Biomedical subjects
Publications and source records attributed to H Holzmann.
Using human fibroblast cultures in vitro, a study was carried out on the effect of sera from patients with psoriasis and from healthy volunteers on DNA and protein synthesis. Thymidine incorporation was enhanced under the influence of psoriatic sera whereas there was no difference in amino acid incorporation in the control sera. Based on these results, we conclude that systemic psoriasis may be under humoral control.
A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic scleroderma (PSS), and 42 patients (32 female, 10 male) with morphea. HLA ABCDR/DQ, glyoxalase and properdin factor B (GLO and BF) phenotypes of patients were compared with 193 healthy controls. Four PSS family studies were performed. The following relative risk (rR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22) and in morphea: A3 (1.43), B7 (1.39), B40 (1.81), BW60 (2.49), DR2 (2.38) and DRW8 (2.55), indicating a relatively weak, HLA-linked genetic predisposition for the manifestation of these dermatological disorders. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies such as those in our PSS group are related to high (or pathologic) immune response (autoimmune disorders). In contrast, A3 B7 DR2 elevations such as those recorded in our morphea group correlate with low immune response. Following exposition to certain suspected environmental factors (quartz, chemical solvents, drugs, viral fragments), the HLA phenotype may thus predipose some individuals--predominantly women--to different clinical patterns of the disease. HLA typing may thus be useful in clinical differential diagnosis (recent subtyping protocols) and possibly also for determination of the prognosis, i.e. HLA-B8 seems to be related to an acute, inflammatory course of PSS, and HLA-B7/DR2, to rather mild morphea patterns.
The anti-psoriatic compound anthralin (dithranol, cignolin) was determined to exhibit a strong cytostatic activity on HeLa-Köln cells; an ED50 concentration of 1.2 microM was determined for the cells. These growth-inhibition data were confirmed by thymidine-uptake experiments. The drug anthralin was determined to be neither direct a mutagen nor a premutagen in the Ames test using Salmonella typhimurium strain TA 100 (anthralin-concentration = 5 microM). Moreover, this compound was a strong inhibitor of benzo(a)pyrene monooxygenase, an enzyme which causes the metabolic conversion of premutagens to mutagens. These data demonstrate anthralin to be an antipsoriatic compound devoid of mutagenic property in vitro with regard to base-pair substitutions and provided at least with some antimutagenic potential.
In various skin diseases with a possible viral and/or autoimmune etiology, the peripheral lymphocytes were studied with regard to serum interferon levels and the interferon-induced activity of (2'-5')-oligoadenylate synthetase (OAS). This enzyme is a sensitive marker of interferon and can be detected even some days after the clearance of interferon from the blood. In patients with pityriasis rosea (n = 13), basal cell carcinoma (n = 12), malignant melanoma (n = 11), and molluscum contagiosum (n = 13), the serum interferon levels were not increased. In comparison to healthy persons, 5 patients with melanoma (Clark's levels I, I-II and II) showed a significantly elevated activity of OAS. In 6 other patients with melanoma (Clark's level III, III-IV and IV), the OAS activity was not increased. Although the elevated activity of OAS found in patients with melanoma of lower Clark's levels indicates a participation of the interferon system in the course of the disease, our results do not allow a clear statement regarding a viral and/or an autoimmune etiology of the skin disease.
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In this study a combination of clinical and experimental investigations demonstrates the antiproliferative effect of the coal tar-containing preparation Berniter. From a concentration of 70 micrograms/ml onwards (= 0.35 micrograms coal tar/ml) Berniter inhibits DNA synthesis of transformed human keratinocytes in vitro. The growth inhibiting effect is reversible up to the ED50 concentration (257 micrograms Berniter/ml = 1.3 micrograms coal tar/ml). The tar-free vehicle has no identifiable effect on the proliferation of the cells at a concentration of 260 micrograms/ml. However, at higher concentrations (ED50 = 1023 micrograms/ml) the vehicle also inhibits cell growth, this inhibition being irreversible. The effect of Berniter and the tar-free vehicle on amino acid metabolism corresponds with the reduced growth rate. The ED50 concentrations (331 micrograms/ml for Berniter and 1445 micrograms/ml for the tar-free vehicle) are higher than those in the investigation of the proliferation. The clinical trial was performed in two groups of 12 and 11 patients, respectively, suffering from Psoriasis capillitii. After 3 days' topical treatment of both groups with salicylic acid for scaling, one group was treated for 4 weeks with betamethasone-17-valerate (in the following briefly called Bet-17-v), as a commercial lotion. The other group received Bet-17-v initially for 3 days and was then treated for 4 weeks with Berniter. The 4 parameters used for evaluation (erythema, scaling, infiltration and itching) showed a more significant improvement in the Berniter group than in the Bet-17-v group. Subjectively, treatment with Berniter was assessed to be preferable.(ABSTRACT TRUNCATED AT 250 WORDS)
The cases are reported of two patients afflicted with acroangiodermatitis (pseudo-kaposi) in paralysed legs. From the pathogenetic point of view, the lack of a muscle pump and, possibly, disturbed innervation of vessels are of importance.
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The corticosteroid and androgen metabolites in the urine of 37 test subjects (11 healthy volunteers, 16 patients with eczema, and 10 patients with psoriasis) were investigated by means of gas chromatography and mass spectrometry. In addition, we studied the cortisol and testosterone levels in the plasma by radioimmunoassay. Those patients who had been treated with corticosteroids during the last two weeks were excluded. Our findings revealed that the excretion rate of steroid metabolites was significantly reduced in dermatological patients. The excretion rate of corticosteroids in urine was decreased an average of 25% (eczema) and 29% (psoriasis). The reduction of the androgen metabolites amounted to 26% and 31%. Cortisol and testosterone levels in the plasma were normal in all the cases.
We report on a 70-year-old woman suffering from diabetes mellitus dependent on insulin and associated with malignant hypertension. Following heart catheter examination for the dilatation of the renal arteries, she developed acute, painful, persistent livedo racemosa of the buttocks and the lower extremities. Histological investigation revealed embolism of cholesterol crystals in arterioles of the corium-subcutis region. On the basis of the cases described in the literature so far, we discuss the clinical spectrum of cutaneous cholesterol embolism.
The anti-psoriatic compound anthralin (cignolin) was determined to exhibit a strong cytostatic activity on HeLa-Köln cells; an ED50 concentration of 1.2 microM are cytotoxic for the cells. These growth-inhibition data were confirmed by thymidine-uptake experiments. The drug anthralin was determined to be neither direct a mutagen nor a premutagen in the Ames test using Salmonella typhimurium strain TA 100 (anthralin-concentration = 5 microM). Moreover, this compound was a strong inhibitor of benzo(a)pyrene monooxygenase, an enzyme which causes the metabolic conversion of premutagens to mutagens. These data demonstrate anthralin to be an anti-psoriatic compound devoid of mutagenic property in vitro with regard to base-pair substitutions and provided at least with some antimutagenic potential.
Bone scintigraphy using 99mTc-EHDP was carried out in 147 psoriatics of both sexes and in 35 nonpsoriatic patients. The psoriatics were subdivided into four groups according to clinical aspects: psoriasis vulgaris (Pv, n = 55), psoriasis inversa (Pinv, n = 32), psoriasis pustulosa of the Königsbeck-Barber type (PpK-B, n = 28), and pustulosis palmaris et plantaris (Ppp, n = 32). The following frequencies of joint involvement were found in the different groups: Pv = 18.3%; Pinv = 22.6%, PpK-B = 11.1%; Ppp = 12.5%; control group 2.3%. In patients suffering from psoriasis vulgaris and psoriasis inversa a pathologic preferential radionuclide uptake was demonstrated in the small peripheral joints of the hands and fingers. The characteristic psoriatic pattern with axial and transverse joint involvement was found in all groups of psoriatic patients. No correlation could be proved between age and pathologic accumulation of the radionuclide or between duration of psoriasis and joint involvement. The so-called anterior chest wall syndrome was found in all patients, but predominantly in those with psoriasis palmaris et plantaris. Finally the indications for bone scintigraphy are discussed.
A new classification of forms of progressive systemic scleroderma (PSS) is presented. Compared with previous classifications, it includes not only frequent, typical forms of PSS, but also rarer manifestations. For the first time, it considers pathogenetic factors, such as the phenomena which have become known concerning the immunological system, and distinguishes between noninflammatory and inflammatory subtypes. Etiological (in this case, immunogenetic) criteria are also considered. This classification is open to further differentiation and development.
The objective of the present investigation was to establish the frequency of systemic spreading of urticaria pigmentosa by means of bone and bone marrow scintigraphy as a noninvasive imaging technique with a low radiation exposure. Bone scintigraphy: Seven of nine patients investigated showed diffuse and focal nuclide accumulation. After exclusion of other causes by reference to the case history and the clinical and chemical laboratory findings, these nuclide accumulations were regarded as mastocytosis-specific in accordance with the atypical localization. Bone-marrow scintigraphy: All the patient investigated showed a peripheral expansion of the bone marrow. This must be interpreted as an expansion of the macrophages of the bone marrow on the basis of the method used. Since the mast cell is regarded as a more highly differentiated form of the same cell-type as macrophages/monocytes, on the basis of the scintigraphic results presented, urticaria pigmentosa can be regarded pathogenetically as a hyperplasia of the macrophages of the bone marrow organ, with increased differentiation in mast cells. The extent of this differentiation and its pathological quality then determine the clinical signs and symptoms (cutaneous, systemic, or malignant mastocytosis). Urticaria pigmentosa thus has the character of a systemic disease.
The diagnosis of Kyrle's disease is based on both clinical and histological findings. The penetration of the keratin plug into the dermis is no pathognomonic feature but the result of pathologic events. Kyrle's disease may be caused and promoted by association with other diseases going along with hyperkeratosis and causing damage to tissue proteins by non-enzymatic glycosylation (e. g., diabetes mellitus and renal failure).
5 patients suffering from T-cell lymphomas at different stages were treated with human alpha-interferone. One of the patients showed mild partial remission, two patients had but a poor and short-lasting improvement of their condition, in one case there was no change at all, and in another case, worsening of the clinical picture was observed. Controls of the relevant laboratory parameters (including NK-cells, T-cell subpopulations, antibodies and complement, oligo-(A)-synthetase, and interferone serum levels) did not always reveal the changes that had been expected to be induced by the therapy.