PubMed Health⌕ Search

Biomedical subjects

E Heiss

Publications and source records attributed to E Heiss.

At least 19 recordsLinked to original sources
PubMed2006

NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative transplantation.

Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 x 10(8)/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation.

Animals↗
PubMed2001

Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms.

Sulforaphane (SFN), an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to investigate anti-inflammatory mechanisms of SFN, we here report a potent decrease in lipopolysaccharide (LPS)-induced secretion of pro-inflammatory and pro-carcinogenic signaling factors in cultured Raw 264.7 macrophages after SFN treatment, i.e. NO, prostaglandin E(2), and tumor necrosis factor alpha. SFN did not directly interact with NO, nor did it inhibit inducible nitric-oxide synthase enzymatic activity. Western blot analyses revealed time- and dose-dependent reduction of LPS-induced inducible nitric-oxide synthase as well as Cox-2 protein expression, which was suppressed at the transcriptional level. To reveal the target of SFN beyond its anti-inflammatory action, we performed electrophoretic mobility shift assay analyses of transcription factor-DNA binding. Consequently, nuclear factor kappa B (NF-kappa B), a pivotal transcription factor in LPS-stimulated pro-inflammatory response, was identified as the key mediator. SFN selectively reduced DNA binding of NF-kappa B without interfering with LPS-induced degradation of the inhibitor of NF-kappa B nor with nuclear translocation of NF-kappa B. Because SFN can interact with thiol groups by dithiocarbamate formation, it may impair the redox-sensitive DNA binding and transactivation of NF-kappa B. Sulforaphane could either directly inactivate NF-kappa B subunits by binding to essential Cys residues or interact with glutathione or other redox regulators like thioredoxin and Ref-1 relevant for NF-kappa B function. Our data provide novel evidence that anti-inflammatory mechanisms contribute to sulforaphane-mediated cancer chemoprevention.

Animals↗
PubMed2001

The yeast SEC20 gene is required for N- and O-glycosylation in the Golgi. Evidence that impaired glycosylation does not correlate with the secretory defect.

The Golgi plays a fundamental role in posttranslational glycosylation, transport, and sorting of proteins. The mechanism of protein transport through the Golgi has been seen as controversial in recent years. During the characterization of N-glycosylation-defective mutants (ngd) previously isolated by this laboratory, it was found that ngd20 is allelic to sec20. SEC20 was reported to be required for transport from endoplasmic reticulum to Golgi, but its precise function remains to be determined. We show now that SEC20 is also required for N- and O-glycosylation in the Golgi but not in the ER, in a cargo-specific manner, and that the glycosylation defect does not correlate with the secretory defect. By pulse-chase labeling experiments in combination with mannose linkage-specific antibodies, invertase and carboxypeptidase were found to be efficiently secreted to their final compartment, even upon shift to the nonpermissive temperature, while glycosylation in the Golgi was severely impaired. Using microsomal membranes isolated from ngd20, we found that mannosyl transfer from GDP-Man to various mannose-oligosaccharides, indicative for Golgi mannosylation, was strongly diminished. Analysis of the carbohydrate component of chitinase, an exclusively O-mannosylated protein, or of the bulk mannoprotein indicates that O-mannosylation is also reduced. The results demonstrate that in addition to secretion SEC20 also affects glycosylation in the Golgi, presumably because it exerts a more general role in maintenance and function of the Golgi compartments.

Carboxypeptidases↗
PubMed2001

Preirradiation gemcitabine chemotherapy for newly diagnosed glioblastoma. A phase II study.

BACKGROUND: The median survival for patients with glioblastoma is reported to be 12 months. To improve the outcome for glioblastoma patients, the authors evaluated the therapeutic efficacy of preirradiation gemcitabine chemotherapy followed by standard radiotherapy. METHODS: Twenty-one patients with newly diagnosed glioblastoma were enrolled in a prospective unicenter trial of preirradiation gemcitabine chemotherapy. Chemotherapy included up to 4 monthly cycles of intravenous gemcitabine (Day 1, Day 8, and Day 15; 1000 mg/m2). Involved field radiotherapy was given after chemotherapy or earlier in the case of disease progression or gemcitabine intolerance. RESULTS: With gemcitabine chemotherapy alone, there was a median progression free survival of 11 weeks and a progression free survival rate at 4 months of 24%. In 18 of 21 patients who subsequently received a full course of radiotherapy, the median progression free survival from the time of diagnosis was 8 months and the progression free survival rate at 12 months was 17% (3 of 18 patients). The median overall survival was 11 months. There was no specific treatment-related neurotoxicity reported. Neither age nor extent of residual postoperative tumor predicted the duration of progression free survival in patients treated with gemcitabine chemotherapy alone or in those treated with gemcitabine plus radiotherapy. CONCLUSIONS: Gemcitabine followed by radiotherapy is a safe regimen for patients with newly diagnosed glioblastoma but the gemcitabine schedule used in the current study did not appear to confer any survival advantage compared with standard involved field radiotherapy alone.

Adult↗
PubMed2000

Role of hydrodynamic processes in the pathogenesis of peritumoral brain edema in meningiomas.

OBJECT: In a prospective study, 28 patients with 32 intracranial meningiomas were examined to determine the role of hydrodynamic interaction between tumor and surrounding brain tissue in the pathogenesis of peritumoral brain edema. METHODS: Gadolinium-diethylenetriamine pentaacetic acid (Gd-DPTA), an extracellular contrast agent used for routine clinical imaging, remains strictly extracellular without crossing an intact blood-brain barrier. Therefore, it is well suited for investigations of hydrodynamic extracellular mechanisms in the development of brain edema. Spin-echo T1-weighted magnetic resonance images were acquired before and after intravenous administration of 0.2 mmol/kg Gd-DPTA. Additional T1-weighted imaging was performed 0.6, 3.5, and 6.5 hours later. No significant Gd-DPTA diffused from tumor into peritumoral brain tissue in 12 meningiomas without surrounding brain edema. In contrast, in 17 of 20 meningiomas with surrounding edema, contrast agent in peritumoral brain tissue was detectable after 3.5 hours and 6.5 hours. In three of 20 meningiomas with minimum surrounding edema (<5 cm3), contrast agent effusion was absent. After 3.5 hours and 6.5 hours strong correlations of edema volume and the maximum distance of contrast spread from the tumor margin into adjacent brain parenchyma (r = 0.84 and r = 0.87, respectively, p < 0.0001) indicated faster effusion in larger areas of edema. CONCLUSIONS: The results of this study show that significant contrast agent effusion from the extracellular space of the tumor into the interstitium of the peritumoral brain tissue is only found in meningiomas with surrounding edema. This supports the hypothesis that hydrodynamic processes play an essential role in the pathogenesis of peritumoral brain edema in meningiomas.

Adult↗
PubMed1999

[The significance of morphological changes in the brain-tumor border area for the pathogenesis of brain edema in meningiomas: magnetic resonance tomographic and intraoperative studies].

PURPOSE: The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. METHODS: 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness = 2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: direct contact between tumor and white matter, 3: tumor infiltration into brain. RESULTS: Edema-associated meningiomas showed a significantly (p = 0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema. CONCLUSIONS: Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas.

Adult↗
PubMed1998

Angiogenesis and brain oedema in intracranial meningiomas: influence of vascular endothelial growth factor.

The correlation between angiographic neovascularization, peritumoural brain oedema (PTBOe) and the expression of vascular endothelial growth factor (VEGF), was analysed in 30 patients with intracranial meningiomas. Pre-operative angiograms were examined for the existence of either an exclusively dural tumour blush or an additionally pial tumour supply from cerebral arteries. Furthermore the presence of macroscopic tumour-neovascularization and dysplastic changes of tumour-draining cerebral veins was evaluated. VEGF expression was investigated on histological tissue samples, using immunohistochemical techniques. VEGF immunohistochemistry and neuroradiological evaluations were performed in double blind fashion. Tumour volume and the amount of oedema were calculated by computerized tomography (CT) or magnetic resonance imaging (MRI). The oedema-tumour volume ratio was defined as oedema index (OeI). Compared to VEGF-negative meningiomas, tumours with striking VEGF staining revealed a significant higher mean oedema index (OeI = 4.2 vs. OeI = 1.5; p < 0.018), and a higher oedema incidence (91.7% vs. 44.4%; p < 0.046). Equally, meningiomas with additionally tumour supply from cerebral arteries were associated with a significant higher mean OeI (OeI = 4.1 vs. OeI = 1.2; p < 0.01) and oedema incidence (94.7% vs. 20.0%; p < 0.0023) than meningiomas with exclusively tumour supply from dural arteries. All meningiomas with striking VEGF-expression were associated with vascular tumour supply from cerebral arteries, but VEGF-negative tumours only in 50% (p < 0.029). These data suggest a link between VEGF-expression, arterial tumour supply and peritumoural brain oedema. The development of tumour supply from cerebral arteries may be important for formation of meningioma-related oedema. Therefore, VEGF may represent a potent mediator in the evolution of this type of vascularization in meningiomas.

Adult↗
PubMed1997

Chondroma of the cerebellopontine angle. Case report.

A patient is reported who had a solitary chondroma of the cerebellopontine angle. The tumor was totally removed. The diagnostic value of CT-scanning and MRI in this rare pathological condition are discussed.

Cerebellar Neoplasms↗
PubMed1997

Peritumoural brain oedema in intracranial meningiomas: influence of tumour size, location and histology.

Peritumoural brain oedema was examined retrospectively in 175 patients with 179 intracranial meningiomas. The influence of tumour size, location and histology were investigated. Tumour volume and localization, and the presence of peritumoural brain oedema (PTBOe) were determined by computed tomography (CT). The oedema-tumour volume ratio was defined as Oedema Index (Oel). All patients underwent microsurgical removal of the tumour. Surgically resected meningiomas were classified histopathologically based on criteria of the new World Health Organization (WHO) classification. A close relationship was found between the tumour size and the incidence of peritumoural oedema: with increasing size of the tumour the incidence of oedema also rises, the oedema index, however decreases. Frontobasal and temporobasal meningiomas showed a significant increase in the oedema incidence and the mean oedema index. If major parts of the surface of meningiomas were adjacent to subarachnoid cisterns only a slight tendency for the development of oedema was observed. WHO-III-meningiomas showed a significantly higher oedema incidence (61.1% vs. 94.4%; p < 0.004) and mean oedema index (Oel = 2.7 vs. 3.7; p < 0.0009) than WHO-I-meningiomas. Brain tissue was affected in 59 cases. 19 meningiomas with infiltration into adjacent brain parenchyma revealed a statistically significant increase in oedema incidence (94.7% vs. 51.7%; p < 0.0003) and mean oedema index (Oel = 3.9 vs. Oel = 2.2; p < 0.0001) when compared to tumours without any brain tissue involvement in the histopathological specimens. Tumours with large volume, fronto-temporo-basal location and anaplastic histology were not only associated with the highest incidence of oedema formation but also presented with an overproportionate infiltrative growth. Thus, a disruption of the arachnoid or a true brain infiltration may be an essential factor for the development of a PTBOe.

Adult↗
PubMed1991

Animal experiments with a new dura graft (polytetrafluorethylene)--results.

A comparative animal experiment study on rabbits was performed to test a synthetic dura (expanded polytetrafluorethylene = ePTFE = Gore-Tex Surgical Membrane). For the purpose of comparison with the ePTFE implanted in the left hemisphere, lyophilized natural dura (Lyodura) was used and removed from the subjects after two, eight and twelve weeks. There were no rejection reactions. The lyophilized dura showed pronounced environmental reaction, with cellular permeation and indications of revitalization. The ePTFE manifested only slight reaction and remained inert in an enclosing sheath of connective tissue. The biocompatibility and other properties, such as simple handling and resteriliziability, of ePTFE can thus be assessed as positive.

Animals↗
PubMed1988

Traumatic giant aneurysms of the intracranial carotid artery presenting long after head injury.

Three patients presented with giant aneurysms of the intracranial internal carotid artery that became symptomatic with expanding mass effects 4-10 years after severe head trauma accompanied by skull base injuries at the site of aneurysm formation. These aneurysms are therefore considered to be late manifestations of traumatic vessel disruption. Posttraumatic aneurysm growth was documented in one case of a supraclinoidal aneurysm. One intracavernous aneurysm was combined with a traumatic carotid-cavernous sinus fistula. Although the origin of intracranial aneurysms is usually considered to be traumatic only within a period of weeks or months after head injuries, giant aneurysms of the intracranial internal carotid may represent late complications of trauma in a number of cases.

Adult↗
PubMed1988

[A lipoma of the cerebellopontile angle].

The case of a 38-year old man with a lipoma of the left cerebellopontine angle is presented. While the clinical signs of that tumour are unspecific, an exact diagnosis is possible by CT and MRI. As in other reported cases only an incomplete removal of the tumours was made because of the adherence of the lipoma to the nerves of the CPA.

Adult↗
PubMed1982

[CT findings in cerebellar hemangioblastomas (author's transl)].

The computed tomographic (CT) findings in 16 personal cases of cerebellar hemangioblastomas are presented. According to other reports in the literature, three-quarters of the tumours were cystic, containing a small mural nodule, whereas the others were predominantly solid. By CT scan the cystic tumours were always identified as roundish or oval space-occupying lesions, sharply demarcated from the surrounding tissue. The solid portion of these tumours, projecting into the cystic part, was delineated more precisely by contrast enhancement, but sometimes escaped identification. On the contrary, even after contrast enhancement the predominantly solid tumours could not be clearly identified as hemangioblastomas. Calcification could not be demonstrated. Additional angiographic investigations were imperative in order to establish the diagnosis, besides visualizing further hypervascular nodules of hemangioblastoma, which CT scanning failed to reveal.

Cerebellar Neoplasms↗
PubMed1982

[Prognosis of acute epidural haematomas since introduction of computerized tomography (author's transl)].

The article reports on the results of treatment of 213 patients who had been operated on because of an acute epidural haematoma before and since the introduction of computerized tomography. CT diagnosis entailed a saving in time. Nevertheless, in the author's series mortality rose by 4.6% since patients with a primarily more unfavourable initial condition had been admitted for treatment. The prognostically decisive factors are, as before, the speed at which the haematoma spreads, and the clinical manifestations of the state of the disease.

Acute Disease↗