Ralf Wienecke

Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study.

Abstract We report an autopsy case of tuberous sclerosis complex (TSC) in a 20-week gestational age female fetus. The brain showed lesions suggestive of early cortical tubers and subependymal hamartomatous nodules. The large cells within these nodular clusters were variably immunoreactive for glial fibrillary acidic protein (GFAP) and vimentin and negative for synaptophysin and neurofilament. Subependymal radial glia expressed both vimentin and GFAP, but subpial radial glia either did not express these markers (in contrast to an age-matched control) or were absent. Tuberin expression was noted in heterotopic neurons in the white matter and brain cells consistent with Cajal Retzius cells in the neocortical molecular layer, very weakly in superficial cortical neurons, neurons in the basal ganglia, Purkinje cells and external granular cells of cerebellum, cranial nerve nuclei neurons, occasional germinal matrix cells, ependymal cells, choroid plexus epithelium, and pituitary gland neuroendocrine cells; it was not seen within the cells of subependymal nodules. The pattern of tuberin immunoreactivity was similar to that which we have observed in older TSC patients. Proliferating cell labeling indexes were comparable in the germinal matrix of the TSC patient and an age-matched control. Abnormal subpial radial glia may be responsible for some of the neuronal migration abnormalities that appear to result in neocortical tubers.

Molecular detection of Borrelia burgdorferi in formalin-fixed, paraffin-embedded lesions of lyme disease

A system for the detection of a Borrelia burgdorferi (Bb)‐specific gene segment in formalin‐fixed, paraffin‐embedded skin lesions is described. A nested polymerase chain reaction technique is used to selectively amplify in vitro a short segment of a Bb‐specific gene recently described by Rosa et al. (J Infect Dis 1989: 160: 1018). The design of oligonucleotide primers for the amplification of a relatively short gene segment allows the successful analysis of DNA which has been altered by fixation in formalin. Using this technique, Bb‐specific DNA was clearly identified in 8 of 12 specimens of erythema chronicum migrans and in 1 case of lymphadenosis benigua cutis. These skin lesions are known to represent cutaneous manifestations of Lyme disease. Negative control reactions, using DNA from borrelial strains not related to Lyme disease, were negative. The system enables the dermatopathologist to identify Bb in routinely fixed clinical specimens and allows the rapid analysis of various skin diseases for which an association with Bb so far has only been hypothesized.

In Vitro Susceptibility Testing of Four Antibiotics against Borrelia burgdorferi: a Comparison of Results for the Three Genospecies Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi Sensu Stricto

ABSTRACT MICs and minimal bactericidal concentrations (MBCs) were evaluated for the four antibiotics azithromycin, amoxicillin, ceftriaxone, and doxycycline against the three main genospecies of Borrelia burgdorferi sensu lato. In MBC testing, statistically significant differences between the genospecies could be found in 7 out of 12 comparative evaluations (P < 0.05).

Loss of tuberin, the tuberous-sclerosis-complex-2 gene product is associated with angiogenesis.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2.

Cowpox virus infection in an 11-year-old girl.

We describe an 11-year-old girl with a cowpox virus infection, who presented with a 14-day-old crusted, ulcerated nodule on the chin/neck and a 6-day-old eroded blister on the left leg. The girl lived in a rural environment, had close contact to several cats from the neighborhood, and had an atopic predisposition. The presence of orthopox virus in the lesion on the left leg was demonstrated by electron microscopy (negative staining, transmission electron microscopy) and virus isolation. Classification as a cowpox virus was determined by polymerase chain reaction (PCR), followed by restriction enzyme digestion of the PCR product.

Analysis of the 14;18 translocation in cutaneous lymphomas using the polymerase chain reaction.

A series of 25 cutaneous B‐cell lymphoid proliferations was analyzed for the presence of the (14;18) translocation using the polymerase chain reaction, functional sequences of rearranged chromosomes 14 and 18 were amplified in vitro, and t (14;18) specific sequences were detected in 1 of 14 primary cutaneous B‐cell lymphomas, in 1 of 14 primary nodal B‐cell lymphomas and in none of 3 B‐cell pseudolymphomas. These results indicate that the t (14;18) may occur in a small subset of primary cutaneous lymphoma. However, the difference in incidence of the t (14;18) between primary nodal and primary cutaneous lymphomas suggests that different molecular mechanisms are involved in the pathogenesis of these lymphomas.

The polymerase chain reaction. Method and applications in dermatopathology.

Since it was first reported in 1985, the polymerase chain reaction (PCR) has revolutionized the way molecular studies are performed, and has developed into one of the most powerful tools in molecular pathology. By use of a cyclic change of temperature, a specific and exponential in vitro amplification of a target DNA sequence can be achieved within hours. As a template for PCR reactions, total genomic DNA is used; this can be readily extracted from clinical specimens. Very low quantities of DNA, as well as DNA degraded by fixation, can also be used as a template for PCR reactions, allowing formalin-fixed, paraffin-embedded tissue to become amenable to detailed molecular analysis. Sequences specific for certain viruses and other microorganisms, as well as molecular marker sequences associated with various types of human cancer, can be readily detected in paraffin-embedded tissue sections. The methodology of PCR, along with various applications in dermatopathology, are reviewed.

Loss of expression of tuberin and hamartin in tuberous sclerosis complex‐associated but not in sporadic angiofibromas

Background:  Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC‐associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC‐associated and sporadic angiofibromas.

Longitudinale Melanonychie bei Einnahme von Hydroxycarbamid

Vier Fallberichte von Patienten mit myeloproliferativem Syndrom, die zur Therapie Hydroxycarbamid (Synonyme: Hydroxyurea, Hydroxyharnstoff; Handelsnamen: Litalir®, Syrea®) einnehmen, und bei denen es einige Monate nach Beginn der Therapie zum Auftreten striärer, longitudinaler Pigmentierungen der Finger‐ und Fußnägel kommt.

Knowledge and attitude regarding human immunodeficiency virus/ acquired immunodeficiency syndrome in dermatological outpatients

Background  Dermatologists are often the first‐line specialists who recognize and diagnose human immunodeficiency virus (HIV) infection because of pathognomic skin signs. It is therefore important to investigate attitudes and knowledge regarding HIV/acquired immunodeficiency syndrome (AIDS) amongst dermatological patients in order to provide information for dermatologists and to draw their attention to the issues.