C5a receptor and interleukin-6 are expressed in tissue macrophages and stimulated keratinocytes but not in pulmonary and intestinal epithelial cells.
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The anaphylatoxin derived from the fifth component of the human complement system (C5a) mediates its effects by binding to a single high-affinity receptor (C5aR/CD88), the expression of which has been traditionally thought to be restricted to granulocytes, monocytes, macrophages (Mphi), and cell lines of myeloid origin. Recent immunohistochemical data suggested that human bronchial and alveolar cells express C5aR as well. To reexamine the tissue distribution of human C5aR expression, transcription of the C5aR gene was investigated in normal and pathologically affected human lung (bronchopneumonia, tuberculosis), large intestine (acute appendicitis, Crohn's disease), and skin (pyogenic granuloma, lichen planus) using in situ hybridization. In contrast to previous evidence, C5aR mRNA could not be detected in pulmonary or intestinal epithelial cells, whereas keratinocytes in inflamed but not in normal skin revealed detectable levels of C5aR transcripts. Additionally, it could be documented that only migrating Mphi express C5aR mRNA, whereas sessile Mphi in normal tissues and epithelioid/multinucleated Mphi found in granulomatous lesions do not. Because C5a has been demonstrated to upregulate the expression of interleukin (IL)-6 in human monocytes, we also studied IL-6 gene transcription in parallel to the C5aR. IL-6 mRNA was detectable in many tissue Mphi. Surprisingly, a tight co-expression of C5aR and IL-6 mRNA was observed in keratinocytes from lesions of pyogenic granuloma and lichen planus. These results point to an as yet unknown role for C5a in the pathogenesis of skin disorders beyond its well-defined function as a chemoattractant and activator of leukocytes. (+info)
Analysis of Chinese herbal creams prescribed for dermatological conditions.
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OBJECTIVE: To determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids. DESIGN: 11 herbal creams obtained from patients attending general and paediatric dermatology outpatient clinics were analysed with high resolution gas chromatography and mass spectrometry. SETTING: Departments of dermatology and clinical biochemistry. MAIN OUTCOME MEASURE: Presence of steroid. RESULTS: Eight creams contained dexamethasone at a mean concentration of 456 micrograms/g (range 64 to 1500 micrograms/g). All were applied to areas of sensitive skin such as face and flexures. CONCLUSION: Greater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids. (+info)
Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder.
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BACKGROUND: The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency characterized by recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum. Associated facial and skeletal features have been recognized, but their frequency is unknown, and the genetic basis of the hyper-IgE syndrome is poorly understood. METHODS: We studied 30 patients with the hyper-IgE syndrome and 70 of their relatives. We took histories, reviewed records, performed physical and dental examinations, took anthropometric measurements, and conducted laboratory studies. RESULTS: Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than eight years. Seventy-two percent had the previously unrecognized feature of failure or delay of shedding of the primary teeth owing to lack of root resorption. Common findings among patients were recurrent fractures (in 57 percent of patients), hyperextensible joints (in 68 percent), and scoliosis (in 76 percent of patients 16 years of age or older). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77 percent of all patients and in 85 percent of those older than eight. In 6 of 23 adults (26 percent), IgE levels declined over time and came closer to or fell within the normal range. Autosomal dominant transmission of the hyper-IgE syndrome was found, but with variable expressivity. Of the 27 relatives at risk for inheriting the hyper-IgE syndrome, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunologic, dental, and skeletal features of the hyper-IgE syndrome. CONCLUSIONS: The hyper-IgE syndrome is a multisystem disorder that affects the dentition, the skeleton, connective tissue, and the immune system. It is inherited as a single-locus autosomal dominant trait with variable expressivity. (+info)
Epidemiology and prevention of group A streptococcal infections: acute respiratory tract infections, skin infections, and their sequelae at the close of the twentieth century.
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Infections of the upper respiratory tract and skin due to group A Streptococcus are common, and the organism is highly transmissible. In industrialized countries and to some extent in developing countries, control efforts continue to emphasize that group A streptococcal pharyngitis should be properly diagnosed and appropriately treated. In developing countries and in indigenous populations where the burden of group A streptococcal diseases appears greatest, the epidemiology is less completely defined and may differ from that in industrialized countries. There is a need for accurately collected epidemiological data from developing countries, which may also further clarify the pathogenesis of group A streptococcal infections and their sequelae. While proper treatment of group A streptococcal pharyngitis continues to be essential in all populations, it may be appropriate in developing countries to consider additional strategies to reduce rates of pyoderma. (+info)
Delayed osteon formation in long-bone diaphysis of an 11-year-old giant cow with dermal dysplasia.
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The transverse sections of radius diaphysis in an 11-year-old giant Holstein cow with dermal dysplasia of a collagen disorder-related skin fragility (Cow 1), probably based on increasing turnover of the dermal collagen as reported previously, were morphologically and physico-chemically investigated. Cow 1 had about one and a half times as much as the body weight of normal Holstein cows, aged 5 to 6.5 years with stabilized growth. The bone samples were compared with those of a 12-year-old Holstein cow as controls (Cow 2). It has been reported that the long-bone diaphysis of young calves and some herbivorous dinosaurs are occupied with laminar bone showing a concentric appositional formation, and that such a laminar bone is characteristically seen during the growing period of some farm animals and large dogs that show very rapid growth rates. Cow 1 had a smaller number of osteons than Cow 2 in the outer-half layer of the diaphysis, and showed an intermediate type between Cow 2 and a 1-year-old Holstein ox in the entire layers, although their bone volumes were similar among them. There were no significant differences in Ca and P concentrations and the Vickers microhardness values between the bone matrix of Cow 1 and Cow 2. The bone-collagen fibrils of Cow 1 showed uneven diameters and a disordered arrangement. Thus, there may be some relation in collagen formation between the bone matrix of Cow 1 and the dermis. From the remaining volume of laminar bone, Cow 1, aged 11 years, had probably shown growth until quite recently, so that we consider that Cow 1 became a giant animal, in the same way as some herbivorous dinosaurs. (+info)
Depletion of cutaneous peptidergic innervation in HIV-associated xerosis.
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Severe xerosis occurs in approximately 20% of human immunodeficiency virus seropositive patients. Changes in cutaneous innervation have been found in various inflammatory skin diseases and in xerotic skin in familial amyloid. We have therefore carried out a quantitative examination of the cutaneous peptidergic innervation in human immunodeficiency virus-associated xerosis. Immunohistochemistry and image analysis quantitation were used to compare total cutaneous innervation (protein gene product 9.5), calcitonin gene-related peptide, substance P, and vasoactive intestinal peptide peptidergic fibers, at two sites in the skin of human immunodeficiency virus-associated xerosis patients (upper arm, n = 12; upper leg, n = 11) and site-matched seronegative controls (upper arm, n = 10; upper leg, n = 10). Measurement of lengths of fibers of each type was carried out for each subject in the epidermis and papillary dermis, and around the sweat glands. Immunostained mast cells in these areas were counted. Epidermal integrity and maturation were assessed by immunostaining for involucrin. There were significant (Mann-Whitney U test; p < 0.02) decreases in total lengths of protein gene product 9.5 fibers in both epidermis/papillary dermis and sweat gland fields; of calcitonin gene-related peptide innervation in the epidermis/papillary dermis; and of substance P innervation of the sweat glands. There were no differences in the distribution of mast cells, or in the epidermal expression of involucrin. Depletion of the calcitonin gene-related peptide innervation may affect the nutrient blood supply of the upper dermis, and the integrity and function of basal epidermis and Langerhans cells. Diminished substance P innervation of the sweat glands may affect their secretory activity. Both of these changes may be implicated in the development of xerosis. (+info)
Faecal composition after surgery for Hirschsprung's disease.
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Diarrhoea and perianal excoriation occur frequently after the endorectal pull-through operation for Hirschsprung's disease. A new method of faecal analysis was performed on 3-day stool collections in 17 postoperative Hirschsprung patients and in 14 normal children, in order to define the faecal abnormality and to establish the cause of perianal excoriation in these patients. Loose stools in postoperative patients were deficient in dry solid content and contained an excess of extractable faecal water. This also had a raised electrolyte concentration, particularly with respect to sodium. Total daily output of faecal water was normal. Formed stools from postoperative patients were also deficient in drysolids but had a normal extractable water content. Excess extractable faecal water, the main abnormality of loose stools in these patients, is the result of abnormal water absorption from the distal colon. Perianal excoriation in these patients is most closely associated with the concentration of sodium in faecal water. (+info)
Inflammatory pseudotumor in a cat with cutaneous mycobacteriosis.
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A 5-year-old, castrated male, domestic Shorthair Cat had an ulcerated mass with fistulous tracts on the left hind paw. Homogeneous tan tissue diffusely infiltrated the dermis and subcutis of the paw and extended proximally so that, short of amputation, complete excision was not feasible. Biopsy specimens consisted of granulation tissue with marked proliferation of spindle cells. Neutrophils and histiocytic cells were scattered among the spindle cells. The histiocytic cells had abundant foamy or vacuolated cytoplasm, but features of granulomatous inflammation, such as epithelioid macrophages or granuloma formation, were not observed. The initial impression was inflammatory granulation tissue, but the degree of fibroplasia prompted inclusion of fibrosarcoma in the differential diagnosis. Cutaneous mycobacteriosis was diagnosed when numerous acid-fast bacteria were identified with Kinyoun's stain; Mycobacterium avium was subsequently cultured. The cat was euthanatized because of lack of response to enrofloxacin therapy. At necropsy, lesions were localized to the hind limb. Not only is mycobacteriosis an uncommon cause of cutaneous masses in cats, but this case was unusual because of the lack of granuloma formation and the similarity of the mass to a spindle cell tumor. (+info)