Biomedical subjects

H Holzmann

Publications and source records attributed to H Holzmann.

At least 73 records · Page 4Linked to original sources

PubMed1990

A new model of epidermal differentiation: induction by mechanical stimulation.

In vivo, epidermal cells are committed to terminal differentiation in which they undergo a series of morphological and biochemical changes. In vitro, keratinocytes are able to undergo some steps of this differentiation process only. In view of the fact that in vivo skin is continuously subjected to mechanical stress, we investigated the stimulation of differentiation of transformed keratinocytes by mechanical stimulation. The cells, grown in plastic culture dishes, were periodically treated with weights exerting a pressure of 0.015 Ncm-2. This stimulation lasted from 1 to 4 days. Then keratinocytes were examined using indirect immunofluorescence, 3H-thymidine and 14C-amino acid incorporation, SDS polyacrylamide gel electrophoresis, and Western blotting. Following pressure treatment, the previously monolayered keratinocytes locally grew up to several layers, the number of horny scales increased and, after 4 days, the pattern of cytokeratin was modified. The total amount of keratin increased, forming granular accumulations, while the proliferation rate of the cells decreased. Both the 67 kDa and 49.5 kDa keratin subunits increased in stimulated cells. Moreover, a weak keratin band of 44 kDa appeared that was not present in controls. The results demonstrate that cyclic pressure promotes differentiation of cultivated epidermal cells.

Amino Acids↗

PubMed1990

Fungal flora of human faeces in psoriasis and atopic dermatitis.

Faeces samples taken from 343 patients with psoriasis and 581 patients with atopic dermatitis were subjected to mycological examination. Yeasts were detected in 68% of the psoriatics and in 70% of the patients with atopic dermatitis but in only 54% of the controls (n = 50). Qualitative analysis revealed a predominance of Candida albicans. Non-pathogenic yeasts constituted only 1% in each of these groups. Of the hyphomycetes, Geotrichum candidum occurred in 22% of the psoriatics, in 10% of the atopic dermatitis patients and in 3% of the controls. Aspergillus species were found in 1% of the patients but not in the controls. Stool samples collected on three consecutive days from 141 patients were examined for yeasts. Qualitative correlation between all three samples was shown in 95% of the patients and quantitative correlation in 38%. Deviations were mainly of exponential magnitude. Germ cell concentration of 10(4) cells per ml and above were measured in 38% of the psoriatics and in 28% of the atopic dermatitis patients but in only 22% of the test subjects with healthy skin. There was no correlation between the concentration levels of yeasts in the faeces and the extent of psoriasis or atopic dermatitis.

Aspergillus↗

PubMed1990

A single amino acid substitution in envelope protein E of tick-borne encephalitis virus leads to attenuation in the mouse model.

We have determined the virulence characteristics of seven monoclonal antibody escape mutants of tick-borne encephalitis virus in the mouse model. One of the mutants with an amino acid substitution from tyrosine to histidine at residue 384 revealed strongly reduced pathogenicity after peripheral inoculation of adult mice but retained its capacity to replicate in the mice and to induce a high-titered antibody response. Infection with the attenuated mutant resulted in resistance to challenge with virulent virus. Assessment of nonconservative amino acid substitutions in other attenuated flaviviruses suggests that a structural element including residue 384 may represent an important determinant of flavivirus virulence in general.

Amino Acid Sequence↗

PubMed1990

[Serum interferon level and (2'-5')-oligo(A) synthetase activity in malignant melanoma].

Both the serum levels of interferon and the activity of lymphocytic (2'-5')-oligoadenylate synthetase (OAS) of 37 patients suffering from malignant melanoma-15 with low (I,I-II,II) and 22 with higher (III,IV,V) Clark levels-were compared with those of a group of healthy controls in order to detect a possible involvement of the interferon system in the pathological process. Previous results obtained in studies on relatively small groups of patients had suggested that melanoma patients with low Clark levels (i.e. biologically early melanoma) show elevated activities of OAS, while those with higher levels show normal values. In our present investigation on a larger sample of patients, we did not find any differences between these two melanoma groups and healthy persons with regard to the OAS activity. Thus we were not able to confirm the provisional results set up by previous studies.

2',5'-Oligoadenylate Synthetase↗

PubMed1990

HLA-antigen frequencies in patients with progressive systemic sclerosis and morphea.

A possible HLA disease association was investigated in 40 patients (38 female, 2 male) with progressive systemic sclerosis (PSS) and 42 patients (32 female, 10 male) with morphea. The HLA A, B, C, DR phenotypes of patients were compared with 193 healthy controls. The following relative risk (RR) values were determined in PSS: A1 (1.38), A2 (1.39), B8 (1.67), B15 (3.22), DRw8 (6.30) and in morphea patients: A3 (1.43), B7 (1.39), B40 (1.81), Bw60 (2.49), DR2 (2.38) and DRw8 (2.55), indication a relatively weak, HLA-linked genetic predisposition for the manifestation of the disease. The HLA "risk" antigens for the two clinically different subtypes of the disease are also different: raised A1/B8 frequencies, like in our PSS group, correlate with a high, pathological immune response (autoimmune disorders). In contrast, A3/B7/DR2 prevalence, like in our morphea group, correlates with a low immune response. HLA typing may contribute to clinical differential diagnosis and possibly also prognosis.

Adult↗

PubMed1990

[Increased expression of the OKM5 antigen in blood monocytes in vitiligo].

In 25 patients suffering from vitiligo, we determined the T-cell profile (OKT3, 4 and 8; anti-Leu7) as well as the peripheral monocytes (OKM5) by means of monoclonal antibodies. Comparing the patients with a control group (n = 8), we found no differences regarding the T-cell count, whereas the expression of OKM5 antigens on peripheral monocytes was significantly elevated in patients with vitiligo.

Adolescent↗

PubMed1990

[Antiproliferative activity of a highly purified coal tar preparation in comparison with clobetasol-17-propionate].

Coal tar and glucocorticosteroids are among the preparations used for the treatment of hyperproliferative inflammatory dermatosis. Coal tar generally seems to have a better effect on psoriasis capillitii than betamethasone-17-valerate. This finding is confirmed by investigations with human skin fibroblasts. The coal tar preparation Berniter has a strongly inhibitory effect on cell proliferation. The action of the preparation with tar can be clearly distinguished from the effect of the vehicle. At the ED50 concentration of the substance with tar, the vehicle without tar causes no inhibition. Based on weight equivalents Berniter has a greater inhibitory effect on proliferation of human skin fibroblasts than clobetasol-17-propionate. In the case of both substances protein biosynthesis is only affected at concentrations higher than those needed for the inhibition of proliferation. Berniter and the vehicle without tar have an equally strong effect on protein synthesis. Berniter affects the nucleoside triphosphatase bound to the nuclear membrane, and thus influences the nucleocytoplasmic transport of mRNA. The effect of the vehicle and the preparation containing tar on this parameter are very similar. Berniter has a positive effect on cell mobility. In preconfluent cultures the mobility of the cell is slightly increased and in confluent cultures significantly. Our results show that Berniter inhibits proliferation in cell cultures of human skin fibroblasts to a higher degree than clobetasol-17-propionate. It is to be assumed that neither the inhibition of protein synthesis nor the inhibition of mRNA transport play a causal role in the antiproliferative effect of coal tar. Inhibition of proliferation as a result of general damage to the cell can also be practically ruled out.

Adenosine Triphosphatases↗

PubMed1990

[The fractals theory and its significance for dermatology].

Classic mathematical methods are frequently not suitable for the investigation of complex "natural" shapes, that cannot be approximated by geometric structures. A theory developed by Mandelbrot has made it possible to analyse such "fractals". Many biological and medical shapes could be identified as fractal. These results suggest fractal structures for some dermatological lesions. This is particularly true for skin lesions related to the vascular system (e.g., livedo racemosa, spider naevus). Furthermore, computer simulation of pathogenetic mechanisms can demonstrate that the lesions of a skin disease are fractal in nature. This method can be applied to skin tumours with horizontal cell growth (e.g., carcinoma and melanoma in situ) and to the architecture of spider naevus.

Computer Simulation↗

PubMed1990

[Early syphilis and the skeletal system].

Eleven patients with early syphilis were selected at the University Dermatology Clinik in Frankfurt/M, and bone scintigraphy was performed to check for bone lesions as sign of a systemic character of the disease. The 99mTc-methylene diphosphonate scintigrams were compared with those in a control group of 50 patients. Focal hot spots indicating early metabolic changes in bone were found in all 11 patients with early syphilis. The difference between the two groups was statistically significant. The most frequent sites of hot spots were the joints of the palmar and plantar first digits. Foci were also found at the tibial tuberosities. The results support the hypothesis that reactive focal osteitis is caused by penetrating treponemes in the very early stages of syphilis. Also, we can confirm the high sensitivity of bone scintigraphy for the early detection of metabolic changes in bone compared with conventional X-ray images.

Adult↗

PubMed1990

[The effect of hydrocortisone aceponate on proliferation, total protein synthesis and collagen synthesis in human skin fibroblasts in vitro].

Effect of Hydrocortisone Aceponate on Proliferation, Total Protein Synthesis and Collagen Synthesis in Human skin Fibroblasts in vitro. Hydrocortisone aceponate, a new topical hydrocortisone derivative with esterification in positions 17 and 21, inhibits the incorporation of 3H-thymidine in DNA in human skin fibroblasts less strongly than the halogenated glucocorticosteroids betamethasone-17-valerate and clobetasol-17-propionate. Prednicarbate, a prednisolone derivative esterified in positions 17 and 21, possesses antiproliferative properties which are stronger than those of hydrocortisone aceponate, but weaker than those of the halogenated corticosteroids. The glucocorticosteroid effect on total protein and collagen synthesis of skin fibroblasts was determined by measurement of amino acid incorporation. In logarithmically growing cultures, the total protein synthesis rate was stimulated by low corticosteroid concentrations and inhibited by high concentrations. The strongest inhibition was obtained with halogenated glucocorticosteroids. In confluent, non-proliferative cell cultures, all glucocorticosteroids had a stimulating effect on total protein and collagen synthesis. Hydrocortisone aceponate and prednicarbate had a more favourable effect on collagen synthesis than the two halogenated glucocorticosteroid derivatives. According to these results, halogenation and the insertion of double bonds in the steroidal skeleton lead more readily to anti-proliferative effects than esterification in positions 17 and 21.

Cell Division↗

PubMed1990

Uptake kinetics and the effect of minoxidil on human keratinocyte cultures.

The antihypertensive drug minoxidil (Lonolox) is rapidly taken up by human keratinocytes (HaCaT-cells). After 3 h the uptake is half of its maximum. Specific minoxidil receptors could not be found. High minoxidil concentrations (greater than 100 micrograms/ml) inhibited the incorporation of thymidine into DNA (ED50 = 263 micrograms/ml) and the incorporation of amino acids into proteins (ED50 = 251 micrograms/ml). The inhibition was reversible up to a concentration of 400 micrograms/ml. In the presence of 100 micrograms/ml minoxidil, the cell division remained active for a longer period of time and a higher cell density was achieved as opposed to the parallel control group. A prolongation of the proliferative capability of keratinocytes may be partially responsible for the positive effect of minoxidil on hair growth.

Amino Acids↗

PubMed1990

[Woronoff rings in a mathematical model].

The width of a Woronoff ring is thought to be constant and independent of the diameter of the lesion. Clinical observations have allowed us to demonstrate that this is true only for lesions of a certain minimum size or greater. It is suggested that the paleness within the ring is caused by diffusion of a mediator from the psoriatic plaque into its environment. A mathematical model is formulated, and it is shown that clinical observations are consistent with the pathogenetic hypothesis. In addition, the mathematical model is used to derive some properties of the hypothetical mediator.

Diffusion↗

PubMed1989

[Alpha-MSH and pregnancy].

In 32 pregnant women, we repeatedly determined the levels of alpha-MSH, melatonin, ACTH and progesterone. In the radioimmunoassay, all of these hormones showed a significant increase from the first to the third trimester. In contrast to progesterone, neither the level of alpha-MSH nor that of melatonin rises significantly until between the 28th and 36th week of pregnancy. The authors suggest that the increasing pigmentation may be due to the rising levels of alpha-MSH, while the preferential hyperpigmentation of sexual areas in additionally mediated by sex hormones.

Adrenocorticotropic Hormone↗

PubMed1989

Characterization of antigenic variants of tick-borne encephalitis virus selected with neutralizing monoclonal antibodies.

Antigenic variants of tick-borne encephalitis virus were selected by the use of six neutralizing monoclonal antibodies (MAbs), each defining a different epitope of the envelope glycoprotein E. These variants were characterized with respect to antigenic changes by analysing the binding of each of 18 precisely mapped MAbs in ELISA and haemagglutination inhibition tests. The results yielded information about interrelations between epitopes exceeding that obtained previously from competitive binding studies. In addition, variants were tested for their specific haemagglutination activities, which revealed a significant reduction of this functional activity in one of the variants.

Animals↗

PubMed1989

Association of HLA antigens with progressive systemic sclerosis and morphea.

The HLA phenotype frequencies of 40 patients with progressive systemic sclerosis (PSS) and 42 patients with morphea (sclerodermia circumscripta) indicate a weak, HLA-linked genetic predisposition of the affected individuals (70 female, 12 male). An "opposite" HLA A1, B8 (high immune response) vs A3, B7, DR2 (low immune response) constellation in PSS and morphea supports the clinical subdivision of scleroderma into these different nosological entities, and may serve as a differential diagnostic tool and prognostic marker.

Female↗

PubMed1989

Antigenic structure of the flavivirus envelope protein E at the molecular level, using tick-borne encephalitis virus as a model.

A model of the tick-borne encephalitis virus envelope protein E is presented that contains information on the structural organization of this flavivirus protein and correlates epitopes and antigenic domains to defined sequence elements. It thus reveals details of the structural and functional characteristics of the corresponding protein domains. The localization of three antigenic domains (composed of 16 distinct epitopes) within the primary structure was performed by (i) amino-terminal sequencing of three immunoreactive fragments of protein E and (ii) sequencing the protein E-coding regions of seven antigenic variants of tick-borne encephalitis virus that had been selected in the presence of neutralizing monoclonal antibodies directed against the E protein. Further information about variable and conserved regions was obtained by a comparative computer analysis of flavivirus E protein amino acid sequences. The search for potential T-cell determinants revealed at least one sequence compatible with an amphipathic alpha-helix which is conserved in all flaviviruses sequenced so far. By combining these data with those on the location of disulfide bridges (T. Nowak and G. Wengler, Virology 156:127-137, 1987) and the structural characteristics of epitopes, such as dependency on conformation or on intact disulfide bridges or both, a model was established that goes beyond the location of epitopes in the primary sequence and reveals features of the folding of the polypeptide chain, including the generation of discontinuous protein domains.

Amino Acid Sequence↗

PubMed1989

Pustulosis palmo-plantaris. Clinical and histological changes during etretin (acitretin) therapy.

We examined the clinical and histological effects of etretin in pustulosis palmo-plantaris (PPP) in a multicentre study. 30 patients with PPP were treated with etretin in a double-blind study. After a 4-week interval of either etretin (50 mg/day) or placebo (randomized), all patients received etretin during a second period of 20 weeks (the dosage was individually varied). The effect of etretin was verified clinically and by immunhistochemical methods. The number of pustules in a 4 cm2 reference area diminished within the first 4 weeks from 8.5 to 1.9 (etretin group) and from 9.0 to 6.2 (placebo group). Within a maximum of 24 weeks 16% of the patients showed a complete remission, 44% a pronounced improvement, and 22% little improvement. The state of 2% of the patients deteriorated. Immunhistologically, the number of granulocytes was reduced in the inflammatory infiltrate and in the pustules. Etretin is therefore a retinoid, which is easily controlled and effective in PPP.

Acitretin↗

PubMed1989

[The significance of yeasts in seborrheic eczema].

The high prevalence of seborrheic dermatitis in HIV-infected subjects has led to intensified the discussion of the etiopathogenesis of this dermatological disease. There is increasing controversy about the significance of Pityrosporum in seborrheic dermatitis. On the other hand, recent clinical and experimental data favor the role of intestinal candidiasis in seborrheic dermatitis: a high quantity of Candida in the feces of the affected patients, elevated phospholipase activity of the Candida sp. with special pathogenic relevance for mucosal adhesion and fast and long-lasting regression of seborrheic dermatitis after vigorous therapy with oral nystatin. Similar findings have been recorded in the seborrheic forms of psoriasis.

Candidiasis↗