RESUMO
OBJECTIVES: People living with HIV (PLWH) have increased risk of cardiovascular diseases compared with uninfected populations. We assessed structural cardiac abnormalities and their associated risk factors in well-treated PLWH and uninfected controls using multidetector computed tomography (MDCT). METHODS: People living with HIV and age- and sex-matched uninfected controls underwent MDCT to determine left atrial volume (LAV), left ventricular diastolic volume (LVDV), right ventricular diastolic volume (RVDV) and left ventricular mass (LVM). All outcomes were indexed to body surface area (BSA) (LAVi, LVDVi, RVDVi and LVMi). RESULTS: A total of 592 PLWH and 1184 uninfected controls were included in the study. PLWH had smaller mean (SD) LAVi [40 (8) vs. 41 (9) mL/m2 ; P = 0.002] and LVDVi [61 (13) vs. 65 (14) mL/m2 ; P < 0.001] but larger RVDVi [89 (18) vs. 86 (17) mL/m2 ; P < 0.001] than uninfected controls. HIV was independently associated with 7 mL (95% CI: -10 to -3) smaller LVDV, and with 12 mL (95% CI: 8-16) larger RVDV, and 4 g (95% CI: 1-6) larger LVM after adjustment for cardiovascular risk factors and BSA. Large RVDV in PLWH was not associated with obstructive lung function. CONCLUSIONS: HIV was independently associated with smaller LVDV and larger RVDV and LVM. Alterations in cardiac chamber volumes in PLWH were mainly minor. The clinical impact of these findings is uncertain, but it seems unlikely that alterations in cardiac chamber volumes explain the increased burden of cardiovascular disease previously observed in PLWH.
Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Infecções por HIV/complicações , Ventrículos do Coração/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Infecções por HIV/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Fatores de RiscoRESUMO
A group of 28 patients with inherited metabolic disease (homocystinuria galactosaemia, maple syrup urine disease and biotinidase deficiency) diagnosed by screening were compared with a group of 17 similar patients identified clinically. The rate of hospitalization was similar for the two groups. The patients diagnosed clinically showed a higher incidence of mental retardation and their parents experienced greater stress and found greater difficulty in meeting their child's needs.
Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Adolescente , Deficiência de Biotinidase/diagnóstico , Criança , Pré-Escolar , Galactosemias/diagnóstico , Homocistinúria/diagnóstico , Humanos , Lactente , Recém-Nascido , Doença da Urina de Xarope de Bordo/diagnóstico , Avaliação de Resultados em Cuidados de SaúdeAssuntos
Estágio Clínico/organização & administração , Ética Médica , Testes Genéticos , Genética Médica/educação , Equipe de Assistência ao Paciente/organização & administração , Atitude do Pessoal de Saúde , Competência Clínica/normas , Currículo , Aconselhamento Genético , Humanos , Profissionais de Enfermagem/educação , Profissionais de Enfermagem/psicologia , Avaliação de Programas e Projetos de Saúde , Saúde Pública , Estudantes de Ciências da Saúde/psicologia , Estudantes de Medicina/psicologia , Estudantes de Enfermagem/psicologia , Inquéritos e QuestionáriosRESUMO
The description of Frasier syndrome until now has been restricted to XY females with gonadal dysgenesis, progressive glomerulopathy, and a significant risk of gonadoblastoma. Mutations in the donor splice site in intron 9 of the Wilms' tumor (WT1) gene have been shown to cause Frasier syndrome and are distinct from WT1 exon mutations associated with Denys-Drash syndrome. The WT1 gene, which is essential for normal kidney and gonadal development, encodes a zinc finger transcription factor. The intron 9 alternative splice donor site mutation seen in Frasier syndrome leads to loss of three amino acids (+KTS isoform), thus disrupting the normal ratio of the +KTS/-KTS isoforms critical for proper gonadal and renal development. This study examines two sisters with identical intron 9 mutations. The proband carries a classic diagnosis of Frasier syndrome with 46,XY gonadal dysgenesis, whereas her sister has progressive glomerulopathy but a 46,XX karyotype and normal female development. This indicates that the proper WT1 isoform ratio is critical for renal and testicular development, but apparently does not affect either ovarian development or function. It is proposed that the clinical definition of Frasier syndrome should be broadened to include 46,XX females with normal genital development and focal segmental glomerulosclerosis associated with a WT1 intron 9 donor splice site mutation. Nephrologists need to consider the possibility of this heritable syndrome in evaluation of females with focal segmental glomerulosclerosis and to consider their risk for gonadal malignancy, as well as the risk for kidney disease, gonadal dysgenesis, and malignancy in their offspring.
Assuntos
Proteínas de Ligação a DNA/genética , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/genética , Aberrações dos Cromossomos Sexuais/diagnóstico , Fatores de Transcrição/genética , Cromossomo X , Adolescente , Biópsia por Agulha , Criança , DNA/análise , Feminino , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Íntrons/genética , Mutação , Núcleo Familiar , Fenótipo , Proteinúria/diagnóstico , Síndrome , Urinálise , Proteínas WT1 , Cromossomo YRESUMO
Pulmonary complications are described in a case of Ehlers-Danlos syndrome type IV, established by studies of collagen biosynthesis. At age 20.5 years the patient, who had previously suffered a spontaneous colonic perforation, developed intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At presentation, imaging studies revealed multiple scattered cavitary lesions in both lungs. On separate occasions large parenchymal cysts ensued and subsequently regressed. Reviews of other reported patients indicate that pulmonary complications do occur in patients with Ehlers-Danlos syndrome type IV but have not resulted directly in patient mortality.
Assuntos
Cistos/etiologia , Síndrome de Ehlers-Danlos/complicações , Pneumopatias/etiologia , Adolescente , Colágeno/genética , Doenças do Colo/etiologia , Cistos/diagnóstico por imagem , Síndrome de Ehlers-Danlos/classificação , Síndrome de Ehlers-Danlos/genética , Hemotórax/etiologia , Humanos , Perfuração Intestinal/etiologia , Pneumopatias/diagnóstico por imagem , Masculino , Pneumotórax/etiologia , RadiografiaRESUMO
In a patient with Hurler-Scheie syndrome, a type of mucopolysaccharidosis (I H/S), an initial presentation was grouped papules on the extensor surfaces on the upper portions of the arms and legs. Other physical findings included progressive flexion contractures and mild developmental delay. The patient had deficient alpha-L-induronidase activity, and electron microscopy showed large cytoplasmic vacuoles and lysosomes, consistent with Hurler-Scheie syndrome. Findings of grouped papules have not been previously reported in patients with this syndrome.
Assuntos
Mucopolissacaridose I/complicações , Dermatopatias Papuloescamosas/etiologia , Pré-Escolar , Humanos , MasculinoAssuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Mutação , Ornitina Carbamoiltransferase/genética , Amônia/sangue , Sítios de Ligação , Pré-Escolar , Códon de Terminação , Sondas de DNA , Éxons/genética , Feminino , Humanos , Ornitina/metabolismo , Ornitina Carbamoiltransferase/metabolismo , Doença da Deficiência de Ornitina Carbomoiltransferase , Ácido Orótico/urinaRESUMO
Gene transfer using yeast artificial chromosome (YAC) clones provides an opportunity to study the expression of several linked genes within an environment more closely approximating their normal chromosomal context. A YAC clone spanning 330 kb of the HLA class II region from centromeric of TAP 1 to telomeric of HLA-DQA1 was retrofitted by homologous recombination with a neomycin plasmid targeted either to an Alu repeat sequence within the YAC genomic insert or to the Ura-3 gene within the right arm of the YAC vector. The modified YAC clones were transferred to Chinese hamster ovary or L cells by spheroplast fusion. Eight of 14 Alu-retrofitted and 10 of 15 right arm-retrofitted neomycin clones retained the six human loci known to be encoded by the YAC as well as portions of the left and right YAC vector arms. All tested L cell transformants showed IFN-gamma-inducible TAP 1 and TAP 2 mRNA expression. Two of eight analyzed clones expressed HLA-DQB mRNA and one of four expressed HLA-DQA. Cells expressing both the HLA-DQA and -DQB mRNA showed HLA-DQ cell surface expression. These studies establish the feasibility of introducing groups of functional genes into mammalian cells by spheroplast fusion with a single YAC clone.
Assuntos
Genes MHC da Classe II , Transfecção , Animais , Sequência de Bases , Células CHO , Fusão Celular , Cromossomos Fúngicos , Cricetinae , Antígenos HLA-DQ/análise , Antígenos HLA-DQ/genética , Humanos , Interferon gama/farmacologia , Células L , Camundongos , Dados de Sequência Molecular , RNA Mensageiro/análise , Leveduras/genéticaRESUMO
Cellular retinol binding protein II (CRBP II) is an abundant, 134-residue protein present in the small intestinal epithelium. It is thought to participate in the uptake and/or intracellular metabolism of vitamin A. We have isolated and sequenced the rat CRBP II gene. Its four exons span 0.65 kilobases and are interrupted by three introns with an aggregate length of 19.5 kilobases. Southern blot hybridization analysis indicated that this gene is highly conserved in rats, mice, and humans. CRBP II belongs to a protein family that contains eight known members. Computer-assisted comparative sequence analyses indicated that a region of internal homology spans its first two exons and that oligopeptide domains specified by these first two exons exhibit significant homology to all other family members as well as to a portion of the all-trans-retinol binding domain that has previously been defined in serum retinol binding protein. The CRBP II gene was mapped in mice using recombinant inbred strains and restriction fragment length polymorphisms. It is located on chromosome 9 within 5.3 centimorgans of the phosphoglucomutase-3 locus and is closely linked (within 3.0 centimorgans) to the gene specifying a highly homologous intracellular retinol binding protein known as CRBP. Mouse-human somatic cell hybrids were used to determine that both the CRBP and CRBP II genes are located on human chromosome 3.
Assuntos
Ligação Genética , Proteínas de Ligação ao Retinol/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Galinhas , Computadores , Enzimas de Restrição do DNA/metabolismo , Peixes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Hibridização de Ácido Nucleico , Ratos , Proteínas Celulares de Ligação ao Retinol , Transcrição GênicaRESUMO
Expression of the apolipoprotein B (apoB) gene was examined in a variety of fetal, neonatal, and adult rat tissues by probing RNA blots with a cloned rat apoB cDNA. Among 10 adult male tissues surveyed, small intestine had the highest concentration of apoB mRNA. Its abundance in liver and adrenal gland was 40% and 0.5%, respectively, of that in small bowel, while none was detected in colon, kidney, testes, spleen, lung, heart, or brain. ApoB mRNA is as abundant in 18-day fetal liver as at any subsequent period of hepatic development. In contrast, the concentration of apoB mRNA remains low in fetal intestine until the last (21st) day of gestation, when it increases sharply to levels that are several-fold higher than in the liver. ApoB mRNA levels in fetal membranes harvested during this late gestational period were 10 times greater than in fetal liver. Since the major lipoprotein species in 19-day fetal plasma is low density lipoprotein, these observations suggest that fetal liver, and particularly its functional homologue, the yolk sac, are the principal sites of fetal lipoprotein synthesis at this stage of development. A 20-fold increase in placental apoB mRNA concentrations during the last 48 hr of pregnancy (to a level that is 50% of that encountered in fetal membrane RNA) suggests a specific role for this organ in maternal-fetal lipid transport immediately prior to parturition. Pulse-labeling experiments using 21-day fetal tissue slices showed that the liver synthesizes both apoB-100 (B-PI) and apoB-48 (B-PIII) albeit in somewhat different ratios than the adult organ. Fetal intestine produces almost exclusively the smaller apoB species, while fetal membranes and placenta synthesize only the larger peptide. The postnatal pattern of apoB mRNA accumulation is similar in liver and intestine. Profound decreases were observed during the late suckling and weaning periods, followed by an increase to adult levels. These final concentrations were similar to those encountered at birth. Analysis of these developmental changes offers an opportunity to generate testable hypotheses about the factors that modulate apoB synthesis.
Assuntos
Apolipoproteínas B/genética , Regulação da Expressão Gênica , Fatores Etários , Animais , Animais Recém-Nascidos/metabolismo , Feminino , Feto/análise , Intestinos/análise , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/análise , Masculino , Placenta/análise , Gravidez , RNA Mensageiro/análise , Ratos , Ratos EndogâmicosRESUMO
The primary structure of rat cellular retinol-binding protein (CRBP) II has been determined from a cloned cDNA. Alignment of this 134-amino acid, 15,580-Da polypeptide with rat CRBP revealed that 75 of 133 comparable residues are identical. Both proteins contain four tryptophan residues, which occupy identical relative positions in the two primary structures, providing a structural explanation for their similar fluorescence spectra when complexed to retinol. Two of the three cysteines in each single-chain protein are comparably positioned. Both polypeptides contain reactive thiol groups, but the rate of disruption of CRBP II-retinol complexes by p-chloromercuribenzoate is greater than that of CRBP-retinol. The small intestine contains the highest concentrations of CRBP II mRNA in adult rats. CRBP II mRNA is first detectable in intestinal RNA during the 19th day of gestation, a time that corresponds to the appearance of an absorptive columnar epithelium. Unlike in intestine, a dramatic fall in liver CRBP II mRNA concentration occurs immediately after birth. The CRBP II gene remains quiescent in the liver during subsequent postnatal development. These data suggest that ligand-protein interactions may be somewhat different for the two rat CRBPs. They also support the concept that CRBP II plays a role in the intestinal absorption or esterification of retinol and suggest that changes in hepatic metabolism of vitamin A occur during development.