Therapy-resistant leg ulcer caused by multiple myeloma.
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Aged↗
Biomedical subjects
M Kiss
Publications and source records attributed to M Kiss.
230-kDa and 190-kDa proteins in addition to desmoglein 1 as immunological targets in a subset of pemphigus foliaceus with a combined cell-surface and basement membrane zone immune staining pattern.
Pemphigus erythematosus, initially described as a combination of pemphigus with lupus erythematosus, and pemphigus foliaceus are now frequently considered localized and generalized variants of superficial pemphigus. Yet diagnostic criteria for pemphigus erythematosus remain controversial. Distinct from pemphigus foliaceus, pemphigus erythematosus displays immune depositions at the dermal-epidermal junction, which suggests additional immunopathological mechanisms. We present three patients with clinical and histopathologic signs of superficial pemphigus, who all exhibited an immunomorphology characteristic of pemphigus erythematosus. Complement depositions in a granular-linear fashion were consistently found at the dermal-epidermal junction besides in vivo bound and circulating antikeratinocyte cell-surface autoantibodies. Histopathology showed subcorneal acantholysis, and all sera contained antidesmoglein 1 but not antidesmoglein 3 autoantibodies detected by enzyme-linked immunosorbent assays (ELISA). Additional autoantibodies against a 230-kDa protein and against a 190-kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin, respectively, were present in all the patients' sera. As two sera specifically reacted with BP230 by ELISA, the presence of BP230-specific autoantibodies could be associated with dermal-epidermal immune staining in these patients. In pemphigus erythematosus, dermal-epidermal immune staining is generally attributed to the deposition of immune complexes, while the presence of BP230-specific autoantibodies has not been reported in this disease previously. Perhaps, the unique autoantibody profile of the patients in the study permits discrimination between patients with superficial pemphigus that display additional dermal-epidermal immune staining from those with conventional pemphigus foliaceus on a molecular basis. Further studies will be required to substantiate the frequency of this occurrence and to unravel its pathogenic significance.
Adult↗
Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus.
We determined the prevalence of antineutrophil cytoplasmic antibodies (ANCAs) in patients with systemic lupus erythematosus (SLE) and evaluated the correlation between ANCA positivity and clinical features. Forty-one patients with SLE and two control groups were examined. One of the control groups consisted of 15 patients with systemic vasculitis, and the other of 12 healthy blood donors. A quantitative enzyme-linked immunosorbent assay technique was used to measure the serum cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA) levels. cANCA positivity was found in three patient samples, and pANCA positivity in 10 SLE patients. The occurrence and titres of both ANCA types in SLE patients were similar to those in healthy controls and significantly lower than those in patients with systemic vasculitis. The clinical picture and antibody profile were similar in ANCA-positive and ANCA-negative SLE patients. We conclude that measurement of ANCAs does not provide any additional diagnostic or prognostic data in SLE.
Adult↗
Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT.
OBJECTIVE: Dithranol is highly effective in the treatment of psoriasis, however its mode of action is still not well known. Since interleukin-8 and interleukin-10 are involved in the pathogenesis of psoriasis, the aim of our study was to investigate the effect of dithranol on interleukin-8, interleukin-10 mRNA production and interleukin-10 receptor expression of the HaCaT keratinocyte cell line which is commonly used in experiments examining the effects of therapeutic drugs on keratinocytes. MATERIALS AND METHODS: Cultured HaCaT cells were treated with 0.1-0.5 microg/ml dithranol for 30 minutes. After 2 and 4 h total cellular RNA isolated from HaCaT cells was reverse transcribed (RT) to cDNA which was subjected to polymerase chain reaction (PCR) with specific primer pairs for interleukin-8, interleukin-10 and interleukin-10 receptor. For immunohistochemistry cultured HaCaT cells were stained with a monoclonal antibody against the human interleukin-10 receptor. RESULTS: Our results showed that dithranol treatment did not change the highly elevated level of interleukin-8 mRNA of HaCaT cells. Interleukin-10 mRNA signal with RT-PCR could not be detected in HaCaT cells. Depending on the concentration dithranol increased the mRNA production of interleukin-10 receptors in HaCaT cells. This dithranol induced dose dependent upregulation of IL-10 receptors in HaCaT cells was also observed on the protein level using immunohistochemistry. CONCLUSIONS: Since the interleukin-10 receptor expression of keratinocytes in psoriatic lesional skin is downregulated, the dithranol induced upregulation of the receptor in our model system might help to reveal the therapeutic action of the drug.
Actins↗
A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans.
Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.
Antibodies, Monoclonal↗
Conformational consequences of coupling bullous pemphigoid antigenic peptides to glutathione-S-transferase and their diagnostic significance.
Recombinant epitopic peptides BP1 and BP2 representing the Bullous pemphigoid autoantigens of BP230 and BP180 bound to the fusion partner glutathione-S-transferase (pGEX-4T-2, Pharmacia) have been previously shown to increase the efficacy of diagnosis of the disease. Using glutathione-S-transferase-bound monomer peptides, the sensitivity of the immunological reaction exceeded that of the free synthetic epitopes and was further increased with the number of epitopic blocks in the multimer fusion products. This has been explained by the avidity effect of the fusion partner dimer formation and the high ligand affinity due to the tandem repetitions of epitopic sequences. However, a beneficial conformation of the bound epitopic peptides might also contribute to the above phenomenon. Circular dichroism (CD) and Fourier transform infrared (FTIR) absorption spectroscopic studies revealed the importance of glutathione-S-transferase to induce and stabilize ordered secondary structures of the epitopic peptides. The free monomer and multimer peptides in aqueous buffer were present as a mixture of unordered and beta-sheet conformation, while binding them to the fusion partner the proportion of ordered secondary structures increased in parallel with the number of antigenic epitopes. The most prominent changes in the conformational state of the monomers in the fusion form were the increase of alpha-helical and beta-sheet and the decrease of unordered conformation, while in the case of oligomeric peptides the adoption of a helical conformation was accompanied by the decrease of beta-sheet structure. An outstanding alpha-helix content (46%) was detected in the case of the trimeric BP1 in its recombinant fusion form.
Autoantigens↗
Development of a system for detection of circulating antibodies against hemidesmosomal proteins in patients with bullous pemphigoid.
Specific antibodies directed against special hemidesmosomal proteins are involved in the pathogenesis of bullous pemphigoid (BP), and detection of these antibodies is crucial for a correct diagnosis. As the BP autoantigen primary structures are known, the question was addressed as to whether it is possible to demonstrate circulating antibodies against BP autoantigens (BPAG1 and BPAG2) by means of an ELISA system, using antigenic epitopes. With the help of the programs Peptidestructure and Plotstructure, antigenic epitopes of BP antigens were predicted, chemically synthesized and screened using serum from 43 proven BP patients. The coding sequences of the best antigenic epitopes were then chemically synthesized and inserted as monomer and homo- or hetero-oligomer forms into fusion-expression plasmids (PGEX-4T, Pharmacia) in-frame to the C-terminus of glutathione-S-transferase. Fusion products were expressed and purified from Escherichia coli cells by affinity chromatography. The recombinant proteins were used for the detection of antibodies in the serum of 43 BP patients and of 60 controls (including 30 healthy persons, 22 patients with pemphigus vulgaris and 8 patients with other bullous dermatoses). Use of the homo- and hetero-oligomers of the recombinant fusion peptides increased the sensitivity of the disease-specific antibody detection. When a mixture of the best recombinant fusion proteins was used, the sensitivity of the ELISA assays in the case of the BP patients' serum was 0.90. This system could form the basis of a rapid and simple system for the diagnosis of BP.
Aged↗
The place of magnetic resonance and ultrasonographic examinations of the parotid gland in the diagnosis and follow-up of primary Sjögren's syndrome.
OBJECTIVE: The aim was to determine the place of magnetic resonance imaging (MRI) and ultrasonographic (US) examination in the diagnosis and follow-up of Sjögren's syndrome (SS). METHODS: Parotid MRI and US examinations were carried out on 44 primary SS patients and 52 controls of similar age. RESULTS: The most important structural changes in SS were different degrees of parenchymal inhomogeneity, which could be detected by both methods, and were found more frequently in the SS patients than in the controls (MRI: 95.4 vs 17. 3%; US: 88.6 vs 7.7%; P<0.001). There was good agreement between the MRI and US findings both in the SS cases (93.2%) and in the controls (86.5%). In one SS patient who developed parotid lymphoma, the US examination showed a hypoechoic 'cobblestones'-like inhomogeneous internal pattern which was coupled with an almost homogeneous MRI pattern. CONCLUSIONS: MRI appears unnecessary as a routine method in the diagnosis of SS; US examination is suitable both for the diagnosis and follow-up of SS. The above combination of the seemingly contradictory US and MRI findings is highly characteristic of lymphoma which has developed in the course of the disease.
Adult↗
Effects of the neuropeptides substance P, calcitonin gene-related peptide and alpha-melanocyte-stimulating hormone on the IL-8/IL-8 receptor system in a cultured human keratinocyte cell line and dermal fibroblasts.
The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and alpha-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10-8 M SP, CGRP or alpha-MSH. The results demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRNA expression in HaCaT cells, but had no influence on their IL-8 production, whereas, alpha-MSH had no effect on either the IL-8 or the IL-8RA mRNA expression in HaCaT cells. In contrast, alpha-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after alpha-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.
Antigens, CD↗
Posterior circulation aneurysms. Technical strategies based on angiographic anatomical findings and the results of 60 recent consecutive cases.
Ninety-eight patients with aneurysms of the posterior circulation were admitted to our department from 1993 to 1997. Sixty of them underwent microsurgical treatment, mostly in the acute stage of subarachnoid hemorrhage. Peri- and intraoperative management were carried out according to a structured treatment strategy. Special aspects of surgical technique included extradural selective anterior clinoidectomy for basilar head aneurysms, lateral suboccipital craniotomy and partial condylectomy without laminectomy for aneurysms of the vertebral artery or posterior inferior cerebellar artery, and a trans-Sylvian approach, as used in selective amygdalohippocampectomy, for aneurysms of the posterior cerebral artery. A careful angiographic evaluation of the aneurysms in relation to the neighboring important arteries and bony structures was essential for optimal surgical planning. Forty-nine patients (82%) made a good recovery by 3 months after surgery. The mortality was 7%.
Acute Disease↗
Identification of a soluble interleukin-8 inhibitor in the supernatant of polymorphonuclear leukocytes.
Interleukin-8 (IL-8) plays a crucial role in the pathogenesis of inflammatory and hyperproliferative diseases in various organs. The purpose of the present investigation was to establish whether there is any naturally occurring inhibitor of IL-8. Here we demonstrate that an IL-8 inhibitor (IL-8INH) is present in the supernatant of polymorphonuclear (PMN) leukocytes. The release of IL-8INH could be increased by stimulating the PMN leukocytes by concanavalin A. IL-81NH blocks the IL-8-induced chemotaxis and Candida albicans killing activity of PMN leukocytes and epidermal cells in vitro, and IL-8-induced neutrophil infiltration in the mouse ear in vivo. The mechanism of action of IL-8INH involves blocking of 125I-IL-8 binding to the IL-8 receptor. Binding of 125I-IL-8 to neutrophils could not be displaced by the IL-8INH, however, preincubation of 125I-IL-8 with IL-8INH increased binding inhibition, suggesting an interaction between IL-8 and the inhibitor. Crosslinking of 125I-IL-8 to IL-8INH shows that IL-8INH binds specifically to 125I-IL-8, and the IL-8INH protein has an apparent molecular weight of 52 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial purification of the IL-8INH on DEAE-Sephadex anion-exchange chromatography column also suggests a 50-60-kDa inhibitor protein which blocks IL-8-induced effects on neutrophils by binding to IL-8.
Animals↗
Chest tube insertion: a prospective evaluation of pain management.
OBJECTIVE: To evaluate pain associated with chest tube insertion in a group of patients with malignant pleural effusions. DESIGN: Prospective case series. SETTING: Acute care cancer center in an academic institution. PATIENTS: Fifty-two patients with symptomatic malignant pleural effusions. Twenty-six evaluated by conventional approach to chest tube insertion (group 1), 26 evaluated after institution of a new chest tube protocol (group 2). INTERVENTIONS: A new protocol was designed to improve pain control during chest tube insertion. The protocol included improved housestaff and nursing education, premedication, proper insertion techniques, and more liberal and precise delivery of local anesthetic. OUTCOME MEASURES: Both groups were evaluated by a verbal self-report scale (1-10) to assess pain and anxiety. RESULTS: The mean pain rating in group 1 was 6.2 (+/-0.76) compared with 3.7 (+/-5.6) in group 2 (p < 0.01). In group 1, pain or anxiety was 9 or 10 in 12 of 26 on a scale of 1 to 10, compared with 2 of 26 in group 2 (p < 0.001). Anxiety rating was 4.5 (+/-0.72) in group 1 compared with 1.5 (+/-0.54) in group 2 (p < 0.01). CONCLUSIONS: Chest tube insertion was associated with an unacceptably high level of pain and anxiety in our hospital. A new protocol, including housestaff education and changes in nursing policies, technical aspects, local anesthetic dose and delivery, and pre-medication, allowed us to approach the goal of a painless chest tube insertion.
Anxiety↗
The use of skin substrates deficient in basement membrane molecules for the diagnosis of subepidermal autoimmune bullous disease.
A case is presented of subepidermal, autoimmune bullous disease in which the initial examinations suggested the combination of epidermolysis bullosa acquisita and bullous pemphigoid. The diagnosis of epidermolysis bullosa acquisita was made by indirect immunofluorescence microscopy: the patient's serum bound to normal skin substrate but not to type VII collagen-deficient skin substrate derived from a patient with mutilating dystrophic epidermolysis bullosa. The use of skin substrates deficient in basement membrane molecules also excluded the presence of concomitant, circulating bullous pemphigoid autoantibodies in our patient. The diagnosis of epidermolysis bullosa acquisita was confirmed by split mapping, fluorescence overlay antigen mapping and Western blot.
Adult↗
[Kaposi sarcoma-associated herpesvirus; human herpesvirus 8].
The discovery of a new human herpesvirus in Kaposi's sarcoma tissues of AIDS patients has opened up new facts in virology and oncology. This herpesvirus was first descriptively named Kaposi's sarcoma-associated herpesvirus, but was recently renamed human herpesvirus 8. Human herpesvirus 8 DNA has been consequently found in all forms of Kaposi's sarcoma, suggesting that it might be involved in the pathogenesis of the disease. Additionally, human herpesvirus 8 can be detected in both malignant and benign lymphoproliferative diseases, such as body-cavity-based B-cell lymphomas and multicentric Castleman disease. The virus was also recently found in rare vascular tumors in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the viral DNA has been sequenced, it has become evident that the new herpesvirus is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission, and also for the development of serologic tests.
AIDS-Related Opportunistic Infections↗
Moyamoya with arterial anomalies: relevance to pathogenesis.
We report five patients with moyamoya associated with arterial anomalies, including five aneurysms, one with ectasia of the parent artery, a basilar artery fenestration and an arteriovenous malformation. Possible pathogenetic factors for moyamoya are discussed, and a prenatal origin is suggested.
Adult↗
Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8: a new virus in human pathology.
The discovery of a new human herpesvirus in Kaposi's sarcoma (KS) tissue of patients with AIDS has opened up new vistas in virology and oncology. This herpesvirus was first descriptively named KS-associated herpesvirus (KSHV), but was recently renamed human herpesvirus 8 (HHV8). KSHV/HHV8 DNA has been found in all forms of KS, suggesting that it might be involved in the pathogenesis of KS. In addition, KSHV/HHV8 can be detected in both malignant and benign lymphoproliferative disease. KSHV/HHV8 was also found in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the virus has been sequenced, KSHV/HHV8 is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission. The recently developed serologic assays for antiviral antibodies suggest that infection with KSHV/HHV8 is not ubiquitous because KSHV/HHV8 seropositivity is limited to a small proportion of the population.
Acquired Immunodeficiency Syndrome↗
Pyodermatitis-pyostomatitis vegetans.
A 43-year-old woman developed annular and pustular cutaneous lesions preceded by tiny yellow pustules coating the surface of the oral mucosa. The clinical, histological and immunopathological evidence clearly showed that the patient had pyodermatitis-pyostomatitis vegetans. It is suggested that this disease is a distinct entity which should be differentiated from pemphigus vegetans.
Diagnosis, Differential↗
Human herpesvirus 8 DNA sequences in angiosarcoma of the face.
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DNA, Viral↗