RESUMO
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that is characterized by frequent nosebleeds, mucocutaneous telangiectases and vascular malformations that cause recurrent haemorrhage and arteriovenous shunting. Linkage analyses in one kindred identified an HHT locus on the long arm of chromosome 9 (maximum multipoint lod score = 6.20 between D9S60 and D9S61). Analyses in two other unrelated HHT families demonstrated that the disease in one was not linked to the locus on chromosome 9q3. We conclude that HHT is a genetically heterogeneous disorder. Based on its map location (9q3) and expression in vascular tissues, type V collagen is a possible candidate gene for HHT.
Assuntos
Cromossomos Humanos Par 9 , Ligação Genética , Telangiectasia Hemorrágica Hereditária/genética , Adulto , Criança , Mapeamento Cromossômico , Europa (Continente) , Feminino , Marcadores Genéticos , Haplótipos , Humanos , Masculino , Linhagem , Polimorfismo Genético , Sequências Repetitivas de Ácido NucleicoRESUMO
Seven new cases are described of near haploid acute lymphoblastic leukemia (ALL) and the findings reviewed together with updated complete remission duration and survival data for the 21 cases already published. The patients were four males and three females, with an age range 2-19 years; all had an immunophenotype consistent with common ALL. The poor prognostic outlook for patients with near haploid ALL is confirmed by the median remission duration of 14 months for these patients, which is comparable to that for the previously published cases. The pattern of chromosome loss was marked particularly by the presence of two copies of chromosomes 10, 14, 18, 21 and both sex chromosomes. Populations of hyperdiploid cells with double the near haploid number were observed in six of the patients, one of whom demonstrated further clonal evolution, and it is proposed that some cases classified as hyperdiploid ALL with greater than 50 chromosomes may also have arisen from a near haploid stem line.
Assuntos
Aberrações Cromossômicas , Haploidia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologiaRESUMO
The nutritional stabilities of four major dietary folates were studied as their corresponding monoglutamates and were compared to pteroylglutamate (folic acid) itself. The study of the monoglutamyl rather than polyglutamyl forms was justified since the former are formed during the course of digestion and also addition of extra glutamyl residues is unlikely to affect the types of nutritional instability associated with these derivatives. Since ability to support growth in Lactobacillus casei is known to reflect nutritional activity in man this organism was used in the stability studies. It was found that pteroylglutamate and 5-formyltetrahydropteroylglutamate had nutritional stabilities of the order of weeks although the stability of the former was decreased by phosphate. Surprisingly 10-formyltetrahydropteroylglutamate was nutritionally more stable than expected, possibly due to its conversion to the more stable oxidized 10-formylpteroylglutamate or to the reduced 5-formyl derivative. In contrast 5-methyltetrahydropteroylglutamate was much less stable nutritionally than expected.Unsubstituted tetrahydropteroylglutamate was most unstable nutritionally but in contrast to the other derivatives examined it was more stable under acidic than basic conditions. Ascorbate was found to be a far superior stabilizing agent than 2-mercaptoethanol at comparable concentrations.
Assuntos
Ácido Fólico/metabolismo , Ácido Ascórbico/farmacologia , Bioensaio , Soluções Tampão , Estabilidade de Medicamentos , Ácido Fólico/análogos & derivados , Formiatos/metabolismo , Glutamatos/metabolismo , Concentração de Íons de Hidrogênio , Lacticaseibacillus casei/metabolismo , Mercaptoetanol/farmacologia , Fenômenos Fisiológicos da Nutrição , Tetra-Hidrofolatos/metabolismo , Fatores de TempoRESUMO
Blast cells from seven out of ten patients with common acute lymphoblastic leukaemia (cALL) developed the myeloid antigen MY7 (CD13) after culture, and one of these coexpressed the myeloid antigen MY9 (CD33). CD13 expression appeared to be independent of maturation since it could be induced more readily in cultures which did not contain the differentiation promoter 12-O-tetradecanoyl-phorbol 13 acetate (TPA). CD13 expression in culture was not seen on one null ALL, or 6 B-CLL investigated or on normal tonsillar B cells or PBMC under similar conditions. CD13 expression on cALL blasts probably represents evidence of abnormal gene expression in the leukaemic cells. However the absence of CD13 expression on the earlier B null ALL or the later B-CLL suggests we cannot exclude the possibility that CD13 expression is a feature of normal precursor B cells.
Assuntos
Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Diferenciação/análise , Antígenos de Neoplasias/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Células Tumorais Cultivadas/imunologia , Adulto , Transformação Celular Neoplásica/análise , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Neprilisina , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais Cultivadas/análise , Células Tumorais Cultivadas/patologiaRESUMO
BACKGROUND: An outbreak of hepatitis A (HAV) occurred in 1992 in Irish haemophilia A patients treated with high purity solvent-detergent (SD) treated factor VIII. Similar outbreaks were reported in Italy, Germany and Belgium. The aim of this study was to investigate the outbreak, and to test the hypothesis that it was caused by exposure to SD-treated factor VIII. METHODS: A case-control study was started in early 1993. Haemophilia A cases with acute HAV (n = 29) were compared with haemophilia A controls for exposure to SD-treated factor VIII and other environmental factors. Details of factor VIII usage were obtained from the National Haemophilia Register and environmental data were obtained by a telephone-administered questionnaire. The response rate was approximately 90%. RESULTS: The incidence of acute HAV infection among haemophilia A patients exceeded the notified national incidence of HAV by a factor of approximately 300. The incidence was higher in younger patients and those with more severe bleeding disorders. Contact with hepatitis, with children, and exposure to factor VIII were associated with increased risk. The association with factor VIII was the strongest risk factor after controlling for other factors (odds ratio = 27.6, 95% confidence interval [CI] 6.5-117.3). A dose-response effect was demonstrated. CONCLUSIONS: Although person-to-person transmission is likely to have caused a few of the cases, the results of our investigation suggest that the major contributing factor was exposure to certain batches of SD-treated factor VIII.
Assuntos
Surtos de Doenças , Contaminação de Medicamentos , Fator VIII/efeitos adversos , Hemofilia A/terapia , Hepatite A/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Detergentes , Relação Dose-Resposta a Droga , Fator VIII/uso terapêutico , Feminino , Hemofilia A/complicações , Hepatite A/etiologia , Hepatite A/transmissão , Anticorpos Anti-Hepatite A , Vírus da Hepatite A Humana/imunologia , Anticorpos Anti-Hepatite/análise , Humanos , Incidência , Lactente , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SolventesRESUMO
Ascorbic acid added to the basal medium increased the growth response of Lactobacillus casei in folic acid standards. The effect in the serum extracts was not marked, resulting in lowered serum folic acid estimations. However, results obtained on prolonged incubation were similar whether ascorbic acid was added or not. The presence or absence of ascorbic acid and variation of the incubation period may account for differences in reported normal ranges of serum folic acid levels.
Assuntos
Ácido Ascórbico/farmacologia , Ácido Fólico , Lactobacillus , Bioensaio , Sangue , Técnicas In VitroRESUMO
A family having two affected siblings with congenital dyserythropoietic anaemia type II (HEMPAS) is described. The proband was diagnosed after referral for investigation of haemolytic anaemia. Clinical evaluation and in vivo red cell (RBC) survival and the sequestration studies in the proband indicated that the anaemia was due to a combination of ineffective erythropoiesis and premature destruction of RBCs in the spleen. Scanning electron microscopic examination of peripheral RBCs was undertaken and is reported. The polypeptide composition of RBC membranes was also examined using polyacrylamide gel electrophoresis after solubilisation in sodium dodecyl sulphate. These results are also reported.
Assuntos
Anemia Diseritropoética Congênita/genética , Anemia Hemolítica Congênita/genética , Anemia Diseritropoética Congênita/sangue , Criança , Eletroforese em Gel de Poliacrilamida , Envelhecimento Eritrocítico , Membrana Eritrocítica/análise , Eritrócitos Anormais/patologia , Humanos , Masculino , Proteínas de Membrana/análise , Microscopia Eletrônica de Varredura , LinhagemRESUMO
IT had previously been reported that the newly introduced use of a chloramphenicol-resistant strain ofLactobacillus casei for microbiological assay of serum folate gives results approximately 20 per cent higher than the conventional method. It has now been shown that in these conventional techniques the prior extraction of the sera by autoclaving results in loss of the vitamin accounting for this decrease.
RESUMO
This report describes a case of aplastic anaemia who underwent bone marrow transplantation from an ABO compatible HL-A identical sibling of opposite sex. Engraftment was observed with transient recovery of haematopoietic function and documentation of donor type sex chromosome patterns in the recipient's marrow cells. The patient died 35 days posttransplant. The transplantation protocol used and the potential for marrow allografts in bone marrow failure are discussed.
RESUMO
Three cases of cryptococcal meningitis in patients with HIV infection are described. A high index of suspicion is required for diagnosis. India ink preparation and culture of the CSF for cryptococcus is mandatory in HIV seropositive patients irrespective of the CSF white cell count and biochemistry.
Assuntos
Criptococose/complicações , Infecções por HIV/complicações , Meningite/complicações , Infecções Oportunistas/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Humanos , Irlanda , Masculino , Pessoa de Meia-IdadeRESUMO
A longitudinal study with follow up to the end of 1989 was carried out on 23 patients with AIDS who had attended St. James's Hospital, Dublin, by the end of 1987. Until then only 33 cases of AIDS had been reported in Ireland. The patients, all of whom had antibodies to human immunodeficiency virus (HIV), were predominantly male, young (mean age 31.3 years) and belonged about equally to three major risk groups: homosexuals, intravenous drug abusers (IVDA) and haemophiliacs. AIDS was diagnosed because of oesophageal candidiasis (8 cases), Kaposi's sarcoma (4), mycobacterial infection (4), pneumocystis carinii pneumonia (3), toxoplasmosis (2) or encephalopathy (2). Malignant lymphoma and a variety of infections occurred in the course of illness, and neurological involvement developed in 11 patients (48%). Mortality following diagnosis of AIDS was 39% at one year and 64% after two years. Autopsy in 10 of the 16 deaths contributed much to defining the extent and nature of the disease. The demographic pattern, risk group status, survival and range of complications were broadly similar to the pattern of AIDS as seen elsewhere in developed countries. However, compared to the profile of disease reported from the United States, oesophageal candidiasis (52%) and Mycobacterium tuberculosis (22%) were more prominent, pneumocystis carinii pneumonia (39%), Kaposi's sarcoma (22%) and Mycobacterium avium intracellulare (13%) were less frequent and cryptococcal infection was not identified. These regional variations in the frequency of the various complications and particularly the prominence of tuberculosis, probably reflect the interaction of the immunocompromised patient with the local environment and may have important diagnostic and therapeutic implications.