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Biomedical subjects

A C Chu

Publications and source records attributed to A C Chu.

At least 19 recordsLinked to original sources

Chloroxylenol and zinc oxide containing cream (Nels cream) vs. 5% benzoyl peroxide cream in the treatment of acne vulgaris. A double-blind, randomized, controlled trial.

Forty-one subjects completed a double-blind controlled randomized study comparing the following: (i) Nels cream (containing chloroxylenol and zinc oxide); (ii) 5% benzoyl peroxide cream; and (iii) the vehicle of the Nels cream. Patients applied the medications twice daily for 8 weeks. At the end of the test period there was no significant difference in the reduction of inflammatory and noninflammatory lesion counts achieved by Nels cream and benzoyl peroxide. Both creams proved superior to the vehicle. Efficacy grading by subjects and investigators showed no significant difference between Nels cream and benzoyl peroxide. However, side-effects such as peeling and dryness caused by the treatment were significantly less in the Nels cream group.

Acne Vulgaris

Diagnostic and therapeutic evaluation of an anti-Langerhans cell histiocytosis monoclonal antibody (NA1/34) in a new xenograft model.

Scintigraphy using monoclonal antibodies has been suggested as a possible adjunct to conventional staging techniques for the routine staging and diagnosis of Langerhans cell histiocytosis. In this study we have developed a model for Langerhans cell histiocytosis comprising a CD1a-positive subcutaneous xenograft in the flanks of nude (nu/nu) mice. The anti-CD1a murine monoclonal antibody NA1/34 was investigated for its potential both as an imaging and as a therapeutic targeting agent in this model. Biodistribution with NA1/34 compared with irrelevant isotype-matched monoclonal antibody demonstrated specific accumulation within the xenografts of 10.0%id per g (percentage injected dose per gram) and 3.3%id per g at 48 h postinjection, respectively. NA1/34 displayed no specific accumulation to CD1a-negative xenografts. F(ab')2 fragments of NA1/34 displayed a faster clearance time of 19.6 h compared with the intact antibody, 122.4 h, resulting in a more rapid maximum xenograft uptake time of 5 h compared with 48 h postinjection for the intact antibody. Although the overall xenograft/tissue ratio for the F(ab')2 was at no time greater than that for the intact antibody, the F(ab')2 did display dramatically greater xenograft/blood ratios, reaching 19:1 at 120 h postinjection Xenograft regression using single doses of 350 microCi and 500 microCi 131I-labeled NA1/34 significantly (p < 0.001) delayed xenograft progression compared with control nonirradiated xenografts, with average delays of 3.2 and 5.7 times the control, respectively. This study suggests that the anti-CD1a monoclonal antibody, NA1/34, offers advantages in the prognosis and staging of Langerhans cell histiocytosis, in a human setting. We discuss the advantages of radioimmunoscintigraphy over conventional differential diagnostic techniques. The potential for the future radioimmunotherapy of Langerhans cell histiocytosis is also discussed.

Animals

p53 induction in normal human skin in vitro following exposure to solar simulated UV and UV-B irradiation.

Exposure of normal human breast skin ex vivo to physiological levels of UV-B and solar simulated UV results in a UV dose- and time-dependent increase in epidermal p53, as determined by PAGE analysis. Peak p53 levels are detected 12 to 24 h post irradiation with UV-B (470-1410 mJ cm-2) and solar simulated UV (5-12 minimal erythema dose (MED) equivalents). Irradiation with an FS20 UV-B lamp, contaminated with UV-A and UV-C (74-1111 mJ cm-2), also induces peak levels after 12 h incubation at 37 degrees C but these levels persist to 36 h post UV irradiation. In all cases p53 levels start to return to normal by 48 h culture. A significant positive correlation is demonstrated between UV-B dose (47-1645 mJ cm-2) and p53 level (p < 0.01, R > 0.977) in explants cultured for 24 h at 37 degrees C post irradiation. The FS20 induces a 'UV-B' dose-dependent increase in p53 to a maximum from 370 to 1111 mJ cm-2. Similarly, solar simulated UV induces a plateau of peak p53 induction between 5 and 15 MED equivalents. Immunohistochemical analysis using microwave retrieval on 5 microns sections shows the same pattern of p53 staining with UV-B and solar UV insult, but proves unreliable as a method of quantification. These results suggest that the skin explant model may be a useful tool in the evaluation of UV-induced epidermal cell damage, providing a valuable alternative to in vivo studies.

Cell Count

Improved remote event marker for use in ambulatory monitoring.

During ambulatory monitoring, physiological signals and other parameters are measured and stored in a portable recorder. To optimise subsequent interpretation, additional information is provided by the subject pressing a button at the onset of any relevant symptoms or events, simultaneously noting these in a personal diary. To distinguish between different events, the subject is instructed to press the event button a specific number of times. Confusion arises when the subject fails to press the button correctly or to record the event accurately on paper. The device described overcomes these problems by providing the subject with separate switches on a single remote unit. Depending on the button pressed, the unit automatically sends a coded signal to the recorder, allowing unequivocal identification of events during data playback and analysis. Although primarily used in urodynamics, this simple device can be used in many other similar recording systems with little or no modification.

Electronics

Langerhans cell histiocytosis of the skin.

Cutaneous involvement in Langerhans cell histiocytosis (LCH) occurs in 50% of cases and may be the presenting feature. It is, therefore, important to recognize the wide spectrum of clinical disease that this disorder may adopt in the skin. Cutaneous involvement is not necessarily a benign feature and many patients progress to multi-system disease. There are a number of treatments available for cutaneous LCH. The rationale is to start with the simplest treatment and progress to systemic or interventional therapy as needed.

Adult

Pigmented Bowen's disease.

We describe two Afro-Caribbean women who presented with pigmented Bowen's disease. One, a 44-year-old woman, developed a sharply demarcated, irregularly marginated, hyperpigmented plaque with a velvety surface in the perianal area. The other, a 25-year-old woman, developed a well defined, verrucous, hyperpigmented patch on the umbilicus. Histology showed that both cases were Bowen's disease, and subsequent treatment with 5-fluorouracil and cryotherapy led to complete resolution.

Adult

Gamma delta T-cells in human cutaneous immunology.

Gamma delta T-Cells represent a minor subpopulation of T-lymphocytes in man and their role in normal and diseased human skin is unknown. This article is a comprehensive review of T-lymphocytes bearing the gamma delta T-cell receptor in normal and pathological human skin. Firstly, we have documented the occurrence of gamma delta T-cells in normal skin and in a range of reactive and malignant skin conditions. We have then discussed the experimental findings regarding the repertoire used by gamma delta T-cells in normal human skin and in cutaneous disorders with an increased percentage of gamma delta T-cells.

Animals

Immunologic protection afforded by sunscreens in vitro.

Several studies have suggested a lack of correlation between sunscreen sun protection factor and protection of the skin immune system, potentially allowing greater damage to the skin by removing the natural protective erythemal response to sun exposure. Despite this, routine testing of immune protection afforded by sunscreens is not performed by industry. Current laboratory methods for investigating the efficacy of sunscreen protection of epidermal immune function use the induction of contact hypersensitivity or epidermal cell alloantigen presentation. Animal models, cell culture systems, and in vivo human studies are commonly employed, but all these systems have significant drawbacks for use in routine testing. The purpose of this study was to develop an in vitro system for testing the immunologic protection afforded by sunscreens in human skin. Five test sunscreens plus a vehicle control were tested in a "blind" fashion for their in vitro level of immune protection. Creams were applied in a standard manner to human whole skin explants and were irradiated over a range of physiologic doses using an Oriel solar simulator. A mixed epidermal lymphocyte reaction was used to quantify epidermal alloantigen-presenting capacity, in the presence or absence of test cream, for five explants. Results consistently demonstrated that all the test sunscreens protected beyond their designated sun protection factors, whereas the vehicle conferred no protection. The explant-mixed epidermal lymphocyte reaction system gave consistent, reproducible results and may prove useful for the allocation of an immune protection factor to all sunscreens.

Administration, Topical

High incidence of a T nucleotide at the second position of codon 97 in Vdelta2-(D)-Jdelta1 junctional sequences of human normal skin gamma delta T-cells.

In this investigation, we have demonstrated that in-frame polyclonal Vdelta2-(D)-Jdelta1 junctional sequences from human skin gammadelta T-cells contain a high incidence of T nucleotides at the second position of codon 97. Analysis of the deduced amino acid sequences based on in-frame Vdelta2-(D)-Jdelta1 junctional nucleotide sequences from normal skin gammadelta T-cells revealed a high incidence of the amino acids valine and leucine at position 97. These results are consistent with the studies in peripheral blood gammadelta T-cells, but not with previous findings in skin gammadelta T-cells, where random nucleotides were observed in the second position of codon 97 of Vdelta2-(D)-Jdelta1 junctional sequences and only a small minority of the deduced Vdelta2-(D)-Jdelta 1 amino acid sequences showed the amino acids valine and leucine at codon 97. Therefore, our findings indicate that the human skin gamma delta T-cells with a T-cell receptor consisting of a Vdelta2-(D)-Jdelta1-C delta1 chain are not a subset distinct from the subpopulation of human peripheral blood gammadelta T-cells expressing the same chain.

Codon

Tumour progression in a patient with granulomatous mycosis fungoides.

We report a patient with granulomatous mycosis fungoides whose disease transformed into a high grade blast lymphoma with angiocentric features within 12 months of the initial diagnosis. This repudiates previous claims that granulomatous inflammation is protective in cutaneous T-cell lymphoma.

Disease Progression

Strict anatomical coexistence of vitiligo and psoriasis vulgaris--a Koebner phenomenon?

We describe a patient who developed typical psoriatic plaques covering completely or partly the vitiliginous areas of her skin. Her psoriasis was strictly limited to the vitiliginous patches with no involvement of the normal skin. Strict anatomical coexistence of both diseases is extremely rare and suggests a causal mechanism, possibly due to a Koebner phenomenon, but genetic and environmental factors may also be involved.

Aged

Langerhans cell histiocytosis--clinicopathological reappraisal and human leucocyte antigen association.

We have examined the clinicopathological correlates of 74 patients with histologically confirmed Langerhans cell histiocytosis. Factors that influenced disease outcome included, three or more organ/systems being involved, a disease onset before the age of 2 years, the involvement of certain vital organs/systems such as liver/spleen, bone marrow and lungs, and male gender. The total number of involved organs/systems was the single most important determinant of disease outcome. Mortality rate in patients with three or more organs/systems involved, was 26%, as compared with 0% in the group with one or two organs/systems involved (chi 2 = 11.2, P = 0.008). There were no familial cases in our series, but we looked for a possible immunogenetic association by tissue typing 46 Caucasian sufferers and comparing the results with 117 controls. We used normal peripheral blood lymphocytes in 39 cases, Epstein-Barr virus-transformed lymphoblastoid cell lines in 12 cases, and both peripheral blood and Epstein-Barr virus-transformed lymphocytes in five cases. The HLA-B7 antigen was significantly increased Langerhans cell histiocytosis patients (19 of 46 = 41.3%) compared with 19 of 117 (16.2%) in the control group chi 2 = 11.2, relative risk = 3.6, P value after correction = 0.013). Attempt to stratify the disease into single-system or multisystem disease did not result in any significant association.

Adolescent

Lack of T-cell receptor gene rearrangements in cells involved in Langerhans cell histiocytosis.

BACKGROUND: Studies using X-chromosome inactivation assays have recently provided evidence in support of a clonal origin of cells affected by Langerhans cell histiocytosis (LCH). A search for more specific clonal markers has led to the investigation for T-cell receptor (TCR) gene rearrangements in cells affected by LCH. METHODS: Conventional southern blot analysis was used to investigate the possibility of clonal TCR gene rearrangements in tissues affected by LCH wherever possible, otherwise, a polymerase chain reaction (PCR)-based technique was employed for amplification of rearranged joint (J) and variable (V) segments of the TCR-gamma gene including the N-region. 32P-labeled PCR products were then resolved using nondenaturing polyacrylamide gel electrophoresis. RESULTS: The results using the PCR-based technique showed a lack of clonal rearrangement of the TCR-gamma gene in affected tissues of eight patients with different stages of LCH. Southern blot analyses performed on two of these samples confirmed germline configurations at both the TCR-C-beta and delta-2 gene loci. CONCLUSIONS: There is no evidence of clonal TCR gene rearrangement in cells involved by LCH. The search for a more specific clonal marker to address whether "'LCH cells" represent a neoplastic clonal transformation of cells with differentiation toward Langerhans cell phenotype continues.

Base Sequence

Functional defect in cells involved in Langerhans cell histiocytosis.

The characteristic cell type involved in Langerhans cell histiocytosis, 'LCH cells', express most of the enzyme histochemical and immunocytochemical markers of normal epidermal Langerhans cells. It is not known, however, whether these LCH cells express the functional characteristics of normal epidermal Langerhans cells. We studied the alloantigen-presenting activity of LCH cells derived from lesional sites of three patients with the disease. Lesional cells expressing the CD1a molecule were enriched using either fluorescein-activated cell sorting or negative selection with indirect immunomagnetic beads, and functional activity was assessed using the 6-day primary allogeneic mixed-cell reaction. Compared to epidermal Langerhans cells from healthy controls, LCH cells showed minimal alloantigen-presenting activity on a per-cell basis. The diminished activity was not reversed by exogenous prostaglandin synthetase inhibitor or recombinant human IL-1 beta. This study confirms our previous report of a child, with fatal multisystem Langerhans cell histiocytosis suggesting that this disease represents a condition in which functionally defective cells of Langerhans cell phenotype accumulate and/or proliferate in various tissues. We postulate that the functional defect is a primary defect of these LCH cells that have acquired an as-yet-undetermined biological insult(s).

Adult