Fatal rhabdomyolysis and multiple organ failure associated with adjuvant high-dose interferon alfa in malignant melanoma.
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Antineoplastic Agents↗
Biomedical subjects
H W Kreysel
Publications and source records attributed to H W Kreysel.
The analysis of tyrosinase-specific mRNA in blood samples of melanoma patients by RT-PCR is not a useful test for metastatic tumor progression.
Reverse transcription (RT) of the tyrosinase mRNA and specific cDNA amplification by nested polymerase chain reactin (PCR) have been reported to facilitate the early detection of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. In the current study we analyzed peripheral blood samples of 65 melanoma patients of different clinical stages for the presence of tyrosinase mRNA by RT-PCR using nested oligonucleotide primers specific for tyrosinase cDNA. Furthermore, blood samples were evaluated for tumor cell growth by cell culture assays in vitro. No tyrosinase mRNA was detectable in blood samples of 26 patients with primary melanoma and 16 patients with regional lymph node metastases. In five of 13 patients with visceral metastases we found at least one blood sample positive for tyrosinase mRNA during a 2-to 4-mo interval. Analyses of different blood samples of patients with visceral metastases taken in a 2-h interval, furthermore, indicate that tumor cells only transiently persist in the peripheral blood. We obtained in vitro proliferating melanoma cells from two blood samples derived from different patients with visceral melanoma metastases. This demonstrates that viable melanoma cells indeed circulate in the peripheral blood with retained proliferative capacity in vitro. The analysis of blood samples by RT-PCR for tyrosinase mRNA, however, is not suitable for the early detection of tumor progression in melanoma patients.
Adult↗
Treatment of aquagenic pruritus using recombinant interferon-alpha.
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Adult↗
[Epithelioid cell histiocytoma].
We report on seven examples of this rare, only recently described benign tumor, which presented clinically as solitary elevated nodules on the lower (n = 5) and upper (n = 2) extremity, measuring between 0.6 and 1.1 cm in diameter. Histologically, all tumors were well-defined with a characteristic epidermal collarette. There were abundant (60-80%) epithelioid cells with prominent cytoplasm, a vesicular nucleus and inconspicuous nucleolus, as well as a number of dilated blood vessels. Immunohistologically, tumor cells did not react with monocyte/macrophage antibodies (KP1, MAC387). In addition, there was no evidence of myofibroblastic differentiation (alpha-smooth muscle actin and desmin negative). Thus, while immunohistological markers are helpful to exclude the diagnosis of other tumors, they do not shed light on the differentiation of epithelioid cell histiocytomas. The present cases are identical to those described originally. Recently similar lesions have been described in deeper parts of the corium as well as more cellular forms. Epithelioid cell histiocytoma represents a characteristic, poorly known variant within the spectrum of benign fibrous histiocytomas; it needs to be distinguished clinically and histopathologically especially from Spitz nevus.
Adult↗
Inflammatory mediators potentiate pain induced by experimental tissue acidosis.
Electrophysiological evidence from cutaneous nociceptors suggested a synergism between excitatory actions of inflammatory mediators (IM) and low pH. In human skin it is possible to induce constant ongoing pain with continuous infusion of acid buffer. This method was used to study the interaction with mediators of inflammation psychophysiologically. A skin area on the palmar forearm of 6 subjects (either gender, age 22-35 years) was continuously infiltrated with a phosphate buffered electrolyte solution (pH 5.2) using a motorized syringe pump that was adjusted so as to produce constant pain of about 20% on a visual analog scale (VAS; extending from 'no' to 'unbearable pain'). Pain was assessed on the VAS at 10-sec intervals; the rating was called up by means of an acoustic signal. An additional cannula was placed in the skin before the infusion of acidic buffer started. Injections of an acidic combination of IM (BK, 5-HT, HIS, PGE2) 0.2 ml were then given through the cannula at intervals of 10 min in a randomized double blind order of concentrations. The other arm was used for negative control, i.e. IM in neutral solution were injected into normal skin continuously infiltrated with a buffer solution at pH 7.4. The IM induced dose-dependent, transient burning pain on both arms-markedly more intense and prolonged, however, in the acidotic skin (P < 0.004, U-test). The difference corresponded to a 10-fold increase in algogenic potency with 10(-7) M IM, being smaller with 10(-6) and 10(-5) M concentration. The interaction between low pH and IM was mutual: additional injections of plain phosphate buffer (pH 5.2) into the acidotic skin were significantly more painful (20-fold) after application of IM than under control conditions. Thus, we tend to conclude that it is the inflammatory mediators that potentiate the algogenic effect of low pH rather than vice versa. Tissue acidosis appears as a dominant factor in inflammatory pain.
Acidosis↗
Dacarbazine, vincristine, bleomycin and lomustine plus natural interferon-alpha for metastatic melanoma.
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Adult↗
Interkeratinocyte adherens junctions: immunocytochemical visualization of cell-cell junctional structures, distinct from desmosomes, in human epidermis.
Vinculin and beta-catenin are intracellular attachment proteins linking transmembrane adhesion molecules (E-cadherin) to the actin microfilament cytoskeleton, thus participating in formation of cell-cell adherens junctions, or zonulae adherentes. This type of junction was only recently described in human epidermis due to the imprecise morphological criteria for its recognition. In this study, we investigated the relationship between the expression of the zonula adherens-associated proteins vinculin, beta-catenin, E-cadherin, and actin, on the one hand, and the presence of electron microscopically discernable structures in normal human epidermis on the other. Mouse jejunal epithelium with its orderly arrangement of various junctional structures served as a positive control. Simple and dual post-embedding immunogold labeling was performed on ultrathin sections of Lowicryl K4M and Lowicryl K11M embedded tissues. The overall distribution of the antigens in human epidermis was evaluated on frozen tissue sections using immunofluorescence and laser confocal scanning microscopy. Antibodies against proteins associated with desmosomes (i.e., keratins, desmoglein 1, and plakoglobin) were used as controls. Vinculin and beta-catenin were localized to junctional structures distinct from desmosomes, thus defining the presence of zonulae adherentes. Labeling of actin and E-cadherin was less clearly restricted to the junctions, but these two proteins were also co-expressed at zonulae adherentes and not at desmosomes. In human epidermis, zonula adherens-associated labeling was consistently detected near desmosomes, indicating the possibility of a functional relationship between the two types of junctions.
Actins↗
High-dose chemotherapy with autologous stem cell transplantation in a patient with a CD30+ anaplastic large cell lymphoma of the skin.
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Adult↗
Diltiazem blocks the PH-induced excitation of rat nociceptors together with their mechanical and electrical excitability in vitro.
1. The effect of the calcium channel antagonist diltiazem on pH-induced sustained nociceptor excitation was investigated in a rat skin-saphenous nerve preparation, in vitro, where receptive fields of identified and isolated single fibers were superfused at the corium side with controlled solutions to assess their chemosensitivity. 2. Unmyelinated mechano-heat sensitive ("polymodal") C fiber terminals (n = 78) were superfused with a CO2-saturated synthetic interstitial fluid (CO2-SIF, pH 6.1). Fibers responding to this acid pH condition (n = 60; 77%) were further stimulated for > or = 30 min and additionally treated with diltiazem in various concentrations (10(-6)-10(-3) M) during the middle 10-min period. Usually only one concentration of diltiazem was applied per fiber, although in some cases diltiazem was applied repeatedly and in increasing concentrations. 3. Diltiazem dose-dependently and reversibly reduced the pH-induced sustained nociceptor discharge to a significant degree or completely abolished it. With higher concentrations, both the relative number of units affected and the average amount of suppression were enhanced. The half-maximal blocking concentration (IC50) was estimated to 1.1.10(-4) M diltiazem, the half-maximal concentration for gradual suppression of the pH response was 2.10(-5) M diltiazem. 4. Also, the delay of onset of the suppressive effect decreased with higher diltiazem concentrations. After diltiazem, a partial recovery of the pH-induced discharge was achieved within 10 min depending on the degree of suppression. 5. Before, after, and sometimes during the superfusion, the mechanical (von Frey) thresholds were determined and found to be significantly increased after partial wash out of diltiazem (10(-4) and 10(-3) M; P < 0.006 and P < 0.008, respectively). After 10(-3) M diltiazem superfusion (and 10 min of wash-out), the responsiveness to mechanical stimulation of the majority of the fibers was still totally lost. 6. Heat thresholds were still found to be significantly increased after treatment with diltiazem at 10(-3) and 10(-4) M concentrations (and 10 min of wash out), but appeared unchanged after wash out of lower concentrations. 7. In five mechano-heat-sensitive C fibers, electrical stimulation via a microelectrode placed in the receptive field was used to demonstrate a diltiazem-dose-dependent (10(-5), 10(-4), 10(-3) M) progressive retardation of the nerve conduction velocity and an increase of the electrical threshold. Superfusion for 6 min of diltiazem 10(-5) M was sufficient to block axonal conduction as well as mechanosensitivity, which both recovered synchronously during wash out. 8. It can be concluded from the results that the suppressive effect of diltiazem on pH-induced nociceptor excitation can be explained by a use-dependent axonal block, comparable with the action of local anesthetics and affecting all modalities of sensory responsiveness. 9. The findings provide no indication that a transformed calcium channel specifically sensitive to diltiazem is involved in pH-induced sustained nociceptor excitation.
Acid-Base Equilibrium↗
[Sclerotic fibroma].
The clinical and histological diagnosis of sclerotic fibroma is important because of its potential association with Cowden's syndrome. Despite its distinctive histological appearance the lesion is often mis-diagnosed. We therefore present five of our own cases (2F, 3M) in which the tumor was located on the head (n = 2), arm (n = 2) and leg (n = 1), respectively. Clinically, the lesions were white to flesh-colored firm nodules ranging in size from 0.5 to 1.2 cm. None of our patients revealed any clinical evidence of Cowden's disease. Simple surgical excision seems to be curative. Histologically, they were well-circumscribed but not encapsulated dermal nodules composed of stori-form-arranged sclerosing collagen bundles and vimentin-positive fibroblastlike cells interspersed in three cases by a number of alpha-smooth-muscle actin-positive myofibroblasts. Approximately 50% of cells (dermal dendritic cells (DD)) also reacted for factor XIIIa evenly scattered throughout the lesion in contrast to the very few (< 5%) CD34+ DD found predominantly at the lower border, thus possibly reflecting the distribution of these cells in normal skin. Sclerotic fibroma expands the spectrum of fibrous lesions that may express alpha-smooth-muscle actin.
Adult↗
Cutaneous angiomyxoma: a benign neoplasm distinct from cutaneous focal mucinosis.
We describe a cutaneous angiomyxoma on the head of a 38-year-old man without evidence of Carney's complex. Complete excision of the tumor appeared to be curative. Histologic examination revealed fibroblast-like cells embedded in a well-demarcated, lobulate, mucinous, and vascularized stroma with a delicate reticulin network. Immunohistologically, the stromal cells were consistently positive for vimentin and focally positive for smooth muscle A-actin but were negative for desmin, KP1, MAC387, factor XIIIa, CD34, Leu-7, and S-100. Cutaneous angiomyxoma appears to represent a myofibroblastic neoplasm that should be distinguished from cutaneous focal mucinosis.
Adult↗
Induction of nuclear contour irregularity during T-cell activation via the T-cell receptor/CD3 complex and CD2 antigens in the presence of phorbol esters.
To determine whether specific T-cell activation pathways could produce nuclear contour irregularity in normal human lymphocytes, purified T cells were stimulated in vitro and subsequently analyzed by electron microscopy. The degree of nuclear contour irregularity was determined with the use of a computerized planimeter. Stimulation via the T-cell receptor (TCR)/CD3 complex using anti-CD3 monoclonal antibodies induced Sézary-like morphology (nuclear contour indices > 6.5) in a significant portion (9% to 28%) of T cells derived from different normal donors. T-cell activation via CD2 antigens showed induction of Sézary-like nuclear morphology in a lower percentage of cells in comparison with stimulation via the TCR/CD3 complex. In contrast, mitogenic stimulation in vitro did not induce alterations of nuclear morphology in T cells. Immunoelectron microscopy showed that nuclear contour irregularity induced in vitro did not correlate with surface-antigen expression of T-cell subpopulations. The results indicate that Sézary-like morphology is associated with cell activation in normal human T cells.
Antigens, Differentiation, T-Lymphocyte↗
[Pemphigus chronicus benignus familiaris (Hailey-Hailey disease) and bipolar affective disease in 3 members of a family].
We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.
Biopsy↗
Cultured autologous keratinocytes in fibrin glue suspension, exclusively and combined with STS-allograft (preliminary clinical and histological report of a new technique).
The use of cultured epidermal cell sheets has become a recognized method for the coverage of extensive burns. The disadvantages are a long time-lag until the cells are available, the fragility and difficult handling of the grafts, an unpredictable 'take' and extremely high costs. In three patients with deep partial and full skin thickness burns we have applied cultured autologous keratinocytes suspended in fibrin glue. In two of these patients the keratinocyte culture in the fibrin matrix (KFGS) was overgrafted with allogeneic, glycerine-preserved split thickness cadaver skin. The area thus covered ranged from 3 to 15 per cent TBSA. Cultured grafts were available between 2.5 and 3 weeks. The non-confluent cells developed a continuous epithelial layer within the 4 days until the first dressing change. Histological examination showed a stratified neoepidermis. Clinically the new skin had satisfactory stability and mechanical quality. The epidermis of the allogeneic overgrafts desquamated within a few days without signs of inflammation, but there are indications that the STS-allograft dermis is at least partly integrated into the new skin and may serve as a scaffold for the grafted cell culture. The fibrin glue matrix seems to give sufficient adherence stability to keratinocytes that are grafted in an actively proliferating state. Further advantages are the easy repetition and application, as well as a reduction in operating time and costs in these severely injured patients.
Adult↗
Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.
BACKGROUND: Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. OBJECTIVE: The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. METHODS: A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. RESULTS: The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. CONCLUSION: Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.
Abdominal Pain↗
CD7-negative helper T cells accumulate in inflammatory skin lesions.
Recently, we identified a particular T-cell subset in the peripheral blood of normal individuals that lack CD7 expression. In this study we determined the portion of CD7- T cells in the peripheral blood and skin of patients with various inflammatory skin diseases. We found that skin-infiltrating lymphocytes isolated from different benign and malignant skin lesions (n = 20) contain a high portion of CD7- helper T cells, whereas the number of CD7- T cells in the peripheral blood was not altered compared to healthy controls. Cell activation in vitro did not induce CD7 expression in negative T cells but increased CD7 expression in CD7-positive cells. Thus, lack of CD7 expression seems to be a stable characteristic in a major subset of skin-infiltrating lymphocytes. During long-term culture of CD7- helper T-cell clones derived from a psoriasis skin lesion, no phenotypic change in the CD7 phenotype could be monitored by sequential flow-cytometric analyses. No CD7 mRNA could be detected by Northern blot analysis, indicating transcriptional regulation of CD7 expression. The results show that CD7- T cells accumulate in certain inflammatory skin lesions without alteration of the circulating CD7- population. These cells may be identical to or derived from CD7- T cells of the peripheral blood.
Antigens, CD↗
Progressive increase of CD7- T cells in human blood lymphocytes with ageing.
CD7 is one of the major surface antigens expressed very early during T cell ontogeny. Lack of CD7 expression on mature T cells is regarded as a classical feature of malignant T cells in certain forms of cutaneous T cell lymphoma. Previously, we identified a CD7- subset of peripheral blood T lymphocytes in normal human individuals. In this study we determined the portion of CD7- T cells in the peripheral blood of healthy volunteers ranging in age from 8 months to 90 years (n = 85) and in cord blood of full-term infants (n = 14). Furthermore, this CD7- subset was characterized in detail by the use of MoAbs and three-colour flow cytometry. In cord blood no CD7- T cells could be detected. After birth, percentage and absolute number of CD7- T cells increased with age. Independently of age, most CD7-CD3+ cells belonged to the CD4+ subpopulation. Focusing on the latter we could demonstrate the predominance of the CD45RO+CD45RA- phenotype in the CD7- subset. Furthermore, CD7- T cells contained a higher number of cells expressing activation markers and the CD57 antigen, but a reduced number of CD62L+ cells in comparison with CD7+ T cells.
Adolescent↗
CD7- T cells represent a subset of normal human blood lymphocytes.
In the peripheral blood of normal adults we identified a subpopulation of mature human T cells that lacks expression of CD7. These CD3+CD7- T cells represent 9% +/- 3.4 SD of PBMC as estimated by analyses of 38 different normal donors. The majority of CD7- T cells express TCR alpha/beta, and are of CD4 helper and CD45RO+CD45RA- "memory" phenotype as determined by three-color fluorescence analysis. We established seven CD4+CD7- T cell clones in vitro from purified CD7- blood T cells and compared these cells to CD4+CD7+ clones. Nonexpression and expression, respectively, of CD7 was a stable feature of all clones during long term culture for more than 6 mo. No CD7 mRNA could be detected by dot blot and Northern blot analysis of purified CD7- T cells and of expanded T cell clones implicating a transcriptional regulation of CD7 Ag expression. Ionomycin/TPA and PHA stimulation were not capable to induce CD7 expression in CD7- cells but up-regulated CD7 expression in CD7+ cells. Whereas CD7- cells of cutaneous T cell lymphoma exhibit a cerebriform nucleus (Sézary cells), no evidence was obtained for cerebriform nuclear morphology in normal CD7- T cells from peripheral blood. We suggest that these CD7- T cells represent a physiologic subset of mature T cells and may be the circulating counterpart of those lymphocytes that are found to be enriched in normal skin and in a variety of benign and malignant skin diseases.
Antigens, CD↗