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A Guimarães

Publications and source records attributed to A Guimarães.

At least 19 recordsLinked to original sources
PubMed2007

Congenital amegakaryocytic thrombocytopenia--report of a new c-mpl gene missense mutation.

A 44-month old girl with congenital amegakaryocytic thrombocytopenia, already with pancytopenia, underwent an unrelated allogeneic cord blood transplantation with recovery of normal blood cell counts. The patient was a compound heterozygote for two c-mpl missense mutations inherited from both parents, one of them, a G578A exon 4 mutation leading to a cysteine to tyrosine replacement of codon 193, previously unreported.

Child, Preschool↗
PubMed2006

Seasonal allergic dermatitis in sheep in southern Brazil caused by Culicoides insignis (Diptera: Ceratopogonidae).

The incidence of seasonal dermatitis was studied in a Hampshire Down flock on a farm in southern Brazil. Epidemiological data, clinical signs and macroscopic pathology were obtained by visiting the farm. Histological lesions were studied in skin biopsies of affected sheep. Biting insects were collected from January to April 2005 in an attempt to identify the etiological agent of the disease. Disease prevalence was 40%; the age of the affected animals was variable. Disease occurred from December to March, some animals had lesions for the entire year. Clinical signs include pruritus on the ears, around the eyes and ventral abdomen. Initially erythema and small red papules were seen, followed by alopecia and crust formation. Histologically the lesions were characterized by perivascular eosinophilic dermatitis. Hyperkeratosis and acanthosis were observed in the chronic lesions. Both Anopheles albitarsis and Culicoides insignis were captured during the study. C. insignis bites caused pruritus in sheep. Both types of insects were caught when they approached the sheep baits approximately 30min after sunset. Results suggested that the disease occurred as a result of an immediate hypersensitivity reaction to C. insignis.

Animals↗
PubMed2006

Two novel CLN5 mutations in a Portuguese patient with vLINCL: insights into molecular mechanisms of CLN5 deficiency.

The neuronal ceroid-lipofuscinoses are the most common neurodegenerative disorders in childhood characterized by progressive blindness, epilepsy, brain atrophy, and premature death. Based on the age at onset, disease progression and ultrastructural features three classical (infantile, late-infantile, and juvenile) and three variant late-infantile forms are generally distinguished (Finnish variant, Costa Rican variant, and epilepsy with progressive motor retardation). The Finnish variant late-infantile form has been associated with CLN5 gene defects, with only five mutations described to date. We report a patient with vLINCL/CLN5 who represents the first evidence of the disease in the Portuguese population. Mutational screening revealed the previously described missense mutation c.835G>A (D279N) inherited from the mother, and two novel mutations, c.565C>T (Q189X) and c.335G>C (R112P) from paternal and maternal inheritance, respectively. Based on data here reported: (i) the number of possible mutations in CLN5 gene is now 7; (ii) the CLN5 Portuguese case represents the third description of the disease outside northern Europe; (iii) the CLN5/mRNA expression level reduced to 45% supports the existence of one mRNA non-producing allele, further noticeable at the protein level; (iv) Western blotting data using a specific antibody to human CLN5p provided evidence for the presence of four integral membrane isoforms in human fibroblasts; (v) data from differential expression of CLN2, CLN3, and CLN5 suggest down-regulation of CLN3 gene expression in CLN2 and CLN5-deficient human patients and this observation strengths the hypothesis of functional redundancy of the CLN system.

Adolescent↗
PubMed2006

Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration.

Amyloid Neuropathies, Familial↗
PubMed2003

Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of autosomal recessive neurodegenerative diseases comprising Batten and other related diseases plus numerous variants. They are characterized by progressive neuronal cell death. The CLN6 gene was recently identified, mutations in which cause one of the variant late infantile forms of NCL (vLINCL). We describe four novel mutations in the CLN6 gene. This brings the total number of CLN6 mutations known to 11 in 38 families. This suggests that the CLN6 gene may be highly mutable. An American patient of Irish/French/Native American origin was heterozygous for a 4-bp insertion (c.267_268insAACG) in exon 3. The other allele had a point mutation (c.898T>C) in exon 7 resulting in a W300R amino acid change. Two Trinidadian siblings of Indian origin were homozygous for a mutation at the 5' donor splice site of exon 4 (IVS4+1G>T), affecting the first base of the invariant GT at the beginning of intron 4. The fourth novel mutation, a double deletion of 4 bp and 1 bp in exon 7 (c.829_832delGTCG;c.837delG), was identified in a Portuguese patient heterozygous for the I154del Portuguese CLN6 mutation. Four of the 11 mutations identified are in exon 4. Three Portuguese patients with clinical profiles similar to CLN6 patients without defects in CLN6 or other known NCL genes are described. We conclude the following: 1) the CLN6 gene may be a highly mutable gene; 2) exon 4 must code for a segment of the protein crucial for function; 3) vLINCL disease in Portugal is genetically heterogeneous; 4) the I154del accounts for 81.25% of affected CLN6 Portuguese alleles; and 5) three vLINCL Portuguese patients may have defects in a new NCL gene.

Base Sequence↗
PubMed2003

Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients.

The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naïve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naïve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naïve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD- and TCD-matched patient groups.

Adolescent↗
PubMed2001

Recessive ataxia with ocular apraxia: review of 22 Portuguese patients.

BACKGROUND: The recessive ataxias are a heterogeneous group of neurodegenerative disorders characterized by cerebellar ataxia associated with a number of different neurologic, ophthalmologic, or general signs. They are often difficult to classify in clinical terms, except for Friedreich ataxia, ataxia-telangiectasia, and a relatively small group of rare conditions for which the molecular basis has already been defined. OBJECTIVES: To study the clinical presentation and to define diagnostic criteria in a group of Portuguese patients with ataxia and ocular apraxia, an autosomal recessive form without the essential clinical and laboratory features of ataxia-telangiectasia. PATIENTS AND METHODS: We reviewed 22 patients in 11 kindreds, identified through a systematic survey of hereditary ataxias being conducted in Portugal. RESULTS: Age at onset ranged from 1 to 15 years, with a mean of 4.7 years. The duration of symptoms at the time of last examination varied from 5 to 58 years. All patients presented with progressive cerebellar ataxia, the characteristic ocular apraxia, and a peripheral neuropathy. Associated neurologic signs included dystonia, scoliosis, and pes cavus. Magnetic resonance imaging was performed in 16 patients, all of whom showed cerebellar atrophy. CONCLUSIONS: Ataxia with ocular apraxia may be more frequent than postulated before, and may be identified clinically using the following criteria: (1) autosomal recessive transmission; (2) early onset (for most patients in early childhood); (3) combination of cerebellar ataxia, ocular apraxia, and early areflexia, with later appearance of the full picture of peripheral neuropathy; (4) absence of mental retardation, telangiectasia, and immunodeficiency; and (5) the possibility of a long survival, although with severe motor handicap.

Adolescent↗
PubMed2001

Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates.

Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. No systematic immunohistochemical data exists relating TTR deposition with FAP progression. We assessed nerves from FAP patients in different stages of disease progression (FAP 0 to FAP 3) for TTR deposition by immunohistochemistry, and for the presence of amyloid fibrils by Congo Red staining. The nature of the deposited material was further studied by electron microscopy. We observed that early in FAP (FAP 0), TTR is already deposited in an aggregated nonfibrillar form, negative by Congo Red staining. This suggested that in vivo, preamyloidogenic forms of TTR exist in the nerve, in a stage before fibril formation. Cytotoxicity of nonfibrillar TTR was assessed in nerves of different FAP stages by immunohistochemistry for macrophage colony-stimulating factor. FAP 0 patients already presented increased axonal expression of macrophage colony-stimulating factor that was maintained in all other stages, in sites related to TTR deposition. Toxicity of synthetic TTR fibrils formed in vitro at physiological pH was studied on a Schwannoma cell line by caspase-3 activation assays and showed that early aggregates but not mature fibrils are toxic to cells. Taken together, these results show that nonfibrillar cytotoxic deposits occur in early stages of FAP.

Adolescent↗
PubMed2000

[Cervical spondylodiscitis in an infant].

Spondylitis in childhood is rare, presenting a great variety of symptoms that are related to the child s age and to the site of the inflammatory process. We present the case of a nine-month-old infant, who presented to the emergency department with a torticollis of six weeks evolution. The diagnosis of spondylitis (C6-C7) was confirmed by MRI. Intravenous antibiotic therapy was administered. The patient showed complete regression of symptoms and imaging tests were normal. The rarity of this disease in patients in this age group, as well as the site and form of presentation are emphasised as is the importance of diagnosing this disease to prevent permanent neurological injuries or bone deformities.

Cervical Vertebrae↗
PubMed1999

The mitochondrial DNA A3243G mutation in Portugal: clinical and molecular studies in 5 families.

Out of 90 Portuguese patients with mitochondrial cytopathy, six harbored the A3243G mutation in the mtDNA tRNA(Leu(UUR)) gene ('MELAS mutation'). They had heterogeneous clinical features, including myopathy with stroke-like episodes, progressive external ophthalmoparesis, diabetes mellitus, and subacute encephalopathy. Histochemical and biochemical analyses of muscle biopsies showed abundant ragged-red fibers reacting positively with the cytochrome oxidase stain, and decreased respiratory chain enzyme activities. On average, the proportion of mutated mtDNA was 67% (20-88%) in tissues from patients and 21% (0-49%) in blood from 20 maternal relatives. The proportion of mutated mitochondrial genomes in muscle did not correlate with clinical presentation or duration of disease. This study, the first in Portuguese patients, confirms the frequent occurrence of the A3243G mutation in patients with mitochondrial diseases, and emphasises the usefulness of genetic testing in reaching a correct diagnosis.

Adolescent↗
PubMed1999

Defibrotide as salvage therapy for refractory veno-occlusive disease of the liver complicating allogeneic bone marrow transplantation.

A 30-year-old woman developed veno-occlusive disease of the liver during an allogeneic BMT for acute leukemia. Treatment with recombinant human tissue plasminogen activator and heparin resulted in an incomplete and transient response followed by progressive disease. The patient was then given defibrotide (DF), a mammalian tissue-derived polydeoxyribonucleotide developed for the treatment of a number of vascular disorders, which has thrombolytic and anti-thrombotic properties. No significant bleeding or other major toxicities were observed during treatment and she made a full recovery. At 6 months after the onset of VOD her liver function tests and color flow Doppler ultrasound scan are normal. Our experience supports the preliminary results already obtained with DF. Its efficacy should be evaluated in a prospective randomized fashion.

Adult↗
PubMed1998

Ultrastructure of familial amyloid polyneuropathy amyloid fibrils: examination with high-resolution electron microscopy.

The ultrastructure of familial amyloid polyneuropathy (FAP) amyloid fibrils was examined with high-resolution electron microscopy and immunolabeling. Sural nerve biopsies from FAP (Met 30) patients as well as control tissues were prepared for thin-section observations. Extracellular spaces in the vicinity of myelinated and unmyelinated peripheral nerves were found to be filled with amyloid fibrils as well as with deposits of an "amorphous" material. The fibril was composed of a surface layer and a core. The surface layer was made up of heparan sulfate proteoglycan and was externally associated with a loose assembly of 0.5- to 1-nm-wide filaments. The core was a microfibril-like structure in which amyloid P component was enclosed in a tight helical structure by chondroitin sulfate proteoglycan. Immunogold labeling showed that the peripheral fine filaments were composed of transthyretin. The dimensions of the transthyretin filament suggest that its basic unit is a modified monomer. The deposited amorphous material was a mixture of individual components of the fibril. These results suggest that the main body of FAP amyloid fibrils is similar to that of recently observed fibrils of experimental murine AA and hemodialysis-associated amyloid as well as of connective tissue microfibrils. The differences in the fibrils of these various types of amyloid are in the peripheral filaments which are composed of a protein specific to each type of amyloid.

Amyloid↗
PubMed1998

Relapsed chronic myeloid leukemia in accelerated phase 10 years after allogeneic bone marrow transplantation: full chimera reconversion with donor peripheral blood stem cells infusion.

We report the case of a 44-year-old male who relapsed in accelerated phase chronic myeloid leukemia 10 years after a successful bone marrow transplantation from his HLA-identical brother, and 3 years after 12 months treatment with interferon-alpha (IFN-alpha) for chronic active hepatitis C (CAH). The patient was infused with G-CSF-primed peripheral blood cells (PBSC) from the original bone marrow donor and a full donor reconstitution, with no detectable molecular disease, was obtained within 4 months without clinical aplasia or GVHD, nor help from other forms of chemotherapy or use of biological response modifiers. We speculate that IFN-alpha for CAH delayed the onset of a clinical recurrence of chronic myeloid leukemia and that in advanced disease PBSCs can provide an advantageous alternative to donor lymphocyte infusion (DLI).

Adult↗
PubMed1998

Mitochondrial DNA analysis in ocular myopathy. Observations in 29 Portuguese patients.

We analyzed 29 patients with progressive external ophthalmoparesis (PEO) either alone or as part of a multisystem disorder. Ragged-red fibers were very abundant (10-20%) in 15 patients, and many of them were also cytochrome c oxidase-negative. Biochemical analysis of the respiratory chain showed partial defects of single or multiple complexes in 18 patients (64%). Eleven PEO patients (38%) harbored single large-scale mtDNA deletions in muscle, which averaged 5.4 kb in size and 47% in relative abundance. One PEO patient harbored the A3243G mutation (MELAS mutation) in muscle (63%). Our findings, the first reported in Portuguese patients, confirm that single large-scale mtDNA deletions are a significant cause of PEO. Although ophthalmoparesis was the main clinical feature in the majority of patients, the clinical spectrum is broad, ranging from severe encephalopathy of childhood to a milder, though disabling, muscle weakness in adults.

Adolescent↗
PubMed1998

Diagnostic electrocardiography in epidemiological studies of Chagas' disease: multicenter evaluation of a standardized method.

An electrocardiographic recording method with an associated reading guide, designed for epidemiological studies on Chagas' disease, was tested to assess its diagnostic reproducibility. Six cardiologists from five countries each read 100 electrocardiographic (ECG) tracings, including 30 from chronic chagasic patients, then reread them after an interval of 6 months. The readings were blind, with the tracings numbered randomly for the first reading and renumbered randomly for the second reading. The physicians, all experienced in interpreting ECGs from chagasic patients, followed printed instructions for reading the tracings. Reproducibility of the readings was evaluated using the kappa (kappa) index for concordance. The results showed a high degree of interobserver concordance with respect to the diagnosis of normal vs. abnormal tracings (kappa = 0.66; SE 0.02). While the interpretations of some categories of ECG abnormalities were highly reproducible, others, especially those having a low prevalence, showed lower levels of concordance. Intraobserver concordance was uniformly higher than interobserver concordance. The findings of this study justify the use by specialists of the recording of readings method proposed for epidemiological studies on Chagas' disease, but warrant caution in the interpretation of some categories of electrocardiographic alterations.

Argentina↗
PubMed1998

[Microsurgical reconstruction of the head and neck: experience of 63 free flaps].

The authors present the experience of 63 clinical cases of microsurgical reconstruction of the head and neck. These reconstructions were accomplished by different microvascular free flaps which were selected according to the type, size and location of the defects. Fasciocutaneous, osteofasciocutaneous, adipofascial, myo, myocutaneous, myosseous, jejunum and great omentum flaps were applied. The etiology was traumatic in 10 cases, tumoral in 41 cases, congenital in 7 cases, iatrogenic in 3 cases and infectious in 2 cases. The reconstructed anatomical regions were the scalp in 6 cases, the skull base in 1 case, the orbit in 3 cases, the nose in 1 case, the hemiface in 7 cases, the lips in 1 case, the intraoral cavity in 21 cases, the mandible in 8 cases, the intraoral cavity plus mandible in 11 cases and the cervical esophagus in 1 cases. An analysis was made of surgical times, selection and survival rate of the free flaps and the morphofunctional quality of the reconstructions. Considering the good quality of reconstructions, the amelioration of quality of life and the low morbidity in these patients, microvascular free flaps are considered a first choice technique for head and neck reconstruction when the size and location of the defect prevents the use of local flaps.

Adult↗