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1.
N Tesavibul D Dorfman VS Sangwan W Christen Z Panayotis B Rojas CS Foster 《Canadian Metallurgical Quarterly》1998,39(6):982-988
PURPOSE: To examine normal and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and its ligands B7-1 (CD80) and B7-2 (CD86). METHODS: Conjunctival biopsy specimens from 12 patients with OCP and from five healthy persons undergoing cataract surgery were analyzed by light microscopy and immunohistochemical examination with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for mononuclear cell subtypes. RESULTS: Epithelium of OCP conjunctiva showed more Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2-positive cells to antigen-presenting cells). In the substantia propria, OCP specimens showed significantly increased numbers of T cells (CD3 +), macrophages (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+ cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were located subepithelially. B7-2 expression was significantly higher in OCP conjunctival substantia propria compared with normal conjunctiva. CONCLUSIONS: The results of this study indicate that the expression of the costimulatory molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This increased subepithelial B7-2 expression may contribute to the sustained immune activation in OCP conjunctiva. 相似文献
2.
Trichiasis is a common and potentially sight threatening complication of ocular cicatricial pemphigoid and is usually secondary to cicatricial entropion. This study aimed to assess the success and complications of eyelid cryotherapy for trichiasis in a group of patients with long term follow up. The case records of all patients with ocular cicatricial pemphigoid that attended the external disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each eyelid was divided into three horizontal zones. Cryotherapy was delivered with an Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was defined as a regrowth of the eyelashes within the treated zone that either required epilation for symptom control or caused keratopathy. Ninety two lid zones were treated, involving 25 lids of 12 patients. The cumulative chance of success decreased rapidly to 40% over the first year. Thereafter, the chance of success declined slowly to 34% at 4 years. Complications included lid notching (n = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised intraocular pressure (n = 1). All patients had quiescent disease at the time of the cryotherapy and no patients showed increased conjunctival disease activity after treatment. Six patients were taking systemic immunosuppression medication. When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an acceptable complication rate. The major reason for recurrence of the trichiasis was attributed to inadequate follicle freezing. 相似文献
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G Kirtschig 《Canadian Metallurgical Quarterly》1998,49(11):818-825
Cicatrical pemphigoid (CP) comprises a group of patients with a chronic subepidermal blistering disease which primarily involves mucous membranes; lesions characteristically heal with scarring. Immunofluorescence investigations typically demonstrate deposits of tissue bound and circulating immunoreactants of the IgG and less frequently of the IgA class in a linear pattern along the basement membrane zone. These autoantibodies are thought to play an important role in the blister formation of CP. Most patients show binding to the bullous pemphigoid antigen 2 (BPag2), collagen type XVII, with a molecular-weight of 180 kD. A smaller group of patients with CP have autoantibodies to laminin 5. Animal models confirm that autoantibodies binding to these two adhesion molecules (BPag2 and laminin 5) are important in blister formation. There are other autoantigens described in CP; however, they are only found in small groups of CP patients and most of them are not further characterised. The described molecules are part of the hemidesmosomal adhesion complex. Impaired function of any component of this complex may lead to a separation of the epidermis from the dermis; better knowledge about the single molecules and the exact localisation of epitopes within these molecules may lead to further understanding of the clinical picture. 相似文献
4.
LS Chan AA Majmudar HH Tran F Meier G Schaumburg-Lever M Chen G Anhalt DT Woodley MP Marinkovich 《Canadian Metallurgical Quarterly》1997,108(6):848-853
To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse. 相似文献
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PE Demers H Robin C Prost M Toutblanc T Hoang-Xuan 《Canadian Metallurgical Quarterly》1998,17(8):823-827
PURPOSE: Optimizing the sensitivity of immunopathologic methods in detecting target antigens in immune-mediated cicatrizing conjunctivitis. Methods: Immunofluorescence was performed on normal and salt-split conjunctival biopsies in fifteen patients with clinical evidence of ocular cicatricial pemphigoid, and results were compared with immunoperoxidase, a technique thought to be more sensitive although more expensive and more difficult technically to perform. RESULTS: Ten of fifteen biopsies (67%) were positive when conventional and salt-split immunofluorescence results were combined. Four of eight patients with positive conventional immunofluorescence showed more marked immunofluorescence with the salt-split method. All patients were positive with immunoperoxidase (100%). CONCLUSION: Immunoperoxidase was more sensitive than conventional or salt-split immunofluorescence in detecting immunoreactant deposition along the basement membrane of the conjunctiva. Salt-split immunofluorescence demonstrated more intense staining of conjunctival samples when compared with conventional immunofluorescence, without however increasing the yield of positive biopsies. Finding solutions for the proper handling of conjunctival tissue in salt may improve the diagnostic yield of salt-split immunofluorescence. 相似文献
6.
ED Donnenfeld HD Perry A Wallerstein RM Caronia AJ Kanellopoulos PD Sforza G D'Aversa 《Canadian Metallurgical Quarterly》1999,106(1):72-8; discussion 79
PURPOSE: The authors performed a prospective evaluation of the efficacy of treating ocular cicatricial pemphigoid (OCP) with subconjunctival mitomycin C. DESIGN: Unmasked, prospective, internally controlled case series. METHODS: Patients were eligible for treatment with subconjunctival mitomycin C under three criteria: (1) significant complications of systemic immunosuppressant therapy; (2) markedly asymmetric conjunctival disease; and (3) end-stage OCP. All patients received monocular subconjunctival injections of 0.25 ml of 0.2 mg/ml mitomycin C to both the superior and inferior bulbar conjunctivae in the eye with the more severe disease. RESULTS: Nine eyes of nine patients (mean age, 74 years) were treated with subconjunctival mitomycin C to the more-involved eye and were followed for a mean of 23.5 months (range, 12-40 months). Eight of nine patients showed quiescence of their OCP in the treated eye based on serial evaluation of conjunctival cicatrization and grading of conjunctival erythema. Five of the nine untreated eyes showed progression of the conjunctival disease. One patient required concomitant systemic immunosuppressive therapy after subconjunctival mitomycin C. Two patients underwent successful visual rehabilitative surgery in the mitomycin C-treated eye. CONCLUSION: The use of subconjunctival mitomycin C may be effective in preventing progression of conjunctival cicatrization and erythema in patients with OCP. No complications of mitomycin C treatment were noted. Long-term follow-up and further investigation into the efficacy of subconjunctival mitomycin C in the management of OCP is warranted. 相似文献
7.
Cicatricial pemphigoid is a chronic mucocutaneous bullous condition. It is a heterogenous autoimmune disease, characterized by the production of autoantibodies against basement membrane zone antigens. The target antigens in cicatricial pemphigoid appear to be lamina lucida proteins involved in human keratinocyte adhesion to extracellular matrix. Cicatricial pemphigoid primarily affects persons older than 40 years and appears to have a 2:1 predilection for women, without racial or geographic bias. 相似文献
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K Bhol A Mohimen R Neumann J Yunis S Foster EJ Yunis AR Ahmed 《Canadian Metallurgical Quarterly》1996,15(5):521-532
Dupuytren's contracture (DC) is a disease of the palmar fascia resulting in thickening and contracture of fibrous bands on the palmar surface of the hands and fingers. For decades, a controversy has existed regarding whether acute traumatic injury or cumulative biomechanical work exposure can contribute to the development of this disorder. To address this controversy, this review considers the following questions: Is there evidence that DC is associated with 1) frequent or repetitive manual work; and 2) hand vibration? The published literature was searched for studies meeting the following criteria: 1) in English or having an English abstract; 2) controlled studies; 3) DC an identified health outcome studied; and 4) the study group exposed to repetitive or frequent manual work, vibration, or acute traumatic injury. Relevant non-English articles identified through English abstracts were translated. The validity of studies meeting the selection criteria was assessed using a series of questions adapted from those of Stock [1991: Am J Ind Med 19:87-107]. Studies that met a priori minimum levels of methodologic quality were taken into account to reach conclusions with respect to the above questions. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Ten studies met the initial selection criteria. Of these, four studies met the criteria for methodologic quality, one addressing the relationship between manual work and DC, and three studies of vibration and DC. No controlled studies of acute trauma and DC were identified. Bennett [1982: Br J Ind Med 39:98-100] found the prevalence of DC at a British PVC bagging and packing plant in which workers were exposed to repetitive manual work to be 5.5 times that at a local plant without packing, and twice the expected prevalence in a U.K. working population previously studied by Early [1962: J Bone Joint Surg 44B:602-613]. DC was observed more frequently among vibration white finger claimants than controls by Thomas and Clarke [1992: J Soc Occup Med 42:155-158] (OR, 2.1; 95% CI, 1.1-3-9), and more frequently among vibration-exposed workers than controls by Bovenzi et al. [1994: Occup Environ Med 51:603-611] (OR, 2.6 95% CI, 1.2-5.5). Cocco et al [1987: Med Lav 78:386-392] found that a history of vibration exposure occurred more frequently among cases of DC than among controls (OR, 2.3; 95% CI, 1.5-4.4). The latter two studies presented some evidence of a dose-response relationship. There is good support for an association between vibration exposure and DC. 相似文献
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Z Popovici M Deac M Rotaru P Ve?temeanu V V?rgatu 《Canadian Metallurgical Quarterly》1997,27(3):234-237
OBJECTIVE: To examine the extent of sun exposure, sun protection and experience of sunburn among young New Zealand children on summer weekends. METHODS: In a telephone survey of 1243 respondents, those with children in the household were asked about sun exposure and protection for the youngest child in the family. Information was obtained for 285 children aged from infancy to 10 years. RESULTS: Over 90% of the children were reported to be outside on the preceding Saturday and/or Sunday; 7% of those outside experienced some degree of sunburn. The worst burning was on the face, head, neck or ears. On either day about half the children were wearing sunscreen and 60% were wearing a hat. Parental use of sun protection was the strongest predictor of sun protection among the children. CONCLUSIONS: While reports of sun protection among young children were encouraging, many children in the community are still at high risk of sunburn. Efforts to promote sun protection as a family responsibility may reduce the experience of burning among the young. 相似文献
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The nature of the laminin alpha chains in the embryonic and adult kidney is still being debated. The present study attempted to clarify this issue by immunofluorescence study using monoclonal antibodies against mouse alpha1, alpha2, and alpha5 chains and in situ hybridization for the alpha2, alpha3B, alpha4, and alpha5 mRNAs. Novel alpha1 chain-specific monoclonal antibodies against E8 fragment revealed a restricted distribution of alpha1 chain in a subset of epithelial basement membranes in the embryo, in agreement with previous mRNA data. The alpha2 mRNA was produced by mesenchyme, although the protein was deposited in epithelial basement membranes. The alpha3B mRNA was found only in a small subset of endothelial cells. The alpha4 mRNA was found transiently in embryonic mesenchyme, with particularly high levels in condensed mesenchyme, close to the tips of the ureteric tree where tubulogenesis is initiated. The alpha5 mRNA was strongly expressed by ureter epithelium but not expressed at early stages of tubulogenesis. Immunofluorescence verified low levels of the alpha5 chain in the early stages of tubulogenesis. However, during the capillary loop stage, the alpha5 chain became strongly expressed in the developing glomerular basement membrane, which matches the in situ hybridization results. During subsequent maturation of the kidney, the alpha5 chain became ubiquitously expressed in basement membranes. Overall, the alpha5 chain exhibited the broadest pattern of expression, followed by the alpha1 chain, particularly in the adult stage. These chains were the only ones produced by epithelial cells. Although some basement membranes contained several alpha chains, we failed to detect any of the five studied chains in some basement membranes. Thus, the identity of the alpha chains of many embryonic kidney blood vessels and several basement membranes in the inner medulla in the developing and adult kidney remain unclear. 相似文献
12.
KM Sivanandaiah VV Babu SC Shankaramma M Lakshmana R Babu MA Arif M Kumar 《Canadian Metallurgical Quarterly》1996,34(7):658-662
The synthetic laminin pentapeptide amide fragment (LF), Tyr-Ile-Gly-Ser-Arg-NH2 corresponding to a part of B1 chain of the glycoprotein, laminin, and six of its analogues having structural modifications at positions 1, 3 and 4 were synthesized by solid phase method employing mainly 9-fluorenylmethoxycarbonyl-amino acid trichlorophenyl esters as coupling agents and Merrifield resin as the solid support. Their biological activities were studied in vivo by lung tumor colonization assay and in vitro by cell adhesion assay. The activity of synthetic LF was found to correlate with the earlier reported results in both in vivo and in vitro assays. Among the analogues made, [Tyr4] LF and [Thr4]LF were found to inhibit the lung tumor colonies more efficiently than LF itself in the in vivo assay whereas [D- Ser4]LF exhibited almost the same inhibition as LF. 相似文献
13.
Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin alpha5 chain is required during embryogenesis. The alpha5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose alpha5 retain or acquire other alpha chains. Embryos lacking laminin alpha5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are alpha5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes. 相似文献
14.
Detachment of basal keratinocytes from basement membrane signals a differentiation cascade. Two integrin receptors alpha6beta4 and alpha3beta1 mediate adhesion to laminin 5 (epiligrin), a major extracellular matrix protein in the basement membrane of epidermis. By establishing a low temperature adhesion system at 4 degrees C, we were able to examine the exclusive role of alpha6beta4 in adhesion of human foreskin keratinocyte (HFK) and the colon carcinoma cell LS123. We identified a novel 80-kD membrane-associated protein (p80) that is tyrosine phosphorylated in response to dissociation of alpha6beta4 from laminin 5. The specificity of p80 phosphorylation for laminin 5 and alpha6beta4 was illustrated by the lack of regulation of p80 phosphorylation on collagen, fibronectin, or poly-L-lysine surfaces. We showed that blocking of alpha3beta1 function using inhibitory mAbs, low temperature, or cytochalasin D diminished tyrosine phosphorylation of focal adhesion kinase but not p80 phosphorylation. Therefore, under our assay conditions, p80 phosphorylation is regulated by alpha6beta4, while motility via alpha3beta1 causes phosphorylation of focal adhesion kinase. Consistent with a linkage between p80 dephosphorylation and alpha6beta4 anchorage to laminin 5, we found that phosphatase inhibitor sodium vanadate, which blocked the p80 dephosphorylation, prevented the alpha6beta4-dependent cell anchorage to laminin 5 at 4degreesC. In contrast, adhesion at 37 degrees C via alpha3beta1 was unaffected. Furthermore, by in vitro kinase assay, we identified a kinase activity for p80 phosphorylation in suspended HFKs but not in attached cells. The kinase activity, alpha6beta4, and its associated adhesion structure stable anchoring contacts were all cofractionated in the Triton-insoluble cell fraction that lacks alpha3beta1. Thus, regulation of p80 phosphorylation, through the activities of p80 kinase and phosphatase, correlates with alpha6beta4-SAC anchorage to laminin 5 at 4 degrees C in epithelial cells of the skin and intestine. Transmembrane signaling through p80 is an early tyrosine phosphorylation event responsive to and possibly required for anchorage to laminin 5 by HFK and LS123 epithelial cells. 相似文献
15.
CF Tiger MF Champliaud F Pedrosa-Domellof LE Thornell P Ekblom D Gullberg 《Canadian Metallurgical Quarterly》1997,272(45):28590-28595
There is currently a great interest in identifying laminin isoforms expressed in developing and regenerating skeletal muscle. Laminin alpha1 has been reported to localize to human fetal muscle and to be induced in muscular dystrophies based on immunohistochemistry with the monoclonal antibody 4C7, suggested to recognize the human laminin alpha1 chain. Nevertheless, there seems to be no expression of laminin alpha1 protein or mRNA in developing or dystrophic mouse skeletal muscle fibers. To address the discrepancy between the results obtained in developing and dystrophic human and mouse muscle we expressed the E3 domain of human laminin alpha1 chain as a recombinant protein and made antibodies specific for human laminin alpha1 chain (anti-hLN-alpha1G4/G5). We also made antibodies to the human laminin alpha5 chain purified from placenta. In the present report we show that hLN-alpha1G4/G5 antibodies react with a 400-kDa laminin alpha1 chain and that 4C7 reacts with a 380-kDa laminin alpha5 chain. Immunohistochemistry with the hLN-alpha1G4/G5 antibody and 4C7 revealed that the two antibodies stained human kidney, developing and dystrophic muscle in distinct patterns. Our data indicate that the previously reported expression patterns in developing, adult, and dystrophic human muscle tissues with 4C7 should be re-interpreted as an expression of laminin alpha5 chain. Our data are also consistent with earlier work in mouse, indicating that laminin alpha1 is largely an epithelial laminin chain not present in developing or dystrophic muscle fibers. 相似文献
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SP Lee ML Cunningham PC Hines CC Joneckis EP Orringer LV Parise 《Canadian Metallurgical Quarterly》1998,92(8):2951-2958
Sickle red blood cell (RBC) adhesion to the endothelium and to exposed, underlying subendothelial proteins is believed to contribute to vascular occlusion in sickle cell disease. Laminin, a major component of the subendothelium, supports significant adhesion of sickle, but not normal RBCs. The purpose of this study was to define the adhesive region for sickle RBCs within a human laminin preparation using a flow adhesion assay designed to mimic physiologic flow through postcapillary venules. Because sickle RBCs did not adhere to the common laminin contaminants entactin or collagen type IV, neither of these proteins are likely to contribute to the observed adhesion to laminin. Known adhesive regions of laminin neither supported nor inhibited sickle RBC adhesion to laminin, suggesting a mechanism of adhesion previously uncharacterized in other laminin adhesion studies. Moreover, sickle RBCs did not adhere to mouse EHS laminin or to human laminin-2 (merosin), eliminating the alpha1, alpha2, beta1, and gamma1 chains as mediators of sickle cell adhesion. The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin alpha5 chain, significantly inhibited sickle RBC adhesion. These results suggest that an adhesive region for sickle RBCs is contained within the laminin alpha5 chain. 相似文献
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DW Richards LA MacPhail N Dekker D Greenspan JS Greenspan F Lozada-Nur JA Regezi 《Canadian Metallurgical Quarterly》1996,75(7):1512-1517
Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate. 相似文献