Biomedical subjects

J Guimarães

Publications and source records attributed to J Guimarães.

26 records · Page 2Linked to original sources

PubMed1997

Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families.

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. One hundred and eighty four index patients with autosomal dominant cerebellar ataxia type I were screened for this mutation. We found expansion in 109 patients from 30 families of different geographical origins (15%) and in two isolated cases with no known family histories (2%). The SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14 repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable mutations, a strong negative correlation was observed between the age at onset and the size of the CAG repeat (r = -0.81). The frequency of several clinical signs such as myoclonus, dystonia and myokymia increased with the number of CAG repeats whereas the frequency of others was related to disease duration. The CAG repeat was highly unstable during transmission with variations ranging from -8 to +12, and a mean increase of +2.2, but there was no significant difference according to the parental sex. This instability was confirmed by the high degree of gonadal mosaicism observed in sperm DNA of one patient.

Adolescent↗

PubMed1995

Correlation between CAG repeat length and clinical features in Machado-Joseph disease.

Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62-84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist.

Adult↗

PubMed1994

Genetic linkage studies of Machado-Joseph disease with chromosome 14q STRPs in 16 Portuguese-Azorean kindreds.

Machado-Joseph disease (MJD) is a dominant multisystem degeneration found mostly among Azoreans and characterized by the adulthood onset of cerebellar, ocular, pyramidal, extrapyramidal, and/or peripheral signs. MJD has been recorded in many other populations, particularly in the United States and Japan. Using the microsatellite DNA polymorphisms (STRPs) D14S53, D14S55, D14S48, and D14S45, we found significantly positive lod scores in 16 Portuguese kindreds, suggesting that the MJD locus is linked to chromosome 14q in this population. Differences in age-at-onset and many untyped individuals seem to explain the lower lod scores. Using HOMOG, no evidence was found for heterogeneity with the five Japanese families in whom linkage was reported.

Adult↗

PubMed1994

Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families.

Hypokalaemic periodic paralysis (HypoPP) is an autosomal dominant muscle disease thought to arise from an abnormal function of ion channels. Performing a genome-wide search using polymorphic dinucleotide repeats, we have localized the HypoPP locus in three families of different geographic origin to chromosome 1q31-32, by linkage analysis. Using an intragenic microsatellite, we also demonstrate that the gene encoding the muscle DHP-sensitive calcium channel alpha 1 subunit (CACNL1A3) maps to the same region, sharing a 5 centiMorgan (cM) interval with the HypoPP locus. Moreover, CACNL1A3 co-segregates with HypoPP without recombinants in the two informative families, and is therefore a good candidate for the HypoPP gene.

Calcium Channels↗

PubMedDate not supplied

[Santa Tereza Windows: a study of the psycho-social rehabilitation process at the Psychiatric Hospital in Ribeirão Preto, São Paulo].

This is a case study of a psycho-social rehabilitation process taking place at Santa Tereza, a psychiatric hospital in Ribeirão Preto, whose objective is to understand possibilities and limitations implied in the rehabilitation process within Pensões Protegidas (Protected Homes) project. The basic strategies for the present study involved participative observation and interviews with individuals living in such homes as well as with the multi-professional staff working in the process. The results reveal a kind of orientation quite distant from the hospital-centered trend, since they reveal remarkable tendency towards deinstitutionalization. Finally, the author emphasizes the contribution of Pensões Protegidas Project at Santa Tereza for the better understanding of the so-called mentally ill.

Brazil↗

PubMedDate not supplied

[Immunoglobin subclasses and determination of specific antibodies. What role in the study of children with recurrent pneumonias?].

BACKGROUND: Recurrent pyogenic infections, including pneumonia, are known to occur in children with a defective immune system. Until recently, diagnosis was made by measuring major immunoglobulin isotypes and IgG subclasses. Recent reports show that in some cases all these measurements are normal, but that there is a defect in the production of specific protein or polysaccharide antibodies. OBJECTIVE: To study immune function in children with recurrent pneumonia to determine the most appropriate immunologic studies for the evaluation of recurrent infections in children. METHODS: Forty-three children (ages 2 to 12 years; mean 5.3 years, 29 male) who were referred to our pulmonology clinic because of recurrent lower respiratory tract infections. Major causes of recurrent infections were excluded by clinical, radiological or laboratory studies. Immunologic studies included serum immunoglobulins, IgG subclasses, IgA subclasses, isohemagglutinins and antibody responsiveness to vaccination with tetanus, rubella, H. influenza b conjugate and pneumococcal polysaccharide. RESULTS: The majority of children had normal or elevated serum immunoglobulin and subclass levels. Three patients had low levels of IgG2 and IgA, alone or simultaneously. Eleven patients failed to respond to Hib or rubella vaccination and one failed to respond to pneumococcal immunisation. CONCLUSIONS: Our preliminary results seem to indicate that a high proportion of children with recurrent pneumonia have a demonstrable immunologic abnormality. There is no direct relationship between low levels of IgG subclass and the child's capacity to form antibodies to several antigens. Defects in antibody production are very specific and an extended panel is necessary. Examination of the antibody-forming capacity seems important in the initial evaluation of children with recurrent pneumonia.

Antibodies, Bacterial↗

PubMedDate not supplied

[A case of Wilson's disease studied using magnetic resonance: a new approach?].

Wilson's disease is a genetically determined disorder of copper metabolism with increased deposition in brain and liver. With current imaging techniques--CT scan and conventional Nuclear Magnetic Resonance (NMR)--it has been possible to demonstrate oedema, neuronal loss and reactive gliosis, but not copper deposition. In the present study we report the observations, done in one patient, using a new high magnetic field (1.5 Tesla) NMR device. In these circumstances, we are able to expand the CT scan analysis by showing not only the oedema and the brain cell death but also the probable existence of copper deposits. Will this be true, it is first instance in which it has been possible to demonstrate, by a non invasive method, increased copper deposition in Wilson's disease. This possibility may be important to monitor the therapeutic efficacy of chelating agents and also to distinguish asymptomatic homozygous patients from heterozygous healthy carriers.

Adolescent↗

PubMedDate not supplied

Evaluation of the effect of sulphametoxazole and trimethoprim in patients with Machado-Joseph disease.

The treatment of Machado-Joseph disease (MJD) has so far been purely symptomatic. Encouraged by previous publications reporting some improvement in spasticity and gait in two patients with MJD treated with sulphamethoxazole and trimethoprim (Bactrim), we carried out a double-blind, placebo controlled cross-over trial in eight patients. Three kinds of parameters were used to evaluate the treatment effect: subjective performance, neurological examination and timed tests. The results showed that Bactrim had a beneficial effect on gait and coordination and that it would be worthwhile undertaking other trials, taking into account the great clinical variability of MJD.

Adult↗