PubMed Health⌕ Search

Biomedical subjects

Hans Wolf

Publications and source records attributed to Hans Wolf.

At least 19 recordsLinked to original sources
PubMed2006

Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C.

Recombinants based on the attenuated vaccinia virus strains MVA and NYVAC are considered candidate vectors against different human diseases. In this study we have generated and characterized in BALB/c and in transgenic HHD mice the immunogenicity of two attenuated poxvirus vectors expressing in a single locus (TK) the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef (GPN) polyprotein of clade C (referred as MVA-C and NYVAC-C). In HHD mice primed with either MVA-C or NYVAC-C, or primed with DNA-C and boosted with the poxvirus vectors, the splenic T cell responses against clade C peptides spanning gp120/GPN was broad and mainly directed against Gag-1, Env-1 and Env-2 peptide pools. In BALB/c mice immunized with the homologous or the heterologous combination of poxvirus vectors or with Semliki forest virus (SFV) vectors expressing gp120/GPN, the immune response was also broad but the most immunogenic peptides were Env-1, GPN-1 and GPN-2. Differences in the magnitude of the cellular immune responses were observed between the poxvirus vectors depending on the protocol used. The specific cellular immune response triggered by the poxvirus vectors was Th1 type. The cellular response against the vectors was higher for NYVAC than for MVA in both HHD and BALB/c mice, but differences in viral antigen recognition between the vectors was observed in sera from the poxvirus-immunized animals. These results demonstrate the immunogenic potential of MVA-C and NYVAC-C as novel vaccine candidates against clade C of HIV-1.

AIDS Vaccines↗
PubMed2006

A variable immunoreceptor in a subpopulation of human neutrophils.

Neutrophils are thought to rely solely on nonspecific immune mechanisms. Here we provide molecular biological, immunological, ultrastructural, and functional evidence for the presence of a T cell receptor (TCR)-based variable immunoreceptor in a 5-8% subpopulation of human neutrophils. We demonstrate that these peripheral blood neutrophils express variable and individual-specific TCRalphabeta repertoires and the RAG1/RAG2 recombinase complex. The proinflammatory cytokine granulocyte colony-stimulating factor regulates expression of the neutrophil immunoreceptor and RAG1/RAG2 in vivo. Specific engagement of the neutrophil TCR complex protects from apoptosis and stimulates secretion of the neutrophil-activating chemokine IL-8. Our results, which also demonstrate the presence of the TCR in murine neutrophils, suggest the coexistence of a variable and an innate host defense system in mammalian neutrophils.

Animals↗
PubMed2006

Automated 10-channel capillary chip immunodetector for biological agents detection.

The automated 10-channel capillary chip immunodetector (10K-IDWG) is a prototype, which has been developed for automatically operated biological agents (BA) point detection. The current technology uses a chemiluminescence capillary immunoassay (EIA) technique in combination with integrated microfluidics and allows the highly sensitive and rapid detection and preliminary identification of multiple BA in aqueous solutions in the laboratory. The chemiluminescence capillary EIA are performed within a disposable capillary chip containing 10 fused-silica capillaries arranged in parallel coated with selected capture antibodies. A multianode-photomultiplier array is used to detect chemiluminescence intensity in each capillary. Reservoirs for reagents and buffers and a waste disposal reservoir are integrated. This paper describes the technology of the 10K-IDWG and its evaluation with three different BA, the toxin staphylococcal enterotoxin B (SEB), the bacterial analyte Escherichia coli (E. coli) O157:H7 as a model for bacterial pathogens, and the bacteriophage M13 as a model for virus pathogens. The 10K-IDWG is able to detect the above mentioned three BA in an aqueous sample within 29 min (single analyte-detection and multiplexing). Limits of detection (LOD) are 0.1 ng/ml for SEB, 10(4)cfu/ml for E. coli O157:H7, and 5x10(5) pfu/ml for M13. Cross reactivities between the three assays were not observed.

Biosensing Techniques↗
PubMed2006

Prediction of maternal complications and adverse infant outcome at admission for temporizing management of early-onset severe hypertensive disorders of pregnancy.

OBJECTIVE: We explored the association between clinical parameters at admission and the subsequent development of major maternal complications or adverse infant outcome in women with hypertensive complications of pregnancy remote from term. STUDY DESIGN: We drew data from a randomized trial of temporizing management in 216 patients with hemolysis, elevated liver enzymes, and low platelets syndrome; severe preeclampsia; eclampsia; or hypertension-related fetal growth restriction and gestational ages between 24 and 34 completed weeks. End points were adverse infant outcome (perinatal death, severe morbidity) and major maternal complications (major morbidity; recurrent and newly acquired hemolysis, elevated liver enzymes, and low platelets; eclampsia) after admission. End point prevalences were comparable between the treatment and control groups. The association with age, parity, ethnicity, body mass index, gestational age, estimated fetal weight, blood pressure, antihypertensive medication, pulse rate, hemoglobin concentration, admitting center, diagnosis at inclusion, chronic hypertension, and thrombophilia was explored by logistic regression analysis. RESULTS: Adverse infant outcome was predominantly influenced by gestational age (odds ratio 0.4 per week increment). Major maternal complications were correlated to multiparity (odds ratio 0.4) and estimated fetal weight (odds ratio 0.9 per 100-g increment). CONCLUSION: Prediction at admission of the clinical course of the disease and the development of additional maternal complications was not feasible.

Birth Weight↗
PubMed2006

Management of sepsis in neutropenia: guidelines of the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

These guidelines from the infectious diseases working party (AGIHO) of the German Society of Hematology and Oncology (DGHO) give recommendations for the management of adults with neutropenia and the diagnosis of sepsis. The guidelines are written for clinicians and focus on pathophysiology, diagnosis, and treatment of sepsis. The manuscript contains evidence-based recommendations for the assessment of the quality and strength of the data.

Cardiotonic Agents↗
PubMed2006

Increased sympathetic activity present in early hypertensive pregnancy is not lowered by plasma volume expansion.

OBJECTIVE: To evaluate whether sympathetic activity is increased in early-onset hypertensive pregnancy and whether this can be influenced by management with plasma volume expansion. METHODS: The study group consisted of 74 subjects, of which 37 had early-onset hypertensive disorders of pregnancy (preeclampsia or gestational hypertension with fetal growth restriction), who were included at 24 to 34 weeks in a randomized controlled trial of management with (n = 18) or without (n = 19) plasma volume expansion. Heart rate and blood pressure variabilities, LF/HF ratio for heart rate, baroreflex sensitivity, and phase difference at low frequency (LF approximately 0.1 Hz) were calculated by spectral analysis from continuous heart rate and blood pressure recordings of the finger pulse wave (Portaprestrade mark, TNO). Measurements were performed at inclusion, after 20 to 40 hours and after 65 to 100 hours. The control group consisted of 29 women with a normal pregnancy and 8 women who had late-onset preeclampsia after 34 weeks. Controls were measured at 32 weeks. All controls had a normal blood pressures at that time. RESULTS: LF variability of heart rate and blood pressure were significantly higher and baroreflex sensitivity was significantly lower in early-onset patients compared with normal controls. A significant trend towards higher LF variability of blood pressure and lower baroreflex sensitivity was found from normal controls to late-onset controls to early-onset patients. Parameters of sympathetic activity were not influenced by plasma volume expansion. CONCLUSION: Sympathetic activity was increased in early-onset hypertensive pregnancy. However, this was not affected by management with plasma volume expansion, suggesting that hypovolaemia in preeclampsia is a secondary phenomenon.

Adult↗
PubMed2006

Sensitivity of spontaneous baroreflex control of the heart and hemodynamic parameters are not influenced by the menstrual cycle.

OBJECTIVE: The purpose of this study was to evaluate if hemodynamic parameters and sympathetic activity vary between the follicular and luteal phase of the menstrual cycle before using sympathetic activity in pre-pregnancy risk assessment for preeclampsia. METHODS: We studied 39 healthy women at days 5 to 10 and days 18 to 25 of the menstrual cycle. Blood pressure, heart rate, cardiac output, and total peripheral resistance were measured continuously using noninvasive finger arterial pressure waveform registration (Portapres Model 2, BMI, The Netherlands). Baroreflex sensitivity (BRS) and sympathetic activity by phase angle difference were studied using spectral analysis and xBRS. RESULTS: There were no differences in hemodynamic parameters, BRS, and phase angle difference. CONCLUSION: There is no difference in blood pressure, BRS, and sympathetic activity between the first and second half of the menstrual period. We recommend using the first half of the cycle to be certain that no pregnancy exists, as the influence of very early pregnancy is unknown.

Adult↗
PubMed2005

An aptamer-based protein biochip.

The establishment of an aptamer-based biochip for protein detection is described. Using a model system comprising human IgE as the analyte and single-stranded DNA aptamers specific for IgE or anti-IgE antibodies as immobilized ligands on chips, we could demonstrate that aptamers were equivalent or superior to antibodies in terms of specificity and sensitivity, respectively. Aptamer-based analyte detection on glass slides could clearly be demonstrated at minimum concentrations of 10 ng/mL IgE. In addition, we successfully showed specific analyte recognition in complex protein samples by the aptamer-based biochip system. Using DNA aptamers specific for human thrombin as an additional model receptor/ligand system, dual protein detection on a single slide could be proven. In conclusion, we could show the suitability of nucleic acid aptamers as low molecular weight receptors on biochips for sensitive and specific protein detection, representing an innovative tool for future proteomics.

Aptamers, Nucleotide↗
PubMed2005

Short-term (0-48 h) effects of maternal betamethasone administration on fetal heart rate and its variability.

The short-term (0-48 h) effects of maternal betamethasone administration on computerized fetal heart rate (FHR) parameters were studied in 36 pregnancies at increased risk for preterm delivery. FHR was recorded for 90 min immediately before the start of betamethasone treatment and again at 6-h intervals during the next 48 h. Multiple linear regression models were used to assess the possible effects on FHR parameters of gestational age, time of day, clinical indication for treatment, and use of tocolytic drugs. Within 12 h after the start of treatment, significant increases occurred in FHR accelerations, and short- and long-term FHR variability (36%, 28%, and 22%, respectively), whereas basal FHR showed a 5% decrease. FHR variability was decreased by 10% at 42-48 h. The observed changes were more pronounced in older (29-33 wk of gestation) compared with younger fetuses (25-28 wk of gestation). Decelerations occurred only in 4 out of 11 compromised fetuses during betamethasone therapy. We conclude that there are significant changes in FHR parameters during the first 48 h after betamethasone administration. These changes are transient in normal fetuses. However, the compromised fetus may be adversely affected by betamethasone.

Betamethasone↗
PubMed2005

A randomized trial of plasma volume expansion in hypertensive disorders of pregnancy: influence on the pulsatility indices of the fetal umbilical artery and middle cerebral artery.

OBJECTIVE: The purpose of this study was to investigate the effect of plasma volume expansion on the pulsatility indices of the fetal umbilical and middle cerebral arteries. STUDY DESIGN: Two hundred sixteen patients with severe preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, hypertension-related fetal growth restriction, and gestational ages between 24 and 34 completed weeks of gestation were assigned randomly for temporizing treatment with plasma volume expansion (n = 111 patients; 250 mL hydroxyethyl starch 6% twice daily in 4 hours, and NaCl 0.9% between doses of hydroxyethyl starch and with intravenous medication) or without plasma volume expansion (n = 105; only NaCl 0.9% when necessary with medication). Measurements of the pulsatility index of the umbilical and middle cerebral arteries were performed at admission, after 16 to 48 hours, 60 to 120 hours, and 7 to 11 days. RESULTS: Median gestational age was 30 weeks in both groups. Infused volumes of plasma volume expansion in the treatment group (total median, 813 mL/d) were associated with a significant decrease of hemoglobin concentration. Changes from baseline measurements of the umbilical and middle cerebral arteries were not different between the groups nor within subgroups during the first 7 to 11 days. CONCLUSION: Plasma volume expansion did not influence the pulsatility indices of the umbilical and middle cerebral arteries.

Adolescent↗
PubMed2005

Recombinant HIV-1 Pr55gag virus-like particles: potent stimulators of innate and acquired immune responses.

Several previous reports have clearly demonstrated the strong effectiveness of human immunodeficiency virus (HIV) Gag polyprotein-based virus-like particles (VLP) to stimulate humoral and cellular immune responses in complete absence of additional adjuvants. Yet, the mechanisms underlying the strong immunogenicity of these particulate antigens are still not very clear. However, current reports strongly indicate that these VLP act as "danger signals" to trigger the innate immune system and possess potent adjuvant activity to enhance the immunogenicity of per se only weakly immunogenic peptides and proteins. Here, we review the current understanding of how various particle-associated substances and other impurities may contribute to the observed immune-activating properties of these complex immunogens.

Antigen-Presenting Cells↗
PubMed2005

Transient hypothyroxinemia in severe hypertensive disorders of pregnancy.

OBJECTIVE: Assess whether and to what extent thyroid function is affected in pregnant women with early and severe hypertensive disorders and in their newborns. METHODS: Patients were 80 women with preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome or gestational hypertension combined with fetal growth restriction in the 24th to 34th week of singleton pregnancies. Maternal thyroid hormone levels and thyroid peroxidase antibodies were determined at admission and 3 months postpartum. Neonatal levels were determined from cord blood at delivery. Maternal hypothyroxinemia was defined as free T(4) (fT(4)) value below 9 pM. RESULTS: At admission 26 (33%) women in the study group had fT(4) levels below 9 pM, with spontaneous normalization during pregnancy. There were no statistically significant differences between thyroid hormone values in women in the study group and 10 normotensive pregnant women in their third trimester. Three months postpartum, 97.5% of patients had normal thyroid hormone levels. Thyroid peroxidase antibodies were elevated in 10% of women postpartum. Their infants, born at a median gestational age of 30 6/7 weeks, had lower cord blood fT(4) and thyroid-stimulating hormone values compared with preterm infants of the comparison group, appropriate for gestational age. Cord blood fT(4) had no correlation with gestational age or maternal fT(4), but there was a significant correlation of cord blood fT(4) with umbilical artery pH. CONCLUSION: Women with severe hypertensive disorders of pregnancy may have transiently lower fT(4) levels, without evidence of a thyroid disorder. Their neonates have lower fT(4) levels at birth unrelated to maternal fT(4), but related to prenatal acidosis. LEVEL OF EVIDENCE: II-2.

Adult↗
PubMed2005

A randomised controlled trial comparing two temporising management strategies, one with and one without plasma volume expansion, for severe and early onset pre-eclampsia.

OBJECTIVES: Plasma volume expansion may benefit both mother and child in the temporising management of severe and early onset hypertensive disorders of pregnancy. DESIGN: Randomised clinical trial. Setting Two university hospitals in Amsterdam, The Netherlands. POPULATION: Two hundred and sixteen patients with a gestational age between 24 and 34 completed weeks with severe pre-eclampsia, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or severe fetal growth restriction (FGR) with pregnancy-induced hypertension, admitted between 1 April 2000 and 31 May 2003. METHODS: One hundred and eleven patients were randomly allocated to the treatment group, (plasma volume expansion and a diastolic BP target of 85-95 mmHg) and 105 to the control group (intravenous fluid restriction and BP target of 95-105 mmHg). MAIN OUTCOME MEASURES: Neonatal neurological development at term age (Prechtl score), perinatal death, neonatal morbidity and maternal morbidity. RESULTS: Baseline characteristics were comparable between groups. The median gestational age was 30 weeks. In the treatment group, patients received higher amounts of intravenous fluids (median 813 mL/day vs 14 mL/day; P < 0.001) with a concomitant decreased haemoglobin count (median -0.6 vs-0.2 mmol/L; P < 0.001). Neither neurological scores nor composite neonatal morbidity differed. A trend towards less prolongation of pregnancy (median 7.4 vs 11.5 days; P= 0.054) and more infants requiring oxygen treatment >21% (66 vs 46; P= 0.09) in the treatment group was observed. There was no difference in major maternal morbidity (total 11%), but there were more caesarean sections in the treatment group (98%vs 90%; P < 0.05). CONCLUSION: The addition of plasma volume expansion in temporising treatment does not improve maternal or fetal outcome in women with early preterm hypertensive complications of pregnancy.

Adult↗
PubMed2005

Phased array magnetic resonance imaging for staging clinically localised prostrate cancer.

Patients suffering from intra-capsular prostate cancer (T1-2, N0, M0) are potential candidates for curative treatment by radical prostatectomy or radiation therapy. Curative intended therapy is frequently associated with substantial side effects, which makes accuracy of preoperative staging important. However, up to 40% of the patients with clinically localized disease turn out to be under-staged and should not have been subjected to curative surgery. The aim of this study was to assess the value of preoperative phased array MRI staging in patients who are candidates for radical prostatectomy.Ninety-five potential candidates for radical prostatectomy suspected of suffering from clinical prostate cancer underwent pre-diagnostic and pre-operative staging by magnetic resonance imaging (MRI). The results were compared with the postoperative pathological findings including evidence of extra-capsular extension (ECE) of the tumor. The MRI results were not taken into consideration when staging the patients preoperatively or offering treatment. Radical prostatectomy was performed within a few weeks after MRI. In 48 patients the diagnostic biopsy did not detect carcinoma but benign hyperplasia of the prostate (BPH), while 9 patients had T3 disease. Thirty-eight patients had clinically localized prostate cancer and underwent radical prostatectomy. In 16 cases (42%) ECE was postoperatively proven by the pathologist, while only 22 (58%) of the patients suffered from true localized prostate cancer. The sensitivity and specificity of MRI detecting ECE were 24% and 86% respectively, while the positive and negative predictive value of MRI with regard to ECE were only 57% and 61% respectively. Phased array MRI did not in its present form provide the necessary accuracy in preoperative staging in clinically localized prostate cancer patients.

Biopsy↗
PubMed2004

Protein arginine methylation during lytic adenovirus infection.

Arginine methylation of proteins affects major processes in the cell, including transcriptional regulation, mRNA metabolism, signal transduction and protein sorting. Arginine methylation of Ad (adenovirus) E1B 55-kDa-associated protein E1B-AP5 was recently described by us [Kzhyshkowska, Schutt, Liss, Kremmer, Stauber, Wolf and Dobner (2001) Biochem. J. 358, 305-314]. In this first example of protein arginine methylation analysis in Ad-infected cells, we investigated methylation of the E1B-AP5 and the viral L4-100 kDa protein. We demonstrate that E1B-AP5 methylation is enhanced during the course of infection in a cell-type-specific manner. We also show that L4-100 kDa is efficiently methylated in Ad-infected cells. L4-100 kDa formed complex with methyltransferase in vivo during productive infection, and can be methylated by HRMT1L2 (human protein arginine methyltransferase 1) in vitro. Comparative analysis of E1B-AP5 and L4-100 kDa protein methylation in Ad-infected HeLa, MCF-7 and H1299 cells revealed that the profile of protein arginine methylation correlates with the efficiency of Ad proteins production. Our results suggest that protein arginine methylation is an important host-cell function required for efficient Ad replication.

Adenoviridae↗
PubMed2004

EBV-associated neoplasms: alternative pathogenetic pathways.

We propose that there are two main classes of Epstein-Barr virus (EBV) associated lymphomas: primarily malignant Burkitt's Lymphoma (BL) and Hodgkin's Disease (HD), on one hand, and primarily benign lymphoproliferations, e.g., post-transplant lymphoproliferative disease (PTLD) on the other hand. PTLD may start as a benign lymphoproliferation which becomes malignant if out of T cell control for too long. Our discovery of a binding site for the oncoprotein c-Myc at a central position of the EBV genome favours a distinction of pathogenetic pathways or scenarios for the proposed lymphoma classes. In the first scenario nuclear maintenance of the EBV genome and activation of viral anti-apoptotic functions with the help of c-Myc are indispensable for the origin of malignant tumours (BL, HD) from the germinal centre B-cell. In the second scenario expression of the main viral transforming protein EBNA2 is essential for immortalisation and non-malignant morphological transformation of any (germinal centre derived or non-germinal centre) B-cell in the absence of T cell control. Although EBNA2 expression is permissible, under specific circumstances, in malignant B-cells, it is not required for oncogenesis.

Burkitt Lymphoma↗
PubMed2004

The LCR of EBV makes Burkitt's lymphoma endemic.

The spectacular ability of Epstein-Barr virus (EBV) to immortalize and morphologically transform human B cells in vitro to lymphoblastoid cell lines (LCLs) is central to most molecular models of viral oncogenesis. However, binding of transcription factor and oncoprotein c-Myc to the major locus control region (LCR) of the viral genome directs us to an alternative model for the origin of Burkitt's lymphoma (BL). In this model, improved nuclear maintenance of the viral genome and the continuous expression of anti-apoptotic functions in B cells exhibiting class I EBV latency contribute to the generation of BL, without any detour through EBV nuclear antigen (EBNA) 2-driven B-cell immortalization (also called class III latency).

Apoptosis↗