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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 253 records · Page 14Linked to original sources
PubMed1985

Epidermal cells as accessory cells in the generation of allo-reactive and hapten-specific cytotoxic T lymphocyte (CTL) responses.

The capacity of epidermal cells (EC) to stimulate T cell activation is a Langerhans cell (LC)-dependent phenomenon. In all in vitro assays probed, LC subserve antigen-presenting cell functions in that they display surface-bound foreign or altered-self structures and thereby activate T cell responses. In contrast, attempts to demonstrate accessory cell (ACC) function of LC-containing EC have yielded negative results, i.e., EC lacking foreign cell surface antigens were not able to restore cytotoxic T lymphocyte (CTL) responses in Ia+ adherent cell-depleted cultures. Reasoning that the ACC function of EC might be critically linked to cluster formation between LC and other cell types involved, we tested the ACC function of EC under experimental conditions that allow a close physical contact between the cell types involved (round-bottomed microtiter plates and brief centrifugation of culture plates). By using these modifications, the failure of highly purified B6 T cells to develop alloreactive CTL activity when stimulated with either highly purified, mitomycin C-treated C3H or B6CF1 T cells was restored by the addition of B6 EC. The CTL thus generated produced significant lysis of Con-A-stimulated C3H or BALB/c, but not B6, spleen cell targets. In a similar fashion, TNP- or FITC-specific CTL were generated when (in a syngeneic system) mitomycin C-treated TNP- or FITC-modified stimulator T cells and responder T cells were co-cultured in the presence, but not in the absence, of unmodified EC. The capacity of EC to restore CTL activity in a culture system depleted of Ia-bearing cells was not dependent upon their H-2 type, but was critically linked to the presence of Ia-bearing LC. We therefore conclude that LC-containing EC can subserve the ACC function in the generation of H-2-restricted CTL, provided that culture conditions are chosen that allow a close physical contact between the cell types involved.

Animals↗
PubMed1985

Thymopentin treatment of herpes simplex infections. An open, monitored, multicenter study.

Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.

Adjuvants, Immunologic↗
PubMed1985

[Photochemotherapy (PUVA): pro and con].

Photochemotherapy (PUVA) clears severe psoriasis in 90% of cases and is therefore the most effective treatment available for this disease. Stringent criteria are required with regard to patient selection, dosimetry and follow-up. Therefore PUVA should only be performed by appropriately trained and experienced dermatologists who are sufficiently qualified to weigh the severity of the disease against potential side-effects, and to consider the respective risk/benefit ratio of other alternative treatment methods before initiating treatment. As is the case with other forms of chemotherapy, PUVA also carries the risk of long-term side-effects (particularly actinic carcinogenesis) similar to those of long-term, high-intensity ultra-violet radiation. As yet it is not sufficiently clear whether PUVA acts as a true carcinogen or as a promoter and whether the immunosuppression exerted by PUVA under experimental conditions is clinically relevant. For these reasons and because PUVA requires continuous monitoring of patients, it is neither suitable for minor cases, nor for mass therapy or treatment at home. It is, however, the treatment of choice for severe psoriasis and for those forms of psoriasis which represent a decisive professional and social handicap for the patient. Before a decision is made to employ PUVA as a treatment for psoriasis, its benefits and risks should be compared with those of alternative forms of treatment, which should be subjected to equally stringent evaluation criteria.

Animals↗
PubMed1984

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Epidermis↗
PubMed1984

Photochemotherapy for cutaneous T cell lymphoma. A follow-up study.

In 1975 we started a prospective study on oral methoxsalen photochemotherapy (PUVA) in cutaneous T cell lymphoma (CTCL). The first short-term follow-up of nineteen patients (1978) showed that PUVA may induce long-lasting remission in early stages, and that eventual relapses respond comparably well when PUVA is resumed. We now present the follow-up data of the original nineteen patients, covering a period of up to 7 years, and of an additional twenty-five patients who have entered the trial since April, 1977. Similar to earlier reports, all patients with eczematoid and plaque lesions (stages IA and IB) cleared. Likewise, eczematoid and plaque lesions in patients with early tumors (stage IIB) were cleared. During a mean follow-up of 44 months, 55% of stage IA patients and 39% of stage IB patients remained free of disease. In patients who experienced relapses, the mean disease-free interval was 20 months for stage IA and 17 months for stage IB. All patients with stage IIB experienced multiple relapses and only three of seven were alive after 6 years, despite additional x-ray or cytotoxic therapy. The observation in this study that five of nine stage IA patients and ten of twenty-six stage IB patients have remained in continuous remission after a single PUVA course for up to 79 months indicates that PUVA may induce long-lasting disease-free intervals if used in the early stage of disease. However, the observation period still does not prove whether permanent cure can be achieved in some cases or not.

Combined Modality Therapy↗
PubMed1984

Dysplastic nevus syndrome with multiple primary amelanotic melanomas in oculocutaneous albinism.

Melanomas are rare in albinos, although the incidence of solar radiation-induced skin tumors is extremely high because of the absence of photoprotective melanin. This report describes a 40-year-old white woman with tyrosinase-negative oculocutaneous albinism who developed four primary amelanotic melanomas--three of the superficial spreading and one of the nodular type-and, in addition, displayed nevi that exhibited histologically the characteristic features of dysplastic nevi. The concomitant occurrence of multiple primary melanomas and several dysplastic nevi classifies the patient's condition as "dysplastic nevus syndrome," which to our knowledge has not been described in albinism so far.

Adult↗
PubMed1984

Safety and therapeutic effectiveness of selected psoralens in psoriasis.

This review summarizes the most important facts regarding the clinical effectiveness of oral photochemotherapy for psoriasis with UV radiation at 320-400 nm (UVA) and selected furocoumarins. The most widely used compound is 8-methoxypsoralen (8-MOP); its effectiveness has been documented by many clinical trials. Oral 5-methoxypsoralen (5-MOP) has been evaluated as an alternative drug because it is less erythemogenic and thus reduces the danger of accidental over-exposure. It has been as effective as 8-MOP in clearing psoriasis, but the UVA doses required were considerably higher. Although oral 4,5',8-trimethylpsoralen does not clear psoriasis satisfactorily, excellent treatment results have been recorded when it was applied topically. The 3 drugs produce bifunctional adducts with DNA (cross-links), which may be of particular importance for mutagenesis and tumor formation. In an attempt to reduce possible oncogenic hazards, investigators are currently testing non-crosslinking furocoumarins for their therapeutic effectiveness. At present, these compounds are available for topical use only. 3-Carbethoxypsoralen has been reported to produce excellent treatment results by others but was ineffective in our clinical trials. Similarly disappointing was the application of 4,5'-dimethylangelicin and 5-methylangelicin. Although monofunctional compounds also inhibit cell proliferation in vitro, it appears that cross-linking is a prerequisite for the therapeutic success in psoriasis. The actual important of cross-links, however, remains to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxypsoralen↗
PubMed1984

[Systemic lupus erythematosus in hereditary complement 4 deficiency].

A genetically determined complete absence of the fourth component of complement, C4, associated with systemic lupus erythematosus has been detected in one member of another family. Observations made in this patient, the ninth described so far in whom systemic lupus erythematosus and C4 deficiency occur have confirmed that this condition presents with a characteristic clinical picture: there is pronounced sensitivity to sunlight and to cold with Raynaud's phenomenon; skin lesions are found predominantly in locations typical for subacute cutaneous lupus erythematosus and, remarkably, on the palms and soles. As was the case in two families described earlier, the C4-deficient gene was associated with the HLA-haplotype AW30, B18, DR7; BfS1.

Adult↗
PubMed1983

Efficacy of triclabendazole against Fasciola hepatica in sheep and goats.

Triclabendazole (Fasinex), a new fasciolicide of the benzimidazole group, was tested in sheep and goats. A controlled test with 24 artificially-infected sheep revealed a 100% efficacy of triclabendazole at a dose of 10 mg kg-1 body weight against Fasciola hepatica aged 4 and 13 weeks, respectively. In naturally-acquired severe subacute to chronic fascioliasis in 66 sheep and 10 goats, the drug was highly effective in three trials when applied at 10 mg kg-1 in sheep and at 5 mg kg-1 in goats. Triclabendazole was well tolerated, whereas side effects occurred in one trial with niclofolan (Bilevon-M) (3 mg kg-1) which was used for comparison.

Animals↗
PubMed1983

Epidermal cell-induced generation of cytotoxic T-lymphocyte responses against alloantigens or TNP-modified syngeneic cells: requirement for Ia-positive Langerhans cells.

The role of epidermal cells (EC) in the activation of T-cell proliferation is well established. In this study we asked whether EC can provide a stimulus resulting in the generation of genetically restricted T-cell cytotoxicity. For this purpose, C57Bl/6 or C3H/He highly purified, accessory cell-depleted responder splenic T lymphocytes, were stimulated in 5-day cell-mediated cytotoxicity cultures with mitomycin C-treated allogeneic or trinitrophenyl (TNP)-modified syngeneic EC, or, for control purposes, with unfractionated spleen cells (SC). Untreated and complement (C')-treated EC induced strong cytotoxic T lymphocyte (CTL) activity in highly purified allogeneic T cells and, in analogy, TNP-modified EC led to the generation of TNP-self CTL, as tested in 4-h 51Cr release assays against allogeneic or TNP-modified syngeneic EC or SC targets. These cytotoxic responses were comparable in magnitude to those seen with allogeneic or TNP-modified syngeneic SC stimulators. In contrast, alloreactive or TNP-self CTL responses were not generated when stimulating EC were depleted of Langerhans cells by pretreatment with anti-Ia monoclonal antibodies plus C' or, for control purposes, when highly purified T-cell stimulators were used. These results demonstrate that EC induce the generation of alloreactive and TNP-self CTL in the absence of Ia-positive splenic accessory cells and that Ia-bearing Langerhans cell are required for this process to occur.

Animals↗
PubMed1983

Expression of Thy-1 antigen by murine epidermal cells.

We report on the occurrence of a cell population within the murine epidermis which, by both morphologic and surface property criteria, is distinct from all other epidermal cell types known so far. These previously unrecognized cells are evenly distributed within the epidermis, display a primarily dendritic shape, exhibit a lobulated nucleus, contain large amounts of vimentin type intermediate-sized filaments, but lack desmosomes, melanosomes, Merkel cell granules, and Birbeck granules. As opposed to melanocytes, these cells fail to display tyrosinase activity. Surface marker analysis reveals these cells to uniformly express the Thy-1 antigen and to lack I-A and I-E/C antigen specificities. A major portion of these Thy-1-bearing cells are reactive with a monoclonal antibody to the Ly-5 determinant whereas attempts to demonstrate Lyt-1,2,3 antigens consistently yield negative results. These findings strongly suggest that Thy-1+ epidermal cells originate from the bone marrow; however, their precise relationship to distinct members of the hemopoietic differentiation pathway remains to be established.

Animals↗