Topical tacrolimus, genital lichen sclerosus, and risk of squamous cell carcinoma.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Neill.
Explore the source record for details and available documents.
Psoriasis is a chronic inflammatory skin disorder which is generally not associated with scarring. We report two patients with long-standing severe anogenital psoriasis, that was associated with loss of the labia minora, thus clinically mimicking the scarring associated with lichen sclerosus. Histopathological finding were however, consistent with psoriasis with no evidence of lichen sclerosus. Elastic fibres were present and there was no evidence of abnormal collagen or fibrous tissue. The association of vulval psoriasis with scarring has not been reported previously.
BACKGROUND: Photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA) has been suggested as an effective and tissue-conserving method of treating carcinoma in situ of the vulva. OBJECTIVES: To evaluate PDT in patients with vulval intraepithelial neoplasia type III (VIN III). METHODS: Topical PDT was performed in six patients with VIN III. Five of the six patients had persistent disease following treatment with other modalities including 5-fluorouracil cream, cryotherapy, carbon dioxide laser ablation and excision. Each patient was treated once with a fluence of 150 J cm-2 using a broad-band light source (580-740 nm) 4 h after topical application of 20% 5-ALA. Patients were reviewed clinically at 1 month and 6 months after treatment. RESULTS: All of the patients developed initial erythema of treated sites, three with subsequent erosions. All patients had clinically evident persistent VIN III at 1-month review. Five patients have subsequently undergone surgical treatment and one is regularly reviewed. CONCLUSIONS: This small uncontrolled study indicates that, as currently administered, a single episode of topical PDT is not effective in the management of treatment-resistant VIN III.
We report a large family with ichthyosis bullosa of Siemens (IBS) including eight affected members spanning three generations. The classical features of the disease were consistently observed with blistering, superficial peeling of the skin, and localized lichenified hyperkeratosis mainly confined to the limbs. Phenotypic variation, however, was also observed with some individuals exhibiting unusual clinical features. Specifically, the index patient was erythrodermic at birth; she subsequently developed a widespread pustular eruption. Erythroderma is classically absent in IBS and pustulation is very unusual. She also had hypertrichosis of the limbs, as did an affected female first cousin. This has not previously been reported in IBS. Electron microscopy showed complex aggregates of keratin in the spinous and granular layers associated, in places, with remarkably little cell lysis. Sequencing of genomic DNA revealed a mutation (E493K) in keratin 2e. A review of the literature on IBS indicates that E493K is the most commonly reported mutation to date and might represent a mutational hotspot for this disease.
Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently associated with scarring of involved clinical sites. At present, therapeutic intervention in the form of immunomodulating or immunosuppressive agents is often reserved until the onset of significant inflammation and/or early cicatrization. We have therefore studied the clinical and immunopathological findings in 67 patients with MMP in order to try to establish a reliable prognostic indicator by which patients at high risk may be identified early in the disease. Inclusion criteria were a predominantly mucosal disease and the detection of IgG and/or C3 anti-basement membrane zone (BMZ) immunoreactants using immunofluorescence techniques. Patients were allocated to three disease subgroups on the basis of the modality and duration of therapeutic intervention required to achieve effective control of disease. In addition, at presentation and at each follow-up visit, a clinical score for severity of involved clinical sites was awarded and serum collected for indirect immunofluorescence (IIF). A dual circulating anti-basement membrane zone (anti-BMZ) antibody response with IgG and IgA was significantly associated with a more severe and persistent disease profile (P < 0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients in whom there was a clinical score > or = 5 compared with a score < 5, and 31.3 and 66.9 among patients with IgG alone and both IgG and IgA, respectively, compared with negative IIF. The findings suggest that an assessment based upon a combination of site severity score and the presence of circulating IgG and IgA by IIF using 1 mol/L salt-split human skin substrate may be considered a useful prognostic indicator.
Explore the source record for details and available documents.
A new network for RCN members interested in child health or children's nursing research is due to be launched at the end of June. The Research in Child Health (RiCH) network is part of the RCN Society of Paediatric Nursing and aims to promote research and research-based nursing in the specialty. Network co-ordinator Sarah Neill explains how interested nurses can become involved.
An adaptation of the conventional procedure for fixation of brain impressions prior to rabies testing was developed using a microwave oven to fix slides in less than 1 min. A total of 2394 routine specimens were examined to evaluate the efficacy of microwave fixation of brain impressions as an aid to shortening the turnaround time for reporting. Slides were fixed for 55-60 s in a standard household microwave oven at 50%, power using phosphate buffered saline supplemented with 3% Tween 20 as a fixative medium. They were then stained using the standard rabies immunofluorescent staining procedure with minor modifications. This process potentially could allow results to be reported to submitters within 1.5 h after specimens arrive in the laboratory. Microwave fixation was in complete agreement with conventional acetone fixation for detection of positive rabies specimens.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Serum neutralization (Nt) is used most often to type enterovirus isolates, but it is labor-intensive, expensive, and supplies of reference antisera for Nt are limited. Alternative methods of enterovirus typing are needed. OBJECTIVES: To investigate the use of indirect immunofluorescence (IFA) with commercially available monoclonal antibodies (MAbs) as an alternative to Nt for the identification of enteroviruses. STUDY DESIGN: Two MAb blends (one for coxsackie B viruses and one for echoviruses 4, 6, 9, 11, 30, and 34) and a coxsackie A9 MAb were used to screen 465 clinical isolates over a period of two years. Virus isolates which tested positive with one of the blends were typed with the individual MAbs of the respective blend. Individual MAbs for polioviruses 1, 2, and 3 acquired late in the study were used to screen 45 viral isolates. RESULTS: The antibodies identified 251/465 (54%) of the total number of isolates tested. IFA results for 451 of 465 viral isolates were in agreement with conventional identification methods. The sensitivity of the IFA screen using the MAb blends and coxsackie A9 MAb was 93% and the specificity was 99%. Thirteen discrepant isolates were negative by IFA, with twelve positive by Nt for echovirus 30 and one isolate positive by Nt for coxsackie A9. The remaining discrepant isolate was positive by IFA for both coxsackie A9 and coxsackie B5, but positive by Nt for coxsackie A9 only. CONCLUSIONS: IFA is highly specific for the identification of enteroviruses, but may not be sensitive enough to identify all strains within an enterovirus type. Procedures which utilize an IFA screen and confirm final results by Nt decrease turnaround time and reduce the number of cell culture tubes required for the identification of each enterovirus isolate.
Explore the source record for details and available documents.
A point mutation in the mtDNA-encoded ATP6 gene (T-->G at nt 8993) associated with Leigh syndrome in two pedigrees was found to decrease ADP-stimulated (state III) respiration and the ratio of ADP molecules phosphorylated to oxygen atoms reduced (ADP/O ratio) but did not affect 2,4-dinitrophenol (DNP)-uncoupled respiration, suggesting a defective mitochondrial H(+)-translocating ATP synthase. Intact mitochondria isolated from patient and control lymphoblastoid cell lines were tested for state III, ADP-limited (state IV), and DNP-uncoupled respiration with various substrates. Mitochondria isolated from patient lymphoblasts harboring 95-100% of mtDNAs carrying the nt 8993 T-->G mutation showed state III respiration rates 26-50% lower than controls while having normal DNP-uncoupled rates. This resulted in state III/DNP ratios of 0.52-0.70 in patient mitochondria versus 0.88-0.97 in controls. The ADP/O ratio was also decreased 30-40% in patient mitochondria. Patient lymphoblasts heteroplasmic for the nt 8993 mutation were enucleated by using Percoll gradients and the cytoplasts were fused to mtDNA-deficient (rho 0) cells by electric shock. Cybrid clones homoplasmic for the wild-type nucleotide (T) at nt 8993 gave state III/DNP and ADP/O ratios similar to those of control cybrids, whereas cybrid clones homoplasmic for the mutant nucleotide (G) showed a 24-53% reduction in state III respiration, a state III/DNP ratio of 0.53-0.64, and a 30% decrease in the ADP/O ratio. Thus, the reduced state III respiration rates and ADP/O ratios are linked to the T-->G mutation at nt 8993.
Three positive (PR1-3) and one negative (NR1) transcriptional control domain have been tentatively mapped in the promoter of the human F0F1-ATP synthase beta subunit gene (ATPsyn beta) in the context of expression in myogenic cells. Lipofection of promoter-chloramphenicol acetyltransferase fusion constructs into C2C12 myogenic cells revealed that two of the three positive domains (PR1 and PR2) function in both myoblasts and myotubes, whereas the third positive domain (PR3) and the sole negative domain (NR1) seem to function only in myotubes. PR1 contains a cluster of four CCAAT cis-elements, PR2 is a small 44-base pair region containing an SP1-like motif, and PR3 is a region previously shown to be recognized by both OXBOX- and REBOX-binding factors. By site-directed polymerase chain reaction linker mutations, the activity of the OXBOX/REBOX cis-element in myoblasts is shown to be masked by flanking sequences in PR3. The negative domain, NR1, is located between 300 and 1,000 base pairs upstream from the OXBOX/REBOX elements in a region containing multiple Alu repeats. Mobility gel shift analysis of DNA-protein complexes using competitor DNAs verified the involvement of both OXBOX- and REBOX-binding factors in PR3. Similar experiments show SP1-specific binding at PR2. These data with observations of OXBOX and REBOX-specific binding of an OXBOX/REBOX-like region within the conserved sequence block C of the human mitochondrial DNA D-loop sequence are consistent with the idea that OXBOX- and REBOX DNA-binding factors coordinate the expression of mitochondrial energy genes in highly oxidative tissues by working with well characterized general transcription factors such as SP1 and CCAAT DNA-binding proteins, which exist in the nucleus, and MTF, which exists in the mitochondrion.
The sequence and expression characteristics are described of a wilt-inducible gene in Arabidopsis thaliana. A1494 encodes a potential thiol protease whose mRNA accumulates rapidly in shoot tissue upon the loss of turgor. A1494 mRNA levels peaked after ca. 4 h and declined thereafter. Dehydration also induced rapid biosynthesis of the phytohormone abscisic acid (ABA), which continued for at least 9 h. Exogenous ABA induced the accumulation of A1494 mRNA, with kinetics similar to those after wilting. Rehydration of wilted shoots led to a rapid decline in the content of both ABA and A1494 mRNA. Wilting and ABA independently induced A1494 expression as evidenced by the effects of ABA and wilting on the ABA-deficient aba-1 and ABA-insensitive abi-1 and abi-3 genotypes. A1494 mRNA was not detectable in aba-1 shoots but accumulated rapidly after either wilting or ABA treatment, whereas the shoot ABA content was increased only by ABA treatment. ABA had no effect on A1494 mRNA levels in the abi-1 and abi-3 mutants but wilting did result in enhanced A1494 expression. Heat shock had only a minor effect on A1494 mRNA levels, whereas exposure to low temperature resulted in substantial accumulation of A1494 mRNA in wild-type shoots. However, this latter response, unlike that to drought, was mediated exclusively via ABA synthesis as demonstrated by the lack of A1494 mRNA accumulation in cold-treated aba-1 shoots.
Aberrant p53 immunoreactivity has been found in skin pre-malignancies and dysplasias such as Bowen's disease and actinic keratoses. Vulval lichen sclerosus (LS) has been reported to be pre-malignant, with an association of vulval carcinoma in 3% to 6% of patients. In contrast, non-genital LS appears to have no malignant potential. In this immunocytochemical study, we investigated p53 expression in 10 cases of histologically proven vulval LS and 9 cases of non-genital LS using the murine monoclonal antibody Do-1 raised against recombinant human p53 which reacts with both wild-type and mutant p53. None of the vulval specimens had epithelial dysplasia or malignancy. Normal vulval (7 cases) and non-genital skin (5 cases) were used as tissue controls, respectively. The cell proliferation index was also studied using the MIB 1 monoclonal antibody which detects the cell-cycle associated Ki-67 antigen. The technique of microwave irradiation for antigen unmasking was employed on formalin-fixed and paraffin-embedded tissues. There was a significant increase in p53 immunoreactivity in vulval LS (32.13 +/- 15.11 epidermal cells per 100 basal cells) compared to normal vulval skin (7.52 +/- 5.04 epidermal cells per 100 basal cells) (p < 0.001), whereas the MIB 1 labelling index was lower in vulval LS (39.45 +/- 15.88 epidermal cells per 100 basal cells) than in normal controls (86.26 +/- 32.31 epidermal cells per 100 basal cells) (0.001 < p < 0.01). In contrast, there was no significant difference in p53 immunoreactivity or MIB 1 labelling index between non-genital LS and normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.