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This article proposes and develops a theory of leadership that utilizes five levels of being as context for effective leadership: 1) the physical world; 2) the world of images and imagination; 3) the level of the soul; 4) the level of the Spirit; and 5) the non-dual level. We first explore how each of the five levels of being provides a means for advancing both the theory and the practice of leadership. Second, we utilize these five levels to create the foundation for a theory of leadership based on being that goes beyond current theory which emphasizes having and doing -- either having appropriate traits and competencies or doing appropriate actions depending on the situation. We present propositions for future research as we discuss each of the five levels of being. Finally, we discuss implications for leadership development and future research that arise from such a being-centered leadership theory. [ABSTRACT FROM AUTHOR]

The article discusses the use of positive capsule endoscopy to diagnose and treat the small-bowel disorders. Topics include the emergence of spiral enteroscopy as an alternate method for enteroscopy, the assessment of the impact of capsule endoscopy in patients with double-balloon enteroscopy (DBE) and obscure gastrointestinal bleeding (OGIB) conducted by L. C. Fry and colleagues, and the challenges posed by the diagnosis of Crohn's disease.

We have previously postulated that surviving invasive streptococcal infections may have been a factor in psoriasis becoming a common skin disease in some parts of the world. Many of the candidate genes linked to psoriasis are associated with the acquired or innate immune system, which are also important in host defence to invasive streptococcal infections. High rates of positive streptococcal throat swabs among patients with chronic plaque psoriasis suggest that they are efficient at internalizing/carrying β-haemolytic streptococci. Internalization of streptococci in the throat is dependent upon the transforming growth factor (TGF)-β/fibronectin/α5β1 integrin pathway. The immune cell Th17 and its related cytokine network are important in mucosal defence, being very effective against extracellular microbes but having little effect on intracellular organisms. The TGF-β/fibronectin/α5β1 integrin pathway and the Th17 cell network also appear to be operative in psoriasis, animal models of both TGF-β and α5β1 cutaneous overexpression being associated with characteristic psoriasis lesions. We postulate that some of the genotypic/phenotypic changes in different immunological pathways in psoriasis, including the acquired T-cell response, the innate immune response, the TGF-β/fibronectin/α5β1 integrin pathway and the Th17 cell system, confer protection against mortality during epidemics of invasive streptococcal infections, heightened efficiency in internalizing and allowing carriage of streptococci as well as predisposition to the development of psoriasis. [ABSTRACT FROM AUTHOR]

Background Double-balloon enteroscopy (DBE) is a useful method for evaluation of obscure gastrointestinal bleeding (OGIB). Aim To determine the incidence of lesions within reach of conventional upper and lower endoscopes as the cause of OGIB in patients referred for DBE. Methods All patients undergoing DBE for OGIB during a 3.5-year period at a university hospital were studied. OGIB was defined according to American Gastroenterological Association (AGA) guidelines. Results One hundred and forty-three DBEs were performed in 107 patients for obscure overt ( n = 85) and obscure occult ( n = 22) GIB. Lesions outside the SB as possible sources of GIB were found in 51 patients (47.6%) and a definite source of bleeding outside the small bowel (SB) was detected in 26 patients (24.3%). Lesions considered to explain a definite source of GIB were: gastric ulcer ( n = 3), duodenal ulcer ( n = 3), Cameron’s lesions ( n = 2), gastric antral vascular ectasias ( n = 4), radiation proctitis ( n = 1), radiation ileitis ( n = 2), duodenal angiodysplasias ( n = 1), haemorrhoids with stigmata of recent bleed ( n = 1), colon angiodysplasias ( n = 3), colon diverticulosis ( n = 3), colonic Crohn’s disease ( n = 1), anastomotic ulcers ( n = 1). Conclusions The frequency of non-SB lesions definitely explaining the source of GIB in patients referred for DBE was 24.3%. Therefore, repeat esophago-gastroduodenoscopy (EGD) and ileocolonoscopy should be taken into consideration before DBE. [ABSTRACT FROM AUTHOR]

Background Double-balloon enteroscopy has allowed us not only to inspect deeply the small bowel but also to carry out interventions for diseases of the small bowel. Aim To evaluate the utility of double-balloon enteroscopy for the diagnosis and therapy of these lesions. Methods All patients undergoing double-balloon enteroscopy for evaluation of small bowel polyps and tumours during a 3.75-year period at a university referral hospital were studied. The types of polyps and tumours as well as endoscopic technique of removal, surgery and complications were documented. Results The incidence of small bowel polyps and tumours in-patients undergoing DBE was 9.6%. A total of 40 double-balloon enteroscopy procedures were performed in 29 patients [13 female (44.8%), mean age 51 years, range 22–74]. The following lesions were found most frequently: adenomas in familial adenomatous polyposis syndrome, n = 8; hamartomas, n = 4 (Peutz-Jeghers and Cronkhite Canada syndromes), jejunal adenocarcinoma n = 5, neuroendocrine tumour n = 4 and others n = 6. Conclusions The incidence of small bowel tumours in those in-patients who were undergoing double-balloon enteroscopy was 10%. Double-balloon enteroscopy is useful for the diagnosis and treatment of small bowel polyps and tumours. [ABSTRACT FROM AUTHOR]

For nearly 200 years it has been appreciated that plaque psoriasis consists of a number of distinct clinical phenotypes. However, a reliable and simple stratification of clinical presentation of psoriasis is lacking. In the era of immunogenetic association studies and an advanced understanding of the pathomechanisms of psoriasis it is important that a classification of the disease according to phenotype is readily available. Such a classification would facilitate clinically relevant interpretation of investigational data. A meeting of the International Psoriasis Council produced a consensus on clinical phenotypes of psoriasis equally relevant to clinical practitioners and psoriasis researchers. [ABSTRACT FROM AUTHOR]

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Background Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. Objectives To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. Methods The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n = 64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n = 41). Results The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different ( P = 0·1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) ( P < 0·0001 vs. GG and P < 0·0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) ( P = 0·0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. Conclusions Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined. [ABSTRACT FROM AUTHOR]

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0. The frequency of C4A*Q0 was increased in Icelandic patients with coeliac disease (0·50;P < 0·001), Grave's disease (0·30;P = 0·002) and insulin-dependent diabetes mellitus (0·23;P = 0·04) and in British patients with dermatitis herpetiformis (0·42;P = 0·002) and this was reflected in low levels of C4A. In spite of this, PIP was normal in these patients, and in marked contrast to our previous observations on connective tissue diseases, PIP measurements in these patient groups correlated more strongly with levels of C4B (r = 0·51,P = 0·0000004) than C4A. Patients with increased levels of anti-C1q antibodies had significantly lower PIP than patients without such antibodies (P < 0·01) and a negative association of PIP with anti-C1q antibodies was also reflected in an increased prevalence (P = 0·006) and levels (P = 0·006) of anti-C1q antibodies in patients with subnormal PIP, as well as a negative correlation between PIP and anti-C1q antibodies (r = − 0·25,P = 0·02). These results show that the PIP defect cannot be explained by low levels of C4A alone and suggest that measurements of anti-C1q antibodies may be useful in future studies on the molecular cause of the PIP defect in autoimmune connective tissue disease. [ABSTRACT FROM AUTHOR]

Abstract We have recently described a dermal Th-1 subset in skin lesions of psoriasis which recognizes cell-wall extract isolated from group A streptococci (GAS). As a first step in the identification of the streptococcal proteins involved, dermal T-cell lines (TCL) cultured from the lesional skin of 12 human leucocyte antigen (HLA)-typed psoriasis patients were stimulated with GAS cell-wall extract and 14 fractions (MWt approximately 20–100 kDa) separated from the cell-wall extract by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroelution, stained for intracellular interferon-γ(IFN-γ) expression and analysed by flow cytometry. All the TCL responded to GAS cell-wall extract to varying extents (3.5–27.6% IFN-γ[sup +] ). This response was consistently directed against 20–50 kDa cell-wall fractions and inhibited by anti-HLA-DR antibody. TCL with higher responses to GAS cell-wall extract recognized a larger number of fractions within this range than the lower responder TCL. No difference between the level and pattern of response to the fractions was observed for TCL from HLA-DR7[sup +] (n = 6) and HLA-DR7[sup –] (n = 6) individuals. This preliminary study has shown a selective response to lower MWt proteins expressed on GAS cell wall by skin Th-1 cells in psoriasis. Further studies are required to identify the proteins involved. [ABSTRACT FROM AUTHOR]

Summary Background Toll-like receptors (TLRs) are part of the innate immune system involved in the response to microbial pathogens. TLR2 recognizes various ligands expressed by Gram-positive bacteria, while TLR3, TLR4 and TLR5 are specific for double-stranded RNA, Gram-negative lipopolysaccharides and bacterial flagellin, respectively. Objectives To determine, firstly, whether epidermal keratinocytes of normal skin express TLRs and, secondly, whether modulation of TLR expression occurs in psoriasis, an inflammatory skin disease associated with certain microorganisms such as streptococci, staphylococci and yeasts. Methods Eight samples of normal, and 15 samples of lesional and nonlesional psoriatic skin were stained with polyclonal antibodies specific for TLR1-5 using an avidin–biotin–peroxidase technique. Results Epidermal keratinocytes in normal skin constitutively expressed TLR1, TLR2 and TLR5, while TLR3 and TLR4 were, in most cases, barely detectable. Cytoplasmic TLR1 and TLR2 were expressed throughout the epidermis, with higher staining of the latter on basal keratinocytes, while TLR5 expression was concentrated in the basal layer. In contrast, in lesional epidermis from patients with psoriasis, TLR2 was more highly expressed on the keratinocytes of the upper epidermis than on the basal layer, while TLR5 was downregulated in basal keratinocytes compared with corresponding nonlesional psoriatic epidermis. In addition, nuclear TLR1 staining was observed in the upper layers of both nonlesional and lesional psoriatic epidermis, but not in that of normal skin. Conclusions These findings suggest that TLRs expressed by epidermal keratinocytes constitute part of the innate immune system of the skin. The relevance of altered keratinocyte TLR expression in psoriasis remains to be determined. [ABSTRACT FROM AUTHOR]

Abstract: Chronic plaque psoriasis is a T cell mediated disease associated with group A streptococci (GAS). We have previously shown the presence of a psoriasis-specific dermal Th1 subset that recognizes GAS antigens. To assess whether GAS-reactive T cells are also present in lesional epidermis, fresh cell suspensions or T cell lines isolated from lesional epidermis of 33 psoriasis patients were stained for intracellular interferon-γ after stimulation with GAS antigens. The patients were typed by PCR for HLA-DR7 and HLA-Cw6 expression. A subset of GAS-reactive CD8+ T cells (2.4% ± 2.4) was found in 14/21 (67%) fresh cell suspensions. A smaller subset of GAS-reactive CD4+ T cells (0.9% ± 0.9) was found in 13/21 (62%) fresh cell suspensions, which was expanded in the T cell lines. There was a significant inverse correlation between the proportions of GAS-reactive CD4+ and CD8+ T cells in the fresh suspensions (r = -0.48, P = 0.0277). The presence of GAS-reactive CD4+ or CD8+ T cells did not correlate with HLA-DR7 or HLA-Cw6 expression, respectively. This study has demonstrated GAS-reactive CD8+, and to a lesser extent CD4+, T cell subsets in psoriatic epidermis and provides further evidence that GAS antigens may play a role in the pathogenesis of chronic plaque psoriasis. [ABSTRACT FROM AUTHOR]

To determine and compare the T cell response to M protein and other group A streptococcal (GAS) antigens, T cell lines (TCL) were cultured from the lesional skin of 33 psoriatic patients and 17 disease controls. GAS-reactive skin TCL were tested in proliferation assays with recombinant M6 protein, and extracts of cell wall and membrane from type M6 GAS and its corresponding M gene deletion mutant. Initially, GAS-reactive skin TCL were obtained from 16 of 25 (64%) psoriasis, and from seven of 17 (41%) control patients. Eleven psoriatic and four control GAS-reactive TCL proliferated to M6 cell wall extract, whereas all the TCL from both groups responded to the extract of M6 membrane proteins. This difference in response to the two extracts was significant for both groups of patients (psoriasis, P = 0·0335, controls, P = 0·0156). GAS-reactive TCL from a further eight psoriasis patients showed no difference in response to cell wall extract from M6 GAS (containing the M protein minus its C-terminus) compared to that of its corresponding M gene deletion mutant. Furthermore, GAS-reactive TCL did not proliferate to recombinant M6 protein. However, a small, but significant reduction in proliferation by the eight psoriatic GAS-reactive TCL to the M-negative (lacking the M protein C-terminus) compared to M6-positive membrane extract was observed (P = 0·01). These findings suggest that GAS-reactive T cells in skin lesions of chronic plaque psoriasis proliferate to streptococcal membrane and, to a lesser extent, cell wall proteins. However, psoriatic skin T cells do not recognize cell wall M protein. [ABSTRACT FROM AUTHOR]

Abstract: The majority of epidermal CD8+ T cells in chronic plaque psoriasis are activated Tc1 cells producing interferon-γ and no interleukin-4, a small proportion of which express NK-T receptors. To quantitate their level of cytokine production and characterize them further, CD8+ T cells were isolated from epidermal cell suspensions of lesional biopsies from 24 patients with chronic plaque psoriasis. T-cell lines (TCL) were established by culture of CD8+ T cells with feeders and IL-2 for 11 days and expansion with PHA. Ten TCL were stained for surface markers; 6 were cloned with PHA by limiting dilution. Interferon-γ, interleukin-4 and interleukin-10 production was measured by ELISA after PMA/anti-CD3 activation of 15 TCL and 39 CD8+ T-cell clones. The 10 TCL stained were CD8αβ+ (93.3%), T-cell receptor-αβ+ (99.5%), costimulatory molecule CD28+ (90.1%), with a small CD8αα+ population (2.3%). No NK-T-cell receptor CD158a or CD158b expression was detected, whilst CD94 was expressed on 6.2% of cells in 6/9 TCL. All the TCL and 37/39 CD8+ T-cell clones produced interferon-γ but no or minimal interleukin-4 or interleukin-10. The TCL produced a wide range of interferon-γ levels (138 to 15,020 pg/ml). Clones from 3 patients showed low levels (60 to 1,410 pg/ml), from 2 patients high levels (6,105 to 43,040 pg/ml) and from 1 patient a wide range (405 to 36,010 pg/ml) of interferon-γ production. Thus epidermal CD8+ Tc1 cells in chronic plaque psoriasis produce highly heterogeneous levels of interferon-γ, which may reflect clinical diversity. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the OH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with OH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that OH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin. [ABSTRACT FROM AUTHOR]

To determine whether psoriatic keratinocytes differ from normal keratinocytes in their response to gamma interferon, epidermal cell suspensions from normal and from lesional and uninvolved psoriatic skin were cultured in the presence of gamma interferon and the induction of HLA-DR expression and inhibition of cell growth were measured. The addition of 102 units of gamma interferon/ml during a 7-day culture period significantly increased mean HLA-DR+ cell numbers in 21 epidermal suspensions of normal from 3.9 to 24.1% (P<0.0001), uninvolved psoriatic from 8.4 to 33.1% (P<0.0001), and to a lesser extent lesional psoriatic biopsies from 12.6 to 18.3% (P<0.01). However, the increase in HLA-DR+ cell numbers in these latter cultures was significantly less than that observed in either normal or uninvolved psoriatic epidermal cell cultures (P<0.0001). Furthermore, [3H]thymidine incorporation was substan- tially decreased by gamma interferon in 16 out of 22 (73%) cultures of normal epidermal cells; this decrease was statistically significant (P<0.01). In contrast, only 4 out of 11 (36%) lesional and 9 out of 21 (43%) uninvolved psoriatic epidermal cultures showed comparable inhibition of proliferation. These findings suggest that psoriatic keratinocytes have an altered response to gamma interferon: this could explain the infrequency of keratinocyte HLA-DR expression in psoriatic plaques in vivo and may also contribute to the increased epidermal proliferation that characterizes this disease. [ABSTRACT FROM AUTHOR]

We describe the effects of treatment with topical steroids or dithranol on T and dendritic cells in the skin of patients with chronic plaque psoriasis. Resolution of lesions by both types of topical treatments was accompanied by a marked decrease in epidermal T cells. In steroid treated lesions there was also a reduction in DR+ dendritic cells to normal numbers during treatment and the rate of disappearance of both cell types correlated with the rate of resolution. However, a significant reduction of dendritic cells was not usually observed until after the T ceils had almost disappeared from the epidermis and substantial healing of lesions had taken place. Dendritic cells in steroid-treated uninvolved skin had decreased to a lower level than in normal skin. In contrast, dithranol did not affect dendritic cell, either in lesional or in unaffected psoriatic epidermis. The decrease in dermal T cells observed with both treatments was more marked in steroid-treated lesions and correlated with resolution. However, blood T cells were unaffected by both treatments. The findings provide further support for the role of T cells in the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

We describe a patient with AIDS who developed a cutaneous nodule of the face from a localized nontuberculous mycobacterial infection. [ABSTRACT FROM AUTHOR]

Thirteen patients with severe persistent psoriasis, intolerant of, or unresponsive to, other current treatments have been treated with cyclosporin (Cys) for periods varying from 12–25 (mean 18) months. The dose ranged from 1–4 mg/kg/day (mean 2.8 mg). There was a 72% reduction in the mean PASI score at 4 weeks, and at the end of the study, an 81% reduction. Adjuvant therapy with topical steroids was used in 11 of the 13 patients after the first 3 months of Cys treatment to persistent patches on an intermittent basis with beneficial effect. Six patients developed mild to moderate hypertension, in three this was controlled by a reduction in the dose of Cys, and in the other three by hypotensive agents. The mean serum creatinine rose from 72 to 90 μm/1 during the study. Hypertrichosis occurred in seven of the 13 patients. Low dosage Cys is an effective treatment for clearing psoriasis and maintaining improvement on a long-term basis. [ABSTRACT FROM AUTHOR]

On each of 10 patients with untreated plaque psoriasis, two symmetrical plaques were injected with cyclosporin A or placebo on six occasions over 12 days, in a double-blind manner. Biopsies taken from these lesions at 14 days were examined for differences in cellular composition using a double-labelling immunofluorescent technique. The cyclosporin-injected plaques cleared significantly better than those injected with placebo (P < 0.001). In the epidermis of the cyclosporin-injected plaques, total and HLA-DR+ CD4+ and CD8 + T cell numbers were significantly decreased compared to corresponding plaques treated with placebo (total CD4+, total CD8+, DR+ CD4+, P < 0.01; DR+ CD8+, P < 0.02). Similarly, T lymphocyte numbers in the dermis were decreased in the cyclosporin compared to placebo-treated plaques; the reduction in total CD4+ and DR+ CD8+ T cell numbers was statistically significant (P < 0.05). Although total numbers of epidermal dendritic cells were not significantly altered, the DR + CD1 - dendritic cell subpopulation was markedly decreased (P < 0.01) and DR-CD1 + dendritic cells increased (P < 0.05) in the plaques injected with cyclosporin compared to corresponding placebo-treated plaques. These findings show that cyclosporin injected in situ is effective in clearing psoriasis and probably exerts this beneficial effect by its action on T lymphocytes. A suitable topical preparation that allows penetration of the drug should prove helpful in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Provides information about psoriasis based from the scientists in Great Britain. Types of diseases associated with psoriasis; Symptoms of the disease; Factors contributing the epidemiology of psoriasis.

The prevalence of IgG class thyroglobulin and microsomal antibodies, estimated using a sensitive ELISA, was 48% in 115 patients with dermatitis herpetiformis, which was significantly greater than the prevalence of 16% in 107 unselected controls without dermatitis herpetiformis. IgA class thyroid antibodies were found in 29% of dermatitis herpetiformis patients. Overt thyroid disease had been diagnosed in six (5%) of the dermatitis herpetiformis group and a further six patients had elevated TSH levels. the presence of thyroid antibodies was not associated with particular HLA-DR antigens. These results demonstrate the frequent occurrence of thyroid antibodies in dermatitis herpetiformis, although thyroid failure is less commonly associated with this condition. Immune response genes outside the HLA-DR region may be involved in the immune hyper-responsiveness seen in dermatitis herpetiformis which is reflected in the high prevalence of thyroid autoimmunity. [ABSTRACT FROM AUTHOR]