys residues, in contrast, have little effect when placed in the two C-terminal turn but give rise to a more substantial shift in position when placed 9-11 residues from the helix end. We suggest that this difference between the effects of positively and negatively charged residues can be explained by the so-called snorkel effect, i.e. that the very long side-chains of Arg and Lys can reach up along the transmembrane helix to allow the terminal, charged moiety to reside in the lipid headgroup region while the Calpha of the residue is positioned well below the membrane/water interface.

Membrane topology of the 60-kDa Oxa1p homologue from Escherichia coli.

We have characterized the membrane topology of a 60-kDa inner membrane protein from Escherichia coli that is homologous to the recently identified Oxa1p protein in Saccharomyces cerevisiae mitochondria implicated in the assembly of mitochondrial inner membrane proteins. Hydrophobicity and alkaline phosphatase fusion analyses suggest a membrane topology with six transmembrane segments, including an N-terminal signal-anchor sequence not present in mitochondrial Oxa1p. In contrast to partial N-terminal fusion protein constructs, the full-length protein folds into a protease-resistant conformation, suggesting that important folding determinants are present in the C-terminal part of the molecule.

[Mortality and hospital stay adjusted for severity as indicators of effectiveness and efficiency of the care provided to critically ill patients. European and North American Study of Severity Systems]. / Mortalidad y estancia hospitalaria ajustadas por gravedad como indicadores de efectividad y eficiencia de la atención a pacientes en estado crítico. European and North American Study of Severity Systems.

BACKGROUND: Hospital mortality and length of stay, both adjusted for severity of illness, have been used as indicators of effectiveness and efficiency of health care in critical patients. PATIENTS AND METHODS: 1,270 adult critical patients, consecutively admitted in 17 intensive care units (ICU) from Catalonia and the Balearic Islands, Spain, have been included. For each hospital, effectiveness has been assessed with a quality performance index (QOI) obtained by dividing the number of observed deaths by the number of deaths expected according to the MPM system (MPM II0). Efficiency has been assessed with a resource utilization index (RUI) obtained by dividing the number of observed weighted hospital days (WHD) by the number of expected WHD. WHD is a measure of resource use which weights ICU days more heavily than non-ICU days. Expected WHD have been obtained by a regression model including severity of illness and the presence/absence of surgery. RESULTS: Ten of the 17 hospitals life within one standard deviation of the mean on both clinical and economical indices. There are 3 hospitals with optimal values on both indices. There is no evidence of association between effectiveness and resource utilization. CONCLUSIONS: Clinical and economical performance of hospitals can be quantified with simple indicators which allow to compare centers. Hospitals can be effective and efficient at the same time.

A comparative analysis of prostate-specific antigen gene sequence in benign and malignant prostate tissue.

OBJECTIVES: Different molecular forms of prostate-specific antigen (PSA) appear to be expressed by benign prostatic hyperplasia (BPH) compared with prostate cancer. These differences are not well understood and may arise from aberrant RNA splicing, altered protein glycosylation, or variant PSA complexing to macroglobulins. To our knowledge, a direct comparison of PSA mRNA sequences in BPH versus prostate cancer to account for these differences has not been reported. The purpose of this study was to compare the complete PSA mRNA gene sequences in benign and malignant prostate tissue to determine whether altered PSA phenotypes are a result of gene mutations and to compare the published PSA sequences. METHODS: Total RNA was extracted from 17 prostate specimens from 8 patients, including matched benign and malignant prostate tissue in 6 patients. The samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) of the PSA coding sequence and part of the 3' untranslated region. Directed DNA sequencing was performed on these fragments. RESULTS: The benign and malignant prostate tissue cDNA sequence data of both strands were aligned and a computer analysis revealed 100% match with no evidence of mutation in prostate cancer compared to normal tissue. Sequence analysis did not reveal point mutations or aberrant splicing in any of the samples, including the matched malignant and nonmalignant tissues. Comparison with published sequences revealed infrequent and inconsistent sequence differences. CONCLUSIONS: These findings suggest that the PSA gene expressed in malignant prostate tissue is the wild type. PSA structural alterations previously reported in the literature may occur through post-transitional mechanisms. A detailed understanding of the possible differences in the PSA gene sequence is essential as we develop newer techniques that utilize RT-PCR to perform molecular diagnosis and staging of prostate cancer.

[Use of mortality probability models (MPM II) in the evaluation of the effectiveness of care of critically ill patients. European and North American Study of Severity Systems]. / Utilización de los modelos probabilísticos de mortalidad (MPM II) para evaluar la efectividad de la atención a pacientes en estado crítico. European and North American Study of Severity Systems.

BACKGROUND: The performance of the Mortality Probability Models (MPM II) has been assessed in Intensive Care Units (ICUs) in Catalonia and the Balearic Islands. The MPM II system has been customized to that geographic area and quality performance has been evaluated in each ICU. METHODS: 1,270 adult critical patients, consecutively admitted in 16 ICUs from Catalonia and 1 from the Balearic Islands have been included. Probability of dying in the hospital has been calculated at admission in the ICU and at 24 hours using the models MPM II0 and MPM II24. Goodness-of-fit of the MPM II system in the overall group of 17 ICUs has been analyzed. Logistic regression has been used to customize the MPM II system to all the ICUs together. A Quality Performance Index (QPI) for each ICU has been obtained by dividing the number of the observed deaths by the number of deaths expected by the MPM II system. RESULTS: The overall QPI was 1.15 when using the MPM II0 and 1.17 when using the MPM II24. The QPI in the 17 ICUs ranged from 0.58 to 2.05. Three ICUs showed excess of mortality and 2 ICUs had less deaths than expected. The process of customization of MPM II to the 17 ICUs as a group improved the estimation of expected mortality. CONCLUSIONS: The use of severity indexes allows to compare the outcome of patients in the ICU and provides an indicator of quality of care. The excess of mortality observed in some ICU should produce a watchful follow-up of outcome. Risk factors for excess of mortality should be studied.

Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue.

Prostate specific antigen (PSA) is a tumor marker used widely for the diagnosis and monitoring of prostatic adenocarcinoma. Recently, we provided evidence that PSA may also be produced by breast tumors. In this report we examined quantitatively the PSA levels in 199 breast tumors, 48 tissues with benign breast disease (BBD, 34 fibroadenomas), and 36 normal breast tissues. Significant amounts of PSA (> or = 0.030 ng of PSA per mg of total protein) were found in 28% of breast tumors, 65% of BBD tissues, and 33% of normal breast tissues. PSA positivity in breast tumors was highest in stage I disease (34%) and decreased with disease stage (24% in stage II and 18% in stage III-IV). Using polymerase chain reaction amplification we have shown PSA mRNA presence in patients with PSA protein-positive tissues (benign and malignant) but not in patients with PSA protein-negative tissues. Our data suggest that PSA is expressed frequently by normal breast tissue, by tissue of benign breast diseases, and by breast cancer tissue. Highest expression is seen in benign breast disease and lowest expression in advanced stage cancerous tissue. As PSA production is mediated by steroid hormones and their receptors, we propose that PSA may be a new marker of steroid hormone action in the normal or diseased female breast. The role of this enzyme in the development of breast diseases including breast cancer is currently unknown.

The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells.

The regulatory Tat protein of human immunodeficiency virus type-1 (HIV-1) exerts a pleyotropic activity on the survival and proliferation of different cell types in culture. In this report, we investigated the effect of either endogenous or exogenous Tat on Bcl-2 proto-oncogene expression and cell survival in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Stable and transient transfections of Jurkat cells with the cDNA of tat and a plasmid containing Bcl-2 promoter in front of CAT (Bcl-2 Pr/CAT) stimulated CAT activity and showed an increase of Bcl-2 mRNA and protein expression. This effect was specifically related to tat, because Jurkat cells transfected with the cDNA of tat in antisense orientation, tat carrying a mutation in the amino acid cys22-gly22, or the control vector alone (pRPneo-SL3) did not show any significant difference in Bcl-2 promoter activity with respect to parental Jurkat cells. We also observed a specific correlation between tat-induced Bcl-2 gene expression and inhibition of apoptosis induced by serum withdrawal. Our results suggest that the structural integrity of the activation domain of Tat was required for the promotion of the Bcl-2 promoter and Jurkat cell survival, because a single mutation in the aminoacid cys22 was sufficient to completely block the upregulation of Bcl-2 and inhibition of apoptosis. Moreover, picomolar concentrations of native or recombinant Tat were able to upregulate Bcl-2 expression both in Jurkat and primary peripheral blood mononuclear cells, suggesting that extracellular Tat, actively released by infected cells, may also play a significant role in suppressing apoptosis. An aberrant cell survival of lymphoid cells consequent to the upregulation of Bcl-2 may represent an additional pathogenetic mechanism that could help explain both the dysregulated immune response and the frequent occurrence of hyperplastic/neoplastic disorders in HIV-1-seropositive individuals.