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C Schaefer

Publications and source records attributed to C Schaefer.

At least 19 recordsLinked to original sources
PubMed2005

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.

Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4+CD25+ (Treg) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of Treg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry. Expression of CCR7, CD62L, zeta chain and Annexin V binding to Treg and non-Treg CD4+ lymphocyte populations were evaluated. Treg were confirmed to be Foxp3+ and GITR+. The Treg frequency was significantly elevated in patients with active disease and those with no evidence of disease (NED) following curative therapies. Both Treg and non-Treg CD4+ T cells in patients were significantly enriched in CCR7- and CD62L- cell subsets. Although Treg in patients contained a higher proportion of double negative (CCR7-CD62L-) cells, the majority of Tregs were CCR7-CD62L+. The proportion of Annexin V+CD4+ T cells was higher in patients (P<0.00005) than normal controls (NC), and Treg were significantly more sensitive to apoptosis than non-Treg in patients and NC. Expression of zeta was reduced in all subsets of CD4+ T cells obtained from patients vs NC. The data suggest that Treg in patients with SCCHN largely contain T cells with the 'effector' phenotype, which bind Annexin V and have low zeta expression, consistent with their activation state and a rapid turnover in the peripheral circulation.

Antibodies, Monoclonal↗
PubMed2005

The safety of proton pump inhibitors in pregnancy: a multicentre prospective controlled study.

BACKGROUND: Proton pump inhibitors are used to treat gastro-oesophageal reflux and peptic ulcers. Gastro-oesophageal reflux is a common condition in pregnancy. Human pregnancy experience with lansoprazole or pantoprazole is very limited. More data exist on the safety of omeprazole in pregnancy. AIM: To assess the safety of proton pump inhibitors in pregnancy. METHODS: The rate of major anomalies was compared between pregnant women exposed to omeprazole, lanzoprazole, or pantoprazole and a control group counselled for non-teratogens. The study design is a multicentre (n = 8), prospective, controlled study of the European Network of Teratology Information Services. RESULTS: We followed up 295 pregnancies exposed to omeprazole [233 in the first trimester (T1)], 62 to lansoprazole (55 in T1) and 53 to pantoprazole (47 in T1), and compared pregnancy outcome to that of 868 European Network of Teratology Information Services controls. The rate of major congenital anomalies did not differ between the exposed and control groups [omeprazole nine of 249 (3.6%), lansoprazole two of 51 (3.9%) and pantoprazole one of 48 (2.1%) vs. controls 30 of 792 = 3.8%]. No differences were found when exposure was limited to the first trimester after exclusion of genetic, cytogenetic or infectious anomalies. CONCLUSIONS: This study suggests that proton pump inhibitors do not represent a major teratogenic risk in humans.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2005

Femur window--a new approach to microcirculation of living bone in situ.

BACKGROUND: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis. METHODS: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIs) in femoral bone tissue of c57-black mice (n=11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested. RESULTS: Microvascular permeability and LEIs showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. CONCLUSION: The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis.

Animals↗
PubMed2004

ANP preconditioning does not increase protection against experimental pancreatitis, observed after general anesthesia and jugular vein catheterization.

It has been widely shown that preconditioning, inducing heat shock proteins, can protect against experimentally induced pancreatitis. Solid evidence indicates that HSP70 plays a central role in this context, possibly by inhibition of premature intracellular trypsinogen activation. Current preconditioning protocols such as whole body hyperthermia are, however, quite strenuous and clinically not applicable. There is little data on other means to induce pancreatic HSPs such as pharmacologic pretreatment.However, in models of ischemic liver reperfusion injury, it has been demonstrated that atrial natriuretic peptide (ANP) can be used for such pharmacologic preconditioning. Evidence indicates that ANP exerts its protective effects via increased cGMP levels, activation of heat shock transcription factor (HSF) and, increased protein levels of HSP70. Pancreatic acinar cells express ANP receptors and respond to ANP treatment with increased cGMP levels. We have, therefore, investigated whether intravenous ANP pretreatment could be used to protect the pancreas against experimental pancreatitis. When given 20 minutes prior to pancreatitis induction, ANP pretreatment had no effect on cerulein-induced pancreatitis. In contrast, 24 hours after preconditioning, induction of HSP70 protein expression and protection against experimental pancreatitis were found. However, controls treated with NaCl without ANP showed a similar response. This indicates that stress caused by general anesthesia and jugular vein catheterization can be sufficient for preconditioning while ANP, in contrast to models of ischemic liver reperfusion injury, does not confer additional protection.

Anesthesia, General↗
PubMed2003

[Recreational drugs and environmental contaminants in mother 's milk].

In Germany and many other countries breast milk contamination in particular with persistent organochlorines and lead declined substantially by 50-70% or more during the last decade. Generally also mercury compounds, cadmium and other environmental contaminants do not pose a toxic threat to the fully breast fed infant, which, according to the current knowledge, could outweigh the advantages of breast-feeding. Industrial regions, large cities and frequent consumption of contaminated fish are factors still positively correlated with elevated breast milk contamination. However, recent study results do not support routine measurement of milk contaminants for decision making on prolonged breast-feeding (more than 4-6 months). Exposure to recreational drugs including tobacco smoking and alcohol drinking is preventable. In case of ongoing abuse decisions on breast-feeding restrictions must be taken individually.

Breast Feeding↗
PubMed2002

Cell surface bound and soluble adhesion molecules in CSF and blood in multiple sclerosis: correlation with MRI-measures of subclinical disease severity and activity.

BACKGROUND: The expression of soluble cell adhesion molecules (AM) in cerebrospinal fluid (CSF) and blood and their significance as measures of disease activity has been extensively studied in patients with multiple sclerosis (MS). In previous studies, we found that cell surface bound AM on mononuclear cells (MNC) in CSF and blood might be useful markers of clinical disease activity in MS patients. OBJECTIVE: To analyze the correlation of cell surface bound and soluble AM in CSF and blood with magnetic resonance imaging (MRI) markers of subclinical disease severity and activity in patients with MS. METHODS: Expression levels of cell surface bound AM on peripheral blood and CSF MNC were determined by flow cytometry analysis in 77 (CSF: 33) MS patients. Concentration levels of the soluble forms of AM were measured by enzyme-linked immunosorbent assay (ELISA). In corresponding cerebral gadolinium (Gd)-enhanced MRI scans, we determined both measures of subclinical disease severity and subclinical disease activity. RESULTS: The expression levels of cell surface bound AM in peripheral blood correlated inversely with parameters for subclinical disease severity and activity on cerebral MRI scans as well as with the disease duration. Furthermore, we found significant correlations between serum levels of soluble AM and patient age but not with disease duration. CONCLUSIONS: Our results suggest that subclinical disease progression may be associated with a decrease of the expression of cell surface bound AM on peripheral blood MNC. This might be a result of activated MNC migration into the CNS.

Adult↗
PubMed2001

Adverse effects of prenatal methimazole exposure.

BACKGROUND: A specific phenotype of methimazole (MMI) induced malformations has recently been postulated. MMI embryopathy is characterized by minor dysmorphic features, choanal atresia and/or esophageal atresia, growth retardation, and developmental delay. METHODS: We prospectively studied the outcome of pregnancy in 241 women counseled by 10 Teratology Information Services (TIS) of the European Network of Teratology Information Services (ENTIS) because of MMI exposure, and compared them with those of 1,089 pregnant women referred to TIS because of exposure to nonteratogenic drugs (control group). Information was obtained by mail or telephone interview. RESULTS: There was no increase in the general rate of major anomalies or of spontaneous or induced abortions in the MMI-exposed group in comparison with the control group. Two newborns were affected with one of the major malformations that are part of the postulated embryopathy. CONCLUSIONS: The results of this study indicate that choanal as well as esophageal atresia may have a higher incidence than expected in fetuses exposed to MMI between 3 and 7 gestational weeks. Until further data are available, thyrotoxicosis should be treated with propylthiouracil, as it is apparently safer for use during the fertile period.

Abnormalities, Drug-Induced↗
PubMed2001

Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells.

Transforming growth factor-beta (TGF-beta) inhibits pancreatic acinar cell growth. In many cell types, TGF-beta mediates its growth inhibitory effects by activation of Smad proteins. Recently, it has been reported that Smad proteins may interact with the mitogen-activated protein (MAP) kinase signaling pathways. In this study, we report on the interactions between the TGF-beta and MAP kinase signaling pathways in isolated rat pancreatic acinar cells. TGF-beta activated the MAP kinases extracellular signal-related kinases (ERKs) and p38 in pancreatic acinar cells, but had no effect on c-jun NH2-terminal kinase activity. Activation of MAP kinase by TGF-beta was maximal 4 h after treatment. The ability of TGF-beta to activate ERKs was concentration dependent and dependent on protein synthesis. TGF-beta's stimulation of ERK activation was blocked by PD-98059, an inhibitor of MAP kinase kinase 1, and by adenoviral transfer of dominant negative RasN17. Furthermore, adenoviral-mediated expression of dominant negative Smad4 blocked the ability of TGF-beta to activate acinar cell MAP kinase, demonstrating that this activation is downstream of Smads. The biological relevance of ERK activation by TGF-beta was indicated by demonstrating that inhibition of ERK signaling by PD-98059 blocked the ability of TGF-beta to activate the transcription factor activator protein-1. These studies provide new insight into the signaling mechanisms by which TGF-beta mediates biological actions in pancreatic acinar cells.

Adenoviridae↗
PubMed2001

Gender differences in pharmacokinetics of alcohol.

BACKGROUND: The enhanced vulnerability of women to develop alcohol-related diseases may be due to their higher blood alcohol levels after drinking, but the mechanism for this effect is debated. METHODS: Sixty-five healthy volunteers of both genders drank 0.3 g of ethanol/kg of body weight (as 5%, 10%, or 40% solutions) postprandially. Blood alcohol concentrations were monitored by breath analysis and compared with those after intravenous infusion of the same dose. First-pass metabolism was quantified (using Michaelis-Menten kinetics) as the route-dependent difference in the amount of ethanol reaching the systemic blood. Gastric emptying was assessed by nuclear scanning after intake of 300 microCurie of technetium-labeled diethylene triamine pentacetic acid in 10% ethanol. The activities of alcohol dehydrogenase isozymes were assessed in 58 gastric biopsies, using preferred substrates for gamma-ADH (acetaldehyde) and for final sigma-ADH (m-nitrobenzaldehyde) and a specific reaction of chi-ADH (glutathione-dependent formaldehyde dehydrogenase). RESULTS: Women had less first-pass metabolism than men when given 10% or 40%, but not 5%, alcohol. This was associated with lower gastric chi-ADH activity; its low affinity for ethanol could explain the greater gender difference in first-pass metabolism with high rather than with low concentrations of imbibed alcohol. Alcohol gastric emptying was 42% slower and hepatic oxidation was 10% higher in women. A 7.3% smaller volume of alcohol distribution contributed to the higher ethanol levels in women, but it did not account for the route-dependent effects. CONCLUSIONS: The gender difference in alcohol levels is due mainly to a smaller gastric metabolism in females (because of a significantly lesser activity of chi-ADH), rather than to differences in gastric emptying or in hepatic oxidation of ethanol. The concentration-dependency of these effects may explain earlier discrepancies. The combined pharmacokinetic differences may increase the vulnerability of women to the effects of ethanol.

Adult↗
PubMed2001

A study of moss (Marchantia polymorpha) thylakoid membrane lipids in monolayers.

Monolayers of seven fractions of natural lipids (phosphatidyl inositol, sulfoquinovosyl diacylglycerol, phosphatidylcholine, digalactosyl diacylglycerol, phosphatidyl glycerol, phosphatidylethanolamine, monogalactosyl diacylglycerol), isolated from the photoautotrophic cell culture of the moss Marchantia polymorpha grown under normal and light-stress conditions, have been prepared for the first time. We have shown that the high-intensity light affects the area occupied by the lipid molecule. In the case of digalactosyl diacylglycerol and phosphatidyl glycerol fractions, after the light stress the area significantly increased from 0.50 to 0.80 nm2 and from 0.47 to 0.63 nm2, respectively, and in the case of the sulfoquinovosyl diacylglycerol fraction, the area decreased from 0.40 to 0.32 nm2. These results are in agreement with our previous data on the redistribution of the double bonds in the aliphatic chains of these lipids and can be used to characterize the state of the lipid bilayer of the thylakoid membranes.

Bryopsida↗
PubMed2000

Naturally processed and concealed HLA-A2.1-restricted epitopes from tumor-associated antigen tyrosinase-related protein-2.

In this study, a computer-assisted reverse immunology approach was utilized in order to identify potentially antigenic peptides derived from the differentiation antigen TRP-2, a melanosomal protein frequently expressed in melanoma. Among the seven peptides complying with HLA-A2.1-binding motifs, two induced specific CD8(+) cytotoxic T lymphocytes. HLA-A2.1(+) melanoma cells expressing TRP-2 were lysed by clones specific for TRP-2(360-368) (TLDSQVMSL) peptide, thus identifying it as a naturally processed epitope. Other T-cell clones directed against TRP-2(476-484) (VMGTLVALV) were unable to lyse HLA-matched TRP-2(+) cell lines. The role of intracellular proteolytic processing in the generation of this epitope was investigated by transfecting mini-genes encoding the TRP-2(476-484) peptide alone or carrying N- or C-terminal extensions. Specific T-cell clones recognized target cells expressing the cytotoxic T-lymphocyte (CTL)-defined epitope or its C-terminally extended precursor, but failed to recognize cells expressing the N-terminally extended TRP-2(476-484) peptide, suggesting the presence of a negative processing signal (NPS). Regarding C-terminus-flanking regions, mutational analysis indicates that the GLY485 residue plays a key role in the processing of the TRP-2(476-484) epitope. Interestingly, proteasome inhibitors preventing the generation of the MART-1/Melan-A(27-35) immunodominant melanoma tumor-associated antigen (TAA) promoted detectable presentation of TRP-2(476-484) epitope in HLA-A2.1(+) and TRP-2(+) tumor lines, as witnessed by cytokine release by specific T-cell clones.

Acetylcysteine↗
PubMed2000

CD45RA+ ICAM-3+ lymphocytes in cerebrospinal fluid and blood as markers of disease activity in patients with multiple sclerosis.

OBJECTIVES: Autoreactive T cells targeted against antigens of the myelin sheath are suggested to play an important role in the pathogenesis of multiple sclerosis (MS). Naive (CD45RA+) T cells and intercellular adhesion molecule-3 (ICAM-3) are markers for un-activated lymphocytes. This study was performed to investigate, whether the expression levels of these antigens both on cerebrospinal fluid (CSF) and peripheral blood lymphocytes can be used as activity markers in MS. MATERIALS AND METHODS: Corresponding blood and CSF samples were obtained from 31 patients with relapsing-remitting MS. Of the 31 MS patients 23 were suffering from acute relapses at the time of examination and all of them were treated with high-dose methylprednisolone (MP). Blood was collected again on the 10th day of therapy and after 3 months. The control group consisted of 12 healthy persons. Two-color flow cytometry was performed to evaluate the percentage of both CD45RA+ and ICAM-3+ cells within the lymphocyte population. RESULTS: The percentage of CD45RA+ ICAM-3+ cells in the CSF of MS patients with relapses was significantly increased compared to patients in remission (P<0.05). In blood, a significantly lower percentage of CD45RA+ ICAM-3+ lymphocytes was found in both patient groups compared to healthy controls (Relapse: P<0.05, Remission: P<0.10). Additionally, we found a significant increase (P < 0.01) in the percentage of CD45RA+ ICAM-3+ lymphocytes in blood of MS patients suffering from acute relapse on the 10th day of high-dose MP treatment. CONCLUSION: Our data suggest that the percentage of CD45RA+ ICAM-3+ lymphocytes in CSF can be used as marker of disease activity in MS patients.

Acute Disease↗
PubMed2000

Economic impact of febrile morbidity and use of permethrin-impregnated bed-nets in a malarious area I. Study of demographics, morbidity, and household expenditures associated with febrile morbidity in the Republic of Benin.

In preparation for a study on the effect of bed net use on malaria, this article describes febrile morbidity and malaria expenditures in a sub-Saharan area (Benin) of hyperendemic malaria. The 325 randomly selected households were visited weekly between April 1994 and March 1995 to determine febrile morbidity and household expenditures for prevention and treatment. The results indicate that rural children had two febrile episodes annually compared with 0.3 episodes among children living in the city. There was no difference in mean annual febrile episodes between adults and children (adults = 1.5, children = 1.5; P = 0.48) and in the expenditures per febrile episode (adults = US$1.85, children = US$1.62; P = 0.45). Annual prevention expenditures were higher for adults than for children (US$1.73 and US$1.28, respectively; P < 0.001), although there was no significant difference in expenditures for annual treatment for adults and children (US$2.15 and US$2.34, respectively). These and other findings are analyzed further and discussed.

Adult↗
PubMed2000

Economic impact of febrile morbidity and use of permethrin-impregnated bed nets in a malarious area II. Determinants of febrile episodes and the cost of their treatment and malaria prevention.

The objective of this study is to determine the effect of permethrin insecticide-treated bed net (PITN) use on the incidence of febrile episodes and on household malaria expenses in Benin. Over the course of one year, 208 randomly selected PITN user and non-user households were visited weekly to determine expenditures on febrile morbidity and its treatment, and to monitor spending on malaria prevention. Multivariate analyses were performed to distinguish the effects of PITN use from other important determinants of morbidity, such as malaria-related beliefs and practices, income, and other socio-economic variables. Results from the logistic regression analysis show that the use of PITNs decreases the risk of febrile episodes by 34% in children living in the rural zone. Multiple regression analysis reveals that PITN use does not reduce prevention and treatment expenses. These expenses are significantly associated with women's income. This report also discusses other factors associated with febrile morbidity and malaria-related expenditures.

Adult↗
PubMed1999

Exposure to yellow fever vaccine in early pregnancy.

We report on a data collection concerning exposure to yellow fever vaccine (YFV) during early pregnancy, ascertained through the European Network of Teratology Information Services (TISs) and the Pharmacovigilance Department of Pasteur Merieux Connaught (PMC). Six TISs had had no inquiry about YFV. Five submitted prospectively collected cases. Seventy-four cases were analyzed, 58 with a completed follow-up. Pregnancies ended in 46 births, five voluntary abortions and seven spontaneous abortions. Three newborns had minor anomalies and two had major defects (ureteral stenosis and triphalangeal hallux). Although the sample is too small to rule out a moderate increased risk of adverse reproductive effect of YFV, it gives no argument for such an effect and should lead to reassure pregnant women who might be inadvertently vaccinated.

Congenital Abnormalities↗
PubMed1998

Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules.

In this work, we addressed the possibility to enhance the "in vitro" generation of CTLs recognizing tumor-associated antigens (TAAs) by using an inactivated recombinant vaccinia virus encoding B7.1 and B7.2 costimulatory molecules (rVV-B7.1/2). Antigen presenting cells (APCs) infected by rVV-B7.1/2 and pulsed with MART-1/Melan-A27-35 HLA-A2.1-restricted peptide induced significantly higher specific cytotoxic activity than peptide-loaded APCs infected by wild-type VV, both in VV-sensitized and naive donors. When APCs were infected with a rVV encoding both MART-1/Melan-A27-35 and B7-1/2 (rVV-B7.1/2-M), a significantly more effective CTL generation was observed as compared with cultures stimulated by APCs infected with a rVV encoding the TAA epitope only (rVV-M). These enhancing effects were detectable irrespective of a previous VV-specific sensitization. Most importantly, fibroblasts, devoid of antigen-presenting capacity upon peptide pulsing or infection with rVV-M, could be turned into effective APCs after infection by rVV encoding TAA epitopes and costimulatory molecules. In these experiments, by using separate recombinant viral constructs, we observed a predominant role of B7-1 as compared with B7-2 in the induction of TAA-specific CTLs. Taken together, our data indicate that replication-incompetent rVV encoding TAA epitopes and costimulatory molecules are able to induce highly effective generation of tumor-specific CTLs. Therefore, these vectors could represent valuable clinical tools for immunotherapy of melanoma patients.

Antigen-Presenting Cells↗
PubMed1998

Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study.

BACKGROUND: Though among the most abundant human steroid hormones, the physiologic role of dehydroepiandrosterone and its sulfate (DHEAS) is not known. Our goal was to determine if DHEAS is associated with cognition and mood in older women, and if baseline DHEAS levels are predictive of cognitive decline. METHODS: In a prospective cohort, we studied 394 randomly selected community-dwelling women, aged 65 years or older, currently enrolled in the Study of Osteoporotic Fractures. Subjects were administered a modified Mini-Mental State Exam, Trials B, Digit Symbol, and the Geriatric Depression Scale-Shortened (GDSS), at study onset and 4-6 years later. Serum was obtained at study initiation for DHEAS analysis. RESULTS: DHEAS levels declined with age, as expected. There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes, even after multivariate adjustment. Change in cognitive performance overtime was not associated with DHEAS levels. Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS (mean score 3.4 +/- 3.6 compared with 1.6 +/- 2.3, p = .028) and a higher percentage with depression (21.7% compared with 4.6%, p = .001). CONCLUSIONS: Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women; however, nondetectable levels may be associated with depression.

Aged↗