摘要:

SummaryThe Dundee experimental bald rat (DEBR) undergoes hair loss associated with perifollicular infiltrates of mononuclear cells (MNC), a pathological characteristic of human alopecia areata (AA). To investigate further the pathogenesis of the disease in this animal model, we have studied the development, composition and extent of the perifollicular MNC infiltration in young (6‐week‐old), prelesional (3‐month‐old), active lesional, and established lesional DEBR rats, using 6‐week‐ and 6‐month‐old Wistar rats as normal controls. The proportions of hair follicles showing infiltration by MNC and their main subsets were determined using immunohistochemical staining of serial cryostat sections of flank skin biopsies.There was a good correlation between the degree of leucocyte (OX‐1+) infiltration of anagen hair follicles and the development of hair loss. In 6‐week‐old DEBR skin, there were few perifollicular cells expressing MHC class II, with positively stained dendritic cells in the dermis above the sebaceous gland. There was a sparse perifollicular distribution of CD4+cells (W3/25) and macrophages (ED‐1+). No CD8+cells (OX‐8+) were seen associated with DEBR hair follicles, and only small numbers were present in Wistar rats.In prelesional DEBR rats there was an increased perifollicular presence of MHC class II+cells, macrophages, and particularly of CD8+cells, with little change in CD4+cells. Active and established lesional rats, i.e. animals with overt loss of hair, showed a significant increase in the degree of MNC infiltration and the proportion of infiltrated follicles, the majority of which were in dystrophic anagen. In the perifollicular infiltrate the CD4+:CD8+ratio was approximately 2:1. An intrafollicular infiltrate was prominent, and was composed of CD8+cells and macrophages, with bulbar and suprabulbar keratinocytes expressing MHC class II antigens. CD4+cells were not detected in follicular epithelium. ICAM‐1 expression correlated with MNC infiltration. These results show marked similarities to lesional human AA. They also focus on a possible active role for CD8+cells in the pathogenesis o

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03371.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryWe have used both pulse‐chase radiolabelling and morphometric techniques to investigate the ability of whole‐organ cultures of human hair follicles to synthesize hair fibre. Anagen hair follicles were obtained from human facial skin by microdissection. Follicles were pulse‐labelled with3H‐leucine, and radioactivity in alkali‐soluble protein (ASP) and alkali‐insoluble hair fibre protein (HFP) fractions was determined by differential extraction. There was a slow decline in ASP radioactivity over 7 days of culture, with a half‐life of 4 days. In contrast, leucine incorporation into HFP increased linearly from day 1 to day 5, following an initial delay of 17 h. Morphometric analysis revealed that hair follicles and hair fibres grew at the same rate (0.25 mm/day) for 4 days in culture, after which the rate of hair follicle growth declined progressively, whereas fibre growth continued at the initial rate for a further 3 days. Concurrent with the onset of the decline in follicle growth, the base of the hair fibre began to descend towards the follicle base, until hair fibre occupied almost the full length of the hair follicle at day 15. The decline in follicle growth was preceded by a decline in the rate of follicular3H‐thymidine incorporation, with a delay of approximately 1 day. Overall, these data demonstrate that human hair follicles in whole‐organ culture are capable of the production of hair fibre, and suggest that cessation of hair growthin vitroresults from depletion of the pool of differentiated follicular keratinocytes. secondary to a loss of matrix cell proli

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03372.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary1,25‐Dihydroxyvitamin D3(1,25(OH)2D3: calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)2D3, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T‐cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)2D3and calcipotriol on the human allogeneic mixed epidermal cell‐lymphocyte reaction. All experiments were performed both with 1,25(OH)2D3, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)2D3resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC‐depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle‐treated LC. These calcitriol‐pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected. LC‐depleted keratinocytes failed to stimulate allogeneic lymphocytes. When added to autologous unmodified EC, however, calcitriol‐pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle‐treated keratinocytes. The phenotypic expression of HLA‐DR, ‐DQ, and ‐DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2‐h or 24‐h pulse with 1,25(OH)2D3or calcipotriol. The inhibitory effect of vitamin D compounds on EC was not modified by indomethacin, but was partially reversed by the addition of anti‐TGF‐β neutralizing antibodies.In conclusion, 1,25(OH)2D3and calcipotriol may limit the immune response in human skin through decreased antigen presentation, mediated both by a direct effect on LC and indirectly through modulation of the producti

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03373.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryAlthough myoepithelial cells are detectable in many benign sweat gland tumours, little is known about their role in sweat gland carcinomas. To specifically demonstrate myoepithelial cells, paraffin sections from 46 sweat gland carcinomas were stained, using a standard avidin‐biotin‐peroxidase complex method, with the monoclonal α‐smooth muscle actin antibody 1A4. Myoepithelial cells were not found in adenoid cystic eccrine carcinoma (n=2), malignant nodular hidradenoma(n=2), porocarcinoma (n=4), extramammary Paget's disease (n= 12), sclerosing sweat duct carcinoma (n=4) or in adenosquamous mucoepidermoid carcinoma (n=l). In contrast, myoepithelial cells were demonstrated in two of eight apocrine adenocarcinomas, one of six mucinous eccrine carcinomas and two of seven eccrine adenocarcinomas. In all these tumours myoepithelial differentiation was found in peripheral cells of solid tumour islands, or in basal cells of tubular structures. However, in most areas of the tumours, myoepithelial layers were discontinuous. Cells in the centre of solid tumour nodules, and luminal cells of tubular structures, were negative for α‐smooth muscle actin. In analogy to breast tumours, in which malignancy and invasiveness correlate with scattered or absent myoepithelial cells, we suggest that disrupted myoepithelial layers in sweat gland carcinomas may be interpreted as a loss of the invasio

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03374.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOrf is a disease of sheep and goats which is caused by a parapox virus. It can be transmitted to human.s, and is considered an occupational hazard by those handling sheep. In this paper we present the first report of both cell‐mediated and humoral immune responses to naturally acquired orf virus infection in humans.Lymphoproliferative responses of peripheral blood mononuclear cells of patients to an orf virus antigen were vigorous soon after infection, but rapidly declined. Orf virus antibody levels, detected by KLISA, were shown to rise during infection. Western blot analysis confirmed this, and demonstrated that the antibody produced in response to the infection was directed against the 40‐kDa viral surface tubule protein. Where direct comparisons were possible, the immune response of humans to orf virus infection was similar to that previously reported for sheep.Evidence was obtained suggesting that prior exposure to vaccinia virus (smallpox vaccination) provided no protection from subsequent orf virus infection. In addition, orf virus infection did not enhance immune responses to vaccinia virus antig

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03375.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummarySpecimens of hypertrophic scar tissue (n= 9). non‐hypertrophic, flat scar tissue (n= 5) and control skin (n= 3) were obtained from eight adult females (aged 22–56) and three adult males (aged 22–59). The specimens were studied histologically and immunohistochemically for vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene‐related peptide, substance P, somatostatin, [Met]enkephalin, [Leu]enkephalin, and the enzyme dopamineβ‐hydroxylase. The non‐hypertrophic scar tissues were not dissimilar to the control tissue, but contained connective tissue in bundles with a greater number of collagen fibres. In the hypertrophic scar tissue of some patients, the dermis contained adipose tissue displaced upwards from the hypodermis. The connective tissue contained densely packed collagen fibres and fibroblasts; this region was devoid of hair follicles, sweat glands and blood vessels, although they were observed in the region of loosely packed connective tissue.The normal skin contained all the neuropeptides studied, except somatostatin‐, and dopamine β‐hydroxylase‐immunoreactive nerves, which were seen as single fibres or in nerve bundles, and were associated with blood vessels in the dermis. Neuropeptide Y‐immunoreactive nerves were found in the arrector pili muscle, and neuropeptide Y‐, vasoactive intestinal polypeptide‐, calcitonin gene‐related peptide‐, [Met]enkephalin‐ and dopamineβ‐hydroxylase‐containing nerves were found within sweat glands. In patients with flat, non‐hypertrophic scar tissue, neuropeptides and dopamine β‐ hydroxylase‐containing nerves were absent. In patients with hypertrophic scars, the density of neuropeptide Y‐, vasoactive intestinal polypeptide‐, substance P‐, calcitonin gene‐related peptide‐ and dopamineβ‐hydroxylase‐immunoreactive nerves was greater in the dermis when compared with controls. They were found at the base of the epidermis, around blood vessels, and in sweat and sebaceous glands. Only substance P‐immunoreactive nerves penetrated the densely packed collagen and fibroblast matrix, whereas neuropeptide Y‐, calcitonin gene‐related peptide‐, vasoactive intestinal polypeptide‐ and dopamineβ‐hydroxylase‐containing nerves were found in the loosely packed connective tissue. [Met]enkephalin‐, [Leu]enkephalin‐ and somatostatin‐immunoreactive nerves were rarely seen in all three groups of patients.In conclusion, neuropeptide‐containing nerves appear to be present in patients with painful, hypersensi

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03376.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryThe expression of type I, III and VI collagens was studied in nine normal and two hypertrophic scars using slot‐blot andin situhybridization techniques. Slot‐blot hybridization indicated that the steady‐state levels of proα 1(I) and proα 1(III) collagen chain mRNAs were moderately elevated in two of the nine normal scars, whereas the two hypertrophic scars analysed displayed markedly elevated mRNA levels when compared with normal skin. The mRNA levels of α2(VI) collagen chain were only slightly elevated in both types of scars studied.In situhybridization was most informative when applied to hypertrophic scars. These lesions were characterized by the presence of intense hybridization signals for type I and III collagen mRNAs, and a moderate signal for type VI collagen mRNA, in nodules which were located in the upper dermis on each side of the original wound. This may explain, in part, why hypertrophic scars rise above the level of the surrounding skin. The results of the present study are in marked contrast to our previous findings on collagen gene expression in keloids and neurofibromas, in which the steady‐state levels of type VI and I collagen mRNAs in particular were shown to be elevated. Thus, our results emphasize that distinct molecular mechanisms are operative in the development of clinically different dermal fibrotic conditions, such as normal and hypertrophic scars, keloids and neu

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03377.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryIn vivoepiluminescence microscopy (ELM) is a non‐invasive technique which improves the clinical diagnosis of naevi and malignant melanoma by providing diagnostic criteria that cannot be appreciated by the naked eye. The present study investigated whether ELM criteria pattern analysis can be employed in an objective, observer‐trained, computer‐aided diagnostic system, and whether artificial neural networks (ANN) can be applied to the diagnosis of pigmented skin lesions (PSL).The ELM criteria patterns of 200 PSL oil immersion images (60 common naevi, 60 dysplastic naevi, and 80 malignant melanomas) were analysed using a standardized questionnaire. One hundred randomly assigned PSL were used as a training set for an ANN, the remaining 100 PSL serving as the test set. The ANN was trained by backward propagation according to the histological diagnosis, and its performance was compared with that of human investigators.Out of the test set the human investigators correctly diagnosed 88% of PSL and the ANN 86%. in a dichotomized model comparing common, compound, and dysplastic naevi vs. malignant melanoma, i.e. benign vs. malignant PSL, the sensitivity and specificity of human diagnosis was 95 and 90%, respectively, whereas the sensitivity and specificity of the ANN diagnosis was 95 and 88%.Our data indicate that artificial neural networks can be trained to diagnose PSL at a human expert level, based on patterns provided by ELM criteria. We suggest that this technique offers a new approach to the diagnosis o

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03378.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryRegional variations in the clinical spectrum of Lyme borreliosis have been described previously. These may be related to strain variations, or reflect selection bias. We compared the clinical and epidemiological profiles of Dutch patients presenting with solitary erythema migrans alone, with the profiles in other European studies, and studies from the U.S.A., and culturedBorrelia burgdorferifrom erythema migrans to identify the genospecies.Seventy‐seven consecutive patients with a final diagnosis of erythema migrans were admitted into the study. Various clinical and epidemiological data were obtained, and serum was evaluated for antibodies toBorrelia burgdorferiwith an enzyme‐linked immunosorbent assay. Skin biopsy specimens were taken from the border of the erythema migrans and cultured in modified Kelly's medium. The different genospecies ofBorrelia burgdorferiwere identified by reactivity with monoclonal antibodies H3TS, LA‐26, LA‐31 and D6, and by rRNA gene restriction patterns. Patients were treated with tetracycline or doxycycline, and were seen for follow‐up 6 weeks after treatment, Long‐term follow‐up was by telephone interview.A tick bite had been noticed by 45% of the patients. The onset of erythema migrans occurred in 97% of these patients within 3 months of the tick bite. Erythema migrans was present for 1–319 days (median 2 months). No concomitant manifestations were spontaneously reported.Borrelia burgdorferiwas cultured from 52 (84%) of 62 skin biopsy specimens. Fifty isolates (96%) were identified asBorrelia burgdorferigroup VS461. No therapy failures occurred among patients treated with tetracycline (follow‐up 1–4 years, median 27 months) or doxycycline (follow‐up 6–31 months, median 19 months).The clinical and epidemiological profile of Dutch patients with erythema migrans alone did not differ from that reported in other European studies. The predominant organism isolated from erythema migrans lesions wasBorrelia burgdorferigroup VS461. Multiple skin lesions and concomitant clinical manifestations appear to be more frequent in patients in the U.S.A. However, selection bias cannot be excluded. At present,Borrelia burgdorferi sensu strictois the only genospecies identified in the U.S.A. Hence, regional variations in the clinical spectrum of Lyme borreliosis may be the result o

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03379.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryPossible risk factors for psoriasis were studied among women aged 18–50 years. The series consisted of 55 consecutive psoriatic patients and 108 unmatched controls with other skin diseases, from the university departments of dermatology in Helsinki, Oulu and Tampere. A questionnaire focused on two specified periods of time, 12 months before the onset of the skin disease and 12 months before the examination date. Before the onset of the skin disease, the recalled mean number of cigarettes smoked daily was 8.6 (1.2 SE) for psoriatics and 4.7 (0.7) for controls (P=0.004). The respective alcohol intake figures (mean±SE) were 8.0 (2.2) and 4.7 (0.8) g/day (P= 0.17). In logistic regression analysis, psoriasis was associated significantly with smoking, but not with alcohol intake, marital status or social group. The odds ratio for psoriasis for those smoking 20 cigarettes daily compared with non‐smokers was 3.3 (95% confidence limits 1.4‐7.9). The odds ratio for psoriasis at an alcohol intake of 20 g/day compared with no intake was 1.8 (1.0–3.3). After the onset of the disease, psoriasis was associated significantly with alcohol intake, smoking, and the occurrence of negative life events. Among psoriatics, skin surface involvement was significantly associated with alcohol intake (P= 0.04), but not with smoking or negative life events. These results suggest that smoking is a risk factor for psoriasis in women, and that alcohol intake worsens their psoriasis. Smoking and negative life events were more common among psoriasis patients than among controls, perhaps as consequences of the

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1994.tb03380.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY