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Biomedical subjects

C Schneider

Publications and source records attributed to C Schneider.

At least 19 recordsLinked to original sources
PubMed2006

Thrombospondin-1 C-terminal-derived peptide protects thyroid cells from ceramide-induced apoptosis through the adenylyl cyclase pathway.

Thrombospondin-1, a multi-modular matrix protein is able to interact with a variety of matrix proteins and cell-surface receptors. Thus it is multifunctional. In this work, we examined the role of thrombospondin-1 in ceramide-induced thyroid apoptosis. We focused on the VVM containing sequence localized in the C-terminal domain of the molecule. Primary cultured thyroid cells synthesize thrombospondin-1 depending on their morphological organization. As it leads thyrocytes to organize into monolayers before inducing apoptosis ceramide can modulate this organization. Here, we established that C(2)-ceramide treatment decreased thrombospondin-1 expression by interfering with the adenylyl cyclase pathway, thus leading to apoptosis. Furthermore, we demonstrated that the thrombospondin-1-derived peptide 4N1 (RFYVVMWK) abolished ceramide-induced thyroid cell death by preventing intracellular cAMP levels from dropping. Finally, we reported that 4N1-mediated inhibition of ceramide-induced apoptosis was consistently associated with a down-regulation of the caspase-3 processing. Integrin-associated protein receptor (IAP or CD47) was identified as a molecular relay mediating the observed 4N1 effects. Taken together, our results shed light for the first time on anti-apoptotic activities of the thrombospondin-1-derived peptide 4N1 and provide new information on how thrombospondin-1 may control apoptosis of non-tumoral cells.

Adenylyl Cyclases↗
PubMed2006

The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells.

Camptothecin and doxorubicin belong to a family of anticancer drugs that exert cytotoxic effects by triggering apoptosis in various cell types. However there have only been few investigations showing that matricellular proteins like thrombospondin-1 (TSP-1) could be involved in the underlying mechanism of this cytotoxicity. In this report, using Hoechst reagent staining, reactive oxygen species production and caspase-3 activity measurement, we determined that both camptothecin and doxorubicin induced apoptosis in human thyroid carcinoma cells (FTC-133). On the one hand, we demonstrated that camptothecin and doxorubicin inhibited TSP-1 expression mainly occurring at the transcriptional level. On the other hand, drug-induced apoptosis determined by western blot analysis for PARP cleavage and caspase-3 activity measurement, was significantly decreased in presence of exogenous TSP-1. In order to identify the sequence responsible for this effect, we used the CD47/IAP-binding peptide 4N1 (RFYVVMWK), derived from the C-terminal domain of TSP-1, and known to play a role in apoptosis. Thus, in presence of 4N1, camptothecin and doxorubicin-induced pro-apoptotic activity was considerably inhibited. These findings suggest that induction of apoptosis by camptothecin or doxorubicin in FTC-133 cells is greatly dependent by a down-regulation of TSP-1 expression and shed new light on a possible role for TSP-1 in drug resistance.

Apoptosis↗
PubMed2005

Laparoscopic surgery in the old patient: do indications and outcomes differ?

BACKGROUND AND AIMS: In view of the increasing numbers of old and very old people in the general population, we evaluated the short-term outcomes of laparoscopic colorectal surgery for differences between younger and older patients. METHODS: A total of 4,823 patients with complete data sets from a prospective, clinical observational multicentre study initiated by the "Laparoscopic Colorectal Surgery Study Group" were analysed for this investigation. RESULTS: Of the patients, 909 (18.8%) were older and 3,914 (81.2%) younger than 75 years. In the older patient group, malignant disease was a significantly more common indication for surgery. As was expected, the rate of general complications (pneumonia, cardiopulmonary problems, urinary tract infection) was significantly higher in the older patient group with its greater prevalence of preoperative comorbidity, but there no differences in terms of intraoperative or postoperative surgical complications or conversion rate between the groups. CONCLUSION: The higher rate of postoperative complications resulting from preoperative comorbidity in the older patients makes it necessary that the indication for surgery be established with care. In view of the advantages of the laparoscopic approach with regard to the postoperative course, the preferential use of laparoscopy for the treatment of colorectal problems requiring surgery in older patients should receive serious consideration.

Age Factors↗
PubMed2005

Interleukin-1beta (IL-1beta) induces a crosstalk between cAMP and ceramide signaling pathways in thyroid epithelial cells.

Interleukin-1 beta (IL-1beta) is an important regulator of the thyroid cell function. This cytokine has been largely described to trigger an important biological signaling cascade: the sphingomyelin/ceramide pathway. In this report, we show that IL-1beta induces the transient activation of a neutral sphingomyelinase in porcine thyroid cells. Moreover, IL-1beta and ceramides are demonstrated to inhibit the TSH-induced cAMP production via the implication of alphaGi subunit of the adenylyl cyclase system. This crosstalk between cAMP and ceramide pathways constitutes a preponderant process in the TSH-controlled differentiation state of thyrocytes. All these results argue for the involvement of ceramides and IL-1beta in the thyroid function regulation, leading to a cell dedifferentiated state.

Animals↗
PubMed2005

Evidence for the hydration effect at the semiconductor phospholipid-bilayer interface by TiO2 photocatalysis.

The interactions of TiO2 with phospholipid bilayers found in cell membrane walls were observed to perturb the bilayer structure under UVA light irradiation. The structure changes in the phospholipid bilayers upon contact with TiO2 under light and in the dark were followed by X-ray diffraction. Hydration effects at the semiconductor-phospholipid interface played an important role in the degradation of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) bilayers taken as cell wall lipid bilayer models. Evidence is provided that the fluidity of the phospholipid bilayers plays a significant role when interacting in the dark with the TiO2 or in processes mediated by TiO2 under light irradiation.

Catalysis↗
PubMed2005

[Stalking: unwelcome company. The psychopathology of a modern phenomenon].

The term stalking describes a pattern of behavior in which the victim is pursued, pestered and threatened. In many cases, the stalker resorts to physical violence, and may even commit murder. In the German-speaking areas, the phenomenon is to date not much discussed in the psychiatric and psychological literature, despite the fact that it is a widespread occurrence. While stalkers are diagnosed as suffering from schizophrenia and/or narcissistic as well as borderline disorders, victims have no typical "victim personality". They do, however, respond to stalking with anxiety, depression and post-traumatic stress disorders, which need to be recognized and treated.

Adult↗
PubMed2005

Development of Z-scores for fetal cardiac dimensions from echocardiography.

OBJECTIVES: Z-scores for cardiac dimensions are well established in postnatal life, but have yet to be developed for fetal cardiac dimensions. These would be of real advantage to the clinician in accurately quantifying size and growth of cardiac dimensions and to the researcher by allowing mathematical comparison of growth in differing subgroups of a disease. The purpose of this observational study, conducted at tertiary fetal medicine and cardiology units, was to produce formulae and nomograms allowing computation of Z-scores for fetal cardiac dimensions from knowledge of femur length (FL), biparietal diameter (BPD) or gestational age (GA) using fetal echocardiography. METHODS: Seventeen fetal cardiac dimensions were measured in 130 pregnant women with singleton fetuses of gestational age 15-39 weeks. Regression equations were derived relating all dimensions to FL, BPD and GA. From the calculations, formulae were then developed allowing fetal cardiac Z-score computation. RESULTS: The relationships between cardiac dimensions and FL, BPD or GA were described following natural log transformation. From this analysis, FL (taken as an expression of fetal size) had the highest correlation to fetal cardiac dimensions. From the developed nomograms, Z-scores of specific fetal cardiac structures could be estimated from knowledge of the FL, BPD or GA and echocardiographically derived measurements. CONCLUSIONS: This study allowed computation of Z-scores in fetal life for 17 cardiac dimensions from FL, BPD or GA. Previous studies of normal data allowed qualitative assessment of where abnormal cardiac dimensions lay with regard to the normal range. Z-scores from this study allow quantitative analysis of where such dimensions lie relative to the mean. This permits exact assessment of growth of fetal cardiac structures in normal hearts and particularly in congenitally abnormal hearts where quantitative assessment of the growth of cardiac structures is important in analyzing and planning treatment strategies.

Echocardiography↗
PubMed2005

Discovery of 342 putative new genes from the analysis of 5'-end-sequenced full-length-enriched cDNA human transcripts.

In this work we describe the process that, starting with the production of human full-length-enriched cDNA libraries using the CAP-Trapper method, led us to the discovery of 342 putative new human genes. Twenty-three thousand full-length-enriched clones, obtained from various cell lines and tissues in different developmental stages, were 5'-end sequenced, allowing the identification of a pool of 5300 unique cDNAs. By comparing these sequences to various human and vertebrate nucleotide databases we found that about 40% of our clones extended previously annotated 5' ends, 662 clones were likely to represent splice variants of known genes, and finally 342 clones remained unknown, with no or poor functional annotation. cDNA-microarray gene expression analysis showed that 260 of 342 unknown clones are expressed in at least one cell line and/or tissue. Further analysis of their sequences and the corresponding genomic locations allowed us to conclude that most of them represent potential novel genes, with only a small fraction having protein-coding potential.

5' Flanking Region↗
PubMed2005

[MALT-type B-cell lymphoma masquerading as scleritis or posterior uveitis].

PURPOSE: Diagnostic and therapeutic management of masquerade syndromes associated with MALT-type lymphoma. PATIENTS AND METHOD: We report the cases of three patients referred for acute or chronic severe loss of visual acuity. All of them suffered from uveitis or scleritis resistant to corticoid treatment. Each one had posterior uveitis associated with retinochoroidal infiltration, anterior scleritis associated with uveal effusion syndrome, or bilateral pan-uveitis associated with serous retinal detachment. Two patients had medical records of systemic malignancies. They underwent an extensive work-up. Search for an infectious, immune or malignant disease was negative but orbital imaging showed a posterior scleral thickening in all cases. RESULTS: Diagnosis of mucosa-associated lymphoid tissue (MALT) ocular lymphoma was assessed in all cases after scleral biopsy. Immunohistochemical analysis showed CD20(+) and CD5(-) scleral lymphocyte infiltrates. The three patients underwent chemotherapy associated with radiotherapy. Lesions were stabilized in the first case, whereas six lines of visual acuity improvement was noted in the second one, and full recovery was achieved after treatment in the third case. DISCUSSION: Clinical manifestations of this ocular lesion seem to be multiple, masquerading as different types of posterior uveitis or scleritis. In the three cases, we did found other systemic locations of MALT-type lymphoma. Diagnosis was mainly based on pathological analysis. Fast visual recovery in two cases demonstrated the importance of an early diagnosis and a specific treatment. All cases of chronic and corticoid-resistant posterior uveitis require a specialized radiological evaluation followed, if necessary, by multiple orbital biopsies.

Adult↗
PubMed2005

Ceramide triggers an NF-kappaB-dependent survival pathway through calpain.

We have shown that C2 ceramide, a cell-permeable analog of this lipid second messenger, triggers an NF-kappaB dependent survival pathway that counteracts cell death. Activation of NF-kappaB and subsequent induction of prosurvival genes relies on calpain activity and is prevented on silencing of the calpain small subunit (Capn4) that is required for the function of ubiquitous calpains. We have demonstrated that p105 (NF-kappaB1) and its proteolytic product p50 can be targets of micro- and milli-calpain in vitro and that a p50 deletion mutant, lacking both the N- and the C-terminal ends, is resistant to calpain-mediated degradation. Capn4 silencing results in stabilization of endogenous p105 and p50 in diverse human cell lines. Furthermore, p105 processing and activation of NF-kappaB survival genes in response to C2 ceramide is impaired in Capn4-/- mouse embryonic fibroblasts defective in calpain activity. Altogether, these data argue for the existence of a ceramide-calpain-NF-kappaB axis with prosurvival functions.

Animals↗
PubMed2005

Protein expression analysis of chromosome 12 candidate genes in chronic lymphocytic leukemia (CLL).

The pathogenic role of trisomy 12 in chronic lymphocytic leukemia (CLL) remains unresolved, but recently an upregulated RNA expression level has been observed for chromosome 12 candidate genes. In the current study, the protein expression of chromosome 12 candidate genes was characterized by comparing CLL cases with (n=58) or without (n=16) trisomy 12, CD19+-B-cells and cell lines (JVM-2, EHEB, JURKAT). Immunoblotting was performed to quantify the levels of AID, APAF-1, ARF3, CCND2, CDK2, CKD4, GLI, MDM-2, p27, Smac/DIABLO and STAT6 (signal transducer and activator of transcription 6). The cell lines showed distinct expression patterns for CCND2, MDM-2, p27, Smac/DIABLO and STAT6, and displayed higher levels of CDK2 and CDK4 than the CLL cases. JURKAT and the CLL cases expressed uniformly high levels of p27, but low levels of CCND2. AID expression in the CLL cases was weak with slight variations regardless of the subgroup affiliation. The expression of the investigated proteins was independent of the trisomy 12 status as well as of the VH mutation status. The comparison of CD19+-B-cells with CLL revealed higher protein levels in CLL for CDK4, p27, Smac/DIABLO and STAT6. Further studies including protein expression experiments in genetic high-risk subgroups of CLL have to elucidate whether these proteins qualify as candidates for targeted CLL therapies.

Antigens, CD19↗
PubMed2005

Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests (Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively, P<0.025), and haplotype-based association tests (L55/R192: HBAT Z=2.430, P<0.025). These results are consistent with our model and provide further support for the hypothesis that concurrent genetic vulnerability and environmental OP exposure may possibly contribute to autism pathogenesis in a sizable subgroup of North American individuals.

Aryldialkylphosphatase↗
PubMed2004

Deep venous thrombosis revealed during ultrasound-guided femoral nerve block.

Ultrasound imaging used to facilitate performance of a femoral nerve block also affords imaging of adjacent anatomical structures. Following a fracture of the femur, an ultrasound guided femoral nerve block (UGFNB) was performed to provide analgesia; this led to the incidental finding of a previously undiagnosed femoral vein thrombosis (DVT), resulting in a change in patient management before surgery. An inferior vena cava (IVC) filter was placed before intramedullary nailing of the fracture.

Adult↗
PubMed2004

Adverse reactions to drugs: in vitro studies with isolated cells.

OBJECTIVE AND DESIGN: Drug-induced adverse reactions can be allergic or pseudoallergic in nature, in this study the histamine releasing ability of 4 radiographic contrast media and 2 opioid analgesics was tested on a variety of mast cell containing cell suspensions. MATERIAL: Mast cell containing cell suspensions were obtained from porcine lung, liver, kidneys and heart, as well as rat lung and rat peritoneal lavage. TREATMENT: Cells were incubated for 10 min with Angiographin (amidotrizoate), Hexabrix (ioxaglate), Rayvist (ioglycate) or Telebrix (ioxithalamate) all 10-500 microl/ml or with levomethadone (0.1-5 mM) or pethidine (0-10 mM). METHODS: Histamine was measured using an automated fluorometric method and percentage histamine release calculated. RESULTS: All agents caused histamine release from porcine cells and rat lung cells. However, rat peritoneal mast cells were refractory to the action of pethidine. Cardiac cells were the most sensitive to the radiographic contrast media but the least sensitive to the opioid analgesics. CONCLUSIONS: The data indicate that mast cells isolated from animal models can provide an indication of those agents likely to induce an adverse pseudoallergic reaction. However, these data should be used together with those obtained from human mast cells, in vivo animal experiments as well as studies using human volunteers and clinical trials as advocated in the Marburg Model.

Analgesics, Opioid↗
PubMed2004

[Large solitary fibrous tumors of the pleura as incidental finding. 2 case reports of a rare tumor entity].

The solitary fibrous tumor (SFT) is a very rare and usually benign neoplasm. This tumor is mostly located in the thoracic cavity, but it has also been reported in numerous sites including liver, skin, and meninges. Due to its rarity diagnosis is often difficult. Accordingly, histopathological differentiation is of major importance. Solitary fibrous tumors consistently express CD 34 and react negatively to epithelial markers. This absence of expression of epithelial markers, especially cytokeratin, is also useful to distinguish these rare entities from sarcomatous mesotheliomas. The treatment of choice for solitary fibrous tumors is extensive surgical resection. Up to now there is no evidence that radiation and chemotherapy are effective. The local recurrence or onset of metastases depends on histologic parameters. In cases of benign classification (60-80%), the recurrence rate was only 2% after surgical excision. One-half of the patients with malignant tumors can be cured; the rest develop recurrences and metastases more often. Especially in those cases, emphasis should be placed on continual follow-up examination. We report two cases of a 65- and a 75-year-old male patient with huge intrathoracic solitary fibrous subpleural tumors, discovered incidentally on routine chest X-ray.

Aged↗
PubMed2004

Complications in laparoscopic colorectal surgery: results of a multicentre trial.

BACKGROUND: We present a prospective observational multicentre study of 4834 consecutive cases undergoing laparoscopic colorectal procedures. METHODS: The study was initiated on 1 August 1995, with centres from Germany, Austria and Switzerland participating. All patients undergoing laparoscopic colorectal surgery were included, and no selection criteria were applied. RESULTS: Between August 1995 and April 2004, the participating centres treated 4834 patients. Three thousand, one hundred and sixty-six operations were performed for benign indications, and 1668 for cancer, with most operations being done for diverticulitis (2019, 41.8%). The conversion rate was 5.6%, and the overall morbidity was 20.1%. Intra-operative complications occurred in 5.9%, postoperative complications in 14.0%, and the overall anastomotic leak rate was 3.1% (colon 2.6%, rectum 11.9%). The 30-day mortality rate was 1.3%. CONCLUSIONS: It has been our experience that laparoscopic surgery for colorectal disease is safe. Morbidity and mortality are comparable to those of conventional colorectal surgery.

Adolescent↗
PubMed2004

The influence of the 5-HT3 receptor antagonist tropisetron on pain in fibromyalgia: a functional magnetic resonance imaging pilot study.

OBJECTIVE: Central pain processing is altered in patients with fibromyalgia syndrome (FMS). The serotonin metabolism, especially the 5-HT3 receptor, seems to play an important role. METHODS: We investigated the effect of the local injection of the 5-HT3 receptor antagonist tropisetron on the perception and central processing of pain in FMS patients using painful mechanical stimulation and functional magnetic resonance imaging (fMRI) within the framework of a pre-/posttreatment double-blind design. RESULTS: In the contralateral primary somatosensory cortex, contralateral posterior insula, and anterior cingulate cortex, we found that the activation was significantly reduced after treatment. On average, patients rated the stimulation-induced pain intensity as stronger in the session after treatment compared to before treatment, although the individual data revealed a heterogeneous pattern. All patients showed sensitisation during the painful stimulation, which was not influenced by the treatment. CONCLUSIONS: Both the sensory-discriminative and motivational-affective components of pain as measured by fMRI were altered by tropisetron.

Brain↗