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Biomedical subjects

C A Egan

Publications and source records attributed to C A Egan.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of strategies with potential for producing a phosphorylcholine-free version of the filarial nematode immunomodulator, ES-62.

Phosphorylcholine (PC) is found attached to N-type glycans of proteins secreted by filarial nematodes, where it appears to act as an immunomodulator. Based on information on the structure and biosynthesis of the PC-glycan of a major secreted protein, ES-62, strategies were designed with potential for preparing PC-free material to better understand the importance of PC in filarial nematode immunomodulation. The strategies involve either enzymatic removal of PC or inhibition of its attachment during ES-62 synthesis. No method tested was found to be 100% effective although approximately 70% removal was obtained by culturing worms in Et18OCH3. Reasons for failure to obtain complete absence of PC moieties are discussed in relation to the structure and synthesis of PC-glycans and in addition PC-glycan biosynthesis is briefly commented on as a target for chemotherapy.

Animals↗
PubMed2005

Functional observations in vitamin A deficiency: diagnosis and time course of recovery.

AIMS: To describe the effects of vitamin A deficiency (VAD) on retinal function and the subsequent recovery following treatment in three patients with systemic conditions (two with Crohn disease; one secondary to IgE syndrome). METHODS: Electrophysiological testing (including pattern electroretinogram, PERG; electroretinogram, ERG; visual-evoked potential) established the diagnosis of VAD. Repeat testing was carried out in two patients to monitor the time course of recovery following intramuscular vitamin A injection. The third patient had repeat recordings following 13 months of oral supplementation. RESULTS: All three patients initially displayed a characteristic absence of rod function associated with VAD. In addition, delayed and reduced amplitude cone ERGs, loss of short wavelength cone (S-cone) function and subnormal macular function were observed in two patients. Restoration of rod and generalised cone function was rapid in the two patients who received intramuscular injection, with normalisation of some electrophysiological responses after only 3 days. Normal S-cone amplitudes and cone latencies were reached within 12 days of vitamin A injection. Macular function returned to within normal limits by 12 days postinjection in one patient, but remained mildly subnormal in the second patient. Full recovery was present after 13 months oral supplementation in the third patient. CONCLUSIONS: Novel observations regarding dark-adapted cone function, S-cone function, and PERG are presented. The differences between the effects of VAD on rod and cone function, and their rate of recovery, may reflect differences in the visual cycle between the two photoreceptor classes. The importance of rapidly and accurately diagnosing VAD, a treatable condition, is noted.

Administration, Oral↗
PubMed2005

Lack of immunological cross-reactivity between parasite-derived and recombinant forms of ES-62, a secreted protein of Acanthocheilonema viteae.

The longevity of filarial nematodes is dependent on secreted immunomodulatory products. Previous investigation of one such product, ES-62, has suggested a critical role for post-translationally attached phosphorylcholine (PC) moieties. In order to further investigate this, ES-62 lacking PC was produced, using the Pichia pastoris recombinant gene expression system. Unlike parasite-derived ES-62, which is tetrameric the recombinant material was found to consist of a mixture of apparently stable tetramers, dimers and monomers. Nevertheless, the recombinant protein was considered to be an adequate PC-free ES-62 as it was recognized by existing antisera against the parasite-derived protein. However, subsequent to this, recognition of parasite-derived ES-62 by antibodies produced against the recombinant protein was found to be absent. In an attempt to explain this, recombinant ES-62 was subjected to structural analysis and was found to (i) contain 3 changes in amino acid composition; (ii) demonstrate significant alterations in glycosylation; (iii) show major differences in protein secondary structure. The effects of these alterations in relation to the observed change in immunogenicity were investigated and are discussed. The data presented clearly show that recognition by existing antibodies is insufficient proof that recombinant proteins can be used to mimic parasite-derived material in studies on nematode immunology and vaccination.

Amino Acid Sequence↗
PubMed2004

An atypical phenotype of macular and peripapillary retinal atrophy caused by a mutation in the RP2 gene.

AIMS: To determine the molecular basis and describe the phenotype of an atypical retinal dystrophy in a family presenting with bilateral, progressive central visual loss. METHODS: Family members were examined. Investigations included Goldman perimetry, electrophysiology, and autofluorescence imaging. Candidate gene screening was performed using SSCP and sequence analysis. The proband's lymphoblastoid cells were examined for protein expression. RESULTS: Fundal examination of the proband, his mother, and brother revealed peripapillary and macular atrophy. Autosomal dominant retinal dystrophy was suspected, but less severe disease in the mother led to screening for mutations in X linked genes. A 4 bp microdeletion in exon 3 of the RP2 gene, segregating with disease, was identified. No RP2 protein expression was detected. CONCLUSION: The distinct phenotype in this family, caused by this frameshifting mutation in RP2, broadens the phenotypic spectrum of X linked retinitis pigmentosa. The absence of RP2 protein suggests that loss of protein function and not novel gain of function could account for the atypical phenotype. A definitive diagnosis of X linked retinitis pigmentosa permits appropriate genetic counselling with important implications for other family members. Clinicians should have a low threshold for screening RP2 in families with retinal dystrophy, including posterior retinal disease, not immediately suggestive of X linked inheritance.

Adult↗
PubMed2001

Anti-epiligrin cicatricial pemphigoid and relative risk for cancer.

It is not known whether patients with anti-epiligrin cicatricial pemphigoid (AECP) have an increased risk of malignancy. We calculated the expected numbers of cancers in a cohort of 35 such patients based on respective incidence rates for all cancers in the National Cancer Institute's Surveillance, Epidemiology, and End Results (NCI SEER) Registry. Ten patients in this cohort had solitary solid cancers; eight patients developed cancer after onset of AECP (seven within 14 months). The relative risk (RR) for cancer in this cohort was 6.8 (95% confidence intervals [CI]: 3.3-12.5). AECP seems to be associated with an increased relative risk for cancer.

Adult↗
PubMed2001

Treatment of epidermolysis bullosa acquisita with the humanized anti-Tac mAb daclizumab.

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease characterized by IgG anti-basement membrane autoantibodies to collagen VII. Since autoantibody formation in EBA patients is thought to be T-cell-dependent, the degree of T cell activation in three patients (all males, ages 33-44 years) was assessed by quantitation of soluble Tac, a fragment of the alpha-subunit of the high-affinity IL-2 receptor (CD25). Soluble Tac levels in all patients were elevated [highest random values, 2430, 920, and 560 IU/ml (normal range, 112-502)]. Based on such findings, these patients were treated with the humanized murine monoclonal anti-Tac antibody daclizumab (1 mg/kg, 6-12 iv treatments at 2- to 4-week intervals). All patients had a significant, rapid, and persistent decrease in lymphocyte CD25 expression. Though a moderate decrease in lymphocyte expression of 7G7, an IL-2 receptor epitope not bound by daclizumab, was noted, stable levels of CD3 cells and in vitro saturation studies indicated that daclizumab effectively bound CD25 and did not promote clearance of such cells from peripheral blood. There were no complications and no patient developed antibodies against daclizumab. While no apparent clinical benefit was seen in two patients with dermolytic disease, one patient with inflammatory EBA had a favorable response. While on daclizumab, this patient stopped prednisone, significantly reduced dapsone, and improved clinically. Furthermore, his disease flared when treatment was stopped, and resumption of daclizumab again effected improvement within 2 weeks. Daclizumab therapy is safe and well tolerated in EBA patients. It may be effective as a corticosteroid sparing agent in patients with inflammatory EBA.

Adult↗
PubMed2001

Neurologic variant of epidermal nevus syndrome with a facial lipoma.

A 1-year-old girl presented for evaluation of a linear plaque on her forehead. She was born at 36 weeks' gestation following an uncomplicated pregnancy and delivery. At birth, she was noted to have an enlarged right cheek. She had no seizure history, but developed grand mal seizures 1 year later. On examination, she had a yellow plaque on her forehead which extended onto her nose. Under her right jaw, extending onto her anterior neck, there was a café-au-lait macule within which there was a yellow plaque which followed the lines of Blaschko. Her right cheek was enlarged and was erythematous (Fig. 1). Magnetic resonance imaging (MRI) of her face showed a mass in the right cheek deep to the subcutaneous fat tissue layer. The signal from the mass was identical to that from the fat, indicating that the mass represented a lipoma. This was later excised surgically and was histologically a lipoma. MRI of the brain demonstrated enlargement of the right lateral ventricle in addition to enlargement of the right cerebral hemisphere. There was also evidence of abnormal gyral architecture. Computerized tomography (CT) three-dimensional reconstruction of the skull demonstrated overgrowth of the right maxilla, right mandible, and right orbit (Fig. 2).

Facial Neoplasms↗
PubMed2001

Linear IgA bullous dermatosis responsive to a gluten-free diet.

Dermatitis herpetiformis is associated with a gluten-sensitive enteropathy in >85% of cases. Both the skin lesions and the enteropathy respond to gluten restriction. Linear IgA bullous dermatosis has a much lower prevalence of histological small bowel abnormalities, and lesions are not known to respond to gluten restriction. We report a patient with linear IgA bullous dermatosis and gluten-sensitive enteropathy. This report addresses the issue of whether linear IgA bullous dermatosis can be associated with gluten-sensitive enteropathy. We evaluated the response to gluten restriction and normal diet by following the status of the patient's jejunal biopsies and skin lesions. The patient responded to gluten restriction, as shown by resolution of jejunal abnormalities and skin lesions and subsequently by recurrence of jejunal abnormalities and skin lesions with reinstitution of a gluten-containing diet. This report demonstrates that linear IgA bullous dermatosis can respond to gluten restriction if an underlying gluten-sensitive enteropathy is present.

Adult↗
PubMed2000

Pemphigoid: clinical, histologic, immunopathologic, and therapeutic considerations.

Autoimmune blistering diseases are generally distinct entities characterized by relatively consistent clinical, histologic, and immunopathologic findings. These disorders may cause impaired adhesion of epidermis to epidermal basement membrane (eg, the pemphigoid group of disorders [bullous, gestational, and mucous membrane]) or impaired adhesion of epidermal cells to each other (eg, the pemphigus group of disorders). Recent studies have shown that these disorders are characterized by autoantibodies that often display pathogenic (ie, blister-forming) activity in passive transfer models. Interestingly, the autoantigens targeted by these patients' autoantibodies represent important structural proteins that promote cell matrix (eg, pemphigoid) or cell-to-cell (eg, pemphigus) adhesion in skin. Autoimmune blistering diseases are characterized by substantial morbidity (pruritus, pain, disfigurement), and in some instances, mortality (secondary to loss of epidermal barrier function). Treatment with systemic immunosuppressives has reduced morbidity and mortality in patients with these diseases. JAMA. 2000;284:350-356

Aged↗