Biomedical subjects
Publications and source records attributed to H H Wolff.
A case of atopic dermatitis in a 12-year-old boy with spontaneous clearing of skin lesions in areas of paraplegia after trauma is reported. This observation might confirm the important pathogenetic role of neuropeptides in the development of atopic dermatitis.
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Monoclonal antibody HMB-45 was previously thought to be melanoma specific antibody and was taken recently as a marker for melanocyte proliferation or activation. A single UV-irradiation system which may induce a functional activity change in melanocytes was used to test the irradiated epidermal melanocyte for expression of HMB-45. Melanocytes, in the epidermis of the biopsies taken 7 days after a single UV exposure, showed markedly stained HMB-45, accompanied by morphological changes such as enlarged size, rich cytoplasma and elongated dendrites. We conclude that since morphological changes in irradiated melanocytes may be interpreted as signs of functional activity changes, melanocytes are exposed to stimulatory factors induced by UV light and get into a functional activating state to produce melanosome and HMB-45 antigen. Besides, the presence of HMB-45 in a single UV exposed epidermal melanocyte may support the hypothesis that its expression is inducible and is closely related to the functional activity of melanocyte.
Relapsing polychondritis is a systemic disease associated with a destruction of cartilage in various parts of the body. Sera from six patients with relapsing polychondritis and one patient with microscopic polyarteritis nodosa as well as from six controls were analyzed by immunoblotting and ELISA. All patients had autoantibodies against native collagens II and IX. The serum from one patient showed a strong reaction with all three collagen chains of the high molecular weight fraction of collagen IX after denaturation; sera from four patients showed autoantibodies against alpha 2 (XI) and sera from three patients showed autoantibodies against the covalently cross-linked gamma component of collagen XI. The presence of autoantibodies against collagens II, IX, and XI, which form the major fibrillar scaffold in cartilage and mediate the interaction of collagen fibrils and proteoglycan, suggests that autoantibodies against cartilaginous collagen may play a crucial role in the pathogenesis of relapsing polychondritis and microscopic polyarteritis nodosa.
Application of liposomal phospholipids (Natipide II) caused a significant decrease in erythema induced by UVB (280-312 mm) in patients with skin types II and III (n = 31). In accordance with findings in other organs, e.g. liver, the present findings suggest that phospholipids are capable of reducing H2O2 formation and/or increasing glutathione synthesis in human skin, thus reducing erythema formation by preventing oxidative stress.
In the present study different selective inhibitors of the multifunctional serine/threonine kinase protein kinase C (PKC) were investigated on classical activation pathways of basophils in comparison to the nonselective protein kinase inhibitor staurosporine. The potent inhibitors Ro 31-7549, Ro 31-8220, calphostin C and ilmofosine (BM 41.440), which show selectivity for PKC in vitro, significantly potentiated Fc epsilon RI-mediated histamine release up to 50% vs. controls at concentrations > 10(-7) mumol/l but were without any intrinsic histamine releasing activity. Direct activation of cellular PKC by phorbol ester was suppressed by all compounds apart from ilmofosine at the same concentrations. We did not observe statistically significant effects of selective PKC inhibitors on exocytosis induced by the peptide formylmeth-leu-phe (FMLP) or the ionophore A23187, whereas staurosporine potentiated the FMLP-induced histamine release in a dose-dependent fashion: maximum potentiation was 63.5 +/- 8.9% vs. control at 1 mumol/l (n = 4). The findings suggest that PKC exhibits differential functions during biochemical events of stimulus-secretion coupling in human basophils supposedly by its distinct subtypes. With respect to the present data, TPA-induced and IgE-mediated signals are not closely correlated.
After repeated contact, many surfactants will cause skin irritation and, especially, dryness and scaliness. Earlier in vitro investigations suggested that the irritation potential of anionic surfactants was related to the induction of hydration of isolated stratum corneum membranes. We have now investigated early surfactant-stratum corneum interaction in vivo. Sodium salts of n-alkyl sulfates with variable carbon chain length (n = 8-14) were tested for the promotion of stratum corneum hydration by measurements of skin surface water loss and electrical capacitance measurements in healthy adult human volunteers. The surfactant-induced increase in water uptake was confirmed in vitro by means of isolated stratum corneum samples and surfactant solutions labeled with tritiated water. In a parallel experiment the irritation potential of these compounds was investigated by 24-h patch testing in human volunteers. The irritant responses were quantified non-invasively by erythema (skin color reflectance measurements) and transepidermal water loss measurements. Hydration of stratum corneum exposed for 5 min to surfactant solutions significantly exceeded that of controls (phosphate-buffered saline). It increased with application time and was concentration dependent, saturable with increasing concentration, and rapidly reversible. Baseline hydration was re-established only 10-15 min after treatment termination. Induction of hydration was closely correlated with the irritation potential of the investigated compounds. It initially increased with increasing carbon chain length. The maximum response was obtained for the C12 analogue (sodium lauryl sulfate). With further increases in molecular size induction of stratum corneum hydration subsequently decreased. We have demonstrated that anionic surfactants increase stratum corneum hydration in vivo. The present results suggest that the mechanisms responsible for the hydration are related to the irritation properties of these compounds.
Two infertile men heterozygous for a 13;14 Robertsonian (Rb) translocation were investigated by means of synaptonemal complex studies, testicular histology, and semen analysis. In both individuals interaction between the Rb trivalent and the XY pair was observed. Twenty percent of pachytene cells analyzed in one patient showed XY-trivalent association which correlated with malformed spermatids; the higher rate of XY-trivalent association (approximately 47%) in the second proband corresponded with complete spermatogenic arrest. The data presented indicate a positive correlation between increased frequency of XY trivalent association and the degree of germ-cell impairment.
The process of high-affinity IgE receptor (Fc epsilon RI)-mediated signal transduction in human basophils and mast cells is accompanied by activation of protein kinase C (PKC). The present study investigated the effects of a novel protein kinase inhibitor with in vitro selectivity for PKC (CGP 41251) in comparison with the potent but non-selective PKC inhibitor staurosporine on the activation of human peripheral basophilic leukocytes and enzymatically isolated human skin mast cells. CGP 41251 exerted strong concentration-dependent inhibitory effects on Fc epsilon RI-mediated histamine release from both cell populations. In addition, the IgE-mediated generation of arachidonic acid metabolites (leukotriene C4/D4 and prostaglandin E2) from human basophils was also significantly inhibited by this compound. Its action was not significantly different from the action of staurosporine. Direct activation of cellular PKC by the phorbol ester 12-o-tetradecanoyl-phorbol-13-acetate and subsequent histamine release from basophils was also inhibited by both compounds. CGP 41251 did not suppress N-formyl-met-leu-phe- or A23187-induced activation of basophils, whereas A23187-induced mediator release from human skin mast cells was inhibited in a concentration-dependent fashion. We conclude that an increase of in vitro selectivity for PKC does not significantly enhance inhibitory effects on immunological activation of histamine-containing cells. Moreover, nonimmunological pathways of signal transduction in basophils and mast cells appear to be mediated by distinct biochemical events.
Protein kinase C (PKC) is suggested to be important for signal transduction of histamine-containing cells. The present study investigated the putative role of PKC in enhanced mediator release of basophils in atopic dermatitis (AD). Basophils were isolated from patients with severe AD (mean serum IgE level of 5,165 U/ml) and from healthy controls, and the effects of potent activators of PKC on histamine release were studied. The phorbol esters 12-o-tetradecanoyl-phorbol-13-acetate and phorbol-12,13-dibutyrate and the nonphorbol mezerein induced a dose-dependent mediator release, which was significantly lower in 'atopic' basophils at concentrations > or = 1 microM. Recently, PKC levels have been shown to be lowered in atopic leukocytes compared to cells from healthy controls. The lowered response of PKC towards direct activation and lowered PKC levels may be due to high serum IgE levels and allergen exposure in vivo with subsequent down-regulation of different key elements of signal transduction.
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We report a hibernoma located on the forehead in a 52-year-old female patient. The hibernoma is a rare tumour derived from brown adipose tissue. Location on the forehead is unusual and has not been reported before.
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Recent investigations have demonstrated that activation of basophils involves the activation of protein kinase C (PKC). In the present study the effects of different nonselective and selective PKC inhibitors on IgE-mediated histamine release from human basophils were investigated. While potent but nonselective inhibitors such as staurosporine exerted a dose-dependent inhibition of Fc epsilon-receptor-mediated histamine release, staurosporine derivatives with high selectivity for PKC potentiated the IgE-mediated response. The results provide evidence that the histamine release-inhibiting activity of protein kinase inhibitors is inversely correlated with their specificity for PKC. This may confirm the hypothesis that PKC exerts a negative modulatory role during the process of stimulus secretion-coupling following receptor aggregation in basophils. Moreover, investigations with phorbol esters and diacylglycerol derivatives as potent PKC activators show that direct cellular PKC activation and antigen-stimulated mediator release are not closely correlated.
We report the case of a 20-year-old homosexual man with HIV-1 infection presenting with AIDS. An erythemato-squamous, papulo-crustous, non-itching dermatosis of 4 months duration was finally diagnosed as Norwegian scabies in the immunosuppressed. For clinical and epidemiological reasons the high contagiosity of this rare entity requires an appropriate therapy without delay.
A 75-year-old patient presented with bullae, poilokilodermatic skin and nail dystrophy as signs of systemic amyloidosis 1 year before an IgG myeloma of the lambda type was diagnosed. The skin lesions appeared at mechanically irritated locations on the trunk and at the tensor sites of the extremities. Histology showed a subepidermal blister and necrotic keratinocytes in the epidermis. There were amyloid deposits in the papillary dermis perivascular, and in the deep dermis around eccrine glands and in arrectores pilorum muscles. Polyclonal antibodies allowed classification of the deposits as amyloid composed of lambda light-chain immunoglobulins. Electron microscopy revealed globoid deposits of non-branching filaments typical of amyloid. The blister was formed at the level of the lamina lucida, with the lamina densa at the base of the bottom of the bulla. So far, junctional blister formation in bullous amyloidosis of the skin has been described only once. Our case is the second report of this blister type, and to our knowledge the first published report of a junctional blister in myeloma-associated systemic amyloidosis.
The case of a newborn boy with ichthyosiform erythroderma, asymmetrical shortening of the femur and sectorial cataract is reported. The hyperkeratotic areas cleared within 2 months, resulting in follicular atrophoderma. The clinical findings and course of the disease, and also the histological and ultrastructural features, indicate an X-linked dominant chondrodysplasia punctata (Happle). Since a normal male karyotype (46, XY) is present, a half-chromatid mutation of the maternal gamete and a somatic mutation are considered as possible explanations for this mosaic phenotype.