Augensymptome und elektronenmikroskopische Befunde des M. orbicularis oculi bei dystrophischer Myotonie (Curschmann-Steinert)

Zusammenfassung Bei einem 54jährigen Patienten mit dystrophischer Myotonie bestanden ophthalmoskopisch Pigmentierungen und leichte Aufhellungen des Maculabereiches. Erst fluorescenzangiographisch zeigten sich deutlich sternförmige, asymmetrische Degenerationen.Das bei der Ptosisoperation gewonnene Muskelgewebe des M. orbicularis oculi wurde elektronenmikroskopisch untersucht. Im M. orbicularis überwiegen degenerative vor atrophischen Prozessen. Keine der pathologischen Reaktionen ist als Einzelbefund spezifisch für die myotone Dystrophie. Erst die Gesamtheit der muskelcellulären Befunde ergibt ein bei diesem Krankheitsbild wiederkehrendes Reaktionsmuster, wie es teilweise von der peripheren Muskulatur bekannt ist. Neben den muskelcellulären Veränderungen wurden regenerative Vorgänge in Form von verschmelzenden Myoblasten nachgewiesen. Degenerative Veränderungen an den Myelinscheiden der Nerven werden in Zusammenhang mit der muskelcellulären Reaktion zur Diskussion gestellt.

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Ocular symptoms and electron microscopic results of the orbicularis oculi in myotonic dystrophy

Summary A 54 year old patient with a myotonic dystrophy ophthalmoscopically showed pigmentations and light spots of the macular region. Distinct asymmetrical degenerations with stellate configuration of this region could be seen (only by fluoreszence angiography).The muscle tissue of the m. orbicularis oculi which was gained by ptosis operation was investigated by electron microscopy. In the m. orbicularis degenerative processes are prevalent over atrophic changes. None of the pathological reactions is on its own specific for the myotonic dystrophy. Only the whole of the muscle cellular findings show a recurring pattern which is partly known from the peripheral musculature. Besides the muscle-cellular changes, regeneration in the form of fusing myoblasts were found. Degenerations of the nerves' myelin-sheaths are discussed in context with muscle cellular reaction.

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Für Ihre freundliche Unterstützung bei der Ausführung dieser Arbeit danken wir Frau Prof. Dr. E. Freund-Mölbert (Institut für Biologie II der Universität Freiburg).

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Infiltration patterns of macrophages and lymphocytes in chronically rejecting rat kidney allografts

The migration of circulating leukocytes to sites of inflammation or antigen is based, at least in part, on the activities of adhesion molecules. In the context of organ transplantation, some of these have been shown to be upregulated during acute allograft rejection. As their role during chronic rejection has not been examined, we have used an established rat model to compare sequentially the presence of host cells within the grafts, as defined immunohistologically, with patterns of in vitro leukocyte binding and their dependence upon particular adhesion molecules. Various donor populations of peripheral blood lymphocytes (PBL), lymph node lymphocytes (LNL), and splenic monocytes were interacted with snap-frozen sections of allografted, isografted, and native kidneys at serial intervals up to 24 weeks after transplantation. Monocyte binding in the allografts rose at 8 weeks and peaked at 12 weeks, a period preceding the maximum numbers of macrophages noted immunohistologically in the chronically rejecting grafts at 16 weeks. Lymphocyte binding and infiltration patterns were similar, remaining stable throughout the follow-up period and consistently greater than those noted in isografts. In vitro binding of the monocytes was inhibited by mAbs against ICAM-1, LFA-1, CD18, and MAC-1; MAC-1 did not influence lymphocyte binding, although the other mAbs were effective. We conclude that adhesion molecules are responsible, at least in part, for patterns of cell populations infiltrating chronically rejecting renal allografts.     

Systemic dermatological treatment with relevance for male fertility

The dermatologist employs systemic agents with likely gametotoxic side effects, including cytotoxic, immunosuppressive, immunomodulatory and biological agents. The impact of chemotherapy on male fertility depends on the treatment protocol as well as the pre‐treatment spermatogenesis status. Sperm concentration starts to drop about 2 weeks after beginning chemotherapy and reaches a maximum after 2–3 months. About half show recovery after 12–36 months. One year after therapy is completed, a treated patient has no increased risk of fathering a malformed child. There are no reports of methotrexate patients fathering children with malformations, most likely because impaired fertility or embryogenesis arrest. Cryopreservation of male gametes should be recommended prior to cytotoxic treatment, since the likelihood of post‐treatment fertility is unpredictable. The cryopreservation causes a loss of vital spermatozoa by 30–70% but does not influence the genetic information of gametes. Males treated with retinoids have no reproductive safety risk. Biologicals inhibiting TNF α show a positive effect on sperm function in vitro.     

Distinct effects of acute and chronic nicotine application on microvascular thrombus formation and endothelial function in male and female mice

Background and aims Cigarette smoking is linked to thromboembolic events; however, a relationship between nicotine exposition and thrombosis has not been established. Thus, we intended to study the effect of acute and chronic nicotine application in an in vivo mouse model. Materials and methods In microvessels of the dorsal skin fold chamber, light-dye-induced thrombus formation was analyzed using intravital fluorescence microscopy. Male and female C57BL/6J mice received nicotine chronically via the drinking water (100 μg/ml) for 8 weeks. An additional series of experiments was performed with acute iv nicotine treatment (3 mg/kg body weight). Results No significant differences in microvascular thrombus formation were detected after chronic nicotine application in male and female animals when compared with controls. Accordingly, flow cytometric analysis did not show significant effects on platelet activity. Chronic nicotine treatment resulted in a significantly reduced endothelial activation in male, but not in female mice. In contrast, acute iv application of nicotine revealed significantly shorter thrombosis times in arterioles of female mice and a significantly increased endothelial P-selectin expression in mice of both genders. Conclusion Chronic nicotine application does not promote microvascular thrombus formation in mice of either gender, whereas acute high-dose iv administration caused a significant increase of arteriolar thrombosis in female animals probably via a synergistic effect of increased endothelial P-selectin expression and female hormone levels. A gender-dependency of acute nicotine action can be presumed. Best abstracts — Surgical Forum 2007     

Developmental changes in the number,size, and orientation of GFAP-positive cells in the CA1 region of rat hippocampus

Changes in extracellular potassium concentration as measured with ion-selective microelectrodes revealed abnormally large accumulations in the hippocampus during postnatal development. While rises in [K⁺]_o during stimulation of the Schaffer collaterals were limited to about 12 mM in adult animals, identical stimulations elicited rises to levels as large as 18 mM in juveniles. Since astrocytes are believed to play an important role in K⁺ homeostasis, we studied the postnatal development of astrocytes in the CA1 region of rat hippocampus in four age groups using a polyclonal antibody against glial fibrillary acidic protein (GFAP). The main proliferation of GFAP-positive cells (GFAPpc) occurred in all laminae between postnatal days 8 and 16. The number of GFAP-positive astrocytes per unit area was reached in stratum lacunosum-moleculare and stratum oriens at about 2 weeks and in stratum radiatum at about 3 weeks of age. During further development—at the age of 24 days—the orientation of individual astrocytes in stratum radiatum became polar with an orientation almost perpendicular to stratum pyramidale. This was revealed by an analysis based on determination of the quotients between the angular orientation of the processes of single individual GFAP-positive cells. When the crossing points of all glial processes over vertical and horizontal grid lines were determined and respective quotients evaluated, the same development towards a perpendicular orientation of astrocytes was noted in stratum radiatum. The same approach revealed a transient orientation parallel to the fissure in stratum lacunosum-moleculare around day 24. Camera lucida drawings of GFAPpc in stratum radiatum revealed that astrocytes became larger during the first three postnatal weeks, followed by a reduction of various parameters (e.g., cell extension, branching pattern) until adulthood. The observed developmental changes of astroglial cells may contribute to the known delayed maturation of potassium regulation in rat hippocampus.     

Human epidermal keratinocytes are a source of soluble ICAM-1 molecules.

A soluble form of the usually membrane-bound adhesion molecule ICAM-1 was detected in supernatants derived from human epidermal keratinocytes. Specifically, supernatants harvested from long-term cultured normal human keratinocytes, or from the spontaneously immortalized keratinocyte cell line HaCaT, did not contain significant amounts of sICAM-1, but shedding of sICAM-1 was found to be markedly induced upon stimulation of keratinocytes with rh IFN gamma. In contrast, cells from the two epidermoid carcinoma cell lines, KB and A431, constitutively shed significant amounts of sICAM-1 even without cytokine stimulation, and sICAM-1 contents in supernatants harvested from these cells were further increased upon stimulation of cells with rh IFN gamma. These studies indicate, that in addition to peripheral blood mononuclear cells and human melanoma cells, human epidermal keratinocytes constitute an important cellular source of sICAM-1. By binding to leukocyte LFA-1 molecules, keratinocyte-derived sICAM-1 may influence inflammatory responses in the skin. In addition, constitutive shedding of sICAM-1 by transformed human keratinocytes may represent a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.     

Percutaneous renal biopsy: comparison of manual and automated puncture techniques with native and transplanted kidneys

The diagnostic usefulness of the biopsy cylinder and biopsy-inducedcomplications were investigated for 458 percutaneous renal biopsies(315 native, 143 transplant kidneys) on 339 patients (averageage, 44.6±18.5 years) under two different biopsy regimes(regime I, manual biopsy technique with Tru-Cut needle, 14 gauge;regime II, automated biopsy technique using a Biopty instrumentand adapted biopsy needle, 18 gauge). In 435 (95%) of the biopsies, kidney tissue with 9.09 ±5.28 glomeruli was obtained (regime I, 93.5%, 9.5±4.9glomeruli; regime II, 96.5%, 8.7 + 5.6 glomeruli; p>0.05).Neither with native nor with transplant kidneys was there anyevident advantage for a particular regime in terms of the diagnosticusefulness of the cylinder. Bleeding complications (perirenalhaemat-omas, bleeding into the renal pelvis, blood clots inthe urinary bladder) were observed in 69 (15.1%) patients (regimeI, 15.6%; regime II, 14.6% P>0.05). Clinically relevant bleedingcomplications were significantly rarer under regime II (9.1%versus 3.5%; P<0.05). Complications were less frequent withtransplant than with native kidneys (12.6% versus 16.2%). Dopplersonography of the biopsied transplant kidneys revealed arteriovenousfistulae in nine cases (6.3%; regime I, 8.0%; regime II, 5.4%). In general, use of an automated biopsy instrument and a thinnerbiopsy needle reduced the number of significant complicationsfollowing percutaneous renal biopsy, while achieving comparablydiagnostic efficacy.     

MR imaging of experimental meningeal melanomatosis in nude rats

MR imaging of the rat brain has become an increasingly frequently used method in experimental neuroradiology. On a generally available 1.5 T whole body tomograph, supplemented with an individually made small coil and a special SE sequence we obtained fairly fine images of the structures of the rat brain. With gadolinium-DTPA, we were able to visualize posterior fossa and cervical leptomeningeal growth of intrathecally injected B16 melanoma in nude rats. Using MRI to follow experimental leptomeningeal metastasis, may provide a new means for diagnostic evaluation and preclinical testing of treatment modalities.