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Biomedical subjects

M Harbord

Publications and source records attributed to M Harbord.

15 recordsLinked to original sources
PubMed2005

Conditional haploinsufficiency of NCF1 (encoding p47(phox)), a signaling gene with a heterozygous phenotype potentially subject to natural selection.

Even a minor degree of haploinsufficiency could eventually reduce the frequency of an autosomal immunodeficiency disease. Searching for such a condition, we have re-examined the phenotype of mice +/- for the NCF1 gene encoding p47(phox) and humans +/- for NCF1 and NCF2 using a procedure that allowed the respiratory burst of granulocytes and macrophages to be measured simultaneously. The mice showed significant haploinsufficiency in granulocytes but not in macrophages (i.e. conditional haploinsufficiency). Our human data were obtained from blister cells, and were too scattered to allow a firm conclusion. In view of recent re-evaluation of the role of the respiratory burst these findings are compatible with the view that haploinsufficiency occurs particularly among rate-limiting genes that operate in regulatory/signaling pathways.

Animals↗
PubMed2001

Cantharidin blisters: a technique for investigating leukocyte trafficking and cytokine production at sites of inflammation in humans.

A skin blister technique is described which allows the investigation of acute inflammation in humans in vivo. Filter paper discs are placed on the skin, impregnated with cantharidin and covered with impermeable film held by adhesive tape. The assembly is easily applied, unobtrusive, stable and may be worn during normal activities. The blister formed at 24 h contains approximately 5x10(5)-5x10(6) cells, predominantly neutrophils and macrophages. Inflammatory cytokines and chemotactic factors are detectable in the blister fluid. The technique is useful for characterizing the acute inflammatory response in health and disease.

Blister↗
PubMed2001

Levodopa responsive Parkinsonism in adults with Angelman Syndrome.

Two intellectually disabled adults with Angelman Syndrome are reported who developed intermittent episodes of a severe resting tremor, cogwheel rigidity and bradykinesia in their late teens. The Parkinsonism was not due to medications and there was a dramatic improvement with levodopa therapy. The association between Angelman Syndrome and Parkinsonism has not previously been described.

Adult↗
PubMed2001

Correlation between the immune responses to collagens type I, III, IV and V and Klebsiella pneumoniae in patients with Crohn's disease and ankylosing spondylitis.

BACKGROUND: Increased levels of collagen types I, III and V are found in strictures of patients with Crohn's disease (CD) compared with normal gut tissue. Type IV collagen is present in the basement membranes, basal lamina, retina and cornea. Elevated levels of antibody to Klebsiella pneumoniae are found in both active CD and active ankylosing spondylitis (AS) patients compared with healthy controls. METHODS: Reactivities for immunoglobulin class-specific antibodies (IgM, IgG and IgA) against collagen types I, III, IV, V and whole K. pneumoniae were measured by ELISA in nine patients with early CD and 10 with late CD from King's College Hospital and 12 late CD patients and 36 HLA-B27-positive AS patients from Middlesex Hospital and was compared with values for 26 healthy controls from the Blood Transfusion Service in London. RESULTS: Levels of class-specific IgM, IgG and IgA antibodies to collagen types I, III, IV, V and K. pneumoniae were significantly elevated in early and late CD patients compared with healthy controls (P<0.001). Levels of IgM, IgG antibody to the four collagen types and K. pneumoniae were also significantly elevated (P<0.001) in AS patients compared with healthy controls. In addition, the level of IgA antibody to K. pneumoniae was elevated in AS patients (P<0.001). Furthermore, a positive correlation between antibody levels to collagen types I, III, IV and K. pneumoniae was demonstrated in both early and late CD patients and in those with AS, whilst a positive correlation to type V was found in early CD. CONCLUSION: The role of K. pneumoniae and anti-collagen antibodies in the aetiopathogenesis of CD and AS requires further study.

Adolescent↗
PubMed1999

Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent.

We describe a 14-year-old male with dissection of the descending aorta, bilateral iris hypoplasia, striae distensae and brachytelephalangy, the latter being most marked in the thumbs. Inguinal herniae and a patent ductus arteriosus were surgically repaired in infancy. The pattern of abnormalities may constitute a previously undescribed syndrome. The proband died suddenly at the age of 17 years.

Abnormalities, Multiple↗
PubMed1999

A child with hemimegalencephaly, hemihypertrophy, macrocephaly, cutaneous vascular malformation, psychomotor retardation and intestinal lymphangiectasia--a diagnostic dilemma.

Although the clinical delineation of the majority of overgrowth syndromes is straightforward, we believe there is a subset of patients with overlapping features from a number of overgrowth syndromes. We report a patient with hemimegalencephaly, hemihypertrophy, macrocephaly, vascular lesions, psychomotor retardation and intestinal lymphangiectasia. The clinical history and findings posed a diagnostic dilemma as the features overlapped between several conditions, namely macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC), Klippel-Trenaunay-Weber syndrome (KTWS), Proteus syndrome and a provisional unique syndrome described by Reardon et al. (1996, Am J Med Genet 66:144-149). We anticipate that only when the molecular basis is delineated will it become clear whether these disorders are separate entities or merely differing ends of the same spectrum.

Abnormalities, Multiple↗
PubMed1998

The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non-ulcer dyspepsia.

BACKGROUND: The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one-third of adult patients with non-ulcer dyspepsia (NUD). AIM: To observe the effects of cisapride on EGG in adults with NUD. METHODS: Twenty-seven NUD patients who had undergone a pre- and post-prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2-4 cycles per minute) had a repeat EGG at the end of the study. RESULTS: Treatment with cisapride was associated with a significant improvement in the post-prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48). CONCLUSION: In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre-treatment EGG, but not those with a normal EGG, with a significant improvement of the post-prandial EGG.

Adult↗
PubMed1994

Isolated glycerol kinase deficiency in a neonate.

Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme deficiency, or as part of a syndrome resulting from a microdeletion in the p21 region of the X chromosome associated with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. Developmental delay is a consistent feature of the microdeletion syndrome but not of the isolated enzyme defect. We report a case of isolated glycerol kinase deficiency in a neonate presenting with hypotonia, apnea, mild developmental delay, and glyceroluria, without evidence of adrenal insufficiency or myopathy. A mild communicating hydrocephalus was noted on magnetic resonance imaging brain scan. It is important, therefore, to exclude glyceroluria in infants being investigated for apnea and hypotonia.

Apnea↗
PubMed1991

Multiple sulfatase deficiency with early severe retinal degeneration.

We report an unusual case of multiple sulfatase deficiency in which neurodegeneration was accompanied by early, severe visual impairment associated with prominent pigmentary retinopathy, suggesting a diagnosis of neuronal ceroid-lipofuscinosis. The levels of arylsulfatases A, B, and C, heparan N-sulfatase, N-acetylgalactosamine-6-sulfate sulfatase, and iduronate-2-sulfate sulfatase were all markedly decreased in cultured skin fibroblasts. Screening tests for mucopolysacchariduria were consistently negative; however, thin-layer chromatographic analysis of isolated urinary glycosaminoglycans showed increased amounts of heparan sulfate.

Child↗