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Biomedical subjects

U Reinhold

Publications and source records attributed to U Reinhold.

At least 37 records · Page 2Linked to original sources
PubMed2001

Upregulation of C4.4A expression during progression of melanoma.

We have previously described the human homolog of a rat metastasis-associated molecule, hC4.4 A, with a weak homology to the urokinase-type plasminogen activator receptor. By the restricted expression in nontransformed tissues as opposed to expression in roughly 50% of a variety of carcinoma lines of different origins, a possible correlation between hC4.4 A and tumor progression emerged. This was explored in more detail in melanoma by quantitative polymerase chain reaction and in situ hybridization. As shown before, normal human skin weakly expresses hC4.4 A. Melanocytes and nevi are negative, but up to 60% of primary malignant melanoma and 100% of lymph node and skin metastases of melanoma are hC4.4 A positive. Signal intensity in both polymerase chain reaction and in situ hybridization varied considerably between individual samples, which is indicative for regulated expression of hC4.4 A. To test the hypothesis, melanoma lines were incubated with human serum. Whereas expression of hC4.4 was not influenced by heat-inactivated human serum, all melanoma lines responded to noninactivated human serum with upregulation of hC4.4 A expression. Regulated expression with highest level expression on metastases is a feature that hC4.4 A shares with the urokinase-type plasminogen activator receptor. This feature points towards functional activity of hC4.4 A in tumor progression.

Disease Progression↗
PubMed2001

CD4(+)CD7(-) T cells compose the dominant T-cell clone in the peripheral blood of patients with Sézary syndrome.

BACKGROUND: Absence of CD7 antigen expression in T cells defines a subset of normal CD4(+) CD45RO(+) CD45RA(-) memory cells and is furthermore observed in Sézary syndrome (SS). OBJECTIVE: Our purpose was to identify circulating T-cell clones in patients with SS and to elucidate whether the dominant T-cell clones express the CD7 antigen. METHODS: Peripheral blood lymphocytes of patients with SS were analyzed by two-color flow cytometry using antibodies to the V beta region of the T cell receptor (TCR) in combination with an antibody to CD7. In addition, T cells were analyzed for TCR-gamma gene rearrangement by polymerase chain reaction (PCR) techniques. RESULTS: Clonal T-cell expansion was detected in 7 patients with SS by immunostaining of the TCR V beta regions. PCR analysis confirmed the presence of dominant T cell clones. Double-immunostaining revealed that in each case cells of the clonal V beta TCR rearrangement homogeneously express the CD4(+)CD7(-) phenotype. Furthermore, CD4(+)CD7(-) cells express the CD15s antigen but lack expression of CD26 and CD49d. CONCLUSION: Expansion of clonal T cells strongly correlates with the expansion of CD4(+)CD7(-) T cells in 7 tested patients with SS. This supports our model that a subset of late differentiated, normal CD4(+)CD7(-) memory T cells may represent the physiologic counterpart of Sézary cells. Monitoring of circulating T cells with the CD4(+)CD7(-)CD15s(+)CD26(-)CD49d(-) phenotype proved to be useful for the identification of clonal T cells in patients with SS.

Aged↗
PubMed2001

Reliability of PCR-based detection of occult tumour cells: lessons from real-time RT-PCR.

For the molecular detection of rare tumour cells in clinical samples, real-time reverse transcription-polymerase chain reaction (RT-PCR) offers two important advantages over conventional RT-PCR assays: the results are quantitative and, perhaps more importantly, it facilitates exact sensitivity controls on a per sample basis as well as exact comparison of different assay protocols. We report here on quantitative results obtained with different protocols for RNA isolation and cDNA synthesis for amplification of beta2-microglobulin transcripts using the light cycler system. Furthermore, housekeeping gene-specific PCRs were compared with PCRs specific for an artificial transcript (internal standard) detected simultaneously at a level comparable to the wild-type sequence. Artificial tyrosinase transcripts derived from a vector construct stably transfected into a human lymphoma cell line were used as a model to test the usefulness of artificial internal standards as an alternative to housekeeping genes. The highest RNA yields were obtained using a combination of phenol-chloroform extraction and the High Pure RNA Isolation Kit. Analysing beta2-microglobulin transcript-specific RT-PCRs, the highest sensitivity was obtained for cDNAs generated with Omniscript reverse transcriptase and oligo-p(dT)15 primer. Regarding patient blood samples, RT-PCRs specific for beta2-microglobulin, porphobilinogen deaminase and artificial tyrosinase transcripts provided quantitative data for all, for 18 out of 21, and for 10 out of 21 samples, respectively. Quantification of beta2-microglobulin transcripts by the light cycler system defined the protocol revealing the highest cDNA quality. Comparisons of quantitative data from RT-PCRs specific for beta2-microglobulin, porphobilinogen deaminase and artificial tyrosinase transcripts enabled us to determine a close range for crossing points within which sufficient cDNA quality can be guaranteed, even for the detection of rare transcripts. PCRs specific for the artificial internal standard are ideally suited for cDNA quality assessment on a per sample basis.

DNA, Complementary↗
PubMed2001

Identification of TIA-1+ and granzyme B+ cytotoxic T cells in lichen sclerosus et atrophicus.

BACKGROUND: The onset and persistence of cutaneous lichen sclerosus et atrophicus (LSA) are linked to the presence of an inflammatory infiltrate of CD3+ T cells that includes CD4+ and CD8+ cells. The functional relevance of the presence of these cells is unknown. OBJECTIVE: The study intended to quantify resting and activated cytotoxic T cells in LSA lesions. METHODS: Twenty patients with active LSA were studied. Skin-infiltrating T cells were immunohistologically characterized with antibodies against CD3, CD8, T-cell-restricted intracellular antigen (TIA-1) and granzyme B (GrB). TIA-1 labels cytotoxic granules of resting and activated T cells, whereas GrB designates activated cytotoxic T lymphocytes (CTL). RESULTS: In all cases, numerous T cells were consistently found expressing cytotoxic granules. The results indicated a high number of infiltrating CD8+ TIA+ T cells. Furthermore, a notable number of GrB+ activated CTL associated with hydropic degeneration of the basal cell layer were found within the dermal infiltrate and at the dermoepidermal interface. CONCLUSION: This study shows that a high proportion of skin-infiltrating T cells in LSA has a potential cytotoxic function. The results indicate that hydropic degeneration of basal keratinocytes may at least partially be mediated by CTL-dependent mechanisms. Our data also indicate that a cell-mediated immune response may play an important role in the pathogenesis of the disease.

Adult↗
PubMed2001

High-dose pulse corticosteroid therapy in the treatment of severe alopecia areata.

OBJECTIVE: The present monocenter prospective study was designed to evaluate the efficacy of intravenous high-dose methylprednisolone pulse therapy in patients with severe alopecia areata (AA). METHODS: 30 patients (aged 14-56 years) were treated with methylprednisolone (8 mg/kg body weight) intravenously on 3 consecutive days at 4-week intervals for at least 3 courses. RESULTS: 67% of patients with AA plurifocalis showed >50% regrowth of hair. None of the patients with AA totalis or universalis and only 1 patient with ophiasic AA responded to therapy. In patients with AA plurifocalis, higher response rates could be observed in those suffering from long-term disease compared to patients treated during their first episodes of AA (73 vs. 57%). CONCLUSION: High-dose methylprednisolone pulse therapy is an effective and well-tolerated treatment for patients with severe AA plurifocalis but might be less beneficial for patients with ophasic AA, AA totalis or universalis.

Adolescent↗
PubMed2001

[Ocular manifestation of progressive essential telangiectases].

Generalized essential telangiectasia is a rare skin disorder characterized by the development of dilated venules beginning at the lower extremities and progressively spreading out to the rest of the body. It is not related to any known affection and is therefore considered to be essential. The condition tends to affect mostly women in their midthirties. We report the case of a 49-year-old healthy man worried by the progressive extension of dilated vessels on the conjunctivae of both eyes and the progressive worsening at the condition over the last five years. On clinical examination he presented also telangiectasies on both arms and legs which had also grown worse over the last five years. All further investigations and complementary examinations showed no disease. A cutaneous biopsy showed dilated venules in the superior dermis supporting the diagnosis of telangiectases. Several differential diagnoses are discussed. With confirmation of the clinical diagnosis we started treatment with oral tetracycline. Because of the poor response we stopped treatment after a period of three months.

Biopsy↗
PubMed2001

Increased soluble CD95 (sFas/CD95) serum level correlates with poor prognosis in melanoma patients.

Functional impairment of the Fas/CD95 receptor-ligand system is associated with the development and progression of malignancies. One possible cause might be the inhibition of the formation of a functional Fas/CD95-FasL complex by soluble Fas/CD95 molecules (sFas/CD95). In the present study we determined sFas/CD95 serum concentration in 125 melanoma patients of different clinical stages of disease compared with 30 healthy controls using an ELISA. sFas/CD95 serum level was significantly elevated (P < 0.0005) in melanoma patients (mean +/- SE = 8.60 +/- 0.26 ng/ml) compared with healthy controls (mean +/- SE = 6.27 +/- 0.25 ng/ml). Univariate analysis revealed a correlation of sFas/CD95 serum concentration with advanced stages of disease (P = 0.009). Only a slight increase in sFas/CD95 serum level (P = 0.057) could be observed in regard to the tumor burden. Patients undergoing current treatment with cytostatics (n = 18) revealed a strong increase in sFas/CD95 serum level (P < 0.0005), whereas treatment with IFN-alpha alone or combined with cytostatics (n = 19) showed no change in serum sFas/CD95 concentration. According to univariate analysis, elevated sFas/CD95 serum levels were associated with a poor overall (P < 0.005) and a progression-free (P < 0.0005) survival. Multivariate analysis revealed sFas/CD95 serum concentration as an independent predictive factor for progression-free (P = 0.011), but not overall (P = 0.078), survival. Our results show a prognostic relevance of serum sFas/CD95 in melanoma patients, indicating that the evaluation of sFas/CD95 serum level may be important for the selection of therapeutic strategies.

Biomarkers, Tumor↗
PubMed2001

[Olmsted syndrome].

BACKGROUND: The Olmsted syndrome is a rare congenital disorder with palmoplantar keratoderma and hyperkeratotic periorifical plaques. Only 19 cases were reported in the literature. Other cutaneous and organic findings have been reported with different frequencies. CASE REPORT: A 17-year-old girl presented with genital, perigenital and perianal hyperkeratotic plaques extending to the thighs, palmoplantar keratoderma and nail dystrophy. A small erythematokeratotic plaque was localized below the lower lip. Improvement of the palmoplantar and genital lesions was noted after one month of treatment with 25 mg acitretine daily. Further substantial improvement of the palmoplantar and ungueal lesions was observed during the next 7 months. However, discrete erythematous perianal and perigenital lesions persisted in these areas 2 years later. DISCUSSION: Efficacy of retinoids in the Olmsted syndrome is controversially discussed in the literature. However, acitretin seems to be the treatment of choice of this syndrome in adults.

Acitretin↗
PubMed2001

Cutaneous malignant melanoma: from early diagnosis to gene therapy.

Knowledge about diagnostic procedures in melanoma has increased rapidly within the past few years. These new techniques include epiluminescence microscopy and computerized image analysis of pigmented skin lesions, as well as the identification of single tumor cells in normal tissue, such as sentinal lymph node and peripheral blood by molecular approaches. The introduction of polymerase-chain reaction based methods can be regarded as a prototype of this dramatic development that opens up the possibility of clinical use in patients, and of influencing treatment strategies. While early melanoma is highly curable by surgical means, the prognosis of patients with metastatic disease remains poor. A flurry of new treatment strategies are currently in clinical development. These include test-directed chemotherapy, biologic therapy, vaccine therapy, as well as gene therapy. All different therapeutic strategies have to take into account immense resistance and escape mechanisms of malignant melanoma cells, that potentially limit the effectiveness of new treatment concepts.

Antineoplastic Agents↗
PubMed2000

[High dosage steroid pulse therapy. Is there an indication in dermatology?].

In recent years, high-dose steroid pulse therapy has been considered an effective treatment regimen in a number of non-dermatological diseases. This review addresses in the first part the pharmacological basics and mechanisms of action of high-dose glucocorticosteroid therapy. In the second part, we discuss the clinical experience using this treatment for dermatological diseases including pemphigus vulgaris, pyoderma gangrenosum, alopecia areata, and dermatomyositis.

Autoimmune Diseases↗
PubMed2000

Effects of industrial noise exposure on distortion product otoacoustic emissions (DPOAEs) and hair cell loss of the cochlea--long term experiments in awake guinea pigs.

Distortion product otoacoustic emissions (DPOAEs), a sensitive detector of outer hair cell (OHC) function, cochlear microphonics (CM), and hair cell loss have been monitored in 12 awake guinea pigs before and after 2 h exposure to specific, played-back industrial noise (105 dB SPL maximal intensity). All animals had stable DPOAE levels before noise exposure. In the first hours after noise exposure DPOAE levels were reduced significantly. In about 70% a partial recovery of the DPOAEs was found within 4 months after noise exposure. In 16% of the investigated ears no recovery of DPOAEs was observed. However, in a few ears increased DPOAEs were observed after noise exposure. Exposure to industrial noise caused both morphological changes in the middle turns of the cochlea and electrophysiological changes in the middle frequency range. A close correlation existed between reduced DPOAE levels, loss in CM potentials, and area of damaged or lost OHCs, but not with the numbers of damaged or lost OHCs in the cochlea. It can be concluded that continuous industrial noise causes a damage to OHCs which differs form the damage caused by impulse noise.

Animals↗
PubMed2000

Accumulation of CD4+CD7- T cells in inflammatory skin lesions: evidence for preferential adhesion to vascular endothelial cells.

The CD7- subset of CD4+ memory T cells reflects a stable differentiation state of post-thymic helper T cells and represents a small subpopulation in circulating blood. We here demonstrate that CD7- T cells preferentially accumulate in skin lesions under chronic inflammatory conditions irrespective of the particular disease. As adhesion to vascular endothelial cells (EC) is required for migration of circulating lymphocytes into tissues, we analysed the adherence of purified subsets of CD4+ memory T cells to endothelial cells in vitro. Compared with CD4+CD7+ T cells, cells of the CD4+CD7- subset preferentially adhere to EC, which is moreover increased after prestimulation of EC with tumour necrosis factor-alpha (TNF-alpha). Stimulated EC increase expression of intercellular adhesion molecule-1 (CD54) and E-selectin (CD62E), the ligand of which, cutaneous lymphocyte-related antigen (CLA), is highly expressed in CD4+CD7- T cells but not in CD4+CD7+ T cells. LFA-1 is expressed in a bimodal distribution on CD4+CD7- T cells in contrast to CD4+CD7+ cells, whereas VLA-1, VLA-3, and VLA-5 are nearly similarly expressed in both T cell subsets. Our results imply that the preferred adherence of CD4+CD7- memory T cells to vascular EC, which is increased after long-term EC stimulation with TNF-alpha, is likely to facilitate their accumulation in various inflammatory skin lesions.

Antigens, CD7↗
PubMed2000

Use of high-dose methylprednisolone pulse therapy in patients with progressive and stable vitiligo.

BACKGROUND: Although there are several treatment options available for patients with generalized vitiligo, their efficacy is still a matter of debate. Although shown to be effective, corticosteroids applied either systemically or topically carry the risk of significant side-effects in long-term therapy. We evaluated the effectiveness of intravenous methylprednisolone (8 mg/kg body weight) administered on three consecutive days in patients with generalized vitiligo. MATERIALS AND METHODS: A total of 14 patients with progressive or static vitiligo were included in a prospective, open, clinical study. RESULTS: Eighty-five per cent of the patients presenting with progressive disease showed cessation of disease progression after the infusion therapy. Repigmentation was observed in 71% of patients with progressive vitiligo. None of the six patients presenting with static disease showed any repigmentation in response to this form of treatment. The therapy was well tolerated in all but one patient who developed intermittent arterial hypertension during therapy. CONCLUSIONS: High-dose glucocorticoid pulse therapy may represent a therapeutic option in patients with generalized progressive vitiligo, and should be further evaluated in a prospective, randomized, clinical trial.

Adolescent↗