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Biomedical subjects

C Sommer

Publications and source records attributed to C Sommer.

At least 91 records · Page 5Linked to original sources
PubMed1999

Telepathology in neurosurgery.

In most tumor cases of neurosurgery, we need to have a rapid section diagnostic of the tumor during the course of surgery. When we have received the results that diagnose the exact dignity of the tumor, we devise the operation strategy for the continuing course of surgery. The tissue sample is sent by taxi to the pathological institute in Heidelberg. It takes approximately 45-60 min until we receive the results by telephone. Many centers are far away from a pathological institute and the patient may need to be re-operated on there. In stereotaxy it is still more important. We need approximately 15-25 specimens during a stereotaxy, so we can be sure we have a sample with some of the tumor tissue present. With direct contact to a pathological institute we could reduce this dramatically. We prepared a methylen blue slide and used a histological microscope with a video camera attached to it and a digitizer interface for digitized pictures. By use of a modem we send the pictures by telephone line to the pathological institute, where they are assessed. We currently have direct contact with a pathologist so they can tell us from which part of the tumor we should send the other histological pictures. The procedure takes about twenty minutes. By using this procedure the distance to the pathological institute is irrelevant. The system costs approximately $10,000, covering the cost mostly of the microscope and the camera (but we already had the microscope) and can be built by anybody with minimal requirements.

Brain Diseases↗
PubMed1998

Painful mononeuropathy in C57BL/Wld mice with delayed wallerian degeneration: differential effects of cytokine production and nerve regeneration on thermal and mechanical hypersensitivity.

Wallerian degeneration with macrophage influx and production of proinflammatory cytokines is a critical factor in the development of hyperalgesia in animal models of neuropathic pain. We hypothesized that in the mouse strain with delayed Wallerian degeneration, the C57BL/Wld mouse, the temporal course of mechanical allodynia and thermal hyperalgesia as well as the temporal profile of cytokine expression after nerve injury would differ from normal mice. Here we used the model of chronic constriction injury of the sciatic nerve (CCI) to study the correlation of pain related behavior with peripheral nerve de- and regeneration and concomitant cytokine production. Indeed, after CCI, C57BL/Wld mice showed markedly reduced thermal hyperalgesia compared to normal C57BL/6 mice, temporally related to the delayed recruitment of hematogeneous macrophages to the injured nerve. Endoneurial tumor necrosis factor-alpha (TNF)-like immunoreactivity increased rapidly in normal mice but did so with a delayed time course in C57BL/Wld mice. In addition, the duration of mechanical allodynia was significantly prolonged in C57BL/Wld mice as compared to C57BL/6 mice, in accordance with the delay in regeneration of sensory nerve fibers in these mice. These results suggest that macrophage invasion and production of TNF may influence the development of thermal hyperalgesia and that regenerative activity is linked to mechanical allodynia in peripheral mononeuropathy.

Animals↗
PubMed1998

Selective degeneration of sudomotor fibers in Ross syndrome and successful treatment of compensatory hyperhidrosis with botulinum toxin.

We report a 5-year follow-up of a patient with Ross syndrome. A biopsy of the anhidrotic skin immunostained with protein gene product 9.5 visualized by confocal microscopy revealed selective loss of sudomotor fibers, whereas epidermal innervation remained intact, providing the first morphologic evidence of selective loss of sudomotor fibers in this syndrome. Among the different treatment strategies employed for the patient's disabling segmental hyperhidrosis, intracutaneous injection of botulinum toxin A was the most helpful.

Adaptation, Physiological↗
PubMed1998

Hyperalgesia in experimental neuropathy is dependent on the TNF receptor 1.

Recent evidence points to a role of cytokines like tumor necrosis factor-alpha (TNF) in the generation of hyperalgesia not only in inflammatory, but also in neuropathic pain. We used the model of chronic constrictive injury (CCI) of one sciatic nerve in the mouse to investigate which of the two known TNF receptors is involved in the process that leads to hyperalgesia after nerve injury. Neutralizing antibodies to TNF, to the TNF receptor 1 (TNFR1), and to the TNF receptor 2 (TNFR2) were administered by epineurial injection once daily to mice with CCI. Testing of the animals' hind paws with thermal and innocuous mechanical stimuli revealed a reduction in thermal hyperalgesia and mechanical allodynia in mice treated with neutralizing antibodies to TNF and to TNFR1. Neutralizing antibodies to TNFR2 had no effect. We conclude that TNFR1, but not TNFR2, is mediating thermal hyperalgesia and mechanical allodynia after nerve injury.

Animals↗
PubMed1998

Expression of vascular endothelial growth factor (VEGF) in various compartments of the human hair follicle.

Hair follicle vascularization appears to be closely related to the processes involved in hair cycle regulation, in which growth factors, cytokines and other bioactive molecules are involved. In particular, vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around the hair follicle during the anagen growth phase. The aim of our study was to compare the in vitro angiogenic capacity, i.e. the steady-state expression of the VEGF gene, of different cultured cell types derived from normal human hair follicles, corresponding to different follicular compartments. Human dermal papilla cells (DPC), fibrous sheath fibroblasts, dermal fibroblasts, and follicular and interfollicular keratinocytes were cultured and studied in vitro for VEGF expression at the mRNA level using RT-PCR, and for VEGF protein synthesis by radioimmunoprecipitation and immunocytochemistry. In vivo examination for VEGF expression in human terminal hair follicles was performed using immunohistochemical methods. In the present report the expression of four different VEGF molecular isoforms, differing in their angiogenic capacity, are described in different cultured follicular cell types for the first time. Cultured follicular cells strongly expressed mRNA of four VEGF molecular species identified as the 121-, 145-, 165- and 189-amino acid splice variants, the most prominent being the 121-amino acid molecule. DPC, and also other mesenchymal cells such as fibrous sheath fibroblasts and dermal fibroblasts, in vivo and in vitro strongly expressed VEGF mRNA and synthesized a 46-kDa VEGF protein, whereas follicular and interfollicular keratinocytes in vitro expressed lower levels of VEGF mRNA and proteins than mesenchymal cells. As the highest expression of VEGF was found in DPC, we suggest that DPC are mainly responsible for angiogenic processes possibly related to the human hair cycle.

Cells, Cultured↗
PubMed1998

BDNF and TrkB expression in intrastriatal ventral mesencephalic grafts in a rat model of Parkinson's disease.

We investigated the expression of BDNF and its high affinity receptor trkB in fetal dopaminergic grafts in a rat model of Parkinson's disease. Grafts were allowed to differentiate for 7, 14, 28, or 56 days, respectively and were analyzed immunocytochemically thereafter with antibodies directed against tyrosine hydroxylase, BDNF and trkB. At all time points investigated, grafts contained tyrosine hydroxylase immunoreactive neurons. Immature grafts (7 days) displayed no immunoreactivity for BDNF which was restricted to glial cells at the graft-host interface. After longer differentiation periods BDNF-immunoreactivity was detectable in neurons and astrocytes within the grafts. No trkB immunoreactivity was found in immature grafts but a strong signal for trkB emerged in grafted neurons older than 14 days whereas glial cells remained unlabeled at all time points investigated. Expression of BDNF and trkB in grafted neurons and of BDNF in surrounding glial cells suggests an autocrine or paracrine action of BDNF on dopaminergic neurons possibly mediated by activated glia.

Animals↗
PubMed1998

Quantitative characterization of texture used for identification of eggs of bovine parasitic nematodes.

This study investigates the use of texture, i.e. the grey level variation in digital images, as a basis for identification of strongylid eggs. Texture features were defined by algorithms applied to digital images of eggs from the bovine parasitic nematodes, Ostertagia ostertagi, Cooperia oncophora, and Oesophagostomum radiatum. The resulting data served to establish classification criteria by linear discrimination analysis, and the criteria were subsequently evaluated by cross-validations. From 25 texture features, ten features were selected by their significant discriminatory powers. Using a classification criterion based on these ten texture features, an average of 91.2% of eggs from the three species were correctly classified. All O. radiatum eggs were correctly classified, 11.8% of O. ostertagi and C. oncophora were reciprocally misclassified, and 2.9% of O. ostertagi were identified as O. radiatum. When the ten texture features were used singly an average of 51.2 to 37.9% of the species could be classified correctly. When texture was used together with the shape and size features, a higher percentage of eggs were correctly classified compared with the classification based on either texture, or shape and size. Hence, all O. radiatum were correctly classified as well as 88.3% of O. ostertagi and 91.2% of C. oncophora, resulting in an average of 93.1% correctly classified eggs. The rapid and accurate measurements of texture features may serve as a basis for identification or enhance performance of classification criteria based on egg shape/size.

Animals↗
PubMed1998

Quantitative characterization, classification and reconstruction of oocyst shapes of Eimeria species from cattle.

This study reports on morphological variability of Eimeria species, which may be given either by drawings or as quantitative data. The drawings may be used to facilitate identification by eye of 'unknown' Eimeria specimens, whereas quantitative data may serve as a reference set for identification by multivariate statistical techniques. The morphology of 810 Eimeria specimens was defined in binary (b/w) digital images by pixels of their oocyst outline. A Fourier transform of pixel positions yielded size and shape features. To classify coccidia, the quantitative data were employed in an agglomerative clustering by average linkage algorithm with equal weight assigned to size and shape. An inverse Fourier transform served to reconstruct oocyst outlines, i.e. outlines of average shape and size, from mean values of features in resulting clusters. Clusters were subsequently identified based on their average morphology by comparison with drawings of species in an earlier taxonomical work. Five hundred oocyst outlines were simulated for each cluster representing a species, and shape/size variability was presented in contour diagrams. Differences in species shapes, and correspondence in length and width, were seen after reconstruction by inverse Fourier transform and comparison with earlier studies.

Animals↗
PubMed1998

New techniques in indirect reduction of long bone fractures.

The most important and demanding part of operative fracture treatment concerns the reduction and correct alignment of the fracture fragments, which must be gentle to the bone and surrounding soft parts to preserve the essential blood supply to all tissues. The so called indirect reduction techniques apply the principles of nonoperative fracture care (ligamentotaxis) in combination with surgical tools and a number of techniques, where by the exposure of the most critical fracture focus can be minimized. New implant designs, low contact plates, cannulated screws, unreamed nails, pinless and hybrid external fixators, are helpful adjuncts: however, the surgical technique remains of paramount importance. The essence of careful handling of the soft and hard tissues has been stressed time and again. With the introduction of biological or minimally invasive surgery, the techniques of indirect reduction have had a renaissance. A few examples are described.

Bone Screws↗
PubMed1998

[The floating joint injury of the lower and upper extremity--epidemiology, therapy and results in 40 extremities].

GOAL: Floating Joint Injuries (FJI) are resulting from high energy traumas and are often combined with additional neuro/vascular damage. The high incidence of severe open or closed soft tissue injuries is complicating the initial management and requires a broad surgical know-how also in minimal-invasive fixation techniques. In a retrospective analysis of our cases treated between 1980 and 1995, we try to find out some important therapeutical feedback for the future. MATERIAL AND METHODS: Of the 37 patients, 33 had a FJI of the lower (2 bilateral) and 7 patients of the upper extremity. 90% were road traffic injuries, 75% showed an open fracture situation and 25% an associated neuro-vascular injury. All fractures were stabilised within the first hours, femur, humerus and forearm in one step, the tibia in 33% in two steps (initial external fixator ...). 80% of the FJI have been reexamined after 1-2 y. RESULTS: Local complication: Femur: 4/33 (1 infection, 2 refractures, 1 non-union). Tibia: 11/33 (5 infections, 4 delayed/non-unions, 2 malalignements). Humerus: 0/7. Forearm: 1/7 (1 malalignement). 1-2 y-results: Very good-good: Femur: 26/27 (96%). Tibia: 23/27 (85%). Humerus: 4/5. Forearm: 3/5. DISCUSSION: FJI should be stabilised as soon as possible in a way allowing for early functional aftercare of the affected joint. Most complications are observed in the proximal tibia fracture because of the thin and therefore often severely (open or closed) injured soft tissue cover. Despite a staged procedure, there exists a high complication rate, which probably can be reduced in the future by the single-step use of the hybrid external fixateur.

Adolescent↗
PubMed1997

A metalloprotease-inhibitor reduces pain associated behavior in mice with experimental neuropathy.

Tumor necrosis factor-alpha (TNF) is involved in the generation of inflammatory and neuropathic pain. The synthetic hydroxamic acid based metalloprotease inhibitor TAPI blocks cleavage of cell surface TNF and thus reduces levels of the mature 17-kDa TNF polypeptide in activated macrophages and T-cells. We have previously shown that pharmacologic inhibition of TNF production reduces pain related behaviors in mice with chronic constriction injury (CCI). Here we investigated whether blockage of TNF shedding by administration of TAPI would diminish hyperalgesia in animals with partial nerve injury. We injected 0.5 mg of the inhibitor epineurially once daily to mice with CCI for 7 days. The animals were tested for withdrawal thresholds to heat to test for thermal hyperalgesia and to von Frey hairs to assess mechanical allodynia. Mice with CCI developed thermal hyperalgesia and mechanical allodynia by day 3 after the injury. In mice treated with TAPI, a reduction of thermal hyperalgesia and mechanical allodynia of up to 50% occurred. Endoneurial TNF-immunoreactivity was reduced, but not immunoreactivity for IL-1alpha or IL-1beta. The numbers of degenerating axons and endoneurial macrophages were not affected by the treatment as compared to controls. We conclude that the metalloprotease inhibitor TAPI specifically reduces endoneurial TNF-levels after nerve injury and thereby may diminish neuropathic pain in the CCI-model.

Animals↗
PubMed1997

Expression of cerebellar specific glutamate and GABAA receptor subunits in heterotopic cerebellar grafts.

In the cerebellum, up- and downregulation of specific GABAA and NMDA receptor subunits coincide with granule cell migration and differentiation. In this study, in situ hybridization techniques with GABAA and NMDA receptor subunit specific probes were employed to assess whether the molecular phenotype of heterotopically grafted cerebellar granule cells corresponds to that of normal cerebellum. The cerebellar anlage of rat fetuses was stereotactically grafted into the rostral striatum of adult rats. Eight weeks after transplantation, analysis demonstrated acquisition of an adult differentiation status reflected by abundant GABAA alpha 6 and NR2C mRNA expression in granule cells. Complete lack of NR2B transcripts, molecular markers of immature granule cells, argues against persistence of undifferentiated cells. The data suggest that intrinsic cell-autonomous factors largely determine the molecular commitment of granule cells and that a restricted specific environment is not necessary to promote granule cell differentiation.

Animals↗
PubMed1997

Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.

The human homologue of the Drosophila segment polarity gene patched (PTCH) has recently been identified as the tumor suppressor gene responsible for the nevoid basal cell carcinoma (BCC) syndrome (H. Hahn et al., Cell, 85: 841-851, 1996; R. L. Johnson et al., Science (Washington DC), 272: 1668-1671, 1996). In addition to multiple BCCs, patients with nevoid BCC syndrome have a predisposition for the development of primitive neuroectodermal tumors (PNETs) of the central nervous system. We have analyzed 9 sporadic BCCs and 37 PNETs for mutation and expression of the PTCH gene. PTCH mutations were found in 3 BCCs (33.3%) and in 5 PNETs (14%), including 1 of 5 cerebral PNETs, 2 of 15 medulloblastomas, and 2 of 17 desmoplastic medulloblastomas. The sequence changes in six of these tumors (four PNETs, two BCCs) were mutations predicted to result in truncated proteins. Missense mutations were detected in one PNET and one BCC each. In addition, novel sequence polymorphisms were found in exon 2, intron 5, intron 10, and intron 14 of PTCH. Reverse transcription-PCR analysis revealed increased PTCH expression levels compared to nonneoplastic brain tissue and normal skin in the majority of PNETs and BCCs investigated. Our data suggest that genetic alterations of PTCH are not only of significance in hereditary and sporadic BCCs but are also involved in the molecular pathogenesis of a subset of sporadic central nervous system PNETs.

Adolescent↗
PubMed1997

Mitochondrial dysfunction with myoclonus epilepsy and ragged-red fibers point mutation in nerve, muscle, and adipose tissue of a patient with multiple symmetric lipomatosis.

We report a 64-year-old man presenting with multiple symmetric lipomatosis (MSL) and mitochondrial encephalomyoneuropathy. The diagnosis of a mitochondrial cytopathy was based on the typical clinical symptoms and signs, including chronic progressive external ophthalmoplegia, hearing impairment, cerebellar ataxia, proximal myopathy, and polyneuropathy, and on molecular genetic and histological examinations. As a unique finding, the A-->G(8344) myoclonus epilepsy and ragged-red fibers point mutation was found in peripheral nerve, muscle, and adipose tissue. Muscle biopsy revealed multiple ragged-red fibers and other morphological signs of a mitochondrial myopathy. Sural nerve biopsy demonstrated a mixed axonal and demyelinating neuropathy with extensive loss of myelinated fibers and conspicuous onion bulb formations, as well as structural mitochondrial abnormalities on electron microscopy. These findings clearly demonstrate mitochondrial dysfunction in muscle, adipose tissue, and for the first time also in nervous tissue of an MSL patient, and strongly support the concept of mitochondrial cytopathy as one of the possible causes of multiple symmetric lipomatosis.

Adipose Tissue↗
PubMed1997

Enzymology of the degradation of (di)chlorobenzenes by Xanthobacter flavus 14p1.

Xanthobacter flavus 14p1 used 1,4-dichlorobenzene as the sole source of carbon and energy but did not grow on other (chloro)aromatic compounds. 1,4-Dichlorobenzene was attacked by a chlorobenzene dioxygenase, and the intermediate chlorocatechol was metabolized by the modified ortho pathway. All enzymes necessary to convert 1, 4-dichlorobenzene to 3-oxoadipate showed a low substrate specificity and also accepted the respective intermediates of chlorobenzene or 1, 3-dichlorobenzene degradation. Of the three compounds chlorobenzene, 1,4-dichlorobenzene, and 1,3-dichlorobenzene, the latter was the most toxic for X. flavus 14p1. Furthermore, 1,3-dichlorobenzene did not induce chlorocatechol 1,2-dioxygenase activity of the organism. Chlorobenzene, however, induced chlorocatechol 1,2-dioxygenase, dienelactone hydrolase, and maleylacetate reductase activities. As demonstrated by chloride release, also chlorobenzene dioxygenase, chlorobenzene cis-dihydrodiol dehydrogenase, and chloromuconate cycloisomerase activities were present in chlorobenzene-induced cells, but chlorobenzene failed to support growth. Presumably a toxic compound was formed from one of the intermediates.

Biodegradation, Environmental↗
PubMed1997

Effect of global system for mobile communication (GSM) microwave exposure on blood-brain barrier permeability in rat.

We investigated the effects of global system for mobile communication (GSM) microwave exposure on the permeability of the blood-brain barrier using a calibrated microwave exposure system in the 900 MHz band. Rats were restrained in a carousel of circularly arranged plastic tubes and sham-exposed or microwave irradiated for a duration of 4 h at specific brain absorption rates (SAR) ranging from 0.3 to 7.5 W/kg. The extravasation of proteins was assessed either at the end of exposure or 7 days later in three to five coronal brain slices by immunohistochemical staining of serum albumin. As a positive control two rats were subjected to cold injury. In the brains of freely moving control rats (n = 20) only one spot of extravasated serum albumin could be detected in one animal. In the sham-exposed control group (n = 20) three animals exhibited a total of 4 extravasations. In animals irradiated for 4 h at SAR of 0.3, 1.5 and 7.5 W/kg (n = 20 in each group) five out of the ten animals of each group killed at the end of the exposure showed 7, 6 and 14 extravasations, respectively. In the ten animals of each group killed 7 days after exposure, the total number of extravasations was 2, 0 and 1, respectively. The increase in serum albumin extravasations after microwave exposure reached significance only in the group exposed to the highest SAR of 7.5 W/kg but not at the lower intensities. Histological injury was not observed in any of the examined brains. Compared to other pathological conditions with increased blood-brain barrier permeability such as cold injury, the here observed serum albumin extravasations are very modest and, moreover, reversible. Microwave exposure in the frequency and intensity range of mobile telephony is unlikely to produce pathologically significant changes of the blood-brain barrier permeability.

Animals↗
PubMed1997

The phospholipid analogue hexadecylphosphocholine (HePC) inhibits proliferation of keloid fibroblasts in vitro and modulates their fibronectin and integrin synthesis.

Hexadecylphosphocholine (HePC), a topically effective compound, exerts a strong antiproliferative effect on neoplastic cells. In the present study we investigated (1) the antiproliferative effect of HePC on benign mesenchymal cells in vitro, using as examples normal and keloid fibroblasts, and (2) the influence of HePC on various functional properties of these cells, including phosphatidylcholine biosynthesis, their capacity to reorganize a three-dimensional collagen-I matrix, and their expression and synthesis of fibronectin and subunits of the beta 1 integrin family. Fibroblasts derived from keloids (kelfib) and from normal skin (nfib) were cultured in serum-containing medium and treated in the third passage with 50 mumol/l HePC. Proliferative activity was significantly (P < 0.05) more strongly inhibited in kelfib than in nfib under HePC treatment, whereas their phosphatidylcholine synthesis was inhibited to a similar extent. However, the ability of fibroblasts to contract a three-dimensional collagen-I lattice was significantly (P < 0.05) enhanced only in kelfib treated with HePC. These functional differences following treatment with HePC were paralleled by an upregulation of the alpha 2- and beta 1-integrin chains, and a downregulation of fibronectin synthesis and the alpha 5-subunit. Our results indicate a differential modulation of kelfib metabolism by HePC, suggesting a possible new therapeutic approach for keloid and hypertrophic scars in vivo.

Cell Division↗