RESUMEN

Hydropower plants commonly impede the downstream migration of Atlantic salmon (Salmo salar) kelts. Thus, understanding the effects of hydraulic conditions on kelt behaviour and passage performance at dams is crucial for developing effective mitigation measures. In this study, we investigated the influence of hydraulic conditions on kelt passage performance and swimming behaviour at a Norwegian hydropower plant. We combined biological data from 48 kelts collected via acoustic telemetry with hydraulic data modelled using computational fluid dynamics. We assessed kelt passage performance using metrics such as time-to-pass, total number of detections, and total number of detections per day. Additionally, we analysed swimming depths and speeds in relation to the hydraulic conditions created by different dam operating conditions. We found that the dam operation schedule impacted the kelts' ability to find a route past the dam. Though kelts could have passed the dam throughout the study period via a submerged pipe at the dam (which had seemingly sufficient discharge for the kelts to find), 98 % of the kelts instead waited for a spill gate to open partway through the study period. The swimming depth analysis indicated diel variation, with kelts swimming nearer to the water surface during the night. We found that swimming speed increased with increasing kelt body length, particularly under high turbulence kinetic energy and during the day. Furthermore, kelts swam faster as water velocity increased, but slowed down again as turbulence intensity increased. Our findings reveal the effects of hydraulic conditions and dam operations on the migration behaviour of Atlantic salmon kelts. This provides valuable insights for developing strategies to optimise dam operations and improve fish passage performance, including the need to spill enough water to increase passage success and will contribute to sustainable management of Atlantic salmon populations in regulated rivers.

Asunto(s)

Salmo salar , Animales , Natación , Ríos , Migración Animal , Agua

RESUMEN

ETV6/CBFA2 (TEL/AML1) is the most frequent genetic abnormality associated with acute lymphoblastic leukemias in children, and is associated with a favorable prognosis. To investigate the influence of ETV6/CBFA2 on cellular transformation, the fusion gene was cloned into a murine ecotropic retroviral vector and transduced into IL-3-dependent Ba/F3 and 32Dcl.3 and IL-7-dependent IxN/2b murine hematopoietic cell lines. Different variants of ETV6/CBFA2, corresponding to CBFA2 alternatively spliced variants, and the reciprocal product CBFA2/ETV6, were stably expressed in each of these cell lines. However, although Western blot analysis demonstrated expression of each variant, none of the stable cell lines expressing CBFA2/ETV6 or the variants conferred factor-independent growth. We further investigated the effect of ETV6/CBFA2 expression in vivo by generating transgenic mice in which expression of the fusion was directed to lymphoid cells using the immunoglobulin heavy chain enhancer/promoter. Four founder mice were identified showing transmission and expression of the chimeric product. The mice were bred for five generations and followed for more than 24 months. The mice did not develop a malignant hematologic disorder, nor did they display histopathologic, morphologic, or immunophenotypic abnormalities, although ETV6/CBFA2 expression was confirmed in each line. We conclude that the expression of ETV6/CBFA2 alone is not sufficient for induction of growth factor independence in hematopoietic cell lines or hematologic disease in transgenic mice.

Asunto(s)

Transformación Celular Neoplásica , Neoplasias Hematológicas/etiología , Neoplasias Hematológicas/genética , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Proteínas de Fusión Oncogénica/genética , Animales , Western Blotting , Diferenciación Celular , Línea Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Electroporación , Elementos de Facilitación Genéticos , Citometría de Flujo , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia/etiología , Leucemia/genética , Ratones , Ratones Transgénicos , Plásmidos/metabolismo , Regiones Promotoras Genéticas , Retroviridae/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Activación Transcripcional , Transducción Genética

RESUMEN

The molecular cloning of the t(5;10)(q33;q22) associated with atypical chronic myeloid leukemia (CML) is reported. Fluorescence in situ hybridization (FISH), Southern blot, and reverse transcriptase- polymerase chain reaction analysis demonstrated that the translocation resulted in an H4/platelet-derived growth factor receptor betaR (PDGFbetaR) fusion transcript that incorporated 5' sequences from H4 fused in frame to 3' PDGFbetaR sequences encoding the transmembrane, WW-like, and tyrosine kinase domains. FISH combined with immunophenotype analysis showed that t(5;10)(q33;q22) was present in CD13(+) and CD14(+) cells but was not observed in CD3(+) or CD19(+) cells. H4 has previously been implicated in pathogenesis of papillary thyroid carcinoma as a fusion partner of RET. The H4/RET fusion incorporates 101 amino acids of H4, predicted to encode a leucine zipper dimerization domain, whereas the H4/PDGFbetaR fusion incorporated an additional 267 amino acids of H4. Retroviral transduction of H4/PDGFbetaR, but not a kinase-inactive mutant, conferred factor-independent growth to Ba/F3 cells and caused a T-cell lymphoblastic lymphoma in a murine bone marrow transplantation assay of transformation. Mutational analysis showed that the amino-terminal H4 leucine zipper domain (amino acids 55-93), as well as H4 amino acids 101 to 386, was required for efficient induction of factor-independent growth of Ba/F3 cells. Tryptophan-to-alanine substitutions in the PDGFbetaR WW-like domain at positions 566/593, or tyrosine-to-phenylalanine substitutions at PDGFbetaR positions 579/581 impaired factor-independent growth of Ba/F3 cells. H4/PDGFbetaR is an oncoprotein expressed in t(5;10)(q33;q22) atypical CML and requires dimerization motifs in the H4 moiety, as well as residues implicated in signal transduction by PDGFbetaR, for efficient induction of factor-independent growth of Ba/F3 cells. (Blood. 2001;97:3910-3918)

Asunto(s)

Carcinoma Papilar/genética , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 5 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias de la Tiroides/genética , Translocación Genética , Transformación Celular Neoplásica/genética , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 5/genética , Clonación Molecular , Análisis Citogenético , Proteínas del Citoesqueleto , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Reordenamiento Génico , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Mutagénesis , Células Mieloides/metabolismo , Células Mieloides/patología , Proteínas de Fusión Oncogénica , Estructura Terciaria de Proteína , Proteínas/metabolismo , Transfección

RESUMEN

Between 1977 and 1996, cytogenetic investigations were performed on 182 childhood (< or = 16 yr) acute lymphoblastic leukemias (ALL), constituting 94% (182 of 194) of all ALL patients diagnosed and treated at the Departments of Pediatrics, Lund and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic analyses were successful in 152 cases (84%). The failure rate was higher for the ALL investigated before 1987 (30% vs. 4%, p < 0.0001), and also the incidence of cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p < 0.05). Clonal chromosomal abnormalities were found in 103 (68%) ALL. Structural rearrangements were detected, by chromosome banding alone, in 76 cases (50%). Fluorescence in situ hybridization (FISH) was used to identify cases with t(12;21), 11q23 rearrangements, and 9p deletions, using probes for ETV6/CBFA2, MLL, and CDKN2A/B, in 72 cases from which cells in fixative and/or unstained metaphase preparations were available. In total, the most common structural rearrangements were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by FISH harbored cryptic abnormalities; three displayed t(12;21) and four had del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)-positive ALL showed +der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the formation of double fusion genes. Among the more rare aberrations, eight structural rearrangements were identified as novel recurrent ALL-associated abnormalities, and nine cases harbored rearrangements previously not reported. Sixteen cases displayed karyotypically unrelated clones at different investigations. Seven ALL (5%) showed simple chromosomal changes, unrelated to the aberrations detected at diagnosis, during morphologic and clinical remission, and in all but one instance the patients remained in remission, with the abnormal clone disappearing in subsequent investigations. This indicates that the emergence of novel clonal chromosomal aberrations during remission in childhood ALL is rather common and does not by necessity predict a forthcoming relapse.

Asunto(s)

Hibridación Fluorescente in Situ , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Niño , Preescolar , Deleción Cromosómica , Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 12/ultraestructura , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 21/ultraestructura , Cromosomas Humanos Par 9/ultraestructura , Células Clonales/ultraestructura , Sondas de ADN , Femenino , Humanos , Inmunofenotipificación , Lactante , Recuento de Leucocitos , Masculino , Células Madre Neoplásicas/ultraestructura , Oncogenes , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Suecia/epidemiología , Translocación Genética , Resultado del Tratamiento

RESUMEN

Sclerosing epithelioid fibrosarcoma (SEF) is a recently described entity. It is a low-grade sarcoma that occurs primarily in the deep soft tissues of the extremities of adults. It may histologically simulate benign lesions such as fibroma and myxoma or malignancies such as sclerosing carcinoma and lymphoma, extraskeletal myxoid chondrosarcoma, clear cell sarcoma of tendons and aponeuroses, and synovial sarcoma, depending on the lesion's cellularity, degree of fibrosis, and amount of myxoid matrix. There are no previously published cytogenetic studies of this tumor. We found the karyotype 40-45,XY,add(9)(p13),add(10)(p11),-12,-13,-18,add(18)(q11),add(20)(q11) in a SEF of a 14-year-old boy, by using chromosome banding. Fluorescence in situ hybridization showed that both the add(10) and the add(18) contained amplified sequences from 12q13 and 12q15, including the HMGIC gene. Chromosome 18 material was present in the add(9) and terminally in the add(10). The karyotype of this case indicates that SEF is unrelated to extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and synovial sarcoma. When compared with the findings in other soft tissue tumors such as well-differentiated liposarcoma and low-grade malignant fibrous histiocytoma, the chromosome banding and in situ hybridization data add support to the notion that SEF is a relatively low grade variant of fibrosarcoma.

Asunto(s)

Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 12/genética , Fibrosarcoma/genética , Enfermedades del Pie/genética , Translocación Genética/genética , Adolescente , Fibrosarcoma/patología , Enfermedades del Pie/patología , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino

RESUMEN

Jumping translocations (JT) are characterized by the relocalization of the same part of a donor to several recipient chromosomes. Although JT occasionally are constitutional, most are associated with hematologic malignancies. In such cases, JT usually arise during disease progression and are associated with poor prognosis. Despite its clinical importance, this cytogenetic phenomenon has not been characterized at the molecular level. We have analyzed JT in a juvenile chronic myelomonocytic leukemia that subsequently transformed to an acute myeloid leukemia. Detailed fluorescence in situ hybridization (FISH) analyses showed that the cytogenetically identical donor breakpoint at 3q21 was highly heterogeneous. In fact, more than 10 distinct breakpoints, four of which mapped within YACs, were identified. Analyses of samples during disease progression showed that the breakpoint complexity decreased, indicating clonal selection. Hence, the 3q21 breakpoints displayed a spatial as well as a temporal heterogeneity, revealing that JT are highly unstable, showing great variation in the size of donor segment. The breaks at the recipient chromosomes were mapped within the subtelomeric regions. The general telomere length was not affected and an underlying replication error resulting in microsatellite instability was excluded. We conclude that the emergence of JT is unlikely to cause fusion genes or to affect the expression of genes located in the breakpoint regions. The identification of YACs spanning the breakpoints, ie, YACs 913c7, 937g5, 948c2 and 955g1, may facilitate the isolation of DNA sequences leading to a genetic instability associated with the origin of multiple translocations.

Asunto(s)

Cromosomas Humanos Par 3/genética , Leucemia Mielomonocítica Crónica/genética , Translocación Genética/genética , Preescolar , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 22/genética , Cromosomas Humanos Par 7/genética , Resultado Fatal , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Repeticiones de Microsatélite/genética

Asunto(s)

Fusión Artificial Génica , Proteínas de Unión al ADN/genética , Genes abl , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Crónica Atípica BCR-ABL Negativa/genética , Proteínas Represoras , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-ets , Proteína ETS de Variante de Translocación 6

RESUMEN

Cyclin D2, encoded by CCND2 at 12p13, takes part in the regulation of the cell cycle and has been suggested as a candidate for gene amplification in lymphoid malignancies. CCND2 is often overexpressed in chronic B-cell disorders, and we recently detected genomic amplification of the chromosomal region containing CCND2 in two of three investigated non-Hodgkin lymphomas (NHLs) with cytogenetic abnormalities involving 12p. In the present study, 58 NHLs without karyotypic evidence of 12p aberrations were analyzed by fluorescence in situ hybridization with probes for CCND2. No genomic amplification was found, strongly suggesting that this abnormality is rare in such NHLs.

Asunto(s)

Ciclinas/genética , Linfoma no Hodgkin/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 12 , Ciclina D2 , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ

RESUMEN

Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.

Asunto(s)

Aberraciones Cromosómicas , Cromosomas Humanos Par 12 , Neoplasias Hematológicas/genética , Leucemia/genética , Adulto , Anciano , Anciano de 80 o más Años , Mapeo Cromosómico , Femenino , Eliminación de Gen , Reordenamiento Génico , Marcadores Genéticos , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Linfoma no Hodgkin/genética , Masculino , Persona de Mediana Edad , Policitemia Vera/genética

RESUMEN

A BCR/ABL-negative chronic myeloid leukemia (CML) with t(12;14) (p12;q11-13) as the sole chromosomal abnormality was investigated by fluorescence in situ hybridization (FISH), which disclosed a cryptic insertion of ETV6 (previously called TEL), located at 12p12, into ABL at chromosome band 9q34. ETV6/ABL fusion was confirmed by RT-PCR, revealing that the first five exons of ETV6 were fused in frame with ABL at exon 2. Wild-type ETV6 was expressed, in accordance with the FISH results showing no deletion of the second ETV6 allele. ETV6/ABL chimeric transcripts have previously been reported in acute leukemias, but never before in CML. The present case suggests that ETV6/ABL positivity may constitute a new genetic subgroup of BCR-negative CML.

Asunto(s)

Proteínas de Unión al ADN/genética , Genes abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Represoras , Factores de Transcripción/genética , Adulto , Southern Blotting , Células de la Médula Ósea/química , Bandeo Cromosómico , Mapeo Cromosómico , Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 14/genética , ADN de Neoplasias/aislamiento & purificación , Proteínas de Fusión bcr-abl/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-ets , Translocación Genética/genética , Proteína ETS de Variante de Translocación 6

RESUMEN

The cytogenetically unidentifiable t(12;21)(p12:q22), resulting in ETV6/CBFA2 fusion, is the most frequent chromosomal aberration in childhood acute lymphoblastic leukaemia ALL). We report a variant, ider(21)(q10)t(12:21)(p12;q22), which was shown to contain double ETV6/CBFA2 fusions by fluorescence in situ hybridization. This is the second case of such an ider(21) in childhood ALL, suggesting that it is a new recurrent abnormality. Since the ider(21) is cytogenetically indistinguishable from i(21)(q10) and idic(21)(p11), changes associated with similar clinical features as the t(12;21), i.e. pre-B-cell ALL and age 1-10 years, we suggest that all ALL displaying these changes should be tested for ETV6/CBFA2 fusion transcript.

Asunto(s)

Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 21/genética , Proteínas de Unión al ADN/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Represoras , Factores de Transcripción/genética , Translocación Genética , Niño , Humanos , Hibridación Fluorescente in Situ , Masculino , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-ets , Proteína ETS de Variante de Translocación 6

RESUMEN

Seventy-nine acute myeloid leukemias (AML) and myelodysplastic syndromes without cytogenetic evidence of 12p aberrations were investigated by fluorescence in situ hybridization with probes for ETV6 and CDKN1B (previously called TEL and KIP1, respectively) to ascertain whether abnormalities of these genes are frequently undetected by standard chromosome banding analyses and, if so, whether they are associated with specific karyotypic patterns and morphologic features. One of sixty cytogenetically aberrant myeloid malignancies, an AML with a complex karyotype including del(5q) and del(20q), showed a hemizygous interstitial deletion of the ETV6 and CDKN1B loci. No concomitant rearrangement of the other ETV6 allele was detected. Two of nineteen cytogenetically normal AML displayed a hemizygous interstitial deletion involving CDKN1B, but not ETV6. Thus, cryptic deletions of these genes seem to be rare in cytogenetically abnormal myeloid malignancies without 12p aberrations (2%), whereas they may be more frequent in karyotypically normal AML (10%). Furthermore, the present findings show that the deletions may be narrow, not including the ETV6 gene, and indirectly suggest that CDKN1B, or a closely located genomic segment, is the target of 12p deletions.

Asunto(s)

Proteínas de Ciclo Celular , Deleción Cromosómica , Cromosomas Humanos Par 12 , Proteínas de Unión al ADN/genética , Leucemia Mieloide/genética , Proteínas Asociadas a Microtúbulos/genética , Síndromes Mielodisplásicos/genética , Proteínas Represoras , Factores de Transcripción/genética , Proteínas Supresoras de Tumor , Enfermedad Aguda , Anciano , Aberraciones Cromosómicas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Humanos , Masculino , Proteínas Proto-Oncogénicas c-ets , Proteína ETS de Variante de Translocación 6

RESUMEN

Homology searches in the Expressed Sequence Tag Database were performed using SPYGQ-rich regions as query sequences to find genes encoding protein regions similar to the N-terminal parts of the sarcoma-associated EWS and FUS proteins. Clone 22911 (T74973), encoding a SPYGQ-rich region in its 5' end, and several other clones that overlapped 22911 were selected. The combined data made it possible to assemble a full-length cDNA sequence. This cDNA sequence is 1677 bp, containing an initiation codon ATG, an open reading frame of 400 amino acids, a poly(A) signal, and a poly(A) tail. We found 100% identity between the 5' part of the consensus sequence and the 598-bp-long sequence named TFG. The TFG sequence is fused to the 3' end of NTRK1, generating the TRK-T3 fusion transcript found in papillary thyroid carcinoma. The cDNA therefore represents the full-length transcript of the TFG gene. TFG was localized to 3q11-q12 by fluorescence in situ hybridization. The 3' and the 5' ends of the TFG cDNA probe hybridized to a 2.2-kb band on Northern blot filters in all tissues examined.

Asunto(s)

Proteínas/genética , Neoplasias de la Tiroides/genética , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Cromosomas Humanos Par 3/genética , Clonación Molecular , ADN Complementario/genética , Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Datos de Secuencia Molecular

Asunto(s)

Médula Ósea/patología , Aberraciones Cromosómicas , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Preescolar , Humanos , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Inducción de Remisión

RESUMEN

OBJECTIVES: To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN: A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING: Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS: Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS: Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION: Vertical transmission of HIV-2 appears to be rare.

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PIP: Between May 1987 and December 1988 in Guinea-Bissau, health workers followed 86 HIV-2 seropositive mothers and their infants delivered at the National Hospital Simao-Mendes in Bissau for 20 months to learn the HIV-2 vertical transmission rate and to compare their clinical findings with those of 102 infants of HIV-2 seronegative women. The ELISA and Western Blot analysis used antigen-purified virions of the SBL-6669 strain of HIV-2 grown on U937:2 cells. During the enrollment period, hospital workers tested 3246 women; tests confirmed that 211 (6.5%) and 3 (0.1%) were HIV-2 seropositive, respectively. 1 HIV-2 seronegative mother seroconverted during the study, but none of the infants of HIV-2 seronegative mothers seroconverted. Infant mortality of cases did not differ significantly from that of controls (16.2% vs. 11.7%). After 1 year of age, however, children of HIV-2 seropositive mothers were significantly more likely to die than the controls (15% vs. 3%; p .05). When the researchers added the children lost to follow up, there no longer was a significant difference in mortality after 1 year (23.9% vs. 24.1%). Just 3 of the deceased infants of the HIV-2 seropositive mothers and 1 of the deceased infants of seronegative mothers suffered from symptoms from symptoms that may have been related to HIV-2 infection. 1 of these deceased infants was HIV-2 seropositive at 12 months. These symptoms included prolonged fever, vomiting, diarrhea, and respiratory symptoms. Children in the study group did not experience more frequent clinical symptoms of HIV-2 infection than did the controls during the 3rd and 4th home visits. At the last visit (i.e., 4th visit; when the children were older than 17 months), none of the children of the HIV-2 seropositive mothers tested positive for HIV- 2. Vertical transmission of HIV-2 infection may be rare.

Asunto(s)

Seropositividad para VIH/epidemiología , Seropositividad para VIH/transmisión , VIH-2/patogenicidad , Preescolar , Femenino , Estudios de Seguimiento , Guinea Bissau/epidemiología , Seropositividad para VIH/fisiopatología , Humanos , Lactante , Recién Nacido , Embarazo , Estudios Prospectivos , Análisis de Supervivencia

Asunto(s)

Infecciones por VIH/epidemiología , VIH-2 , Infecciones por HTLV-I/epidemiología , Adolescente , Adulto , Femenino , Guinea Bissau/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Embarazo

RESUMEN

A two-step polymerase chain reaction (PCR), with four double (nested) primer pairs, used for the detection of HIV-2 in clinical samples is described. With these four nested primer pairs we could detect HIV-2 DNA in 17 of 17 virus isolates and in blood mononuclear cell samples from 31 of 37 (83.7%) seropositive individuals after ethidium bromide staining of the amplified DNA. The nested primer PCR was also compared with a single primer pair-based PCR followed by hybridization. The sensitivities of the two methods were almost equal, but the nested primer PCR offered obvious technical advantages.

Asunto(s)

ADN Viral/sangre , VIH-2/genética , Reacción en Cadena de la Polimerasa , Adolescente , Adulto , Animales , Composición de Base , Secuencia de Bases , Sondas de ADN , Femenino , Amplificación de Genes , Humanos , Leucocitos Mononucleares/química , Macaca , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/normas , Virus de la Inmunodeficiencia de los Simios/genética , Integración Viral

RESUMEN

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/inmunología , Seropositividad para VIH/inmunología , VIH-2/inmunología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adulto , Anciano , Relación CD4-CD8 , Estudios de Casos y Controles , Causas de Muerte , Femenino , Estudios de Seguimiento , Guinea Bissau/epidemiología , Seropositividad para VIH/mortalidad , Hospitalización , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro-quine in the treatment of P. falciparum in Africa.

Asunto(s)

Malaria/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Quinina/uso terapéutico , Adolescente , Animales , Niño , Preescolar , Diarrea/inducido químicamente , Mareo/inducido químicamente , Guinea Bissau , Humanos , Quinina/efectos adversos , Quinina/farmacología , Acúfeno/inducido químicamente

RESUMEN

During 11 months in 1989-1990, 1009 consecutive hospitalized adult patients admitted to the medical wards of the National Hospital in Bissau were interviewed, examined clinically, and tested for antibodies to HIV-1 and HIV-2. The prevalence of HIV-2 infection was 20.4% (206 out of 1009) and of HIV-2-associated AIDS 4.4% (44 out of 1009). HIV-2 infection was more frequent in women (25%, 110 out of 440) than in men (16.9%, 96 out of 569). HIV-1 infection was diagnosed in one patient only, and one patient (with AIDS) had reactivity to both HIV-1 and HIV-2. Among HIV-2-seropositive patients, AIDS was demonstrated in 21.3% and AIDS-related symptoms (not fulfilling the AIDS criteria) in 19.4%. The frequency of AIDS-associated symptoms was significantly higher in HIV-2-seropositive patients than in seronegative patients. The clinical profile of the HIV-2-associated AIDS cases was very similar to that described in HIV-1-associated AIDS cases in Africa. Seven out of 51 patients fulfilling the clinical criteria for AIDS were HIV-seronegative. The World Health Organization (WHO) clinical case definition for AIDS in Africa had a specificity of 99% and a positive predictive value of 86%. Tuberculosis was more common in HIV-2-seropositive patients (6.3%) than in HIV-2-seronegative patients (2.2%). A history of blood transfusion was a significant risk factor for HIV-2 infection. HIV-2 infection and AIDS are public health problems in Guinea-Bissau.

Asunto(s)

Infecciones por Deltaretrovirus/epidemiología , Seroprevalencia de VIH , VIH-2 , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Guinea Bissau/epidemiología , Anticuerpos Anti-VIH/análisis , Infecciones por VIH/epidemiología , VIH-1 , Hospitalización , Humanos , Masculino , Persona de Mediana Edad