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Biomedical subjects

H H Wolff

Publications and source records attributed to H H Wolff.

At least 19 recordsLinked to original sources

[Bacillary angiomatosis].

Bacillary angiomatosis (BA) is a rare infectious disease usually associated with HIV infection. Recent molecular biologic investigations confirm that both Rochalimaea henselae and Rochalimaea quintana can cause BA. The bacteria can be identified by Warthin-Starry staining and electron microscopy. The typical clinical signs are solitary or multiple dermal or subcutaneous nodules. Bone, liver, spleen and other organs may also be involved. We describe the clinical and histological features of a 39-year-old HIV-infected patient with cutaneous and bony lesions of BA. All manifestations of BA disappeared during therapy with erythromycin.

AIDS-Related Opportunistic Infections

[The role of basophilic leukocytes in inflammatory skin diseases].

Basophilic leukocytes are effector cells of the peripheral blood. They have several morphological and functional characteristics in common with tissue mast cells, such as expression of the high-affinity IgE receptor (Fc epsilon RI) and a high content of histamine within their granules. Functional comparison of human basophils and human mast cells isolated from different tissues revealed marked heterogeneity of mediator release after incubation with different secretagogues. Owing to their wide range of surface receptors, their (pro)inflammatory mediators released after activation, their mobility, and their rapid turnover, basophils appear basically to be potent effector cells, which migrate transiently into the skin during IgE-mediated (and/or IgE-independent) inflammatory reactions. The present paper reviews recent findings on the possible role of basophils for different immune reactions of the skin. Inhibition of basophil (and/or mast cell) activity seems to be necessary for both effective prophylaxis and therapy of allergic and inflammatory skin diseases. To date, however, the pharmacological modulation of mediator release from basophils lacks potent clinically useful compounds that can suppress the cellular response, since mast cell stabilizers such as cromoglycate and nedocromil are not effective. With a view to the development of active compounds, further in vitro studies should focus on the mechanisms of cell activation.

Basophils

[The Malignant Melanoma Central Register of the German Society of Dermatology 1983-1993. Epidemiologic developments and current therapeutic management of malignant melanoma of the skin].

The Central Malignant Melanoma Registry of the German Dermatological Society was founded in 1983 and has meanwhile developed into a major continuously updated multicentre project. Up to June 1994, 19,250 reports of cutaneous melanoma had been received, from 41 departments of dermatology in the former Federal Republic of Germany, from 14 departments in the former German Democratic Republic, from 2 departments in Austria, and from 1 department in Switzerland. Analysis of the data revealed some epidemiological trends over time during the years 1983 to 1993. (1) During the last 10 years the percentage of male patients has steadily increased, from an average of 38% in the year 1983 to 46% in 1993. (2) Early diagnosis of malignant melanoma improved during the period of time investigated. The percentage of diagnoses of primary tumour alone increased between 1983 and 1993. The mean tumour thickness (Breslow) decreased in the West Germany from 1.8 mm to 1.3 mm and in East Germany from 2.5 mm to 1.7 mm. The proportion of nodular melanoma decreased correspondingly from 29% to 14% in the former Federal Republic of Germany and from 40.6% to 22.6% in the former Germany Democratic Republic. During the years 1990 and 1993, 64% of melanoma patients with the primary tumour alone were operated on in two consecutive sessions in the former Federal Republic of Germany and 34.2% of those in the former Germany Democratic Republic. During this period 73.7% of all melanoma patients were operated on under local anaesthesia. In recent years surgical operations were more often performed in two consecutive sessions, mostly under local anaesthesia and with decreasing safety margins, in keeping with the decrease in tumour thickness. The present analysis shows that the Central Malignant Melanoma Registry is an important instrument for investigating trends in clinical epidemiology and treatment of malignant melanoma in the German-speaking countries.

Adult

Functional comparison of different histamine-containing IgE-receptor positive cells.

The present study was performed to investigate the histamine-releasing activity of non-immunological stimuli on cultured mast cell lines in comparison to isolated skin mast cells and basophils as human therapeutic target cells. The ionophore A23187 induced a dose dependent histamine release from all cell populations (enzymatically isolated human skin mast cells, human peripheral basophils and rat basophilic leukemia cells, RBL-1 and RBL-2H3). The lectin concanavalin A and the tripeptide formyl-methionyl-leucyl-phenylalanine activated only basophils, while the neural mediator substance P and compound 48/80 were active only in experiments with skin mast cells. Activators of protein kinase C (different phorbol esters and the non-phorbol mezerein) induced direct histamine release only from basophils. The data provide further evidence for heterogeneity of mast cells and indicate different signal transduction mechanisms following non-immunological activation.

Animals

Direct effects of second-generation H1-receptor antagonists on the activation of human basophils.

The present study was performed to investigate the putative suppressive effects of H1-receptor antagonists (HRA) of the second generation (astemizole (AS), cetirizine (CT), loratadine (LO), oxatomide (OX) and terfenadine (TF)) on the mediator release from human basophils activated by two classical stimuli. Anti-IgE-mediated histamine release was inhibited in a dose-dependent fashion by TF (maximum inhibitory value: 33.8 +/- 7.6%, 100 microM, n = 7), whereas the other HRA exhibited weaker activity. The anti-IgE-induced LTC4 production was strongly suppressed by TF, LO and OX (92.4 +/- 6.3%, 90.8 +/- 6.0% and 88.5 +/- 5.6%, 100 microM, n = 4-5), while AS was less active (56.4 +/- 4.1%, 100 microM, n = 5). Histamine release induced by incubation with grass pollen antigen (0.01%) was inhibited by TF (40.7 +/- 4.1%, 50 microM, n = 4), but the other HRA showed only low activity. The present findings suggest that some HRA might exhibit direct inhibitory effects on activation of IgE-receptor bearing cells.

Basophils

Immunohistochemical studies with skin mast cells.

Using different histochemical and immunohistochemical methods we demonstrate that isolated skin mast cells used for different pharmacological and biochemical studies exhibit the same staining pattern compared to skin mast cells in situ. Surface structures and enzyme content of the cells appear not to be influenced by the isolation technique. We also observed no differences in the staining pattern of mast cells in neurofibroma, a cutaneous disorder characterized by an increase of mast cell numbers.

Chymases

Investigations with the selective PKC inhibitor chelerythrine on human basophils.

Modulation of protein kinase C (PKC) activity in basophils (B) can influence IgE-mediated histamine release (HR). The present study investigated the effects of chelerythrine, which inhibits isolated PKC (IC50 0.7 microM), on different activation pathways in B. Fc epsilon RI-mediated HR was strongly inhibited by chelerythrine (86.5 +/- 5.4%, 5 microM, n = 11). TPA-induced mediator release was also suppressed: 77.1 +/- 8.5% inhibition (7.5 microM). HR due to non-immunological stimuli (A23187, FMLP) was strongly inhibited by chelerythrine. Previously, other selective PKC-inhibitors have been shown to potentiate IgE-mediated HR from B suggesting a negative modulatory role of PKC, whereas non-specific inhibitors such as staurosporine inhibited HR. Chelerythrine might therefore be less selective for PKC. This may be indicated by the fact that chelerythrine inhibits PKC at its catalytic domain, which is homologous with other protein kinases.

Alkaloids

Pharmacological investigations with different protein kinase C inhibitors on IgE-dependent and IgE-independent activation of human basophils.

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.

Alkaloids

Pharmacological studies on the role of protein kinase C in signal transduction of human basophils.

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.

Basophils

[Scabies norvegica sive crustosa in a patient with AIDS].

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.

AIDS-Related Opportunistic Infections

[Bullous poikilodermatitic amyloidosis of the skin with junctional bulla development in IgG light chain plasmacytoma of the lambda type. Histology, immunohistology and electron microscopy].

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.

Actin Cytoskeleton

[X-chromosome dominant chondrodysplasia punctata (Happle) in a boy].

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.

Biopsy

[Tryptophan-induced fasciitis-scleroderma-eosinophilia syndrome].

A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily).

Aged

Cutaneous metastases from follicular thyroid carcinoma: histology, immunohistology, and electron microscopy. A report of two cases.

Cutaneous metastases from thyroid carcinoma are extremely rare. We report 2 cases of skin metastases from a follicular thyroid carcinoma. A 53-year-old female patient underwent subtotal thyroidectomy because of the clinical suspicion of malignancy. Histological examination of the resected tissue did not clearly prove malignant features. Eight years later a cutaneous metastasis erupted next to the operation site at the neck. A 66-year-old female patient noticed a growing solitary skin nodule in the occipitoparietal region of her scalp 2 years before a follicular thyroid carcinoma was detected.

Adenocarcinoma