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Biomedical subjects

A Cao

Publications and source records attributed to A Cao.

At least 91 records · Page 5Linked to original sources
PubMed1996

Control of beta-thalassaemia by carrier screening, genetic counselling and prenatal diagnosis: the Sardinian experience.

Homozygous beta-thalassaemia in a number of at-risk populations (Greek and Turkish Cypriots, Greeks, Continental Italians and Sardinians) has been prevented at the population level by programmes based on carrier screening, genetic counselling and prenatal diagnosis. The Sardinian experience is based on a 20-year programme. Voluntary screening has been offered to prospective parents and, primarily, to women with an ongoing pregnancy. Education of the population at large, training of health personnel, and use of posters and informative booklets have been critical elements for the success of the programme. Genetic counselling has been carried out in a non-directive manner following well-established guidelines. The use of extended family screening magnified the efficacy of the screening programme, allowing the identification of the large majority of parents at risk by screening only 13% of the population at child-bearing age. Following counselling, the large majority of parents accepted prenatal diagnosis. Definition of the parents' mutation and prenatal diagnosis were carried out by a number of PCR-based procedures. The programme was effective, as indicated by the reduction of the birth rate of thalassaemia major from 1:250 live births to 1:4000.

Genetic Counseling↗
PubMed1996

HLA class II genes in chronic hepatitis C virus-infection and associated immunological disorders.

To investigate the factors that may confer susceptibility or protection to hepatitis C virus (HCV) infection and to HCV-associated immunological disorders, we designed two studies on 420 Sardinian transfusion-dependent thalassemia patients followed in our department in Cagliari since 1974. The first one was an epidemiological survey aimed to evaluate the prevalence of HCV infection and HCV-associated immunological disorders. In the second study, the distribution of different HLA class II genes was examined by DNA analysis in 116 HCV positive patients, 30 HCV negative patients, and 606 healthy controls. Three hundred fourteen patients became infected with HCV (74.7%) after 5.6 +/- 2.8 years of regular transfusion program. Mixed cryoglobulinemia, purpura, arthritis, proteinuria, decreased complement levels, rheumatoid factor and anti-GOR, smooth muscle antibody (SMA), anti-nuclear antibody (ANA), and liver, kidney microsome (LKM) autoantibodies were significantly more represented in HCV positive patients than in negative ones (P < .05). A significant increase of HLA class II DR2 subtype (DRB1*1601,DQB1*0502) was observed in a group of 30 HCV negative patients who despite 10.3 +/- 2.2 years in a regular blood transfusion program did not show any evidence of HCV infection (Pc < .0092). Our results represent clear evidence for a relationship between HCV infection and immune extrahepatic abnormalities. A gene(s) located in the human major histocompatibility complex (MHC) region may play an important role in conferring protection against HCV infection.

Adolescent↗
PubMed1996

Wilson disease mutations associated with uncommon haplotypes in Mediterranean patients.

This study reports 12 novel mutations of the Wilson disease (WD) gene which have been detected by the molecular analysis of 29 patients of Mediterranean descent carrying uncommon chromosomal haplotypes at the WD locus. These mutations include two nonsense, one splice site and nine missense. The missense mutations lie in regions of the WD gene critical for its function, such as the transmembrane region, the transduction domain and the ATP loop and ATP-binding domain, indicating that they are disease-causing mutations. These new findings improve our knowledge for the role played by functional domains on the ATP7B function.

Albania↗
PubMed1996

Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition characterized by pre- and postnatal overgrowth with visceral and skeletal anomalies. To identify the causative gene, breakpoints in two female patients with X;autosome translocations were identified. The breakpoints occur near the 5' and 3' ends of a gene, GPC3, that spans more than 500 kilobases in Xq26; in three families, different microdeletions encompassing exons cosegregate with SGBS. GPC3 encodes a putative extracellular proteoglycan, glypican 3, that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. Initial western- and ligand-blotting experiments suggest that glypican 3 forms a complex with insulin-like growth factor 2 (IGF2), and might thereby modulate IGF2 action.

Abnormalities, Multiple↗
PubMed1996

Behçet's disease and the neuropathic bladder: urodynamic features: case report and a literature review.

We report on a 16-year old patient with a neuropathic bladder secondary to Behçet's disease, which is an uncommon vasculitis usually involving venules. The genitourinary manifestations of this disease are discussed, a neuropathic bladder being a rare complication of the involvement of the nervous system. Urodynamic assessment is important when voiding dysfunction is present; three patients previously reported revealed a bladder function changing from normal detrusor to overactivity. Our patient showed early and severe involvement of the nervous system, and detrusor areflexia two years after the onset of the disease. Spontaneous voiding was restored two months after urological management (intermittent catheterization) was started.

Adolescent↗
PubMed1996

Localization of sequences regulating ancestral and acquired sites of esterase6 activity in Drosophila melanogaster.

We have broadly defined the DNA regions regulating esterase6 activity in several life stages and tissue types of D. melanogaster using P-element-mediated transformation of constructs that contain the esterase6 coding region and deletions or substitutions in 5' or 3' flanking DNA. Hemolymph is a conserved ancestral site of EST6 activity in Drosophila and the primary sequences regulating its activity lie between -171 and -25 bp relative to the translation initiation site: deletion of these sequences decrease activity approximately 20-fold. Hemolymph activity is also modulated by four other DNA regions, three of which lie 5' and one of which lies 3' of the coding region. Of these, two have positive and two have negative effects, each of approximately twofold. Esterase6 activity is present also in two male reproductive tract tissues; the ejaculatory bulb, which is another ancestral activity site, and the ejaculatory duct, which is a recently acquired site within the melanogaster species subgroup. Activities in these tissues are at least in part independently regulated: activity in the ejaculatory bulb is conferred by sequences between -273 and -172 bp (threefold decrease when deleted), while activity in the ejaculatory duct is conferred by more distal sequences between -844 and -614 bp (fourfold decrease when deleted). The reproductive tract activity is further modulated by two additional DNA regions, one in 5' DNA (-613 to -284 bp; threefold decrease when deleted) and the other in 3' DNA (+1860 to +2731 bp; threefold decrease when deleted) that probably overlaps the adjacent esteraseP gene. Collating these data with previous studies suggests that expression of EST6 in the ancestral sites is mainly regulated by conserved proximal sequences while more variable distal sequences regulate expression in the acquired ejaculatory duct site.

Animals↗
PubMed1996

HB Hinwil or beta 38(C4)Thr-->Asn: a new beta chain variant detected in a Swiss family.

This paper reports a new hemoglobin variant which was identified while investigating the cause of a mild erythrocytosis. The abnormal beta-globin chain was detected by reversed phase chromatography. Mutation mapping of the beta-globin gene by polymerase chain reaction and denaturing gradient gel electrophoresis followed by sequence analysis revealed a C-->A transversion at codon 38, predicting a Thr-->Asn substitution. Tryptic peptide mapping by liquid chromatography electrospray mass spectrometry, followed by conventional Edman peptide sequence analysis, confirmed the predicted amino acid substitution. In contrast to the only other known mutation at codon 38, Hb Hazebrouck (Thr-->Pro), this hemoglobin is stable and shows elevated oxygen affinity.

Amino Acid Sequence↗
PubMed1996

[Determination of chlorogenic acid in Epimedium koreanum Nakai by HPLC].

The chlorogenic acid content in Epimedium koreanum was determined by HPLC. The result shows that this method is simple, specific and accurate. The recovery was 97.5% and relative standard deviation was 1.4%. With good reproducibility and wide response linearity, the method can be used for the quality control of this herbal medicine.

Chlorogenic Acid↗
PubMed1995

Isolation of a differentially regulated splicing isoform of human NF-E2.

The transcription factor NF-E2 (nuclear factor erythroid 2), interacting via DNA motifs within regulatory regions of several hematopoietic genes, is thought to mediate the enhancer activity of the globin locus control regions. By screening a human fetal liver cDNA library with probes derived from mouse NF-E2, we have isolated a splicing variant of the NF-E2 gene (fNF-E2) that differs in the 5' untranslated region from the previously reported cDNA (aNF-E2). The fNF-E2 isoform is transcribed from an alternative promoter located in the 3' end of the first intron and joined by alternative splicing to the second and third exons, which are shared by both RNA isoforms. Although the two forms produce the same protein, they are expressed in different ratios during development. fNF-E2 is more abundant in the fetal liver and less abundant in the adult bone marrow compared to the previously described form. Their distribution apparently follows the differential expression of fetal and adult hemoglobins.

Alternative Splicing↗
PubMed1995

The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci.

The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of HLA-DRB1*04 haplotypes in 630 Sardinian newborns and 155 Sardinian IDDM patients. The different RRs and ARs of the various DR4-DQB1*0302 haplotypes, significantly ranging from the strongly associated DRB1*0405, DQB1*0302 to the protective DRB1*0403, DQB1*0302 haplotypes, provides clearcut evidence that the DRB1 locus is crucial in conferring IDDM predisposition or protection. Also, the DQB1 locus influences IDDM predisposition or protection by restricting the disease-positive association to DRB1*0405 haplotypes carrying the susceptibility DQB1*0302 or DQB1*0201 alleles but not the protective DQB1*0301 allele. Haplotype analysis not only suggests that the DRB1 and DQB1 loci influence IDDM risk in the same way, but also that the HLA-linked protection is "dominant" compared with "susceptibility." These results, obtained from a population with one of the highest IDDM incidences in the world, define more clearly the contribution of the various HLA loci to IDDM protection or susceptibility and allow a more precise calculation of AR.

Adolescent↗
PubMed1995

A specific cystic fibrosis mutation (T3381) associated with the phenotype of isolated hypotonic dehydration.

We carried out molecular screening for mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in eight children of Sardinian descent seen because of hypotonic dehydration associated with hyponatremia, hypochloremia, hypokalemia, and metabolic alkalosis; none had pulmonary or pancreatic involvement. All the patients had the T3381 mutation either in homozygosity or compound heterozygosity with another CF mutation. The T3381 mutation was not detected in patients with CF who had classic symptoms or in healthy persons of the same descent. These data suggest that the T3381 mutation is associated with a specific mild CF phenotype.

Child↗
PubMed1995

A promoter mutation, C-->T at position -92, leading to silent beta-thalassaemia.

This study describes the clinical phenotype of the C-->T mutation at position -92 of the beta-globin gene. Excluding two cases with HbA2 levels within the range of the beta-thalassemia carrier state, heterozygotes for this mutation showed normal or borderline red blood cells count, Hb levels, MCV, MCH and HbA2 values, and unbalanced globin chain synthesis. Compound heterozygotes for the -92 C-->T mutation and a beta zero-thalassaemia mutation (beta zero 39) (two cases) or severe beta+-thalassaemia (beta+ IVSII nt 745) (two cases) developed thalassaemia intermedia. According to these characteristics, the -92 promoter mutation should be added to the list of silent beta-thalassaemias.

Base Sequence↗
PubMed1995

Relationship between transfusion regimen and suppression of erythropoiesis in beta-thalassaemia major.

In the management of beta-thalassaemia major, different transfusion schemes are employed with baseline haemoglobin levels ranging from 8 to over 12 g/dl. We studied the relationship between transfusion regimen and suppression of erythropoiesis in 52 patients with beta-thalassaemia major whose mean pretransfusion haemoglobin levels ranged from 8.6 to 10.9 g/dl. Multiple, regression analysis showed that serum transferrin receptor was the parameter more closely related to mean pretransfusion haemoglobin (r = -0.77, P < 0.001). As measured through serum transferrin receptor, erythroid activity was 1-2 times normal for pretransfusion haemoglobin levels between 10 and 11 g/dl. 1-4 times normal for levels from 9 to 10 g/dl, and 2-6 times normal for levels from 8.6 to 9 g/dl. Mean pretransfusion haemoglobin was also inversely related to serum erythropoietin (r = -0.72, P < 0.001), whereas it showed no or a weak relationship with Hb F, reticulocyte count, or circulating nucleated red cell count. This study suggests that serum transferrin receptor is a reliable indicator of suppression of erythropoiesis in beta-thalassaemia major. On the basis of our findings, pretransfusion haemoglobin values of < or = 9 g/dl should be adopted with caution, because these levels can be associated with an insufficient inhibition of erythroid marrow expansion. However, a transfusion programme, with a baseline haemoglobin of 9-10 g/dl, may provide enough suppression of erythropoiesis and allow a reduction in blood consumption as compared with the classic hyper- or supertransfusion schemes. Since fixed haemoglobin levels may not be the best target for transfusion treatment in all thalassaemic patients, assay of serum transferrin receptor may be helpful for individualizing the transfusion regimens.

Adolescent↗