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Abstract Background One main research challenge in the post-genomic era is to understand the relationship between protein sequences and their biological functions. In recent years, several automated annotation systems have been developed for the functional assignment of uncharacterized proteins. The underlying assumption of these systems is that similar sequences imply similar biological functions. However, it has been noted that matching sequences do not always infer similar functions. Results In this paper, we present the correlation between protein sequences and protein functions for the yeast proteome in the context of gene ontology. A novel measure is introduced to define the overall similarity between two protein sequences. The effects of the level as well as the size of a gene ontology group on the degree of similarity were studied. The similarity distributions at different levels of gene ontology trees are presented. To evaluate the theoretical prediction power of similar sequences, we computed the posterior probability of correct predictions. Conclusion The results indicate that protein pairs of similar biological functions tend to have higher sequence similarity, although the similarity distribution in each functional group is heterogeneous and varies from group to group. We conclude that sequence similarity can serve as a key measure in protein function prediction. However, the resulting annotations must be verified through other means. A method that combines a broader range of measures is more likely to provide more accurate prediction. Our study indicates that the posterior probability of a correct prediction could serve as one of the key measures.

Abstract Background Mice with a single copy of Mclk1 (a.k.a. Coq7), a gene that encodes a mitochondrial enzyme required for the biosynthesis of ubiquinone and other functions, live longer than wild-type mice. The prolonged survival implies a decreased mortality from age-dependent lethal pathologies. Atherosclerosis is one of the main age-dependent pathologies in humans and can be modeled in mice that lack Apolipoprotein E (ApoE-/-) or mice that lack the Low Density Lipoprotein Receptor (LDLr-/-) in addition to being fed an atherosclerosis-inducing diet. We sought to determine if Mclk1 heterozygosity protects against atherosclerosis and dyslipidemia in these models. Results We found that Mclk1 heterozygosity did not protect against dyslipidemia, oxidative stress, or atherosclerosis in young (6 or 10 months) or older (18 months) mice. Furthermore, the absence of ApoE suppressed the lifespan-promoting effects of Mclk1 heterozygosity. Conclusion These findings indicate that although Mclk1 heterozygosity can extend lifespan of mice, it does not necessarily protect against atherosclerosis. Moreover, in the presence of hyperlipidemia and chronic inflammation, Mclk1 heterozygosity is incapable of extending lifespan.

Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. Conclusion This case illustrates that the brain can be a sanctuary site to treatment of GISTs with imatinib. Maintaining dosing of imatinib in the face of isolated sites of disease progression is also important, as other metastatic sites may still be sensitive.

Immune Checkpoint Inhibitors (ICI) have revolutionised cancer care in recent years. Despite a global improvement in the efficacy and tolerability of systemic anticancer treatments, a sizeable proportion of patients still do not benefit maximally from ICI. Extensive research has been undertaken to reveal the immune- and cancer-related mechanisms underlying resistance and response to ICI, yet more limited investigations have explored potentially modifiable lifestyle host factors and their impact on ICI efficacy and tolerability. Moreover, multiple trials have reported a marked and coherent effect of time-of-day ICI administration and patients' outcomes. The biological circadian clock indeed temporally controls multiple aspects of the immune system, both directly and through mediation of timing of lifestyle actions, including food intake, physical exercise, exposure to bright light and sleep. These factors potentially modulate the immune response also through the microbiome, emerging as an important mediator of a patient's immune system. Thus, this review will look at critically amalgamating the existing clinical and experimental evidence to postulate how modifiable lifestyle factors could be used to improve the outcomes of cancer patients on immunotherapy through appropriate and individualised entrainment of the circadian timing system and temporal orchestration of the immune system functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hughes, Shanaz, Ismail-Sutton, Wreglesworth, Subbe and Innominato.)

Background: Vulval intraepithelial neoplasia (VIN) is a precancerous condition that may progress to invasive malignancy. VIN is associated with human papillomavirus (HPV) infection in most cases, and with inflammatory skin disorders in a smaller proportion of patients. Treatment of VIN has traditionally been surgical excision; however, topical treatments, including imiquimod cream, are becoming increasingly used. Patient factors influencing response to imiquimod therapy, in particular smoking, have not yet been published., Aim: To assess the impact of smoking and other patient characteristics that may influence the treatment response to topical imiquimod for VIN., Methods: This was a retrospective cohort study of 46 women treated with topical imiquimod for VIN in a single centre dermatology unit from January 2011 to July 2017., Results: Complete clinical resolution of VIN was observed in 28 of 46 patients (61%), but was significantly reduced in the smoking cohort., Conclusions: Smoking may impair response to imiquimod for VIN, and should be considered when discussing VIN treatment options with patients., (© 2019 British Association of Dermatologists.)

Cell-cell communication plays a critical role in a myriad of processes, such as homeostasis, angiogenesis, and carcinogenesis, in multi-cellular organisms. Monolayer cell models have notably improved our understanding of cellular interactions. However, the cultured cells on the planar surfaces adopt a two-dimensional morphology, which poorly imitates cellular organization in vivo, providing physiologically-irrelevant cell responses. Non-planar surfaces comprising various patterns have demonstrated great abilities in directing cellular growth and producing different cell morphologies. In recent years, a few topographical substrates have provided valuable information about cell-cell signalling, however, none of these studies have reported a three-dimensional (3D) cell morphology. Here, we introduce a structurally tunable topographical platform that can maintain cell coupling while inducing a true 3D cell morphology. Optical imaging and fluorescence recovery after photobleaching are used to illustrate these capabilities. Our analyses suggest that the intercellular signalling on the present platform, which we propose is mainly through gap junctions, is comparable to that in natural tissue., Statement of Significance: A better understanding of direct cellular communication can help treating neurological diseases and cancers, which may be caused by dysfunctional intercellular signaling. To investigate cell-cell contact, cells are conventionally plated onto planar surfaces, where they flatten and adopt a two-dimensional cell morphology. These unrealistic models are physiologically-irrelevant since cells exhibit a three-dimensional (3D) shape in the body. Therefore, porous scaffolds and topographical surfaces, capable of inducing various cell morphologies, have been introduced, in which the latter is more desirable for sample imaging and screening. However, the few non-planar substrates used to study cell coupling have not produced a 3D cell shape. Here, we present a tunable culture platform that can control direct cell-cell communication while maintaining true 3D cell morphologies., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The data presented in this article were the basis for the study reported in the research articles entitled "Evaluation of a two-sided windcatcher integrated with wing wall (as a new design) and comparison with a conventional windcatcher" (P. Nejat, J.K. Calautit, M.Z.A. Majid, B.R. Hughes, I. Zeynali, F. Jomehzadeh, 2016) [1] which presents the effect of wing wall on the air flow distribution under using the windcatchers as a natural ventilation equipment. Here, we detail the wind tunnel testing and numerical set-up used for obtaining the data on ventilation rates and indoor airflow distribution inside a test room with a two-sided windcatcher and wing wall. Three models were integrated with wing wall angled at 30°, 45° and 60° and another windcatcher was a conventional two-sided device. The computer-aided design (CAD) three-dimensional geometries which were produced using Solid Edge modeler are also included in the data article.

This article presents the datasets which were the results of the study explained in the research paper 'Anti-short-circuit device: a new solution for short-circuiting in windcatcher and improvement of natural ventilation performance' (P. Nejat, J.K. Calautit, M.Z. Abd. Majid, B.R. Hughes, F. Jomehzadeh, 2016) [1] which introduces a new technique to reduce or prevent short-circuiting in a two-sided windcatcher and also lowers the indoor CO2 concentration and improve the ventilation distribution. Here, we provide details of the numerical modeling set-up and data collection method to facilitate reproducibility. The datasets includes indoor airflow, ventilation rates and CO2 concentration data at several points in the flow field. The CAD geometry of the windcatcher models are also included.

The data presented in this article were the basis for the study reported in the research articles entitled 'A validated design methodology for a closed loop subsonic wind tunnel' (Calautit et al., 2014) [1], which presented a systematic investigation into the design, simulation and analysis of flow parameters in a wind tunnel using Computational Fluid Dynamics (CFD). The authors evaluated the accuracy of replicating the flow characteristics for which the wind tunnel was designed using numerical simulation. Here, we detail the numerical and experimental set-up for the analysis of the closed-loop subsonic wind tunnel with an empty test section.

The data presented in this article were the basis for the study reported in the research articles entitled 'Climate responsive behaviour heat pipe technology for enhanced passive airside cooling' by Chaudhry and Hughes [10] which presents the passive airside cooling capability of heat pipes in response to gradually varying external temperatures and related to the research article "CFD and wind tunnel study of the performance of a uni-directional wind catcher with heat transfer devices" by Calautit and Hughes [1] which compares the ventilation performance of a standard roof mounted wind catcher and wind catcher incorporating the heat pipe technology. Here, we detail the wind tunnel test set-up and inflow conditions and the methodologies for the transient heat pipe experiment and analysis of the integration of heat pipes within the control domain of a wind catcher design.

Lung surfactant protein B (SP-B) is an essential protein found in the surfactant fluid at the air-water interface of the lung. Exposure to the air pollutant ozone could potentially damage SP-B and lead to respiratory distress. We have studied two peptides, one consisting of the N-terminus of SP-B [SP-B(1-25)] and the other a construct of the N- and C-termini of SP-B [SP-B(1-25,63-78)], called SMB. Exposure to dilute levels of ozone (~2 ppm) of monolayers of each peptide at the air-water interface leads to a rapid reaction, which is evident from an increase in the surface tension. Fluorescence experiments revealed that this increase in surface tension is accompanied by a loss of fluorescence from the tryptophan residue at the interface. Neutron and X-ray reflectivity experiments show that, in contrast to suggestions in the literature, the peptides are not solubilized upon oxidation but rather remain at the interface with little change in their hydration. Analysis of the product material reveals that no cleavage of the peptides occurs, but a more hydrophobic product is slowly formed together with an increased level of oligomerization. We attributed this to partial unfolding of the peptides. Experiments conducted in the presence of phospholipids reveal that the presence of the lipids does not prevent oxidation of the peptides. Our results strongly suggest that exposure to low levels of ozone gas will damage SP-B, leading to a change in its structure. The implication is that the oxidized protein will be impaired in its ability to interact at the air-water interface with negatively charged phosphoglycerol lipids, thus compromising what is thought to be its main biological function.

Cherry angiomas (Campbell de Morgan spots) are common acquired red skin papules composed of dilated capillary loops, usually of unknown aetiology. Extragenital lichen sclerosus (LS) presents as porcelain-white scaly atrophic lesions with or without genital involvement. We report two cases of segmental multiple cherry angiomas in association with extragenital LS. Two unrelated women, aged 46 and 66 years, presented with extragenital LS affecting their axillae and lower abdomen. During the examination, both patients were noted to have several hundred red skin papules in a segmental distribution, affecting the left thigh and flank of one woman, and the right abdomen and back of the other. Clinically and histologically, the papules were consistent with cherry angiomas. The striking segmental distribution of multiple cherry angiomas may be due to genetic mosaicism; however, segmental Fabry disease was excluded by sequence analysis of the α-galactosidase A gene. Any causal link between cherry angiomas and LS remains uncertain., (© The Author(s) CED © 2013 British Association of Dermatologists.)

The presence of unsaturated lipids in lung surfactant is important for proper respiratory function. In this work, we have used neutron reflection and surface pressure measurements to study the reaction of the ubiquitous pollutant gas-phase ozone, O3, with pure and mixed phospholipid monolayers at the air-water interface. The results reveal that the reaction of the unsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC, with ozone leads to the rapid loss of the terminal C9 portion of the oleoyl strand of POPC from the air-water interface. The loss of the C9 portion from the interface is accompanied by an increase in the surface pressure (decrease in surface tension) of the film at the air-water interface. The results suggest that the portion of the oxidized oleoyl strand that is still attached to the lipid headgroup rapidly reverses its orientation and penetrates the air-water interface alongside the original headgroup, thus increasing the surface pressure. The reaction of POPC with ozone also leads to a loss of material from the palmitoyl strand, but the loss of palmitoyl material occurs after the loss of the terminal C9 portion from the oleoyl strand of the molecule, suggesting that the palmitoyl material is lost in a secondary reaction step. Further experiments studying the reaction of mixed monolayers composed of unsaturated lipid POPC and saturated lipid dipalmitoyl-sn-glycero-3-phosphocholine, DPPC, revealed that no loss of DPPC from the air-water interface occurs, eliminating the possibility that a reactive species such as an OH radical is formed and is able to attack nearby lipid chains. The reaction of ozone with the mixed films does cause a significant change in the surface pressure of the air-water interface. Thus, the reaction of unsaturated lipids in lung surfactant changes and impairs the physical properties of the film at the air-water interface.

The reaction between gas-phase ozone and monolayers of the unsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC, on aqueous solutions has been studied in real time using neutron reflection and surface pressure measurements. The reaction between ozone and lung surfactant, which contains POPC, leads to decreased pulmonary function, but little is known about the changes that occur to the interfacial material as a result of oxidation. The results reveal that the initial reaction of ozone with POPC leads to a rapid increase in surface pressure followed by a slow decrease to very low values. The neutron reflection measurements, performed on an isotopologue of POPC with a selectively deuterated palmitoyl strand, reveal that the reaction leads to loss of this strand from the air-water interface, suggesting either solubilization of the product lipid or degradation of the palmitoyl strand by a reactive species. Reactions of (1)H-POPC on D(2)O reveal that the headgroup region of the lipids in aqueous solution is not dramatically perturbed by the reaction of POPC monolayers with ozone supporting degradation of the palmitoyl strand rather than solubilization. The results are consistent with the reaction of ozone with the oleoyl strand of POPC at the air-water interface leading to the formation of OH radicals. The highly reactive OH radicals produced can then go on to react with the saturated palmitoyl strands leading to the formation of oxidized lipids with shorter alkyl tails.

We report a patient with Darier's disease successfully treated with photodynamic therapy. She had previously been recalcitrant to treatment with emollients, topical corticosteroids and retinoids. Photodynamic therapy was trialled with significant clinical improvement in her cutaneous symptoms and signs that was maintained for over 27 months.

Infantile haemangioma is a common childhood condition, which usually resolves spontaneously and is managed expectantly. In a small percentage of complex cases, haemangiomas may be associated with complications such as persistent bleeding, ulceration, feeding difficulties or visual impairment. Active treatment is often necessary in such cases. Current interventions include surgical, laser and immunomodulatory treatments. Imiquimod 5% cream is a novel alternative topical treatment that may have a potential role in management of these patients. We present our experience of imiquimod 5% cream in the treatment of five children with difficult haemangiomas. We discuss its efficacy and some of the side effects that may be encountered, which have not previously been reported.

The results of an experimental study into the oxidative degradation of proxies for atmospheric aerosol are presented. We demonstrate that the laser Raman tweezers method can be used successfully to obtain uptake coefficients for gaseous oxidants on individual aqueous and organic droplets, whilst the size and composition of the droplets is simultaneously followed. A laser tweezers system was used to trap individual droplets containing an unsaturated organic compound in either an aqueous or organic (alkane) solvent. The droplet was exposed to gas-phase ozone and the reaction kinetics and products followed using Raman spectroscopy. The reactions of three different organic compounds with ozone were studied: fumarate anions, benzoate anions and alpha-pinene. The fumarate and benzoate anions in aqueous solution were used to represent components of humic-like substances, HULIS; alpha-pinene in an alkane solvent was studied as a proxy for biogenic aerosol. The kinetic analysis shows that for these systems the diffusive transport and mass accommodation of ozone is relatively fast, and that liquid-phase diffusion and reaction are the rate determining steps. Uptake coefficients, gamma, were found to be (1.1 +/- 0.7) x 10(-5), (1.5 +/- 0.7) x 10(-5) and (3.0-7.5) x 10(-3) for the reactions of ozone with the fumarate, benzoate and alpha-pinene containing droplets, respectively. Liquid-phase bimolecular rate coefficients for reactions of dissolved ozone molecules with fumarate, benzoate and alpha-pinene were also obtained: kfumarate = (2.7 +/- 2) x 10(5), kbenzoate = (3.5 +/- 3) x 10(5) and kalpha-pinene = (1-3) x 10(7) dm3 mol(-1) s(-1). The droplet size was found to remain stable over the course of the oxidation process for the HULIS-proxies and for the oxidation of alpha-pinene in pentadecane. The study of the alpha-pinene/ozone system is the first using organic seed particles to show that the hygroscopicity of the particle does not increase dramatically over the course of the oxidation. No products were detected by Raman spectroscopy for the reaction of benzoate ions with ozone. One product peak, consistent with aqueous carbonate anions, was observed when following the oxidation of fumarate ions by ozone. Product peaks observed in the reaction of ozone with alpha-pinene suggest the formation of new species containing carbonyl groups.

These guidelines stemmed from a consensus meeting held by the British Photobiology Group (BPG) in 1999. Following this meeting one of the authors (J.M.M.) was invited to draw up guidelines for the management of actinic keratoses by the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee. Relevant evidence was sought using the search terms 'solar keratosis' and 'actinic keratosis' in Medline from 1966 onwards. Additional and earlier literature was reviewed on the basis of references within post-1966 publications. All articles of apparent relevance were reviewed independently of the nature of the publication. The quality of the evidence elicited has been indicated. The National Ambulatory Medical Care Survey (U.S.A.) was used for further data on topical chemotherapy. Papers were reviewed and discussed by the contributors to the BPG Workshop (see Acknowledgments). Recommendations are evidence based where possible. Strength of recommendation is coupled with quality of evidence. Strength of recommendation includes consideration of apparent cost-benefit and practical considerations. Quality of evidence reflects the nature of the trial structure that provides data of efficacy.

A live male infant was born at 37 weeks' gestation after a normal pregnancy to a 34-year-old mother. The baby developed bacteraemia with Streptococcus pneumoniae and recovered completely following treatment with antibiotics. The mother simultaneously developed bacteraemia with the same organism and died from septic shock. Blood culture isolates from mother and child were both serogroup 23F, and were shown to be identical by DNA fingerprinting. The literature reports rare cases of vaginal carriage and/or endometritis with this organism resulting in neonatal sepsis. Transmission to the neonate may have been ascending or haematogenous. A postmortem examination was refused.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Childhood exposure to sunlight is a risk factor for melanoma. To formulate a meaningful program to educate children about the ill effects of the sun, their extant knowledge base must be determined. We have used the "draw-and-write" technique to assess children's perceptions about the sun, suntans, and skin cancer. A total of 693 school children aged 4 to 13 years were asked to draw pictures and label them in response to a series of carefully worded questions. Awareness of the need to apply sunscreen increased from 44% in children aged 4 to 6 years to 95% in children aged 9 to 10 years. Ten percent of children aged 4 to 6 years already perceived a suntan as attractive. While almost all children were aware of the negative immediate effects of sun exposure, namely sunburn, just 30% of American children aged 11 to 13 were aware that sun exposure is a risk for skin cancer. No differences between boys and girls were seen. The "draw-and-write" technique allows assessment of the attitudes and perceptions of children regarding the sun and skin cancer. It also provides valuable information on which to base health education and evaluate its cost-effectiveness.

Excessive sunlight in early childhood is thought to be a risk factor for skin cancer. We report the use of the 'draw and write' technique for determining changing perceptions, attitudes and knowledge of young children (aged 4-12 years) to the sun and skin cancer. Children were asked to draw pictures and label them in response to a series of carefully worded invitations and questions. The captions were then analysed to assess changing views and perceptions about particular issues in relation to behaviour in the sun. Four hundred and sixty children completed the exercise. An increasing spiral of knowledge with age about effects of the sun and appropriate behaviour was demonstrated. The study revealed a relatively high level of knowledge. Misconceptions and stereotypes were demonstrated. This technique is a simple and effective way of eliciting information from children about health issues. It provides baseline data for producing material for health education for children in relation to sun and skin. It is also a method of assessing the effectiveness in young children of health promotion initiatives.

This study compared the pattern of keratin expression in pilosebaceous follicles in uninvolved trunk skin of acne patients, comedones, and normal control skin by immunohistochemistry, using both immunofluorescent (IF) and immunoperoxidase (IP) techniques. The shape, size and gross morphology of truncal follicles varied greatly. There was no difference in keratin expression between normal skin and uninvolved skin of patients with acne. The upper part of the pilosebaceous duct expressed keratins K1, K5, K10 and K14, whereas the lower duct expressed keratins K5, K6, K14, K16, K17 and K19. The sebaceous gland showed considerable heterogeneity in keratin expression, with some lobules expressing keratins K1, K5, K7, K10, K14 and K17. The comedone wall showed a pattern of keratin expression similar to that of the upper follicle, except that there was, in addition, expression of keratins K6 and K16 suprabasally, and panepithelial expression of K17 in the comedone wall. IF techniques were found to be less sensitive than the IP method in the detection of individual keratins, but the use of multiple antibodies and many different transverse and longitudinal sections of follicles permitted full conclusions to be made. The increased expression of keratins K6, K16 and K17 in the comedone wall is likely to represent a secondary effect of increased cell turnover due to the primary underlying mechanism of comedogenesis, which is as yet unknown.

Desmosomes contribute towards adhesion between adjacent keratinocytes. In acne vulgaris, increased intercellular adhesion is thought to contribute to the retention of keratinocytes within the follicular lumen during comedogenesis. Therefore, the distribution of different desmosomal components was investigated in normal and acne subjects. Biopsies were cryostat-sectioned (6 microns), and stained with antibodies to different desmosomal components: desmoplakin 1/2, desmoglein 1, desmocollin 3a/3b, and a late desmosomal antigen, G36-19. Desmoplakin 1/2, desmoglein 1 and desmocollin 3a/3b shared a similar distribution in follicles from control skin, from acne-affected skin, and in non-inflamed lesions. All three proteins were expressed around the periphery of keratinocytes of all the intrafollicular epidermis, except the basal lamina and the upper stratum corneum. In inflamed lesions, the expression of desmoglein 1 and desmocollin 3a/3b was diminished; in 12.5%, staining for these two proteins was completely abolished, and in 81.25% of the lesions investigated the staining was patchy. The antibody G36-19 bound to an antigen in the upper granular layer in the infundibular epidermis. No differences were noted in the staining pattern of the follicular epithelia of controls, non-inflamed, and inflamed lesions. This study, using monoclonal antibodies, did not identify any changes in the desmosomal components which might explain the increased adhesion between follicular keratinocytes during comedogenesis.

Background and Design: A prospective study of 30 patients with moderate to severe acne was performed. The follicular reservoir and sustainable sebum excretion rates were measured before and after a 4-month course of isotretinoin at a dose of 1 mg/kg per day., Results: The follicular reservoir and sustainable sebum excretion rates were profoundly reduced at the end of the course of isotretinoin (79% and 83%, respectively) and remained significantly suppressed at 1 year following therapy (43% and 36%, respectively). Those patients who relapsed clinically at 1 year after treatment had a significantly higher follicular reservoir rate., Conclusions: These data support the concept that up to 1 year after therapy, there is a reduction in the sebum secretion rate accompanying the remission of acne. This suppressed sebum secretion may modulate the microenvironment of the pilosebaceous canal through an effect on the follicular reservoir.

The effectiveness of an education package for secondary schools about the sun and skin cancer was assessed using questionnaires. A variety of teaching methods was used, including pamphlets, workbooks, and a video. The effect of this material was assessed by asking pupils to complete questionnaires immediately after receiving the package (July), and after the summer holiday (September). Five-hundred and forty-three children from seven schools were recruited into the study. Results of the questionnaire demonstrated a significant difference in knowledge (P < 0.001) and reported attitude (P < 0.001) compared with a control group. There was no significant difference in behaviour of the taught groups compared with the control group. The only significant activity associated with increased knowledge was wearing a sunscreen (P < 0.005). In contrast, in terms of attitude, those who covered up in the sun (P < 0.0001), wore a sunscreen (P < 0.004), and sat in the shade (P < 0.02), had significantly better attitudes than those who did not behave in this way. This project is a first attempt to assess health education in schools, and reports changes in knowledge, attitudes, and some aspects of behaviour. Adolescents are a group who are difficult to influence, but our study has produced some useful information about how these children respond to such teaching measures.

A large variety of cutaneous reactions to malignancy have been described but to our knowledge none include psoriasis. Two cases of psoriasiform reactions in association with malignancy were first documented by Braverman, and Bazex's syndrome is now well documented in the literature. Both conditions, although clinically psoriasiform, are said to demonstrate an eczematous histology. A number of patients with psoriasis and malignancy have presented to us in the Dermatology Department. The appearance or behaviour of their psoriasis appeared to be linked to their malignancy. We have collected them together to report on this phenomenon which appears infrequently in the literature.

Solution-phase N-fluorenylmethoxycarbonyl (Fmoc) mediated peptide synthesis has been adapted to the synthesis of glutathione (gamma-glutamyl-cysteinyl-glycine) analogs. A protecting group strategy has been devised in which all of the masking groups are removed with mild base. This allows for the synthesis of acid-sensitive materials and lessens concerns about the alkylation at sulfur by carbocations known to be present in the trifluoroacetic acid mixtures usually employed for deprotection of peptides made by the Fmoc methodology. A series of structurally varied glutathione analogs were prepared by modifying the peptide in two ways. The first involved C-terminal substitution for glycine by one of several different amino acids. The second involved substitution of one of five alkyl or aryl groups onto the cysteine sulfhydryl. The complete set of all combinations would yield 48 reagents, of which 25 have actually been synthesized. Following confirmation of the structures by FAB mass spectrometry, the peptides were immobilize by conjugation to epoxyfunctionalized Sepharose at pH 11-12. The amount and identity of immobilized peptide was assayed by amino acid analysis of acid-hydrolyzed resin. One of the tripeptides was purified by ion-exchange and preparative HPLC.

The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide. In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response. This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min. These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less. The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne.

A double-blind, randomized study comparing isotretinoin gel (Isotrex), its vehicle base, and benzoyl peroxide was performed on 77 patients with mild to moderate acne vulgaris. The effect of treatment was assessed by acne grade and lesion count. The vehicle base had no effect, but both active groups produced significant improvements. Benzoyl peroxide and isotretinoin significantly reduced non-inflamed lesions at 4 (P < 0.05), 8 (P < 0.01), 12 (P < 0.01) weeks. Benzoyl peroxide had a more rapid effect on inflamed lesions, their being significant reductions at 4, 8 and 12 weeks (P < 0.01), whereas with isotretinoin there was a significant improvement at 12 weeks (P < 0.01). In addition, compared to placebo, both active treatments significantly reduced inflamed and non-inflamed lesions. Acne grade had improved significantly in the benzoyl peroxide group by 4 weeks (P < 0.01) and in the isotretinoin group by 8 weeks (P < 0.05). No significant change in haematological or biochemical parameters occurred. An irritant dermatitis occurred equally with both treatments but was well tolerated by the patients. This data confirms the clinical benefit of benzoyl peroxide in acne. The initial effect of isotretinoin on non-inflamed lesions in this study suggests that the prime mode of action is on comedone formation or separation whereas benzoyl peroxide has an effect on both comedones and inflammation.

Sixteen patients with minimal facial acne but with symptoms of dysmorphophobia related to their acne were treated with isotretinoin, 0.5 mg/kg/day, (n = 5); 1 mg/kg/day (n = 11) for 16 weeks. All 16 had previously received long-term antibiotic therapy with no 'perceived' improvement in their acne. Formal psychiatric assessment was not possible through lack of cooperation. Fourteen of 16 patients derived benefit from isotretinoin therapy in that all 14 were subsequently satisfied with the cosmetic results achieved. However, the incidence of relapse was greater than that for a control group, 14 requiring additional therapy in the form of antibiotics or further isotretinoin (seven patients) within 20 months of completing the original course. Patients with acne and dysmorphophobia represent an important group of patients who benefit from treatment with isotretinoin; if possible this should be in conjunction with psychotherapy.

A proprietary topical tetracycline preparation (Topicycline) was compared with an alcohol-based 5% benzoyl-peroxide gel and with oral oxytetracycline (250 mg twice daily) using a randomized group-comparative double-blind study in 69 patients with mild to moderate acne. Facial acne grades improved significantly in all three treatment groups over the 12-week study period but chest acne grades did not change significantly and only oxytetracycline produced a significant improvement in back grade. All three treatment groups produced a significant reduction in facial inflamed and non-inflamed lesions apart from oxytetracycline which failed to produce a significant reduction in inflamed lesions. However, there were no overall significant differences between the three treatment groups either in improvement of acne grade or in reduction of inflamed and non-inflamed lesions. We conclude that topical tetracycline is as effective as either 5% benzoyl-peroxide gel or 250 mg oxytetracycline twice daily in the treatment of mild to moderate acne.