Biomedical subjects

A Pagenstecher

Publications and source records attributed to A Pagenstecher.

27 records · Page 2Linked to original sources

PubMed1997

RNAse protection assays for the simultaneous and semiquantitative analysis of multiple murine matrix metalloproteinase (MMP) and MMP inhibitor mRNAs.

Matrix metalloproteinases (MMPs) are a family of proteinases that play a major role in the metabolic degradation of extracellular matrix proteins. In order to examine the expression pattern of different MMP or MMP-inhibitor genes two RNase protection assays (RPAs) were developed that allow the simultaneous and semiquantitative assessment of their respective mRNAs. Probes for the detection of MMPs stromelysin 1, 2 and 3, matrilysin, metalloelastase, gelatinase A and B, collagenase and membrane type MMP (MT1-MMP) were included in the first RPA probe set, while probes for tissue inhibitor of matrix metalloproteinase (TIMP) 1, 2, 3 and alpha 2-macroglobulin (alpha 2-M) were included in the second probe set (inhibitor of matrix metalloproteinase-IMP set). Titration experiments revealed that this method allows the detection of MMP and inhibitor mRNAs present in at least 0.03 microgram of spleen poly(A)+ RNA. Both RPA sets were further evaluated by analyzing the expression of MMP and IMP genes in brain, kidney, spleen and liver in a murine model for endotoxemia after intraperitoneal LPS injection. Control animals showed an organ-specific constitutive expression of one or more MMPs and a high expression of TIMPs. Following LPS injection, an organ-specific upregulation or induction of MMP and TIMP RNA species was found. This change was most pronounced in the spleen, while liver, kidney and brain showed minor or no changes in MMP expression. An IMP upregulation was detected in all organs. These RPA probe sets provide a valuable tool for the simultaneous assessment of MMP and IMP gene expression under physiological and pathological conditions.

Animals↗

PubMed1997

Lipopolysaccharide-induced IL-12 expression in the central nervous system and cultured astrocytes and microglia.

We examined whether the cytokine IL-12 could be induced locally in the brain or in glial cell cultures following LPS treatment. In the brain, expression of IL-12 p35 mRNA was constitutive and did not alter following i.p. injection of LPS. In contrast, IL-12 p40 mRNA was only detectable in the brain of mice given two staggered injections of LPS. Dual labeling in situ analysis revealed IL-12 p40 RNA-positive cells scattered throughout the brain parenchyma, with a small number of these cells being identified as astrocytes, while the majority of IL-12 p40 RNA-expressing cells appeared to be microglia. In cultured microglia or astrocytes, LPS and to a much lesser degree IL-1beta, but not IFN-gamma or TNF-alpha, induced the expression of IL-12 p40 mRNA. Numerous glial fibrillary acidic protein-immunopositive cells colabeled for IL-12 p40 RNA; indicating that LPS-stimulated astrocytes expressed IL-12 in vitro. Immunoblot analysis of lysates from LPS-treated astrocytes revealed the presence of multiple species of 40, 43, 75, and 120 kDa containing the IL-12 p40 protein. Finally, secretion of the IL-12 p75 heterodimer was detectable by ELISA from astrocytes treated with LPS plus IFN-gamma, but not with LPS alone. The findings indicate that IL-12 gene expression can be activated in the brain, with the resident glial cells being a prodigious source of this cytokine. The localized production of IL-12 may have a significant impact on the development of cell-mediated immune responses within the central nervous system.

Animals↗

PubMed1997

Poly-lactic-acid coating for endovascular stents. Preliminary results in canine experimental arteriovenous fistulae.

RATIONALE AND OBJECTIVES: The authors evaluate polylactic-acid (PLA) as a coating of vascular endoprostheses in the treatment of experimental arteriovenous fistulae (AVF) in a canine model. METHODS: Bilateral carotid external jugular AVF were created in five adult dogs. Seven PLA-coated nitinol stents were placed using a transfemoral approach to cover five AVF. Contralateral controls remained untreated. Angiography was performed immediately after stent placement and at weeks 1 and 3, as well as at months 3, 6, and 9. All grafts were removed and underwent histologic examination. RESULTS: In two cases, the occlusion of the AVF was successful, but misplacement of stents occurred in three cases, which showed occlusion of the parent vessel between week 1 and month 3. One thrombembolic stent occlusion was evident during angiographic control. One vessel occlusion was disclosed distal to the stented arterial segment. Histologic examination revealed a mild inflammatory reaction with the presence of macrophages. However, there was no foreign-body reaction of fragmentation of the vessel wall. CONCLUSIONS: Histologic examination revealed good biocompatibility of PLA, which is a well-known biodegradable material. Elastic mismatch of the nonelastic coating and the self-expandable nitinol stent led to misplacement, whereas vessel occlusion was probably due to PLA filaments fraying into the vessel lumen. Using a different textile structure, PLA might be a material suitable for coated stents.

Alloys↗

PubMed1996

Large, virus-like sinuous tubules in the endoplasmic reticulum of human neurons: report from a case of encephalopathy and brief critical review.

We report a case of a rapidly progressive, fatal non-inflammatory demyelinating disease, distinct from multiple sclerosis and lysosomal disorders, in a patient with progressive dementia. Electron microscopy of stereotactic brain biopsy samples revealed the presence in neurons of sinuous, double-walled cylindrical membranous structures within the cisterns of the endoplasmic reticulum. These structures were 75-80 nm in overall diameter, up to 1.5 mm long and had a 40- to 45-nm diameter core. The possibility that they might be viruses of the Filoviridae or Paramyxoviridae families was considered, but the inclusions differed in key morphological aspects from members of both virus families and there were no supporting clinical or pathological data. Neither was it possible to assign the structures to any other known virus family on the basis of their morphology. Such inclusions have been the subject of only three published reports over the past 20 years. Evidence suggests that they may be confined to human central nervous system neurons, but occur in unrelated disorders (Alzheimer's disease, amyotrophic lateral sclerosis, meningoencephalitis, low-pressure hydrocephalus, demyelination). The possibility that they are formed in certain neurons by an abnormal internal budding process, as a response to a variety of pathological insults, is considered most likely, although an infectious origin (such as an unrecognised virus with variable clinical effect) cannot be ruled out.

Adult↗

PubMed1996

Stereotactic management of lesions of the pineal region.

OBJECTIVE: The relevance of the computed tomography-guided stereotactic approach for the management of lesions of the pineal region is analyzed. METHODS: In a retrospective analysis conducted between 1985 and 1993, the risk profile, the diagnostic accuracy, and the therapeutic relevance of the stereotactic approach in 106 patients was studied. Survival analysis was used to assess the reliability of the stereotactically obtained diagnosis in terms of follow-up observation. RESULTS: A histological diagnosis was obtained in 103 of the 106 patients. In three patients, a conclusive diagnosis could not be established because of intraoperative complications. One lesion was misdiagnosed as a pineocytoma instead of a pineoblastoma. Two of the 106 patients died; 9 patients experienced perioperative morbidity. In 38 patients, the stereotactic approach was also useful for therapy. Cyst aspiration and/or internal drainage was performed in 18 patients with symptomatic cystic lesions, and radiosurgical treatment with use of interstitial 125iodine was performed in 16 patients with low-grade tumors and in 4 patients with solitary metastases. In 12 patients, the obtained tissue diagnosis was the basis for deferring additional therapy. In 43 patients with germ-cell tumors, pineoblastomas, or malignant gliomas, a stereotactic biopsy was the starting point for additional radiotherapy/chemotherapy. Open tumor resection played a minor role (five patients). CONCLUSION: The stereotactic approach to the pineal region is a relatively safe procedure in experienced hands. The diagnosis obtained by computed tomography-guided stereotactic biopsy is a valid basis for treatment decisions. Long-term follow-up observation of the benign lesions is necessary for a definite confirmation of diagnostic accuracy.

Adolescent↗

PubMed1995

Exclusively intracranial cranial fasciitis in a child. Case report.

The authors present a case of an intracranial tumor in a 7-year-old girl leading to increasing hemiparesis. The lesion arose from the dura and consisted of fibroblasts in a myxoid matrix. The diagnosis of cranial fasciitis was made. The histological, immunohistological, and ultrastructural features of the tumor are described and the differential diagnosis is discussed.

Brain Diseases↗

PubMed1994

[A case of paraneoplastic limbic encephalitis in autoptic occult primary malignancy].

We report a case of limbic encephalitis in a 71-year-old male who presented with amnesia, confusion and disorientation. The patient's history of long standing alcoholism suggested the diagnosis of Korsakow syndrome. Autopsy, however, revealed a regional lymph-node metastasis of a small-cell bronchial carcinoma. No primary malignoma could be detected. These findings indicate that in cases of limbic encephalitis without detectable primary malignoma a paraneoplastic syndrome cannot be excluded. This has to be taken into consideration when discussing the etiology of limbic encephalitis (paraneoplastic versus virus-induced).

Aged↗

PubMed1991

[Lichen ruber only in skin areas exposed to light].

In a patient with lichen ruber, skin lesions appeared exclusively on sun-exposed sections of the body. This localization is atypical in Europe. In tropical and subtropical countries lichen ruber actinicus can be observed in up to 30% of the population.

Aged↗

PubMedDate not supplied

Transgenic models to study the actions of cytokines in the central nervous system.

To better understand the actions of cytokines in the mammalian central nervous system (CNS), we have developed transgenic mice in which the expression of various cytokines including interleukin (IL)-3, IL-6, IL-12, interferon-alpha or tumor necrosis factor-alpha was targeted to astrocytes under the transcriptional control of the glial fibrillary acidic protein (GFAP) promoter. Transgenic lines displaying low astrocyte expression of the respective cytokine were developed and characterized. The findings indicate that expression of these different cytokines in the intact CNS produces divergent inflammatory responses which are associated with the development of wide-ranging and progressive molecular, cellular and functional CNS impairments. These transgenic mice provide a powerful tool which we are now exploiting further to define novel mechanisms that might underlie the individual cytokine-driven neuroinflammatory responses. To date the results clearly show there are distinct model-associated patterns of cerebral expression of key molecules involved in the inflammatory response including the cellular adhesion molecules, chemokines, major histocompatibility complex molecules and the matrix metalloproteinases. In conclusion, these GFAP-cytokine transgenic mice highlight the potent and diverse array of actions mediated by cytokines when expressed in the CNS and provide a valuable resource to further our knowledge of the mechanisms by which cytokines exert their effects.

Animals↗