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Biomedical subjects

M F Waters

Publications and source records attributed to M F Waters.

At least 19 recordsLinked to original sources
PubMed2005

An autosomal dominant ataxia maps to 19q13: Allelic heterogeneity of SCA13 or novel locus?

The autosomal dominant spinocerebellar ataxias (ADCAs) represent a growing and heterogeneous disease phenotype. Clinical characterization of a three-generation Filipino family segregating a dominant ataxia revealed cerebellar signs and symptoms. After elimination of known spinocerebellar ataxia (SCA) loci, a genome-wide linkage scan revealed a disease locus in a 4-cM region of 19q13, with a 3.89 lod score. This region overlaps and reduces the SCA13 locus. However, this ADCA is clinically distinguishable from SCA13.

Adult↗
PubMed2005

Nitrous oxide inhalation as a cause of cervical myelopathy.

Current evidence suggests that the incidence of recreational nitrous oxide inhalation is on the rise. Due to the possibility of clinically significant myelopathy, as well as potential response to treatment, it is important to consider this diagnosis when appropriate. We present a case of acquired ataxia and myelopathy due to nitrous oxide abuse and discuss diagnosis, pathophysiology, and response to treatment.

Administration, Inhalation↗
PubMed2001

Cytokine-induced changes in chromatin structure and in vivo footprints in the inducible NOS promoter.

Transcription of the human inducible nitric oxide synthase (iNOS) gene is regulated by inflammatory cytokines in a tissue-specific manner. To determine whether differences in cytokine-induced mRNA levels between pulmonary epithelial cells (A549) and hepatic biliary epithelial cells (AKN-1) result from different protein or DNA regulatory mechanisms, we identified cytokine-induced changes in DNase I-hypersensitive (HS) sites in 13 kb of the iNOS 5'-flanking region. Data showed both constitutive and inducible HS sites in an overlapping yet cell type-specific pattern. Using in vivo footprinting and ligation-mediated PCR to detect potential DNA or protein interactions, we examined one promoter region near -5 kb containing both constitutive and cytokine-induced HS sites. In both cell types, three in vivo footprints were present in both control and cytokine-treated cells, and each mapped within a constitutive HS site. The remaining footprint appeared only in response to cytokine treatment and mapped to an inducible HS site. These studies, performed on chromatin in situ, identify a portion of the molecular mechanisms regulating transcription of the human iNOS gene in both lung- and liver-derived epithelial cells.

Base Sequence↗
PubMed1996

Induction of Th1 cytokine responses by mycobacterial antigens in leprosy.

Twelve mycobacterial antigens were compared for induction of gamma interferon (IFN-gamma) secretion by human blood mononuclear cells of patients with leprosy. Fractionated Mycobacterium leprae antigens containing cell wall proteins or cytosolic and membrane proteins induced good IFN-gamma responses in tuberculoid leprosy patients. Lipoarabinomannan from M. tuberculosis Erdman and M. leprae mycolylarabinogalactan peptidoglycan were the poorest IFN-gamma inducers.

Antigens, Bacterial↗
PubMed1996

Leprous neuropathies.

Once a terrifying disease, leprosy today has a very hopeful prognosis, provided that it is diagnosed early and treated with modern multidrug chemotherapy, any immunological reactions being recognized quickly and controlled well to prevent (further) peripheral nerve damage after commencing treatment. The diagnosis should be considered in all patients who present with peripheral neuropathy and/or anaesthetic skin lesions who come from or have lived in the tropics and subtropics. Although M. leprae cannot yet be grown in vitro, it is readily grown in experimental animals. A complete gene library has been developed, much of the genome mapped and a number species-specific and common mycobacterial antigens identified. The intricacies of the host-parasite relationship, especially of cell-mediated immunity, and of the important immunological reactions of ENL and reversal reaction have been widely investigated. Modern MDT has caused a dramatic fall in prevalence, although the world annual case detection rate remains at around 600,000 new patients, many being at an early stage of the disease. WHO has launched a campaign to eliminate leprosy as a significant public health risk by the 2000 (with a prevalence of less than 1:10 000 population), which may well be achieved in some endemic countries. Leprosy will, however, remain an important cause of peripheral neuropathy for at least several more decades.

Biopsy↗
PubMed1994

Effect of Mycobacterium leprae in peripheral nerve trunk on the evolution of skin lesions.

Comparative histological studies were made of a) 41 peripheral nerve lesions and the skin in the area of supply, and b) 12 peripheral nerve lesions and concurrent but unrelated skin lesions. In the first study, small, relatively early, histologically classifiable skin lesions were found in all cases, even though there were no clinical lesions. In every case the lesion was centered on a dermal nerve. In some cases disruption of the perineurium was associated with emergence of the lesion into the dermis and a small silent local reaction. It was concluded that there was a descending spread of the disease down the neural pathway to the dermis, although it was not necessarily associated with transport of bacilli. Although the first study showed a discrepancy in the classification between skin and nerve lesions in nearly 50% of the cases (as previously reported), the second study showed no discrepancies. It is suggested that discrepancies are relatively uncommon, and that those in the first study are exceptional. The probable explanation is that microreactions in the nerve trunks had caused a shift in classification, which was not yet reflected in the immature skin lesions. In the second study, the mature skin lesions had reached immunological equilibrium. Discrepancies in classification between skin and nerve lesions, as between concurrent skin lesions, are the result of reaction. Attention is drawn to the probable role of subliminal reactions in the evolution of infections.

Humans↗
PubMed1993

Difference in methylation patterns within the D15S9 region of chromosome 15q11-13 in first cousins with Angelman syndrome and Prader-Willi syndrome.

Abnormalities of chromosome region 15q11-13 are associated with Angelman syndrome (AS) and Prader-Willi syndrome (PWS). Differences between the methylation patterns of the region of chromosome 15q11-13 which hybridizes to the highly conserved DNA, DN34, in normal individuals and in patients with AS and PWS have been described. We report on a family in which first cousins are affected by AS and PWS as a result of a familial paracentric inversion of 15q11-q13. The results of the studies on this family demonstrate the differences in the methylation patterns in the 2 conditions and the phenomenon of genomic imprinting, whereby genetic information is expressed differently dependent on the parent of origin.

Angelman Syndrome↗
PubMed1993

Cytogenetic and molecular analysis in Angelman syndrome.

We report on cytogenetic and molecular analyses of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG- and GBG-banded chromosomes were studied. Standard molecular analysis with six 15q11q13 DNA sequences was used to analyze copy number and parental origin of 15q11q13. Concordance between molecular and cytogenetic data was excellent. The combined data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15q11q13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone to de novo deletion.

Angelman Syndrome↗
PubMed1992

A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes.

The Angelman (AS) and Prader-Willi (PWS) syndromes are two clinically distinct disorders that are caused by a differential parental origin of chromosome 15q11-q13 deletions. Both also can result from uniparental disomy (the inheritance of both copies of chromosome 15 from only one parent). Loss of the paternal copy of 15q11-q13, whether by deletion or maternal uniparental disomy, leads to PWS, whereas a maternal deletion or paternal uniparental disomy leads to AS. The differential modification in expression of certain mammalian genes dependent upon parental origin is known as genomic imprinting, and AS and PWS represent the best examples of this phenomenon in humans. Although the molecular mechanisms of genomic imprinting are unknown, DNA methylation has been postulated to play a role in the imprinting process. Using restriction digests with the methyl-sensitive enzymes HpaII and HhaI and probing Southern blots with several genomic and cDNA probes, we have systematically scanned segments of 15q11-q13 for DNA methylation differences between patients with PWS (20 deletion, 20 uniparental disomy) and those with AS (26 deletion, 1 uniparental disomy). The highly evolutionarily conserved cDNA, DN34, identifies distinct differences in DNA methylation of the parental alleles at the D15S9 locus. Thus, DNA methylation may be used as a reliable, postnatal diagnostic tool in these syndromes. Furthermore, our findings demonstrate the first known epigenetic event, dependent on the sex of the parent, for a locus within 15q11-q13. We propose that expression of the gene detected by DN34 is regulated by genomic imprinting and, therefore, that it is a candidate gene for PWS and/or AS.

Blotting, Southern↗
PubMed1991

Possible transmission of Mycobacterium leprae in a group of UK leprosy contacts.

A case of infectious leprosy in residential accommodation in the UK prompted a study of the cellular and humoral response to Mycobacterium leprae in two groups of individuals who were in contact with the index case for almost a year. In the younger staff group (mean age 44 years) 23 of 30 individuals had positive Mitsuda skin tests, 25 showed lymphocyte transformation to a soluble sonciate of M leprae and 2 had slightly raised IgM antibody concentrations to the terminal disaccharide of M leprae phenolic glycolipid-1. In the older group of residents (mean age 83 years) 7 of 36 individuals were skin-test positive, 25 of 33 were positive by lymphocyte transformation, but none had raised antibody levels. When retested on two further occasions, the same 2 individuals in the younger group still had raised antibody concentrations, 1 of whom had a persistent lepromin skin-test response for over 8 months and showed a pronounced increase in lymphocyte transformation to mycobacterial antigens. The findings suggest that transmission of M leprae may have occurred in these 2 contacts, who were therefore given 6 months' chemoprophylaxis with rifampicin.

Adult↗