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S Gibbs

Publications and source records attributed to S Gibbs.

At least 19 recordsLinked to original sources

Soft-tissue anatomy of the extant hominoids: a review and phylogenetic analysis.

This paper reports the results of a literature search for information about the soft-tissue anatomy of the extant non-human hominoid genera, Pan, Gorilla, Pongo and Hylobates, together with the results of a phylogenetic analysis of these data plus comparable data for Homo. Information on the four extant non-human hominoid genera was located for 240 out of the 1783 soft-tissue structures listed in the Nomina Anatomica. Numerically these data are biased so that information about some systems (e.g. muscles) and some regions (e.g. the forelimb) are over-represented, whereas other systems and regions (e.g. the veins and the lymphatics of the vascular system, the head region) are either under-represented or not represented at all. Screening to ensure that the data were suitable for use in a phylogenetic analysis reduced the number of eligible soft-tissue structures to 171. These data, together with comparable data for modern humans, were converted into discontinuous character states suitable for phylogenetic analysis and then used to construct a taxon-by-character matrix. This matrix was used in two tests of the hypothesis that soft-tissue characters can be relied upon to reconstruct hominoid phylogenetic relationships. In the first, parsimony analysis was used to identify cladograms requiring the smallest number of character state changes. In the second, the phylogenetic bootstrap was used to determine the confidence intervals of the most parsimonious clades. The parsimony analysis yielded a single most parsimonious cladogram that matched the molecular cladogram. Similarly the bootstrap analysis yielded clades that were compatible with the molecular cladogram; a (Homo, Pan) clade was supported by 95% of the replicates, and a (Gorilla, Pan, Homo) clade by 96%. These are the first hominoid morphological data to provide statistically significant support for the clades favoured by the molecular evidence.

Anatomy, Comparative↗

Effect of fibroblasts on epidermal regeneration.

BACKGROUND: There is little information on specific interactions between dermal fibroblasts and epidermal keratinocytes. The use of engineered skin equivalents consisting of organotypic cocultures of keratinocytes and fibroblasts offers an attractive approach for such studies. OBJECTIVES: To examine the role fibroblasts play in generation and maintenance of reconstructed epidermis. METHODS: Human keratinocytes were seeded on collagen matrices populated with increasing numbers of fibroblasts and cultured for 2 weeks at the air-liquid interface. RESULTS: In the absence of fibroblasts, stratified epidermis with only three or four viable cell layers was formed. In the presence of fibroblasts, keratinocyte proliferation was stimulated and epidermal morphology was improved. Epidermal morphogenesis was also markedly improved in epidermis generated in organotypic keratinocyte monocultures grown in medium derived from dermal equivalents or from organotypic keratinocyte-fibroblast cocultures. These observations clearly indicate the proliferation-stimulating activity of soluble factors released from fibroblasts. Under all experimental conditions, onset of keratinocyte differentiation was shown by the expression of keratin 10 in all suprabasal cell layers. With increasing numbers of fibroblasts incorporated into the collagen matrix, the expression of markers associated with keratinocyte activation, e.g. keratins 6, 16 and 17 and the cornified envelope precursor SKALP decreased, and involucrin localization shifted toward the granulosum layer. This fibroblast-mediated effect was even more pronounced when the fibroblasts were precultured in the collagen matrices for 1 week instead of overnight. The basement membrane proteins collagen VII and laminin 5 were present at the epithelial-matrix border. The expression of integrin alpha 6 beta 4 and of E-cadherin was comparable with that seen in native skin and was not significantly modulated by fibroblasts. Under all experimental conditions the expression of integrin subunits alpha 2, alpha 3 and beta 1 was upregulated, indicating keratinocyte activation. CONCLUSIONS: Our results illustrate that numbers of fibroblasts in the collagen matrix and their functional state is a critical factor for establishment of normal epidermal morphogenesis.

Biomarkers↗

Local treatments for cutaneous warts.

BACKGROUND: Viral warts caused by the human papilloma virus represent one of the most common diseases of the skin. Any area of skin can be affected although the hands and feet are by far the commonest sites. A very wide range of local treatments are available. OBJECTIVES: To assess the effects of different local treatments for cutaneous, non-genital warts in healthy people. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (March 1999), the Skin Group trials register (March 1999), MEDLINE (1966 to August 2000), EMBASE (1980 to August 2000) and a number of other key biomedical and health economics databases. In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in local treatments for warts and experts in the field were contacted. SELECTION CRITERIA: Randomized controlled trials of local treatments for cutaneous non-genital viral warts in immunocompetent human hosts were included. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent reviewers. MAIN RESULTS: Forty-nine trials were identified which fulfilled the criteria for inclusion in the review. The evidence provided by these studies was generally weak because of poor methodology and reporting. In 17 trials with placebo groups that used participants as the unit of analysis the average cure rate of placebo preparations was 30% (range 0 to 73%) after an average period of 10 weeks (range 4 to 24 weeks). The best available evidence was for simple topical treatments containing salicylic acid, which are clearly better than placebo. Data pooled from six placebo-controlled trials show a cure rate of 144/191 (75%) compared with 89/185 (48%) in controls, odds ratio 3.91 (95% confidence interval 2.40 to 6.36), random effects model. Most of the bigger trials of cryotherapy studied different regimens rather than comparing cryotherapy with other treatments or placebo. Pooled data from two small trials that included cryotherapy and placebo or no treatment, showed no significant difference in cure rates. In two other trials comparing cryotherapy with salicylic acid no significant difference in efficacy was demonstrated. There was no consistent evidence for the effectiveness of intralesional bleomycin. Four studies, using warts rather than individuals as the unit of analysis, had widely varying results which could not be meaningfully pooled. There was some evidence for the efficacy of dinitrochlorobenzene, a potent contact sensitizer. Pooled data from two small studies comparing dinitrochlorobenzene with placebo showed cure rates of 32/40 (80%) and 17/40 (43%) respectively, odds ratio 5.42 (95% confidence interval 1.99 to 14.75), random effects model. Only limited evidence was found for the efficacy of topical 5-fluorouracil, intralesional interferons and photodynamic therapy. Bleomycin, dinitrochlorobenzene, 5-fluorouracil, interferons and photodynamic therapy are potentially hazardous or toxic treatments. REVIEWER'S CONCLUSIONS: There is a considerable lack of evidence on which to base the rational use of the local treatments for common warts. The reviewed trials are highly variable in method and quality. Cure rates with placebo preparations are variable but nevertheless considerable. There is certainly evidence that simple topical treatments containing salicylic acid have a therapeutic effect. There is less evidence for the efficacy of cryotherapy and no convincing evidence that it is any more effective than simple topical treatments. Dinitrochlorobenzene appears to be effective but no more so than the safer, simpler and cheaper topical treatments containing salicylic acid. The benefits and risks of 5-fluorouracil, bleomycin, interferons and photodynamic therapy remain to be determined.

Administration, Topical↗

MR microscopy of multicomponent diffusion in single neurons.

This study examines multicomponent diffusion in isolated single neurons and discusses the implications of the results for macroscopic water diffusion in tissues. L7 Aplysia neurons were isolated and analyzed using a 600 MHz Bruker wide-bore instrument with a magnetic susceptibility-matched radiofrequency microcoil. Using a biexponential fit, the apparent diffusion coefficients (ADCs) from the cytoplasm (with relative fraction) were 0.48 +/- 0.14 x 10(-3) mm2 x s(-1) (61 +/- 11%) for the fast component, and 0.034 +/- 0.017 x 10(-3) mm2 x s(-1) (32 +/- 11%) for the slow component (N = 10). Diffusion in the nucleus appears to be primarily monoexponential, but with biexponential analysis it yields 1.31 +/- 0.32 x 10(-3) mm2 x s(-1) (89 +/- 6%) for the fast component and 0.057 +/- 0.073 x 10(-3) mm2 x s(-1) (11 +/- 6%) for the slow (N = 5). The slow component in the nucleus may be explained by cytoplasmic volume averaging. These data demonstrate that water diffusion in the cytoplasm of isolated single Aplysia neurons supports a multiexponential model. The ADCs are consistent with previous measurements in the cytoplasm of single neurons and with the slow ADC measurement in perfused brain slices. These distributions may explain the multiple compartments observed in tissues, greatly aiding the development of quantitative models of MRI in whole tissues.

Animals↗

Community participation in road safety: barriers and enablers.

The objectives of the paper were to identify barriers to community participation in road safety activities and to recommend strategies to reduce those barriers. Information was obtained from: a review of relevant literature, from the authors' extensive community-based experiences, from undertaking community-based research, and from interviews with key stakeholders in road safety in Western Australia. Ten significant barriers to community participation were identified. These are classified into two groups: personnel and planning issues. The former includes: reasons why people are often reluctant to become involved in projects in their communities, a lack of leadership, and a lack of skills. The latter includes: inappropriate program foci, inappropriate program evaluation, lack of resources, and a lack of sustainability. It was concluded that the barriers to community involvement in road safety initiatives are similar in many parts of Australia and overseas and apply to a wide range of health promotion interventions besides road safety. Awareness of the barriers and knowledge of their solutions can ensure that appropriate steps are taken to maximise the likelihood of community participation.

Accidents, Traffic↗

Transduction of the E6 and E7 genes of epidermodysplasia-verruciformis-associated human papillomaviruses alters human keratinocyte growth and differentiation in organotypic cultures.

Epidermodysplasia-verruciformis-associated human papilloma virus DNA has been detected in skin cancers, in premalignant and benign skin lesions, and in plucked hairs from immunocompetent and immunosuppressed patients. The role of epidermodysplasia-verruciformis-associated human papilloma virus in the pathogenesis of nonmelanoma skin cancer is still enigmatic. In organotypic cultures we investigated the effects of retroviral transduction of the E6 and E7 genes of epidermodysplasia-verruciformis-associated human papilloma virus types 5, 12, 15, 17, 20, and 38 on the growth and differentiation of human keratinocytes. Differentiation was disturbed to different degrees as revealed by histology and by the expression patterns of differentiation markers keratin 10 and small proline rich protein 2. Conversely, proliferating cell nuclear antigen was induced in some of the suprabasal, differentiated cells to varying extent. No unscheduled DNA synthesis was detected in these cells, however, as probed by 5'-bromo-2'-deoxyuridine incorporation. Most intriguingly, when the E6 and E7 genes of epidermodysplasia-verruciformis-associated human papilloma virus types 15 and 17 were transduced, a broadening layer of basal cells and an accelerated differentiation were observed. In addition, "papilla-like structures" comprising basal-like keratinocytes arose from the basal layer into the differentiated layers. These cells did not express the differentiation markers keratin 10 and small proline rich protein 2, but did actively replicate DNA. These observations warrant further research by using this system to elucidate the replication strategy of epidermodysplasia-verruciformis-associated human papilloma virus types in keratinocytes and to shed light on the role of these human papilloma virus types in the pathogenesis of skin cancer.

Antimetabolites↗

Assembly, annotation, and integration of UNIGENE clusters into the human genome draft.

The recent release of the first draft of the human genome provides an unprecedented opportunity to integrate human genes and their functions in a complete positional context. However, at least three significant technical hurdles remain: first, to assemble a complete and nonredundant human transcript index; second, to accurately place the individual transcript indices on the human genome; and third, to functionally annotate all human genes. Here, we report the extension of the UNIGENE database through the assembly of its sequence clusters into nonredundant sequence contigs. Each resulting consensus was aligned to the human genome draft. A unique location for each transcript within the human genome was determined by the integration of the restriction fingerprint, assembled genomic contig, and radiation hybrid (RH) maps. A total of 59,500 UNIGENE clusters were mapped on the basis of at least three independent criteria as compared with the 30,000 human genes/ESTs currently mapped in Genemap'99. Finally, the extension of the human transcript consensus in this study enabled a greater number of putative functional assignments than the 11,000 annotated entries in UNIGENE. This study reports a draft physical map with annotations for a majority of the human transcripts, called the Human Index of Nonredundant Transcripts (HINT). Such information can be immediately applied to the discovery of new genes and the identification of candidate genes for positional cloning.

Alleles↗

Phase 1/2 study of synchronous methotrexate, cisplatin, vincristine (MOPq10) chemotherapy and radiation for patients with locally advanced bladder cancer.

PURPOSE: This phase 1/2 study was designed to test toxicity and effectiveness of combination chemotherapy and concurrent radiotherapy in the treatment of invasive bladder cancer. METHODS AND MATERIALS: 17 patients with localised muscle-invasive bladder cancer, clinical stages T2-3 N0, M0, were treated with a radiotherapy schedule of 55 Gy in 20 fractions over 4 weeks restricted to the bladder and 3 cycles of concurrent dose-intensive combination chemotherapy consisting of cisplatin 60 mg/m(2), vincristine 2 mg and methotrexate 60 mg/m(2) at 10-day intervals (MOPq10). RESULTS: The complete remission rate following MOPq10 chemotherapy and radiotherapy was 88% as assessed at first cystoscopy with 82% remaining disease-free at 1 year. Risk factor analysis shows those older than 63 years (median) and those with creatinine clearance equal or less than the mean did worse. Actuarial disease-free survival at 2 years was 68% and of the patients treated 4/17 experienced acute G3/4 toxicity. CONCLUSION: This combination regimen was feasible. Its high initial response rate justifies further exploration in a randomised phase 2/3 trial setting with bladder volume and quality of life assessment.

Aged↗

Barrier function in reconstructed epidermis and its resemblance to native human skin.

One of the prerequisites for the use of human skin equivalents for scientific and screening purposes is that their barrier function is similar to that of native skin. Using human epidermis reconstructed on de-epidermized dermis we demonstrated that the formation of the stratum corneum (SC) barrier in vitro proceeds similarly as in vivo as judged from the extensive production of lamellar bodies, their complete extrusion at the stratum granulosum/SC interface, and the formation of multiple broad lamellar structures in the intercorneocyte space. The presence of well-ordered lipid lamellar phases was confirmed by small-angle X-ray diffraction. Although the long periodicity lamellar phase was present in both the native and the reconstructed epidermis, the short periodicity lamellar phase was present only in native tissue. In addition, the SC lipids predominantly formed the hexagonal sublattice. Analysis of lipid composition revealed that all SC lipids are synthesized in vitro. Differences in SC lipid organization in reconstructed epidermis may be ascribed to the differences in fatty acid content and profile indicating that further improvement in culture conditions is required for generation of in vitro reconstructed epidermis with stratum barrier properties of the native tissue.

Animals↗

Soft-tissue characters in higher primate phylogenetics.

Recent research has cast doubt on the reliability of bones and teeth for reconstructing phylogenetic relationships among higher primate species and genera. Herein, we investigate whether this problem is confined to hard tissues by examining the utility of higher primate soft-tissue characters for reconstructing phylogenetic relationships at low taxonomic levels. We use cladistic methods to analyze 197 soft-tissue characters for the extant hominoids and then compare the resulting phylogenetic hypotheses with the group's consensus molecular phylogeny, which is widely considered to be accurate. We show that the soft-tissue characters yield robust phylogenetic hypotheses that are compatible with the molecular phylogeny. Given the strength of the evidence for molecular phylogeny, these results indicate that, unlike craniodental hard-tissue characters, soft tissues are reliable for reconstructing phylogenetic relationships among higher primate species and genera. Thus, in higher primates at least, some types of morphological data are more useful than others for phylogeny reconstruction.

Animals↗

NMR spectroscopy of single neurons.

The first spatially localized NMR spectra of osmolytes and metabolites from single isolated neurons have been obtained using a combination of high magnetic field strengths and NMR radio frequency (RF) microcoils. The proton spectra display peaks at high concentrations (100-300 mM) assigned to betaine and choline, and other metabolite resonances including lactate at lower concentrations in the order of 10s of millimoles. The volumes examined were approximately 10 nl, over two orders of magnitude less than previously possible. In these initial experiments; the cells were unperfused and the signal intensities of the osmolytes decrease with time, a phenomenon consistent with cell swelling. This work demonstrates the technical feasibility of NMR spectroscopy of single cells, further broadening the scope of NMR spectroscopy of living tissues from application to entire living organisms (man and animal models) and isolated tissues (perfused organs and cultured assemblies of cells) and now to single cells. Magn Reson Med 44:19-22, 2000.

Acetates↗

Intrinsic regulation of differentiation markers in human epidermis, hard palate and buccal mucosa.

Different epithelia show extensive variation in differentiation. Epidermis and epithelium from the hard palate are both typical examples of orthokeratinized epithelia whereas buccal mucosa is an example of a non-keratinized epithelium. Each of these tissues can be distinguished morphologically and also by the expression of a number of structural proteins. Tissue explants derived from epidermis, hard palate or buccal mucosa were cultured at the air-liquid interface on collagen gels containing human dermal fibroblasts. Reconstructed epithelia that retained many of the morphological and immunohistochemical characteristics of the original tissue were formed. Cultures derived from epidermis and the hard palate both had a well-defined stratum basale, stratum spinosum, stratum granulosum and stratum corneum whereas cultures derived from buccal mucosa had no stratum granulosum or corneum and the cells retained their nuclei. Significantly more living cell layers were observed in both types of epithelia obtained from the mouth than in epidermis. The specific localization of proliferation and differentiation markers (Ki67, loricrin, involucrin, SPRR2, SPRR3 and keratin 10) closely resembled that of the tissue from which the cultures were derived. As identical three-dimensional culture models were used here, it is concluded that the differences observed between these epithelia were due to intrinsic properties of the keratinocytes.

Biomarkers↗

The influence of external knee moments on the outcome of total meniscectomy. A comparison of radiological and 3-D gait analysis measurements.

Twenty one individuals who had undergone unilateral total meniscectomy, and had no significant antero-posterior (AP) laxity underwent three dimensional (3-D) gait analysis, bilateral radiological assessment of varus/valgus alignment and tibio-femoral osteoarthritis (TFOA). Average foot progression angle during the stance phase of gait was not related to knee adduction moment. The findings support the previously noted correlation between varus/valgus alignment and TFOA. The dynamic gait parameter of the adduction moment in early stance did not correlate with either hip-knee-ankle angle or TFOA, thus the expected influence of external moments on outcome after meniscectomy was not found. Thus the correlation between varus/valgus alignment and TFOA can not be explained by a simple loading algorithm.

Adolescent↗

Melanosome capping of keratinocytes in pigmented reconstructed epidermis--effect of ultraviolet radiation and 3-isobutyl-1-methyl-xanthine on melanogenesis.

Reconstructed pigmented epidermis was established by co-seeding autologous melanocytes and keratinocytes onto a dermal substrate and culturing for up to 6 weeks at the air-liquid interface. Inspection of the tissue architecture revealed that melanocytes are regularly interspersed only in the basal layer and transfer melanosomes to the keratinocytes. We report for the first time, the in vitro formation of supranuclear melanin caps above the keratinocyte nuclei. The formation and abundance of these melanin caps could be enhanced by pigment modifiers such as ultraviolet light and 3-isobutyl-1-methyl-xanthine (IBMX). In untreated cultures, the capping was observed in the spinous layers after 6 weeks of culture, whereas after irradiation or supplementation of the culture medium with IBMX, the capping occurred already in the basal layer 2 weeks after initiation of the stimulus. In this study, we show that IBMX and ultraviolet irradiation stimulate pigmentation via different mechanisms. After supplementation of the culture medium with IBMX the increase in pigmentation was entirely due to the increase in melanocyte activity as observed by increased dendrite formation, melanin production and transport to the keratinocytes and was not due to an increase in melanocyte proliferation. In contrast, after UV irradiation, the increase in pigmentation was also accompanied with an increase in melanocyte proliferation as well as an increase in melanocyte activity. In conclusion, we describe the establishment of pigmented reconstructed epidermis with autologous keratinocytes and melanocytes that can be kept in culture for a period of at least 6 weeks. The complete program of melanogenesis occurs: melanosome synthesis, melanosome transport to keratinocytes, supranuclear capping of keratinocyte nuclei and tanning of the epidermis. This enables sustained application of pigment stimulators over a prolonged period of time and also repeated application of pigment stimulators to be studied.

1-Methyl-3-isobutylxanthine↗

Gianotti-Crosti syndrome in two unrelated adults.

Two unrelated adult patients are described who both developed an exanthem with the characteristic morphology and distribution of the Gianotti-Crosti syndrome. The literature of adult cases of Gianotti-Crosti syndrome is reviewed with the suggestion that the syndrome may not be as uncommon as previously supposed.

Acrodermatitis↗

Losing touch with the healing art: dermatology and the decline of pastoral doctoring.

Technological advance in society and medicine has brought tremendous improvements and convenience but also a degree of depersonalization. The personal and pastoral aspects of medical practice, which are probably more important in helping patients toward health than we realize, are becoming increasingly stifled by health care systems which are increasingly "scientific," technological, and "efficient." Clinical practice in dermatology requires pastoral as well as technical skills, art as well as science, and yet the balance of current medical culture increasingly favors and encourages "science" over "art." In dermatology, this bias is evident in a reductionist focus of research, the move towards evidence-based medicine and the emergence of teledermatology. Although all these developments are extremely important and valuable, their effect on the doctor-patient relationship needs to be considered carefully. Increasingly rapid scientific advance is paradoxically providing diminishing returns for patients and the healing art is still very much in demand.

Dermatology↗

Scabies.

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Humans↗