PubMed Health⌕ Search

Biomedical subjects

M F Waters

Publications and source records attributed to M F Waters.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Positive Mitsuda lepromin reactions in long-term treated lepromatous leprosy.

Twenty-four lepromatous (LL) patients, treated for 22 to 40 years with chemotherapy, including sulphones and with multidrug therapy, were tested with standard Wade-Mitsuda lepromin. Thirteen gave weak positive (3-4 mm) Mitsuda reactions, confirmed histologically in the ten whose reactions were biopsied. Six of the eleven negative reactors were partly accounted for by a history of relapse, and two others had probably taken dapsone irregularly. Eleven control LL patients, treated for less than 20 years, were uniformly lepromin negative. Spontaneous lepromin conversion appears to occur around 24 years after commencing successful chemotherapy. The late Mitsuda conversions are attributed to delayed clearance of the reservoir of bacterial antigen, but a poor correlation between Mitsuda and Fernandez positivity is not explained.

Humans↗
PubMed1990

Tuberculoid relapse in lepromatous leprosy.

It is commonly accepted that the attainment of bacteriological negativity fails to restore the immune state of leprosy patients who have downgraded to lepromatous. We report six patients who had been lepromatous (LLs), and who, after many years of chemotherapy and bacteriological negativity, were found upon relapse to have upgraded to borderline-tuberculoid (BT). Five had become Mitsuda lepromin positive. The relapses could be accounted for by proven or suspected dapsone resistance. The upgrading was associated with minimal signs of reaction, which was attributed to the low level of antigen in the almost resolved lesions. The manner of development of the new high immune lesions resembled the onset of a primary infection, clinically and histologically. The development of a positive Mitsuda reaction in longstanding LL leprosy is not necessarily an indication of cure.

Adult↗
PubMed1987

Events surrounding the recognition of Mycobacterium leprae in nerves.

Histological examination and immunocytochemistry of Schwann cells, macrophages, and mycobacterial antigen were used to study 48 nerves of untreated patients with leprosy. None of the patients was in reaction clinically, but microreactions, involving small clusters of Schwann cells and macrophages in all cases except LL, were marked by progressive degradation of acid-fast bacilli (AFB). This was thought to be the response to the recognition of mycobacterial antigen. In the first phase, the disintegration of one or more Schwann cells caused the release of AFB, accompanied by subacute inflammation. In the second phase, as edema and cellular infiltration subsided, the necrosis of Schwann cells was replaced by granuloma formation, mycobacterial antigen being in a soluble form. Myelinated cells harbored few degraded AFB, and there was evidence that antigen-associated myelin hastened the death of Schwann cells. Only then did antigen become immunologically detectable to induce an inflammatory response whose clearance and resolution was impeded by the restraint on cellular movement due to the structure of neural tissue. These developments were sporadic but continuous. AFB and antigen released by disintegrating Schwann cells were ingested by regenerating Schwann cells and by macrophages, producing a self-perpetuating cycle which might involve either small areas or the greater part of a fascicle, and could conceivably progress to a generalized reaction.

Antigens, Bacterial↗
PubMed1986

Prevalence and specificity of the enhancing effect of three types of interleukin 2 on T cell responsiveness in 97 lepromatous leprosy patients of mixed ethnic origin.

Peripheral blood mononuclear cells from 97 predominantly lepromatous leprosy patients and 11 control subjects were tested in a lymphoproliferative assay for response to Mycobacterium leprae (whole and sonicated), and sonicated M. vaccae, M. tuberculosis, and M. scrofulaceum, in the presence and absence of three types of interleukin 2 (IL-2) (crude, purified, and recombinant). IL-2 enhanced the response to sonicated M. tuberculosis and M. leprae organisms more often in patients than in control subjects, but not significantly so and only in a minority of patients. This effect was significantly more common (though still only found in a minority of 46%) using M. leprae organisms as antigen, than when using sonicates of M. leprae (19%) or M. vaccae (19%). However it was nearly as frequent using sonicated M. tuberculosis, or M. scrofulaceum. Thus in only nine patients was the effect specific to M. leprae. Enhancement by IL-2 could not be related to the type of IL-2 used, the dose of antigen, or the amount of endogenous IL-2 released by the cells tested. Similarly it was not related to the extent to which IL-2 caused increased background proliferation in control wells, which occurred to an equal extent using cells from control subjects, nor was it related to the extent of antigen-driven proliferation. The data have also been analysed in relation to duration of disease (50 years to a few weeks) and ethnic origin. No correlations have been revealed. Thus enhancement by IL-2 of the lymphoproliferative response to mycobacterial antigens does occur using cells from lepromatous leprosy patients, but it is found in a minority of patients, it is not specific to M. leprae, and can occur with cells from normal donors.

Antigens, Bacterial↗
PubMed1978

Rifampicin for lepromatous leprosy: nine years' experience.

Over 100 patients with lepromatous leprosy were treated with rifampicin in a series of pilot, uncontrolled, and controlled trials in 1968-77. The rapid bactericidal effect of rifampicin on Mycobacterium leprae was confirmed. Clinical improvement became apparent sometimes as early as 14 days after the start of treatment. Nevertheless, a few persisting viable M leprae were detected as long as five years after the start of treatment with rifampicin either by itself or in combination with the bacteriostatic drug thiambutosine. Treatment with rifampicin and dapsone for six months reduced the number of persisting leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of treatment in lepromatous leprosy. Therefore initial intensive combined treatment with two or more bactericidal drugs (including rifampicin) warrants further investigation in both untreated leprosy and lepromatous leprosy resistant to dapsone.

Animals↗
PubMed1978

Experimental lepromatous leprosy in the white-handed gibbon (Hylobatus lar): successful inoculation with leprosy bacilli of human origin.

Leprosy bacilli of human origin were inoculated into a white-handed gibbon by the i.v. and i.p. routes, and also locally into ears, testis and around an ulnar nerve. The animal was observed closely during a period of nearly 15 years and did not exhibit any clinical evidence of cutaneous or neurological disease. At death, a wide range of tissues was taken for bacterial counts and histological examination, and a disseminated and progressive infection was demonstrated. Acid-fast bacilli were found in many sites; their morphological appearance distribution in nerves, and pattern of multiplication in mouse foot-pads, and also the presence of anti-mycobacterial antibody in the serum and the absence of specific lymphocyte transformation were all in keeping with an infection by Mycobacterium leprae, at an early lepromatous stage. This is probably the first fully documented report of experimental lepromatous infection in a primate. The findings are discussed in relation to the long incubation period of le promatous leprosy and the difficulties of diagnosing the disease at an early stage in man.

Animals↗