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Biomedical subjects

A Moreira

Publications and source records attributed to A Moreira.

At least 37 records · Page 2Linked to original sources

Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved.

Poly(A) signals of mammalian pre-mRNA have been defined as an AAUAAA sequence 10-30 nt upstream of the cleavage/poly(A) site followed by a GU/U-rich element immediately downstream. However, a number of viral poly(A) signals have been shown to possess additional signals upstream of AAUAAA that increase poly(A) site efficiency. We describe the first non-viral example of such an upstream sequence element (USE) for the poly(A) site of the human C2 complement gene. As this gene is very closely spaced to the related Factor B gene [the C2 poly(A) site is only 421 bp from the transcription start site of Factor B] we have isolated this same intergenic sequence from four other mammals (mouse, cat, rabbit and cow). We show that the USE of the C2 poly(A) site is highly conserved between these five different mammals. Furthermore, extensive mutagenesis of the human USE indicates that most of the 53 nt sequence is required for full activity. The human C2 poly(A) site does not possess any obvious downstream GU/U-rich sequences, although sequences immediately 3' to AAUAAA as well as 13 nt of sequence following the cleavage site are both required for full activity. Interestingly the other mammalian C2 poly(A) sites do possess significant downstream GU/U-rich sequences. Finally we show that all five mammalian C2 poly(A) signals are immediately followed by conserved signals for transcriptional termination, consistent with the close proximity of the downstream Factor B gene.

Animals↗

Naturally occurring antibodies reacting with lipoic acid: screening method, characterization and biochemical interest.

The development of a covalent enzyme-linked immunoassay (CELIA) using lipoic acid covalently bound to modified polystyrene microplates has permitted the detection, in the sera of normal BALB/c mice, of natural antibodies reacting with lipoic acid (LA). Hybridomas producing monoclonal anti-LA antibodies were obtained from splenocytes of non-immune BALB/c mice. Two of them, of IgM isotype, recognized LA but failed to react with dihydrolipoic acid (DHLA, the reduced form of LA), suggesting that the integrity of the dithiolane ring was of importance for antibody recognition. They did not give positive reactions with other disulfide linked biological molecules such as oxidized glutathione or cystine. Anti-LA antibodies, coated on polystyrene microplates, were used for the detection of free LA in a competitive assay based on peroxidase-LA conjugate.

Animals↗

Renal arteriovenous fistula after nephrectomy.

Postnephrectomy renal arteriovenous fistulas are rare. An arteriovenous fistula of the right renal pedicle was discovered in a 37-year-old woman who had undergone nephrectomy for renal tuberculosis nine months previously, after she had complained of dyspnea and pain in the right flank. The fistula was confirmed on arteriograms. Proximal ligation of the artery and distal ligation of the vein were followed by an uneventful recovery. Twelve months later, the patient was asymptomatic. Even though complete excision of the fistula represents the ideal treatment of this type of lesion, simple ligation can provide good results when the size of the fistula contraindicates embolization.

Adult↗

Non-progressive paraparesis in children with congenital ligamentous laxity.

We present clinical data from 11 children with generalised joint laxity complicated by signs of pyramidal dysfunction confined to the lower limbs. Gait abnormalities were observed at the time they started walking or soon afterwards. In some, there was delay in locomotor development but all except one were mentally normal. The neurological component of the condition was non-progressive, and sensory impairment with sphincter involvement was observed in only one case in whom there was radiological evidence of myelomalacia. Whilst co-existing ligamentous laxity and pyramidal dysfunction in the lower limbs may be coincidental, it is also possible that joint laxity is a pre-condition for developing neurological abnormality in the legs because of hypermobility of the vertebral column which thereby damages the spinal cord.

Child↗

Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies.

The in vivo effect of cyclosporin A (CsA) on the murine thymus was investigated by studying the ultrastructural cellular alterations, which are described for the first time, and the immunohistochemical modifications of thymocytes and thymic reticulo-epithelial cells (TREC). A marked reduction of the thymus size became apparent after 6 days of CsA treatment (10 mg/kg/day). Light microscopy studies using polyclonal antibodies (Ab) or monoclonal Ab specific to lymphoid sub-populations (anti-CD4, anti-CD5, anti-CD8), and specific to epithelial cells (anti-keratin: AKs, K8), to cortical TREC (TR4) and to subcapsular/medullary TREC (TR5, 3H9) showed that the number of CD4- 8+ or CD4+ 8- medullary thymocytes dramatically decreased and that the cortical TREC are affected, after 10 days of CsA treatment. These observations were confirmed by electron microscopy studies demonstrated that the medullary lymphoid population disappeared almost entirely. TREC, principally cortical type, presented signs of cellular lysis. A few cortical thymocytes showed some damage. At day 8 the medullary thymic tissue was disorganized, but no change was noted in the subcapsular area right up to the final day (day 10) of CsA treatment. These results suggest that CsA has a harmful effect on cortical TREC, which affects the development of immature thymocytes.

Animals↗

polo encodes a protein kinase homolog required for mitosis in Drosophila.

We show that mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed; normal bipolar spindles with polyploid complements of chromosomes; bipolar spindles in which one pole can be unusually broad; and monopolar spindles. We have cloned the polo gene from a mutant allele carrying a P-element transposon and sequenced cDNAs corresponding to transcripts of the wild-type locus. The sequence shows that polo encodes a 577-amino-acid protein with an amino-terminal domain homologous to a serine-threonine protein kinase. polo transcripts are abundant in tissues and developmental stages in which there is extensive mitotic activity. The transcripts show no obvious spatial pattern of distribution in relation to the mitotic domains of cellularized embryos but are specifically concentrated in dividing cells in larval discs and brains. In the cell cycles of both syncytial and cellularized embryos, the polo kinase undergoes cell cycle-dependent changes in its distribution: It is predominantly cytoplasmic during interphase; it becomes associated with condensed chromosomes toward the end of prophase; and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic.

Amino Acid Sequence↗

A case of GM1 gangliosidosis type I.

A six-month-old female gypsy child, the daughter of second degree cousins, born after a full-term pregnancy and normal delivery, is described. There was generalized neonatal edema. Abnormalities included psychomotor retardation from birth and progressive appearance of facial dysmorphism, organ enlargement, axial hypotonia, hypertonia in limbs, myoclonic jerks, optic atrophy and bilateral cherry-red spots. The diagnosis of GM1 type 1 gangliosidosis was confirmed by biochemical, enzymatic and ultrastructural findings.

Biopsy↗

Generation of hybridoma antibodies to double-stranded DNA from non-autoimmune BALB/c strain: studies on anti-idiotype.

A hybridoma obtained between normal spleen cells from BALB/c mice (a non-autoimmune strain) and SP2-O-Ag 14 myeloma cell line was designated as HB2. These hybrid cells produced an IgM kappa-anti-ds-DNA antibody, but their specificity was limited to some polydeoxyribonucleotides such as natural ds-DNA from calf thymus, poly dG-poly dC, poly d(GC) and poly d(GC)-poly d(GC). In contrast, poly dA-poly dT, poly d(AT) were not recognized. The configuration of the nucleic acid helix plays a small role if any, in the building of the epitopes recognized by the hybridoma HB2 antibodies, while the presence of G and C appeared to be essential. These epitopes could not be found on ss- and ds-polyribonucleotides. B cells able to produce anti-ds-DNA antibodies are therefore present in non-autoimmune BALB/c mice, but not enough to produce the corresponding antibodies at a detectable level in the serum. Following immunization of BALB/c mice with hybridoma HB2 monoclonal antibodies, anti-idiotype antibodies were obtained which also recognized idiotopes present in the serum from both murine MRL/1 and human systemic lupus erythematosus (SLE).

Animals↗

[Free omental autografts revascularized by microsurgery (author's transl)].

The greater omentum is good plastic material and supplies richly vascularized connective tissue for transplants. Some superficial and deep lesions of the soft tissues require extensive excision, and in favorable cases it is possible to use the greater omentum pedicled as described by Kiricuta. Two such cases are reported. In other cases a free transplant of omentum revascularized by microsurgical methods has to be used. This procedure was employed in ten patients and allowed repair of lesions with wide or deep loss of tissue under excellent conditions. An intermediate saphenous graft was necessary in one case. A dermoepidermal graft was applied at the same time in order to obtain results more rapidly. Progress made in microsurgical techniques has allowed omentum revascularization to be carried out under much safer conditions and this procedure should be employed more frequently.

Adolescent↗