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Biomedical subjects

W Hartschuh

Publications and source records attributed to W Hartschuh.

At least 55 records · Page 3Linked to original sources

[Periorbital lipogranuloma following endonasal sinus surgery].

A 60-year-old woman developed a periorbital lipogranuloma after endonasal surgery on her paranasal sinuses. The granulomatous inflammation was caused by nonabsorbable lipids introduced by the postoperative nasal tamponade which was soaked in antibiotic ointment. These lipids were transported into the periorbital tissue by the postoperative hemorrhage. Since the course of the inflammatory process is chronic, surgical removal is the best treatment.

Anti-Bacterial Agents↗

Forms of epithelial differentiation of draining sinus in acne inversa (hidradenitis suppurativa).

The draining sinus is a late complication of several forms of severe acne, leading to extensive, periodically inflamed lesions that are undermined by a system of fistulas, supposed to be of follicular origin. We investigated the expression of various cytokeratins (CKs) and desmosomal proteins in the draining sinus of acne inversa (hidradenitis suppurativa) using monoclonal antibodies in immunohistochemistry on paraffin-embedded sections. We were able to define three different phenotypes of stratified squamous epithelia covering the sinus tracts. Type I epithelium was cornifying and characterized by the presence of CK 10, desmogleins 1-3 and desmocollins 1-3 in an epidermis-like pattern. Type II epithelium was non-cornifying, negative for CK 10 and positive for CK 13. It was negative for desmocollin 1 but strongly immunopositive for desmoglein 1 suprabasally and for desmoglein 2 in the basal cells. Type III epithelium was non-cornifying and strongly inflamed. It was marked by the presence of CK 7, CK 19 and desmoglein 2 and the absence of CK 10, desmoglein 1 and desmocollin 1. In both type II and III epithelium, desmoglein 3, desmocollin 2 and desmocollin 3 showed an inverted staining pattern as compared with normal epidermis and type I epithelium. Desmoglein 2 and CK 5/14 always remained restricted to the basal cell layer. Antibodies against CK 6 and CK 13/15/16 were immunopositive in all three phenotypes and CK 17 was predominantly immunolocalized to suprabasal layers of type II and III epithelium. The three phenotypes are characterized as pathological stratified squamous epithelia reflecting the dynamic process of inflammation, proliferation and stratification taking place in acne inversa.

Antibodies, Monoclonal↗

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell.

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.

Adult↗

Birt-Hogg-Dubé syndrome and Hornstein-Knickenberg syndrome are the same. Different sectioning technique as the cause of different histology.

The autosomal dominant inherited syndromes of Hornstein and Knickenberg (HKS), and Birt, Hogg and Dube (BHDS) are both characterized clinically by the overall spread of multiple flesh coloured papules of the skin. However, it is a matter of debate if colonic neoplasms (adenomas as well as adenocarcinomas) are associated findings in the HKS or rather in the BHDS. Furthermore, histological differences are said to exist between the skin lesions in the two syndromes: whereas perifollicular fibromas were described in the HKS, fibrofolliculomas and trichodiscomas were found in the BHDS. In the present study, we report on a father and his daughter in whom we initially diagnosed a BHDS. We then examined a greater number of the papular lesions in histologic sections cut vertically as well as horizontally to the epidermis. Our results indicate that the histologic differences between the skin lesions in the two syndromes are artificial ones, caused by interpretation of different sectioning planes, and that consequently HKS and BHDS are the same. Therefore, it is necessary to look for colonic polyps in the syndrome in question, regardless if one prefers the name HKS or BHDS for it.

Adult↗

Ultrastructural connective tissue abnormalities in patients with spontaneous cervicocerebral artery dissections.

The cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers-Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.

Adult↗

Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria.

Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the coincidence of at least one sebaceous skin tumor and one internal malignancy. About half of MTS patients are affected by colorectal cancer. In a subgroup of MTS patients the disease has an underlying DNA mismatch-repair (MMR) defect and thus is allelic to hereditary nonpolyposis colorectal cancer (HNPCC). The purpose of this study was to examine to what extent germ-line mutations in DNA MMR genes are the underlying cause of the MTS phenotype. We ascertained 16 MTS patients with sebaceous skin tumors and colorectal cancer, and we examined their skin and visceral tumors for microsatellite instability. All the patients exhibited high genomic instability in at least one tumor. The search for germ-line mutations in the hMSH2 and hMLH1 genes in 13 of the MTS patients revealed truncating mutations in 9 (69%): eight mutations in the hMSH2 gene and one in the hMLH1 gene. This is the first systematic search for germ-line mutations in patients ascertained on the basis of sebaceous skin tumors. Our results indicate that (1) MTS patients exhibit significantly more mutations in the hMSH2 gene than in the hMLH1 gene; and (2) the subpopulation of MTS patients who are also affected by colorectal cancer, irrespective of family history and age at onset of tumors, may have a likelihood for an underlying DNA MMR defect similar to that for patients with a family history fulfilling the strict clinical criteria for HNPCC.

Adult↗

The trichofolliculoma undergoes changes corresponding to the regressing normal hair follicle in its cycle.

The trichofolliculoma is a follicularly differentiated hamartoma, usually described as showing many vellus follicles, spreading from a central infundibular cyst. In spite of the well known regressive changes of normal hair follicles during catagen and telogen, the possibility of corresponding changes in the trichofolliculoma has not yet been discussed in the literature. By examining a total of 31 cases of trichofolliculoma it is demonstrated that this hamartoma undergoes an evolutionary process with great morphological changes, which can be attributed to the anagen, catagen, and telogen phase of the follicular cycle.

Adolescent↗

Folliculo-sebaceous cystic hamartoma is a trichofolliculoma at its very late stage.

Folliculo-sebaceous cystic hamartoma (FCH) was described as an entity recently and was defined as an adnexal hamartoma, showing above all an infundibular cystic structure linked to many sebaceous lobules. Differentiation toward the inferior segment of the hair follicle also occurs, although to a markedly lesser degree. Signs of regression and rest corresponding to the normal follicular cycle are often apparent in these follicular proliferations. Therefore so-called FCH has much in common with the newly described late stage of trichofolliculoma, which also exhibits an infundibular cyst and sebaceous and follicular differentiation with various signs of catagen and telogen. Comparing our 8 cases of FCH and 31 cases of trichofolliculoma, we came to the conclusion that FCH is the very late stage of trichofolliculoma. This stage could be characterized by a nearly complete regression of the transient follicular epithelium, whereas concurrent growth and maturation of sebaceous elements appear.

Adolescent↗

Cutaneous Merkel cells of the rat contain both dynorphin A and vesicular monoamine transporter type 1 (VMAT1) immunoreactivity.

To delineate fully opioid peptide function in cutaneous inflammatory and nociceptive responses, it is necessary to know first which opioid peptides are present in the skin and which cellular elements in the skin store and secrete them. Merkel cells are cutaneous neuroendocrine cells, which may derive from the neural crest or from undifferentiated keratinocytes with stem cell character. The neuroendocrine character of Merkel cells is supported by their immunoreactivity for chromogranin A (CGA) and a variety of neuropeptides, among them the opioid peptide [Met]enkephalin as shown in guinea-pig and mouse. This study investigates in the rat whether the preprodynorphin derived opioid peptide dynorphin A is expressed in cutaneous Merkel cells and possibly related to an aminergic phenotype. Light microscopic immunohistochemistry revealed dynorphin A immunoreactivity in Merkel cells to be codistributed with immunoreactivity for calcitonin gene-related peptide (CGRP) and CGA, two well-established merker peptides of mammalian Merkel cells. Vibrissal Merkel cells stained for the neuroendocrine vesicular monoamine transporter isoform 1 (VMAT1) but not for the predominantly neuronal isoform 2 (VMAT2). Merkel cell staining for dynorphin A, VMAT1, CGA, and CGRP was unaffected by experimental denervation. Dynorphin A and a still unidentified monoamine, possibly serotonin, may cofunction as autocrine or paracrine mediators in the mechanosensory Merkel cell--axon complex and are potentially involved in peripheral analgesia.

Animals↗

Effective treatment of hypertrichosis with pulsed light: a report of two cases.

Hypertrichosis is an often stigmatizing cosmetic problem not only for women but also for male-to-female transsexual patients. The hitherto described therapeutic measures include chemical epilation, razoring, camouflage, electrolysis and thermolysis, and waxing. All of these measures are transient, more or less painful, and may lead to severe side effects (e.g., inflammatory responses and scarring). We report the successful treatment of the perioral and mandibular area of two transsexual patients (male to female), who we treated with a recently introduced intense, pulsed light source--the PhotoDerm VL. Two days after the nearly painless treatment, hair could be epilated easily with forceps. Biopsies of the treated area show an atrophy of the follicles, which can be contributed either to direct thermal injury or to an indirect photothermolytical effect. Six months after the last treatment, there is no local recurrence and no side effects.

Adult↗

Merkel cells are absent in basal cell carcinomas but frequently found in trichoblastomas. An immunohistochemical study.

The possibility of a neuroendocrine differentiation in basal cell carcinomas (BCCs) has been a matter of debate for many years. In the present immunohistochemical study, applying the cytokeratins 8, 18 and 20 as the most established markers for Merkel cells (MCs), we did not find elevated numbers of MCs in any of 205 BCCs. This speaks against a neuroendocrine line of differentiation in BCCs. In contrast, we found various amounts of MCs in 15 of 36 trichoblastomas, which are the main benign differential diagnosis of BCC. In 4 trichoblastomas abundant MCs were spread over the whole epithelial tumor area. Additionally, the trichoblastomas' overlying epidermis exhibited significantly much higher numbers of MCs than the uninvolved adjacent skin or the epidermis overlying the BCCs. These findings might be an additional aid in the distinction between trichoblastomas and BCCs. Furthermore, concerning the recent discussion about the role of MC in growth and development of follicular germ, our observations are another sign of regulative influences of the MC, also in follicular germ under pathological conditions. Trichoblastomas with high numbers of MCs could be characterized as showing advanced differentiation toward the neuroendocrine component of the hair follicle, i.e., the MCs.

Basal Cell Carcinoma↗

Merkel cell hyperplasia in chronic radiation-damaged skin: its possible relationship to fibroepithelioma of Pinkus.

Moderate hyperplasia of Merkel cells (MC) in chronic sun-damaged skin and hypertrophic actinic keratoses is well known. In the present study we investigated the number of MC in 24 samples of chronic radiation dermatitis and 19 cases of fibroepithelioma of Pinkus (FP), which is known to arise preferably in radiation-damaged skin. Using antibodies against the low molecular weight cytokeratins 8, 18, and 20 and chromogranin A to visualize MC, we found hyperplasia of MC in chronic radiation dermatitis. Additionally, in all FPs we could detect many MC, especially in areas with a pronounced fenestrated pattern. Recently, regulative functions of MC on the growth of follicular epithelium under various conditions were discussed. Thus, MC hyperplasia suggests a causal role also in the development of FP. In this context, hyperplasia of MC in chronic radiation dermatitis could explain the frequent occurrence of FP due to radiation exposure. As we recently found MC also in trichoblastomas but not in basal-cell carcinomas, the MC in FP may indicate its relationship to the benign trichoblastoma rather than to the basal-cell carcinoma. It is possible that regulative influences of the MC are important for the clinically rather benign course of FP.

Aged↗

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11.

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.

Chromosome Mapping↗

Merkel cells in nevus sebaceus. An immunohistochemical study.

Nevus sebaceus, considered to be a hamartoma, is known to develop several secondary hyperplastic and neoplastic proliferations. By the use of immunohistochemical studies, we were able to describe a sometimes very striking increase of Merkel cells in nine of 19 nevi sebacei. Only nevi sebacei that formed follicular germ structures and trichoblastomas showed a Merkel cell hyperplasia. In the hyperplastic epidermis of some cases a slight hyperplasia of singular Merkel cells was observed. In foci with follicular germs and trichoblastomas, however, the Merkel cells were much more abundant and sometimes arranged in clusters. Merkel cell hyperplasia is likely to represent another facet of hamartomatous hyperplasia in nevi sebacei. Our observation that trichoblastomas in nevus sebaceus possess, as a rule, hyperplasia of Merkel cells, might be an additional aid to distinguish these tumors from basal cell carcinomas, which are usually devoid of Merkel cells. Furthermore, our findings are a hint that development of follicular germs and trichoblastomas in nevi sebacei may be promoted by Merkel cells.

Adolescent↗

Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study.

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n = 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n = 30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered. Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.

Basal Cell Carcinoma↗

In situ expression of beta 1, beta 3 and beta 4 integrin subunits in non-neoplastic endothelium and vascular tumours.

Endothelial cells play an important role in adhesive interactions between circulating cells and extracellular matrix proteins. In vitro studies have shown that many of these processes are mediated by a superfamily of alpha beta heterodimeric transmembrane glycoproteins called integrins. The distribution patterns of beta 1, beta 3 and beta 4 integrin subunits in endothelial cells (EC) in situ were examined immunohistochemically on serial frozen sections of a wide range of non-neoplastic tissues and of vascular tumours, both benign and malignant. Expression of the beta 1 subunit was a constitutive feature of EC. Among the beta 1-associated alpha subunits, alpha 5 and alpha 6 were broadly distributed in EC, irrespective of vessel size and microenvironment. The alpha 3 subunit displayed intermediate levels of expression with a slight preference for small vessel EC. Presence of alpha 1 was confined to EC of capillaries and venules/small veins. Expression of alpha 2 in EC was inconsistent. With rare exceptions, the alpha 4 chain was absent in EC. The beta 3 and alpha v subunits were expressed in most EC, though not always concomitantly. In contrast to the beta 1 chain, however, these integrin subunits were absent in EC of glomerular capillaries and were expressed variably in sinusoidal EC. The beta 4 chain was evenly present in the great majority of EC, except for those of large vessels. In vascular tumours, the patterns of beta 1 and alpha 1 to alpha 6 subunit expression generally corresponded to those found in their non-neoplastic counterparts. Expression of beta 3, alpha v and beta 4 chains, however, decreased in neoplasia, especially in angiosarcomas. These data show that EC dispose of broad and at the same time differential repertoires of integrin subunits that presumably reflect vessel-type associated functional differences among these cells. In vascular tumours, the orthologous distribution patterns of beta 1 and alpha 1 to alpha 6 chains are conserved in most instances while the amounts of beta 3, alpha v and beta 4 subunits expressed in EC tend to decrease in the course of malignant transformation.

Antibodies, Monoclonal↗

[Erythrokeratolysis hiemalis. Erythematosquamous genetic dermatosis with seasonal manifestation].

Erythrokeratolysis hiemalis, keratolytic winter erythema or Oudtshoorn skin has been reported from the South African district of Oudtshoorn as a dominantly inherited dermatosis beginning in early childhood, in some cases with circinar scaling erythemas. Seasonal manifestation in winter-time and a characteristic multi-form histology distinguish this dermatosis from other childhood scaling erythemas. We present clinical, histological and preliminary immunohistological data of a 4-year-old girl with the attributes of erythrokeratolysis hiemalis. No ancestors from the endemic region were traced. The lack of further cases in the family is interpreted as indicative of a spontaneous dominant new mutation.

Child, Preschool↗

Differential regulation of c-fos, fosB, c-jun, junB, bcl-2 and bax expression in rat skin following single or chronic ultraviolet irradiation and in vivo modulation by antisense oligodeoxynucleotide superfusion.

Single ultraviolet (u.v.) irradiation of mammalian cells in culture evokes the transcriptional activation of various proto-oncogenes, among them members of the fos/jun family which are known to play an important role in cell proliferation and differentiation. u.v. exposure of mammalian skin results in growth arrest and cell death followed by hyperproliferation of epidermal cells. To obtain information in vivo about a possible relationship between u.v.-induced proto-oncogene expression and cellular alterations, we have analysed the expression of c-fos, fosB, c-jun, junB, bcl-2 and bax in rat epidermis after single and chronic u.v. irradiation. We present data demonstrating that the transcripts of these genes are constitutively expressed in the epidermis and that expression is differentially modulated by u.v. exposure. Single u.v. irradiation causes a rapid and sustained increase in c-jun, junB and c-fos mRNA and a decline in bcl-2 transcripts, whereas expression of bax remained unchanged. c-Fos and c-Jun immunoreactivity was localized throughout the epidermal cell layers 1.5 h after single irradiation, but restricted to basal cells at 48 h suggesting an involvement in both u.v.-induced apoptosis and hyperproliferation. 48 h after chronic exposure a significantly higher induction and a totally different pattern of epidermal proto-oncogene expression was detectable which may be associated with malignancy. Superfusion of rat skin with c-fos antisense oligodeoxynucleotides inhibited the increase in c-Fos immunolabeled epidermal cells 1.5 h after single u.v. irradiation demonstrating that antisense oligodeoxynucleotides are capable of penetrating mammalian skin and modulating the u.v. response in vivo. However, suppression of the early c-Fos activation did not significantly affect the formation of sunburn cells in the u.v.-exposed epidermis. Thus, c-Fos does not seem to play a major role in u.v.-induced apoptosis or other members of the fos/jun family may compensate for a loss in c-Fos.

Animals↗