Biomedical subjects
Publications and source records attributed to W Tilgen.
We report on a single case of a lichen planus like contact dermatitis caused by colour developers. We emphasize similarities to lichen planus with regard to clinical, histopathological and immunohistological aspects.
Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous-like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM-1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis.
We report on an ELISA procedure for the quantitative analysis of total human leukocyte (PMN)-elastase, i.e., the simultaneous determination of (i) free (non-complexed) PMN-elastase and of (ii) PMN-elastase that is complexed to alpha 1 proteinase inhibitor. Simultaneous detection of both forms of PMN-elastase was achieved using a monoclonal antibody that recognizes a PMN-elastase-specific epitope present on both the uncomplexed and the complexed form of the enzyme. The test system described is reliable, easy to perform and permits the determination of total PMN-elastase in complex biological fluids such as plasma or seminal fluid. It is to be expected that this test system will be useful for investigations of human PMN-elastase in biological specimens obtained from both normal and pathological conditions.
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After screening a large series (n = 491) of asymptomatic males of infertile partnerships for chlamydial immunoglobulin (Ig) G antibodies (Chlam AB), no significant influence of past chlamydial infection was found with regard to semen analysis, postcoital testing, in vitro sperm-cervical mucus penetration tests with hormonally standardized cervical mucus, circulating antisperm antibodies (detected with three different methods), local IgG and IgA antibodies (detected by means of the mixed antiglobulin reaction test) on the sperm surface, the sperm-cervical mucus contact test, and a microbial screening of semen samples for mycoplasmas and other potentially pathogenic micro-organisms. However, when the findings were correlated with infertility factors of patients' female partners and the subsequent pregnancy rate in a prospective study, a significant positive correlation of male Chlam AB with a tubal factor in their wives as cause of the couple's infertility was found. The results suggest that the main influence of Chlamydia trachomatis on male fertility is based on sexual transmission and negative influence on tubal function of female partners, but not on reduced sperm functional capacity.
Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti-melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect.
Semen samples from 179 patients with longstanding infertility were allowed to penetrate capillaries filled with a fraction of fresh hens' egg white (HEW) as a substitute for cervical mucus (CM) for the in-vitro sperm-cervical mucus penetration test (SCPMT). Results were correlated with those obtained from human CM (HCM) used in parallel on the same semen sample, compared to results of sperm analysis and post-coital testing (PCT) and analysed for their prognostic value for a subsequent pregnancy in a prospective study. The overall pregnancy rate after 6 months was 26.3% (47/179). Whereas routine semen analysis (semen volume, pH, sperm count, progressive motility, morphology and fructose concentration) did not differentiate between patients who achieved pregnancy and those who did not, significant differences were found for the penetration distance (P less than 0.02) and the motility grade of sperm in HEW (P less than 0.02). Although the mean sperm velocity in HEW was reduced compared to HCM, a close positive correlation was found between the sperm density and the penetration distance (P less than 0.001). The percentage of samples with good HEW penetration increased significantly in parallel with better results of post-coital testing (P less than 0.001). The results indicate that, when fresh human CM is not available, HEW can be used as a medium for the SCPMT as a valuable adjunct to semen analysis which provides information about sperm functional capacity.
The urinary excretion of spermatozoa (spermaturia) reflects the achievement of exocrine testis function during male puberty. In order to test the sensitivity and practicability of repetitive urine sampling, we analysed the sediments of 1160 first morning urine specimens obtained on successive days from 129 healthy schoolboys aged 10.1 to 17.8 years for the presence of spermatozoa. The proportion of subjects with sperm positive urines increased from pubic hair stage (PH) 1 (6%) to PH 5 (92%) with a steep rise between PH 2 and 3. Estimated median age of first positive spermaturia ('spermarche') was 14.1 years. While at PH 1 to 4 all positive samples were found within the first five days of collection, at PH 5 cumulative frequency of spermaturia increased up to day 8. We conclude that repetitive morning urine sampling is a useful tool in assessing spermaturia and may be helpful to screen for testicular damage in epidemiological surveys.
The cytokine interleukin 2 (IL 2) has proved to be an effective agent in immunotherapy of human cancers. Natural killer cells and cytotoxic T-lymphocytes are activated via membrane receptors by IL 2. IL 2-activated natural killer cells and cytotoxic T-lymphocytes develop high cytolytic activity against a variety of tumor cells in vitro. After extensive animal experiments, IL 2 was used in humans either alone or in combination with lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Its application in humans is still experimental, although initial results are very promising. Further studies are necessary to establish treatment protocols with high therapeutic efficacy and tolerable side effects.
The case of a 27-year-old woman with recurring and metastasizing clear cell sarcoma (CCS) of tendons and aponeuroses is presented. Clinical setting, protracted course, and light microscopic appearance were in agreement with the original description. Immunohistologically, the tumor cells consistently expressed vimentin, S-100 protein, melanoma-associated antigens p97 and 7 kD peptide (as detected by monoclonal antibodies 96.5 and HMB-45, respectively), and major histocompatibility complex class I and (focally) class II antigens. Furthermore, the lymphocyte-associated antigen CD24 was detectable in the entire tumor cell population. Reactivity of the neoplastic cells with monoclonal antibodies to melanoma-associated antigens provides further evidence for a neural crest origin of CCS.
To evaluate the clinical significance of in vivo and in vitro testing of sperm ability to penetrate cervical mucus (CM), postcoital testing (PCT) and in vitro sperm-cervical mucus penetration testing were compared in a prospective study. Both in vivo and in vitro tests were standardized and performed after an oral course of estrogen therapy. Crossed in vitro sperm-cervical mucus penetration test, evaluated in 277 couples with CM of patients' wives and additionally with CM and semen of fertile donors, revealed that the male factor contributed to a significantly higher extent to deficient sperm-mucus interaction than the cervical factor. The overall pregnancy rate after 6 months was 23% (64/277). Whereas the outcome of PCT did not significantly predict subsequent fertility (PCT good pregnancy rate 24%/PCT poor 20%), significant differences were found for the sperm-cervical mucus penetration test with CM of patients' wives (pregnancy rate, 30.5% versus 8.5%) and for in vitro testing with donors' CM, but not for the mucus penetration test with donors' spermatozoa. Routine sperm analysis did not prove to be of prognostic value for a subsequent pregnancy. The results suggest that the in vitro sperm-cervical mucus penetration test is a good parameter of sperm function and, in particular, when performed as a cross-matching penetrability test, a valuable adjunct to PCT with regard to fertility prognosis.
To analyze the prognostic value of the sperm cervical mucus penetration test (SCMPT), fresh semen samples of 99 male patients under infertility investigation were exposed to capillary tubes filled with freshly obtained cervical mucus (CM) of the patients' wives (WCM), fertile donors (DCM), and bovine CM (BCM). The quality of the human CM was standardized by oral administration of estrogens. The overall pregnancy rate after 6 months was 17.2% (17/99), and was significantly different in couples with poor and good SCMPT with WCM (1/44, 2.3% versus 16/55, 29%; P less than 0.001) in a prospective study. Human CM was superior to BCM as a penetration medium in providing more information about sperm function. The results suggest that in vitro sperm penetration testing with hormonally standardized CM of female partners adds an important dimension to sperm analysis with regard to fertility prognosis.
By following the interaction of labelled anti-tumor antibodies with target cells, it was found that in most systems cross-linking of externally bound antibody by anti-IgG leads to nearly complete internalization, whereas excess unlabelled antibody induces fast release of radioactivity from the cell. Uptake in tumor tissue did not depend on presentation of antigen at the cell surface, as demonstrated with antibody RA96 directed against an intra- and inter-cellular antigen. With respect to permeation into solid tissue, autoradiography revealed highly non-homogeneous distribution of intact IgG, while antibody fragments tended to show a more homogeneous penetration. Small spontaneous metastases showed markedly higher accumulation than large tumor processes.
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The treatment of metastatic malignant melanoma remains unsatisfactory. Recently, immunological approaches have been examined. In this respect, therapy with interleukin 2 (Il 2) and Lymphokine-activated killer cells (LAK-cells) is of special interest. In the present paper, the results from the literature are reviewed, and the first patient is reported, who was treated in our department with this therapeutic regimen in a phase-one study to examine the toxicity of a new Il 2 preparation.
We report the occurrence of mucous membrane manifestations in six patients with HIV-infections: Kaposi sarcomas of the hard palate, of the gingiva, of the larynx and of the glans penis, unusual spreading of condylomata acuminata, bowenoid papulosis, thrush and hairy leukoplakia.