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Biomedical subjects

U F Haustein

Publications and source records attributed to U F Haustein.

At least 73 records · Page 4Linked to original sources

Molecular analysis of different phases in human wound healing.

Cultured granulation fibroblasts grown from punch biopsies of the same lower arm area, obtained 3, 6, 9 and 14 days after wounding, were used as a human wound healing model in comparison to quiescent fibroblasts. We investigated the expression of key extracellular matrix components at the protein level by flow cytometry and mRNA steady state levels by Northern blotting of the different fibroblasts and compared these data to the ability to migrate towards a chemotactic signal. Procollagen alpha 1 (I), fibronectin and matrix metalloprotease-1 synthesis was strongly up-regulated at the mRNA steady state level on days 3 and 14. Tissue inhibitor of metalloprotease-1 mRNA is only 20% down-regulated between day 3 and 14. Chemotaxis towards conditioned medium reflects a net effect of several factors and is distinctly different from chemotaxis towards platelet-derived growth factor, which peaks at day 3. Compared to the protein level, the enhanced expression of the corresponding PDGF receptor beta chain mRNA is delayed by 3 to 6 days. PDGF receptor alpha shows no regulatory changes during the observation period. This data further supports the idea that functionally divergent subpopulations of fibroblasts exist during wound healing.

Adult↗

In situ expression and serum levels of tumor necrosis factor-alpha receptors in patients with early stages of systemic sclerosis.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine in the early stage of systemic sclerosis (SSc), which is characterized by mononuclear cell infiltration and microvascular alterations. Most effects of TNF-alpha are mediated by its interaction with 2 types of TNF receptors and depend on their surface expression on individual cell subsets. Our purpose was to correlate the serum levels of soluble TNF receptors-TNF-RI(p55) and RII(p75)-with (1) their in situ expression and distribution in lesional skin and on peripheral blood mononuclear cells (PBMC), and (2) the clinical disease progression and inflammatory serum variables in patients with SSc. METHODS: Serum samples of 32 patients with SSc and 36 healthy probands were examined by ELISA. We performed immunohistological stainings and in situ hybridization on cryostat sections of skin lesions, cytometric analysis on PBMC, and reverse transcriptase polymerase chain reactions using RNA from cultured skin fibroblasts in 17 of these 36 patients. RESULTS: In contrast to healthy skin and chronic fibrotic SSc, TNF-RI is expressed on about 30% of mononuclear infiltrating cells in early skin lesions. Neither TNF-RI nor RII was detectable on fibroblasts by immunohistochemistry, but specific mRNA could be found on the transcriptional level. TNF-RII is found on most lymphocytes and on 30-50% of endothelial cells, especially in early SSc. Expression of both receptor types on PBMC in patients and controls was not significantly different. Serum levels of soluble TNF-RI and RII correlated well with their in situ expression and with clinical and laboratory signs of inflammation and disease progression in patients with SSc. CONCLUSION: Our data provide evidence for a central role of the TNF-alpha/TNF-R system in the early pathological events of scleroderma with prominent inflammation and endothelial cell damage. Determination of TNF-R serum levels provides a useful diagnostic tool for characterization of the disease stage and progression, and to guide experimental therapy in patients with SSc.

Adult↗

In vitro susceptibility testing of Malassezia furfur against rilopirox.

The in vitro antifungal activity of the new hydroxypyridone antimycotic rilopirox has been evaluated against 29 separate clinical isolates of Malassezia (M.) furfur obtained from patients with pityriasis versicolor, seborrhoeic dermatitis or dandruff. Minimum inhibitory concentrations (MICs) of rilopirox were measured by the agar dilution technique and, in comparison, by a recently described microdilution method with colorimetric detection of the MIC end points. Rilopirox was found to be able to inhibit growth of all clinical yeast isolates. For the investigated M. furfur strains MIC values from 12.5 to 50 micrograms ml-1 with a median of 25 micrograms ml-1 were determined by the agar dilution method. Using the microdilution technique, MIC values between 16 and 128 micrograms ml-1 (median 32 micrograms ml-1) were found for the M furfur isolates. It has to be taken into account that with a 0.3% solution concentrations of 300,000 micrograms ml-1 are applied to the skin. Furthermore, due to its extreme low penetration rilopirox is long-term available in the skin in inhibiting concentrations. In comparison with rilopirox, the in vitro susceptibility of M. furfur against the systemically applicable triazole antimycotic itraconazole and clotrimazole, an established topical antifungal, was tested. As expected, low MIC values for these azoles were found by the agar dilution method. The median of the MIC of M. furfur was 0.1 microgram ml-1 for itraconazole, and 6.25 micrograms ml-1 for clotrimazole. The inhibitory effectivity of rilopirox against clinical isolates of M. furfur seems to justify its therapeutic evaluation in clinical trials. This new antifungal may be a useful alternative not only in pityriasis versicolor but also in seborrhoeic dermatitis due to the growth inhibition of M. furfur.

Antifungal Agents↗

Human papillomavirus infections in nonmelanoma skin cancers from renal transplant recipients and nonimmunosuppressed patients.

BACKGROUND: Nonmelanoma carcinomas of the skin represent the most frequent cancers among the Caucasian population worldwide. They occur with high frequency in renal allograft recipient patients after prolonged immunosuppression. PURPOSE: We analyzed tumors obtained from both immunosuppressed and nonimmunosuppressed patients for human papillomavirus (HPV) DNA. METHODS: Twenty-nine specimens of nonmelanoma carcinomas of the skin were obtained from 19 renal allograft recipient patients; these included 20 specimens of squamous cell carcinoma (SCC) from 11 patients, five specimens of basal cell carcinoma (BCC) from four patients, and four specimens of carcinoma in situ (CIS) from four patients. Forty-one specimens of nonmelanoma carcinomas of the skin were obtained from 32 nonimmunosuppressed patients; these included 26 SCC specimens from 19 patients, 11 BCC specimens from nine patients, and four keratoacanthoma (benign epithelial tumor) specimens from four patients. A polymerase chain reaction method involving use of degenerate oligonucleotide primers, in which the conserved region of the open reading frame of the HPV L1 (major capsid protein) gene is amplified, was used to amplify total cellular DNA purified from individual tumors. The DNA of each specimen was subjected to 16 different amplification reactions; different primer combinations were used in order to increase the sensitivity and specificity of HPV detection. Resulting products were probed with a radioactively labeled, degenerate oligonucleotide. HPV-specific DNA was either sequenced directly after elution from the gel or amplified with semi-nested, degenerate primers, after which the products were cloned and sequenced. Sequences were compared with all known papillomavirus sequences. RESULTS: Thirteen (65%) of the 20 SCC specimens and three of the five BCC specimens from immunosuppressed (renal allograft recipient) patients contained identifiable HPV-related sequences, among them 13 putative novel HPV genomes. In addition, all other malignant tumor specimens from this patient group revealed faint signals upon amplification and hybridization; the origin of these signals has not been identified in the present study. In nonimmunosuppressed patients, eight (31%) of 26 SCC specimens and four (36%) of 11 BCC specimens contained sequences of HPV types. Two putative novel HPV sequences could be identified in this group. Faint signals of yet undetermined origin were observed in eight of the SCC specimens and in two of the BCC specimens. Two of four keratoacanthoma specimens contained sequences of known HPV type. (Keratoacanthoma is a nonmalignant lesion for which the natural history has not been defined.) The spectrum of HPV types in both groups of patients differed substantially. CONCLUSIONS: These data point to the frequent presence of HPV sequences in SCCs and BCCs of the skin. The etiologic relationship of these infections to the respective malignant tumors remains to be evaluated. IMPLICATIONS: The presence of HPV DNA in a large percentage of specimens of nonmelanoma carcinomas of the skin from immunosuppressed patients, as well as from nonimmmunosuppressed patients, renders a papillomavirus infection as a possible factor in the etiology of this disease.

Amino Acid Sequence↗

[Correlation between chronic urticaria and depression/somatization disorder].

In a multicenter study, 100 patients with chronic urticaria were examined with a standardized personality test (Giessen test), a standardized symptom questionnaire (Giessener Beschwerdebogen) and a specially developed questionnaire concerning symptoms, history and behaviour during symptomatic periods. Almost one third of the patients showed elevated scores both for depression and for symptoms that are often associated with depression. It therefore seems worth-while examining such persons more specifically and possibly treating them by psychosomatic methods. The present results do not allow the classification of chronic urticaria as a somatization disorder. Since one-third of the patients had symptoms of depression, combined dermatological and psychosomatic approach may make it possible to offer them an appropriately targeted treatment.

Adolescent↗

[Raynaud phenomenon and scleroderma].

The Raynaud phenomenon occurs in 90-100% of patients with systemic scleroderma. It is caused by dysregulation of the vascular tone between vasoconstrictive and vasodilatory influences. Early damage to the vascular endothelium and the activation of platelets lead to the release of vasoactive substances. Structural and function impairment of the perivascular neural fibers contributes to the vasospasm. New vasodilatory treatment strategies, e.g. infusions with calcitonin gene-related peptides, could be useful in the control of vasospasm in the peripheral extremities as well as internal organs in systemic scleroderma.

Calcitonin Gene-Related Peptide↗

[Dermatologic symptoms of parvovirus B19 infections].

Infections with parvovirus B19 are often characterized by the well-known erythema infectiosum, usually accompanied by fever and arthralgia. Furthermore the virus may cause a lethal hydrops fetalis during the pregnancy or a severe aplastic crisis in patients suffer from chronic hemolytic anemia. We present three patients infected by parvovirus B19. Whose skin lesions included a non-specific exanthem, erythema multiforme, and purpura. The virus infection was confirmed both by serology and PCR identification. In conclusion the diagnosis of acute exanthems should include the search for virus infections.

Adult↗

Transforming growth factor-beta controls cell-matrix interaction of microvascular dermal endothelial cells by downregulation of integrin expression.

Transforming growth factor-beta (TGF-beta) is a pleiotropic regulatory factor of tissue remodeling. Angiogenesis, a prerequisite of tissue repair and tissue expansion, is induced by TGF-beta in vivo, while proliferation and migration of cultured endothelial cells are inhibited by TGF-beta. Indirect mechanisms stimulating angiogenesis and modification of TGF-beta effects by cell-matrix interaction have been postulated to account for this paradigm. Because cellular behavior in tissue remodeling is decisively determined by cell-matrix interactions, which in turn is mediated via integrins, we investigated the effect of TGF-beta on matrix-dependent endothelial cell functions. Integrin expression of human dermal microvascular endothelial cells (HDMEC) was measured by Northern blot and fluorescence-activated cell sorter analysis after TGF-beta treatment and correlated to cell-matrix interactions, which were studied in a colorimetric cell attachment assay as well as the Boyden chamber chemotaxis assay. We found a cell-specific downregulation of integrin expression in HDMEC on the level of mRNA as well as on the cell surface. This effect correlated well with the reduction of integrin-dependent cell adhesion to several matrix proteins, in particular to fibronectin. Moreover, TGF-beta decreased fibronectin-induced chemotaxis of HDMEC. Thus, TGF-beta controls cell-matrix interaction of HDMEC by down-regulation of integrin expression. This effect of TGF-beta reflects direct and cell-specific control mechanisms on microvascular cells that may be critical for the coordinated process of angiogenesis requiring a balance of stimulatory and inhibitory factors.

Cell Adhesion↗

Novel fibroblast-specific monoclonal antibodies: properties and specificities.

Specific detection of fibroblasts has been one of the unsolved problems in cell biology. Because monoclonal antibodies (MoAbs) might provide an easy and reproducible method of fibroblast detection, we have produced a panel of MoAbs raised against cell surface proteins of human dermal fibroblasts. Using flow cytometry and immunohistochemistry, we have shown that two of these MoAbs, FibAS01 and FibAS02, react exclusively with human fibroblasts. They do not react in vitro with human keratinocytes, endothelial cells, or blood cells. Immunohistologic experiments investigating the binding pattern of the MoAbs FibAS01 and FibAS02 in cryostat sections of different tissues confirmed the flow cytometric results. In human skin, the antibodies exclusively labeled fibroblasts. In other human tissues such as lymph nodes, placenta, kidney, muscle, thyroid gland, gall bladder, cartilage, and tendon, the specificity for fibroblasts was borne out. Neither antibody reacts with fibroblasts from mouse, rat, or pig. The isotype was defined as an IgG1 for both. By western blot analysis, both antibodies detected a molecule of 60-65 kDa under reducing and nonreducing conditions. By immunoelectron microscopy, we observed the antigens on the cell surface without any clustering at specific sites. These data demonstrate that the two MoAbs, FibAS01 and FibAS02, exclusively recognize human fibroblasts.

Animals↗

[Invasive mold infections in the university clinics of Leipzig in the period from 1992-1994].

Invasive mould infection, e. g. aspergillosis in the first place, is a common infection in immunocompromised patients. The diagnosis of invasive mould infection is difficult in the absence of confirmation by tissue biopsy and histological studies. Therefore, prevalence of invasive mould infections at the School of Medicine of the Leipzig University between 1992 and 1994 was investigated. The diagnosis of invasive mould infection was suspected on clinical, mycological, and radiological findings. The definitive diagnosis was obtained by identification of characteristic mould hyphae on stained smears, and/or positive culture, and/or the detection of Aspergillus antigen (Pastorex) in serum, bronchial secretion, or bronchoalveolar fluid, and confirmed by histopathology. In altogether 21 patients the definitive diagnosis invasive mould infection was recorded, among them 20 invasive aspergilloses. Underlying diseases were leukaemia (n = 11), aplastic anaemia (n = 2), non-Hodgkin-lymphoma (n = 1), systemic lupus erythematosus (n = 1), kidney transplantation (n = 1), peritonitis after Billroth II anastomosis (n = 1), Polymyalgia rheumatica (n = 1), AIDS plus Burkitt lymphoma (n = 1), glioblastoma (n = 1), and subarachnoid haemorrhage (n = 1). As causative fungi were isolated: Aspergillus fumigatus (n = 13), Aspergillus terreus (n = 1), Aspergillus flavus as rare simultaneous injection with the basidiomycete Coprinus spec. in a leukaemic patient (n = 1), and the dematiaceous fungus Scedosporium prolificans in an AIDS patient with Burkitt lymphoma (n = 1). In four patients the invasive mould infection was confirmed histopathologically without isolation and differentiation of the causative agent. Nineteen of the 21 patients with invasive mould infections died corresponding to a mortality rate of 90%.

AIDS-Related Opportunistic Infections↗

Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro.

The in vitro antifungal activity of tea oil, the essential oil of Melaleuca alternifolia, has been evaluated against 26 strains of various dermatophyte species, 54 yeasts, among them 32 strains of Candida albicans and other Candida sp. as well as 22 different Malassezia furfur strains. Minimum inhibitory concentrations (MIC) of tea tree oil were measured by agar dilution technique. Tea tree oil was found to be able to inhibit growth of all clinical fungal isolates. For the investigated dermatophytes MIC values from 1,112.5 to 4,450.0 micrograms/ml with a geometric mean of 1,431.5 micrograms/ml were demonstrated. Both C. albicans strains and the other strains belonging to the genus Candida and Trichosporon appeared to be slightly less susceptible to tea tree oil in vitro. However, their MIC values, which varied from 2,225.0 to 4,450.0 micrograms/ml (geometric mean 4,080 micrograms/ml), indicated moderate susceptibility to the essential oil of M. alternifolia. The lipophilic yeast M. furfur seemed to be most susceptible to tea tree oil. MIC values between 556.2 and 4,450.0 micrograms/ml (geometric mean 1,261.5 micrograms/ml) were found against the tested M. furfur strains. However, when calculated as percentage tea tree oil of the agar, the above-mentioned concentrations correspond to 0.5-0.44% tea tree oil content. These values are far below the usual relatively high therapeutic concentrations of the agent; approximately 5-10% solution or even the concentrated essential oil are used for external treatment. In comparison with tea tree oil, in vitro susceptibility against miconazole, an established topical antifungal, was tested. As expected, very low MIC values for miconazole were found for dermatophytes (geometric mean 0.2 microgram/ml), yeasts (geometric mean 1.0 microgram/ml), and M. furfur (geometric mean 2.34 micrograms/ml). It is suggested that the in vivo effect of tea tree oil ointment in the therapy of fungal infections of the skin and mucous membranes as well as in the treatment of dandruff, a mild form of seborrheic dermatitis, may be at least partly due to an antifungal activity of tea tree oil.

Antifungal Agents↗

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety.

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.

Adolescent↗

[Effect of hypnosis and autogenic training on acral circulation and coping with the illness in patients with progressive scleroderma].

In 12 patients with systemic sclerosis the influence of hypnosis and autogenic training on the acral blood circulation and the coping with the disease was investigated in a pilot study. In the first step significant increases in the skin temperature of the finger (mean +/- SD: 3.9 +/- 1.2 degrees C) could be found after relaxation hypnosis. In the second step six patients (study group) gained experience with autogenic training. The other six patients served as control group. In the study group, the skin temperature of the fingers (short-term effect) was significantly higher than in the control group (1.9 +/- 1.0 degrees C). Long-term effects of the autogenic training (mean acral rewarning time, duration and course of the Raynaud attacks, acral lesions of the hands, psychosomatic status of complaints, type of relation to the disease as precondition for coping with the disease) were not found within the relatively short follow-up period of 4 months. Two patients, however, reported that they could shorten the duration of Raynaud attacks by autogenic training. In our patients heterogenicity and an increased score of multiple psychosomatic complaints were registered at the outset. As far as the type of relation to the disease is concerned, the patients could be assessed as almost adapted. Hypnosis and autogenic training can be recommended as complementary therapy in systemic sclerosis.

Adaptation, Psychological↗

[Substance P and vasoactive intestinal peptide in patients with progressive scleroderma. Determination of plasma level before and after autogenic training].

In 12 patients suffering from systemic sclerosis (SSc) the influence of autogenic training on the plasma level of the neuropeptides substance P and vasoactive intestinal peptide (VIP) was studied. Compared with healthy controls the SSc patients exhibited significantly elevated levels of substance P (mean +/- SD: 7.1 +/- 3.2 pmol/l vs 1.6 +/- 1.6 pmol/l). Apart from variations the VIP plasma concentration did not significantly differ from that in healthy controls (mean +/- SD 10.7 +/- 7.1 pmol/l versus 12.0 +/- 5.3 pmol/l). Autogenic training did not bring about any significant changes in the plasma levels of neuropeptides.

Adolescent↗