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W Tilgen

Publications and source records attributed to W Tilgen.

At least 73 records · Page 4Linked to original sources
PubMed1999

Malignancies of the uterine corpus and immunoreactivity score of the DNA "mismatch-repair" enzyme human Mut-S-homologon-2.

We analyzed human Mut-S-Homologon-2 expression in normal endometrial tissue (n = 15) and malignancies of the uterine corpus (n = 40). Human Mut-S-Homologon-2 protein was investigated immunohistochemically on frozen sections, using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). Human Mut-S-Homologon-2 labeling pattern was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. A human Mut-S-Homologon-2 immunoreactivity score (human Mut-S-Homologon-2-IRS: negative 0-1; weak 2-3; moderate 4-6; strong 8-12) for semiquantitative analysis of human Mut-S-Homologon-2 expression is presented. In normal endometrial tissue samples we found weak nuclear immunoreactivity for human Mut-S-Homologon-2 in 67%, whereas the remaining 33% were negative for human Mut-S-Homologon-2 (mean human Mut-S-Homologon-2-IRS 1.25 +/- 1.29). All malignancies of the uterine corpus analyzed revealed moderate to strong nuclear immunoreactivity (mean human Mut-S-Homologon-2-IRS 9.00, +/- 3.16). Human Mut-S-Homologon-2 staining was heterogeneous, with visual differences among individual tumor cells. Expression of human Mut-S-Homologon-2 protein was consistently and strongly upregulated in tumor cells of malignancies of the uterine corpus compared with normal endometrial tissue (human Mut-S-Homologon-2-PP p<0.001; human Mut-S-Homologon-2-IS p<0.001; human Mut-S-Homologon-2-IRS p<0.001). No statistically significant correlation in comparing the labeling patterns for human Mut-S-Homologon-2 with the labeling patterns for Ki-67 (mean percentage of Ki-67-positive tumor cells 22.00% +/- 17.20) was observed in malignancies of the uterine corpus (human Mut-S-Homologon-2-PP p=0.443; human Mut-S-Homologon-2-IS p=0.234; human Mut-S-Homologon-2-IRS p=0.173). Our findings indicate that human Mut-S-Homologon-2 is expressed in normal human endometrial tissue and that expression of human Mut-S-Homologon-2 may be of importance for the genetic stability of malignancies of the uterine corpus in vivo. (J Histochem Cytochem 47:113-118, 1999).

Base Pair Mismatch↗
PubMed1999

CD2-mediated CD59 stimulation in keratinocytes results in secretion of IL-1alpha, IL-6, and GM-CSF: implications for the interaction of keratinocytes with intraepidermal T lymphocytes.

Normal epidermal keratinocytes are here shown to express membrane-associated complement inhibitory protein CD59 in vitro that protects keratinocytes from damage by complement because preincubation with blocking antibodies to CD59 renders the cells susceptible to complement mediated lysis. CD59 expression in keratinocytes is constitutive and not modulated by inflammatory cytokines, phorbol myristate acetate (PMA), and a number of other agents tested. Antibody mediated cross-linking of CD59, however, revealed an additional function of CD59: keratinocytes in vitro are activated to secrete the cytokines IL-1alpha, IL-6, and GM-CSF. CD59 mediated induction of these cytokines is regulated at the transcriptional level. Binding of keratinocytes to HL60 cells that express CD59 ligand CD2 induced the same pattern of secreted cytokines whereas binding to CD2-negative HL60 cells did not. Induction of cytokine secretion was completely blocked by preincubation of keratinocytes with both anti-CD58 and anti-CD59 antibodies together. The results demonstrate that CD2-mediated CD59 stimulation in human keratinocytes leads to synthesis of a particular set of cytokines implying a potential activation pathway in the interaction of keratinocytes with intraepithelial CD2+ T cells.

Antibodies, Blocking↗
PubMed1998

Down-modulation of host reactivity by anti-CD44 in skin transplantation.

BACKGROUND: A major goal in transplantation medicine is to achieve donor-specific tolerance while sustaining unaltered immunoreactivity toward donor-independent stimuli. Pretransplant immunization and concomitant blockade of costimulatory molecules may be one way to achieve this goal. We investigated whether transplant acceptance could be achieved by sensitization with semiallogeneic blood and blockade of CD44s (standard isoform) or CD44v6 (variant exon 6), since the adhesion molecule CD44 is known to function as a costimulatory molecule in T-cell activation. METHODS: Immunoregulatory regimens were examined in BDX rats that had received full-thickness (DA x BDX)F1 skin grafts by controlling graft acceptance and immunoreactivity. RESULTS: When BDX rats received full-thickness (DA x BDX)F1 skin grafts together with either anti-CD44s or anti-CD44v6, graft rejection was delayed, but none of the animals accepted the graft. An analysis of immunoreactivity revealed reduced numbers of infiltrating lymphocytes in anti-CD44s- as well as anti-CD44v6-treated rats. Expansion of donor-specific helper and cytotoxic T cells was particularly impaired in anti-CD44v6-treated rats. The effect of anti-CD44s could not be intensified by presensitization with donor-derived blood. However, when rats received anti-CD44v6 concomitantly with presensitization, 75% permanently accepted the graft and 50% accepted a second graft provided they were continuously treated with anti-CD44v6 and received a low dose of cyclosporine (CsA) during the first weeks after grafting. The frequency of graft-reactive helper T cells was reduced to less than 10% of the level in controls, and cytotoxic T cells could hardly be detected. CONCLUSION: According to the in vivo and the vitro analyses of the graft and the draining lymph nodes, anti-CD44s blocked homing of activated lymphocytes into the graft, while anti-CD44v6 inhibited clonal expansion of donor-specific T cells. Suppression by anti-CD44v6 apparently functioned distinctly to cyclosporine and was most effective in combination with presensitization. Since expression of CD44v6 on lymphocytes is restricted to a short period during lymphocyte activation, anti-CD44v6 treatment could lead to a quite specific immunosuppression during a limited time period.

Animals↗
PubMed1998

CD44 variant isoform expression in a variety of skin-associated autoimmune diseases.

CD44 variant isoforms are frequently expressed on tissue-infiltrating lymphocytes. By the high incidence of autoimmune reactions of the skin and aiming at new strategies of therapeutic intervention, we became interested in evaluating the CD44 isoform expression profile in autoimmune reactions of the skin. Expression of CD44s, CD44v3, v5, v6, v7, v7-v8, and v10 was evaluated in 55 biopsies of lupus erythematosus, bullous pemphigoid, vasculitis, morphea, and pemphigus vulgaris. Biopsies did not contain CD44v5-, CD44v6-, CD44v7-, or CD44v7-v8-positive leukocytes. Staining with anti-CD44v10 was seen in vasculitis and occasionally in lupus erythematosus, morphea, and bullous pemphigoid. All biopsies contained CD44v3(+) leukocytes, the percentage of CD44v3(+) leukocytes being increased in autoimmune infiltrates with the exception of pemphigus vulgaris. CD44v3 was expressed by CD4(+) cells as well as by part of CD8(+) cells, Langerhans cells, and monocytes. Vascular endothelium also contained CD44v3(+) cells. Only monocytes expressed CD44v10. We assume that CD44v3 and CD44v10 may be targeting leukocytes toward the skin or allow for their retention and expansion via binding of cytokines and chemokines harbored by activated, skin-associated endothelium or provided by cells surrounding the infiltrate. The absence of CD44v6, frequently associated with lymphocyte activation, appears to be a peculiarity of skin-infiltrating leukocytes.

Autoimmune Diseases↗
PubMed1998

[Familial juvenile macular dystrophy with congenital hypotrichosis capitis].

BACKGROUND: Our knowledge about the pathogenesis of hereditary macular diseases is still very circumscript. For genetic determination, a knowledge of the coincidence of eye symptoms and other defined common symptoms is helpful. The purpose of this paper was to present two sisters of a family of consanguineous parents with the combination of hypotrichosis of the head and macular dystrophy in the context of a tricho-ocular malformation of an ectodermal dysplasia. A review of the recent literature is included. PATIENTS AND METHODS: Two 13- and 17-year-old sisters presented at our hospital with reduced visual acuity because of symmetrical central changes of the retinal pigment epithelium and chorioatrophic scars according to macular dystrophy combined with hypotrichosis capitis. We performed fundus perimetry and histological examinations of the hair. RESULTS: The 13-year-old patient exhibited central changes of the retinal pigment epithelium leading to a relative central scotoma for Goldmann 1/4 during fundus perimetry in both eyes (visual acuity 0.125 and 0.4). We found central chorioatrophic scars, followed by absolute central scotomas, with unstable fixation in the upper retinal hemisphere in her 17-year-old sister with reduced visual acuity (0.16 and 0.2). CONCLUSION: There are few descriptions of the association of macular dystrophy and hypotrichosis. The combination of hypotrichosis and macular dystrophy could make genetical analysis easier. Mutational analysis of the TIMP-3 gene that has previously been associated with Sorsby fundus dystrophy did not reveal any disease-causing mutations in our patients.

Adolescent↗
PubMed1998

Immunohistochemical analysis of 1,25-dihydroxyvitamin D3 receptor in cervical carcinoma.

The immunohistochemical localization and expression of 1,25-dihydroxyvitamin D3 receptors (VDR) has been investigated in normal human cervical tissue (n = 15) and in cervical carcinomas (n = 23). VDR immunoreactivity (monoclonal antibody 9A7gamma) was compared with the staining patterns of transglutaminase K, cytokeratin 10 and Ki-67 in these tumours. Moderate to strong nuclear immunoreactivity for VDR was detected in almost all cervical carcinomas analysed. VDR staining was homogeneous, with no visual differences between individual tumour cells. Some 60% of normal cervical tissues revealed weak immunoreactivity for VDR. In normal cervical tissue, nuclear VDR staining was confined to the lower cervical layers, predominantly to the basal cell layer. Both the intensity of VDR immunostaining and the number of VDR-positive cells were up-regulated in cervical carcinomas compared with normal cervical tissue. No visual correlation was found for the coexpression of VDR with markers of proliferation and differentiation. Our findings indicate that: (1) cervical tissue may be a new target organ for therapeutically applied vitamin D analogues; (2) VDR is up-regulated at the protein level in cervical carcinomas compared with normal cervical tissue; (3) up-regulation of VDR in cervical carcinoma is induced not exclusively by alterations in epithelial differentiation or proliferation, but by different, unknown mechanisms; and (4) calcitriol and new vitamin D analogues exerting fewer calcaemic side-effects may be promising new drugs for the treatment or chemoprevention of metastasizing cervical carcinomas as well as of cervical precancerous lesions.

Adenocarcinoma↗
PubMed1998

Expression of 1,25-dihydroxy vitamin D3 receptor in breast carcinoma.

We investigated immunohistochemically the expression of 1,25 dihydroxy vitamin D3 receptors (VDRs) in normal human breast tissue and in breast carcinomas. For the first time, a VDR immunoreactivity score (VDR-IRS) in breast tissue is presented. Mean VDR-IRS in breast carcinomas was 7.28 compared to 1.55 in normal breast tissue. Comparing staining patterns for VDR and Ki-67, no visual correlation was found, indicating that VDR upregulation in breast carcinomas is not exclusively controlled by the proliferative activity of these tumor cells. Our study adds to the body of evidence that breast tissue may be a sensitive target organ for therapeutically applied new vitamin D analogues that exert few calcemic side effects.

Breast↗
PubMed1997

Detection of circulating melanoma cells by specific amplification of tyrosinase complementary DNA is not a reliable tumor marker in melanoma patients: a clinical two-center study.

PURPOSE: Recently, the reverse-transcription polymerase chain reaction (RT-PCR) of tyrosinase messenger RNA (mRNA) was reported to be a useful tool for the detection of circulating tumor cells in the peripheral blood of melanoma patients. Our aim was to evaluate critically the diagnostic value of this marker by investigating a significant number of patients in different stages of the disease in a two-center study. PATIENTS AND METHODS: Different techniques of blood collection, RNA isolation, and RT-PCR were compared, and the detectability of tyrosinase mRNA was tested using nine different melanoma cell lines. The sensitivity of the method was confirmed by blood spiking experiments and the specificity by restriction enzyme analysis. Subsequently, a total of 153 blood samples from 137 individuals (30 healthy subjects, five basal cell carcinoma, and 102 melanoma patients) were investigated. RESULTS: The detection level of melanoma cells differed between the cell lines tested. However, we could reproducibly detect single melanoma cells by spiking whole blood samples from healthy volunteers. One of 43 patients with primary melanoma (2.3%), zero of 15 patients with regional metastasis (0%), and 12 of 44 patients with advanced disease (27.3%) were found to be RT-PCR positive. All blood samples obtained from controls and patients with basal cell carcinoma were tyrosinose mRNA negative. CONCLUSION: Our data support the recent doubts that the detection of circulating tumor cells in melanoma patients using the tyrosinase mRNA RT-PCR is not sensitive enough to be used either as a melanoma progression marker in early stages of the disease or to monitor therapy in advanced stages of the disease.

Biomarkers, Tumor↗
PubMed1997

Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.

Adolescent↗
PubMed1996

Expression of CD44 splice variants in human skin and epidermal tumours.

Splice variants of the adhesion molecule CD44 (CD44v) are important in the lymphatic spread of rat carcinoma cells. In several human tumours expression of CD44v correlates with tumour progression. However, little is known about the physiological functions of distinct variant exons. Here we report on the immunohistological evaluation of CD44 expression in normal human skin and epidermal tumours which do not metastasise, or do so vary rarely. Frozen tissues were stained with a panel of monoclonal antibodies, recognizing epitopes of the CD44 standard isoform, as well as of variant exons v5, v6, v7, v7-v8 and v10. Stratum basale and spinosum as well as the root shaft of hairs reacted strongly with the whole panel of anti-CD44 antibodies. Stratum corneum, acinar cells of sebaceous and eccrine sweat glands stained with anti-CD44v5, anti-CD44v6 and anti-CD44v7, but not with anti-CD44v10, the latter recognizing the "epithelial isoform" (CD44v8-v10) of CD44. Ductal cells of glands and apocrine glands did not express CD44v. Compared with its expression in normal human skin, CD44v expression was reduced in basal cell carcinoma and squamous cell carcinoma of the skin. This was particularly true of CD44v10. The expression of CD44v in normal skin and dermal appendages indicates that not all combinations of variant exons are involved in tumour progression. Since the epithelial isoform is particularly downregulated in basal cell carcinoma and squamous cell carcinoma of the skin, it is unlikely that exons v8-v10 play a role in tumour progression. Rather, they may be of functional importance in maintenance of the epidermal structure.

Animals↗
PubMed1996

[Unfulfilled desire for children in the man: coping and pain. Results of a psychosomatic-andrologic cooperative study].

115 andrological patients were studied with psychological self-assessment tests to assess both their motivation concerning parenthood, and their own explanations for the causes. Additionally self-esteem was evaluated in 51 patients. The main results were: Motivation concerning parenthood is of greater importance in coping with involuntary childlessness than objective andrological data. Patients assess their situation quite realistically; no tendency to misinterpret the medical data in order to defend negative feelings and to protect self-esteem could be found. Most patients with reduced fertility consider this situation a challenge and are willing to mobilize resources and the help of others in order to cope. Self-esteem was only threatened in those patients with longlasting unvoluntary childlessness and little acceptance of medical infertility treatment and parenting substitutes, e.g. adopting a child.

Adaptation, Psychological↗
PubMed1996

Sperm morphology assessment using strict criteria and male fertility under in-vivo conditions of conception.

The clinical significance of sperm morphology assessment according to very strict criteria was determined using semen samples of randomly chosen males from couples not submitted to assist procreation techniques, with a median duration of infertility of 4 years (range 1-17; n = 89). The relationships of sperm morphological properties to the results of standard sperm analysis, including the differentiation of round cells in semen by monoclonal antibodies and semen cultures, the testing of sperm functional capacity in vitro with the standardized sperm-cervical mucus penetration test (SCMPT) and the subsequent pregnancy rate under in-vivo conditions of conception, were evaluated in a prospective study. The quick staining method (DiffQuick(R) stain) for sperm morphology proved to be practical and suitable for routine use. The percentage of normal forms according to strict criteria ranged from 1 to 36%, with a median of 12%. Morphological findings were not markedly related to the medical history, but significant relationships between standard parameters of sperm analysis, in particular the sperm count, the progressive motility and standard sperm morphology, were found. The percentage of normal forms was not significantly associated with the microbial colonization of semen samples but was negatively related to high leukocyte rates. Semen samples with a higher percentage of normal spermatozoa (shown, for example, for >4,> 7 or >=14% normal) were significantly more frequent in cases of an adequate SCMPT. The subsequent pregnancy rate within an observation period of 12 months was 20.2%. The pregnancy rate under in-vivo conditions was significantly higher when semen samples had a better sperm morphology, with significant differences for thresholds at 4, 7 and 14% of strictly normal forms. Although sperm morphology is only one among a multiplicity of factors determining fertility, the results suggest that the evaluation of sperm morphology using strict criteria provides valuable information during basic infertility investigations.

Adult↗
PubMed1996

The Acridine Orange test: a clinically relevant screening method for sperm quality during infertility investigation?

To determine the clinical usefulness of Acridine Orange (AO) staining of spermatozoa as a screening test for the evaluation of semen quality during basic infertility investigation, semen smears from 103 randomly chosen males of subfertile couples were examined. The median duration of infertility was 4.5 years (range 1-15) and the median age was 33 years (range 21-43). The outcome of AO staining ranged from 5 to 81%, with a median of 24%, green fluorescent spermatozoa. Results were not significantly related to the parameters of semen analysis (sperm count, motility, standard morphology, viability, pH and volume, as well as fructose concentration and number of found cells) or to local sperm antibody testing and semen cultures. Fluorescence after AO staining was also not related to sperm functional capacity (evaluated using sperm-mucus interaction tests in vitro and in vivo), or the medical history of the patient. No significant differences in the AO test outcome were seen in patients with explained and unexplained infertility, or with regard to subsequent fertility [with a median value of 21% (range 5-46) green fluorescence in the fertile group, compared with a median value of 28% (range 9-81) green fluorescence in the other men]. The results of this prospective study indicate that under the usual conditions of conception, the AO test is not clinically useful as a screening procedure to determine semen quality during basic infertility investigation.

Acridine Orange↗
PubMed1996

Fotemustine given simultaneously with total brain irradiation in multiple brain metastases of malignant melanoma: report on a pilot study.

Melanoma patients with multiple brain metastases not amenable to surgery or stereotactic radiotherapy were treated with total brain irradiation in fractions of 2.5 Gy four times weekly, up to 40 Gy. At days 1, 8, and 25100 mg/m2 fotemustine was infused 4 h before irradiation. Of 12 evaluable patients, four showed partial remission and three stabilization in the brain. The median survival in these two groups of patients was 6 months; the survival of the other patients was 2 months. Severe haematological side effects were observed in 6/13 patients. In conclusion, the combination of fotemustine and total brain irradiation seems to be more effective than either treatment alone, but bears the risk of additional bone-marrow toxicity.

Adolescent↗
PubMed1996

Induction of immunoresponse by subclinical male genital tract infection?

OBJECTIVE: To determine the relationship of subclinical infection or inflammation of the male genital tract, as evaluated with seminal markers, with local antisperm antibodies as potential parameter of immunoresponse. PATIENTS: One hundred ninety-one randomly chosen males of subfertile couples who were asymptomatic in terms of genital tract infection. SETTING: Outpatient Infertility Clinic of the University of Heidelberg, Germany. MAIN OUTCOME MEASURES: Determination of leukocytes rates in semen using an immunocytochemical method for differentiation of round cells and measurement of polymorphonuclear (PMN) granulocyte elastase concentration in seminal plasma in addition to semen cultures as screening for subclinical infection of the male genital tract. Determination of local antisperm antibodies (Ab) with the mixed antiglobulin reaction ([MAR] immunoglobulin [Ig] G and IgA) in aliquots of the same ejaculates. RESULTS: Leukocyte rates of the round cells ranged from 0% to 93%, leukocytospermia was found in 6.8%. This was not related significantly to the presence of local antisperm antibodies of the IgG or IgA class. There was also no significant association of antisperm Ab with the concentration of PMN granulocyte elastase in seminal plasma and the outcome of semen cultures. CONCLUSIONS: The results of this prospective study suggest that when the rate or number of leukocytes or the concentration of PMN elastase in semen are taken as markers for subclinical infection or inflammation of the male genital tract, this is not associated significantly with the production of local antisperm Ab of the IgG or IgA class as indicator of immunoreaction.

Adult↗
PubMed1996

Expression of CD44 variant isoforms in malignant melanoma.

In a variety of human tumors, expression of splice variants of the adhesion molecule CD44 (CD44v) has been described as correlating with tumor progression. Here, we report on the expression of CD44v in melanocytes, nevi, primary melanomas, and cutaneous and lymph node metastases. Thirteen nevi, 65 primary melanomas of varying thickness, 39 cutaneous and 15 lymph node metastases, and melanocytes and a panel of melanoma lines were tested for surface expression of the standard form of CD44 and the variant exons v5, v6, v7, v7-v8, and v10 by immunohistology or fluorescence-activated cell sorting. Melanocytes did not express any variant isoform of CD44. However, nevi, as well as primary melanoma and melanoma metastases, stained to a varying degree with anti-CD44v5, anti-CD44v7-v8, and anti-CD44v10. Exons v6 and v7 were not detected on any of these tissue specimens. Compared with nevi, expression of exon v10 was up-regulated in thick primary tumors and skin metastases. Lymph node metastases displayed elevated levels of exon v5. Expression of CD44v in melanoma lines (n = 20) differed, inasmuch as many lines did not express variant isoforms; in particular, exon v10. Interestingly, however, the few CD44v5-positive melanoma lines metastasized in the nu/nu mouse. Because benign as well as malignant growth of melanocytes was accompanied by expression of CD44 variant isoforms, a linkage between expression of CD44 variant isoforms and malignant transformation or tumor progression was excluded. Considering the function of distinct isoforms, one might speculate that expression of exon CD44v5, which was up-regulated in lymph node metastases compared with nevi and primary melanoma, provided a growth stimulus. Exon v10 is present at high density in epidermal cells. The de novo expression of this exon in nevi and the increased expression in thick melanoma and skin metastases would be in line with the assumption of an anchoring advantage in the surrounding epidermal tissue.

Animals↗