Biomedical subjects

D Wilhelm

Publications and source records attributed to D Wilhelm.

At least 19 recordsLinked to original sources

PubMed2006

A family of new instruments for laparoscopic radiofrequency ablation of malignant liver lesions.

Primary and secondary liver tumors may be treated with radiofrequency ablation (RFA) to improve tumor control and to increase patient survival. Lesions are punctured percutaneously or during open surgery. However, not all of the lesions are accessible percutaneously due to their localization: Adjacent structures could be endangered and/or the treatment would cause severe pain. Open surgery is an option in these cases but significantly more invasive. Laparoscopic RFA (LRFA) is an additional possibility in those cases: It offers a better access to difficult lesions than via the percutaneous route and is also less invasive than open surgery. The precision of targeting, however, in LRFA still has to be improved. In an in-vivo feasibility study we used a tumor mimic model in pigs to examine the applicability of laparoscopic RFA in combination with laparoscopic ultrasound using a set of dedicated new instruments to handle the RFA probe. To increase the ablation volume, the liver blood flow was reduced performing a Pringle maneuver. It is demonstrated that this set of specially designed instruments is indeed applicable and facilitates the targeting of liver lesions of any localization. Accordingly, it could significantly enlarge the applicability of LRFA.

Animals↗

PubMed2005

An evaluation of a surgical telepresence system for an intrahospital local area network.

We evaluated a digital telepresence system in an operating theatre (OR) environment which enabled a consultant to join the surgical team from a remote site by audiovisual communication. The system is based on video transmission using a streaming technique, with a server and a client connected via a local area network (LAN). Two cameras can be remotely controlled: one camera is built into the OR lamp and a second, laparoscopic camera is mounted on a robotic arm. Another feature of the system is teledemonstration, which permits the remote consultant to demonstrate points of particular interest. We evaluated the system clinically in 237 cases. In 28 cases (12%), telepresence could not be established for various reasons, mainly human failure. In 42 cases (18%), the full potential of telepresence was used. Technical evaluation showed that a data rate of 2 Mbit/s provides sufficient audio and video quality, as well as reliable teledemonstration. The data transmission delay was acceptable for clinical purposes (video 0.92 s, audio 0.6 s from OR to client, audio 0.7 s from client to OR). The study showed that telepresence is a promising means of providing highly specialized expertise within the OR.

General Surgery↗

PubMed2004

Sox genes and cancer.

Sox genes encode transcription factors belonging to the HMG (High Mobility Group) superfamily. They are conserved across species and involved in a number of developmental processes. In vitro studies have shown at least one Sox gene to be capable of inducing oncogenic transformation of fibroblast cells. In addition, overexpression and/or amplification of Sox genes are associated with a large number of tumour types in vivo. We review here the available evidence linking Sox gene expression and cancer, and show that this link is supported by extensive EST database analysis. This work provides a basis for further studies aimed at investigating the possible role of Sox genes in the oncogenic process.

Animals↗

PubMed2003

[Robotic and navigation systems: surgical practicability and benefit for the patient?].

The use of robotics and navigated systems to prepare, perform and reinforce surgical interventions is described by the term "computer aided surgery" (CAS). CAS is expected to make surgery even more precise, safer and cheaper. It comprehends computer based supporting systems (e. g. therapy planning, simulation, navigation), assisting systems, programmable automates and the so called master-slave-systems. When introducing technical innovations, the potential benefit of the patient is the essential issue. Then only practicability under clinical conditions, and additional aspects can be discussed. Conclusively, less spectacular applications of CAS like computer based supporting or assisting systems are more relevant for current practical use than visionary robotic systems.

Diagnostic Imaging↗

PubMed2003

Molecular characterization of three gonad cell lines.

To facilitate the study of the regulation and downstream interactions of genes involved in gonad development it is important to have a suitable cell culture model. We therefore aimed to characterize molecularly three different mouse gonad cell lines. TM3 and TM4 cells were originally isolated from prepubertal mouse gonads and were tentatively identified as being of Leydig cell and Sertoli cell origin, respectively, based upon their morphology and hormonal responses. The third line is a conditionally immortalized cell line, derived from 10.5-11.5 days post-coitum (dpc) male gonads of transgenic embryos carrying a temperature-sensitive SV40 large T-antigen. We studied by reverse transcription-polymerase chain reaction (RT-PCR) the expression profiles of a number of genes known to be important for early gonad development. Moreover, we assessed these cell lines for their capacity to induce SOX9 transcription upon expression of SRY, a key molecular event occurring during sex determination. We found that all three cell lines were unable to upregulate SOX9 expression upon transfection of SRY-expression constructs, even though these cells express many of the studied embryonic gonad genes. These observations point to a requirement for SRY cofactors for direct or indirect upregulation of SOX9 expression during testis determination.

Animals↗

PubMed2000

Developmental regulation of AMPA-receptor properties in CA1 pyramidal neurons of rat hippocampus.

AMPA-receptor (AMPA-R) currents were recorded from CA1 pyramidal neurons in situ and after acute isolation from the hippocampus of 3- to 45-day-old rats. Membrane currents were analyzed by combining the patch clamp method with fast application techniques. The complete block of receptor currents by GYKI 53655 and the absence of modulation by Concanavalin A indicated that the cells exclusively expressed non-NMDA glutamate receptors of the AMPA subtype while functional kainate receptors could not be detected. The lowest sensitivity to kainate and NBQX was observed at postnatal day (p) 18. These changes might reflect a lower abundance of GluR1 at that developmental stage. A decrease of potentiation of receptor currents by cyclothiazide (CTZ), an acceleration of the recovery from CTZ potentiation and a faster and more complete desensitization of glutamate-evoked currents suggest an up-regulation of flop splice variants with increasing age. These functional data indicate that AMPA-R expression in CA1 pyramidal neurons varies during postnatal development which can be expected to influence the kinetics of synaptic transmission and the excitotoxic vulnerability as well.

Alternative Splicing↗

PubMed2000

[Second opinion in tumor surgery. Valuable--but needing improvement].

In complicated oncological cases, a second opinion is desirable, also in the view of the care-providing surgeon. It serves interdisciplinary therapeutic planning, and helps improve the quality of treatment. In the case of highly consequential interventions, the patient has a legal right to a second opinion. On a practical level, however, the implementation of this possibility encounters problems: organizational shortcomings, incomplete patient documentation, the stresses of patient transportation, loss of valuable time, in particular in the case of postal consultation, following consultation in a center the carrying out of treatment there, whether at the urging of the doctors there or the patient himself, lack of remuneration for the efforts of the consultants. Today, however, all the necessary technical facilities are in place to enable various experts to be consulted, virtually simultaneously, on any case, via video-conferencing.

Germany↗

PubMed1999

JNK/SAPK activity is not sufficient for anticancer therapy-induced apoptosis involving CD95-L, TRAIL and TNF-alpha.

We report here that stress stimuli such as gamma-irradiation or the anticancer drug doxorubicin activate expression of the death-inducing ligands (DILs) CD95-L, TNF-alpha and TRAIL. Apoptosis induced by gamma-irradiation or doxorubicin engages a FADD- and caspase-dependent apoptosis pathway which is inhibited by dominant negative FADD or the caspase inhibitor zVAD. zVAD did not prevent activity of JNK/SAPKs in response to doxorubicin suggesting that JNK/SAPK activity is independent of death receptor triggering during cellular stress-induced apoptosis. In addition, JNK/SAPKs remained activated by doxorubicin in resistant cell lines in which cleavage of caspases and apoptosis was not observed. These data uncouple JNK/SAPK activation and apoptosis signaling and indicate that cellular stress-induced apoptosis involves signaling via DILs which is paralleled by activation of JNK/SAPKs. Activation of these kinases may contribute e.g., to the expression of molecules involved in apoptosis but is not sufficient for induction of the apoptosis program following cellular stress.

Antineoplastic Agents↗

PubMed1999

Increase of segments of elastic-type blood vessel walls in fetal placental stem villi during pre-eclampsia at term.

In recent studies we described the presence of elastic-type blood vessels within trunci and rami chorii of human placental stem villi. For systemic and pulmonary hypertension it is known that elastic fibres are enhanced in arteries. The aim of our study was, therefore, to examine whether pre-eclampsia may lead to an increase of elastic tissue fibres in blood vessel walls of placental stem villi and whether there are differences in the thickness of blood vessel walls within these villi when compared to normotensive pregnant women. Twenty-six women with uncomplicated pregnancies and 25 patients with pre-eclampsia were investigated. Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant higher intensities of orcein staining (P<0.00001) were calculated for blood vessel walls of placentae with pre-eclampsia. The amount of thick stem villus vessels (>41 microm) increased during pre-eclampsia from 39 gestational weeks onwards. Our study demonstrates that segments of thick blood vessel walls and elastic-type vessel walls are increased in placental stem villi of patients with pre-eclampsia. This reaction may protect the fetal placental vessels and avert an increase of the fetal hypertension.

Chorionic Villi↗

PubMed1999

JNK/SAPK activity contributes to TRAIL-induced apoptosis.

We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK activation by TRAIL in these cells is FADD- and caspase-dependent since dominant-negative FADD or the caspase inhibitor zVAD prevented both, apoptosis and JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an agonistic antibody (alphaAPO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to alphaAPO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or alphaAPO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or alphaAPO-1. Therefore, activation of JNK/SAPKs by TRAIL or alphaAPO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.

Antibodies↗

PubMed1999

Soluble cytokine receptor CD30 in atopic disorders: a case-control study.

BACKGROUND: The cytokine receptor CD30 is an activation marker of T cells which preferentially associates with the production of the TH2 cytokine IL-4. Therefore, it may potentially be a candidate marker for atopic disorders and a target molecule for new therapeutic approaches. OBJECTIVE: To test the hypothesis that elevated levels of soluble CD30 (sCD30) are significantly associated with atopic disorders after adjustment for other predictors of atopy. METHODS: The presence of elevated sCD30 (> or = 20 U/mL) in atopic disorders was evaluated in a nested case-control study. Cases (n = 60) were blood donors with specific IgE antibodies, total serum levels of IgE > or = 100kU/L and presence or history of allergic symptoms. Controls (n = 59) were blood donors without presence or history of allergic symptoms and serum levels of IgE < 50 kU/L. sCD30 was determined from serum samples by an enzyme-linked immunosorbent assay. Odds ratios (OR) and confidence intervals (CI) were calculated from logistic regression coefficients. RESULTS: Mean sCD30 levels for cases were 75 U/mL (SD 110U/mL) as compared with 35 U/mL (SD 59 U/mL) for controls. Serum levels of sCD30 were elevated in 65% of cases and 32% of controls (OR 3.9, 95% CI 1.8-8.4). The odds ratio for elevated sCD30 as a predictor of atopic disorders slightly decreased to 3.7 after controlling for smoking, age and gender. Blood eosinophilia which was a strong predictor of atopy (OR 11.7) was a weak confounder of the association between sCD30 levels and atopic disorders. Family history of allergy, another strong predictor of atopy (OR 8.6), did not confound the association. CONCLUSIONS: The results are consistent with the hypothesis that CD30 is involved in the pathogenesis of atopic disorders independent of eosinophilia and family history of allergy.

Adolescent↗

PubMed1999

NFkappaB activation is required for interferon regulatory factor-1-mediated interferon beta induction.

The interferon regulatory factor 1 (IRF-1) acts as a transcriptional inducer of the interferon beta (IFN-beta) gene and interferon-stimulated genes. Here we report that IRF-1-mediated IFN-beta induction depends on NFkappaB activity. IRF-1 by itself initiates NFkappaB activation by inducing a reduction in cellular MAD3/IkappaBalpha, an inhibitor of NFkappaB. After nuclear translocation, NFkappaB synergizes with IRF-1 on the cis-elements positive regulatory domain (PRD)II and PRDI/III to induce transcription of the IFN-beta gene. In contrast with IFN-beta transcription induced by dsRNA or virus, c-Jun/ATF-2 binding to PRDIV is not involved. Recombinant MAD3/IkappaBalpha is phosphorylated in vitro by extracts from IRF-1-expressing cells. IRF-1-dependent MAD3/IkappaBalpha degradation is not detectable in cells expressing a dominant negative mutant of the protein kinase PKR, suggesting that PKR mediates MAD3/IkappaBalpha degradation.

Binding Sites↗

PubMed1998

Physician community involvement. Working within your area to promote better health.

How many times have you been asked to participate in a meeting, forum, or task force to address a community health issue in the last few years? Opportunities seem to crop up almost weekly as non-profit organizations acclimate to meet changing needs and health systems continue to adapt to market forces. But participating in ongoing community projects, or even attending periodic meetings, draws time away from practice and professional obligations and limits an already modest supply of personal time. Is involvement in a community collaborative effort worth the time? And, if so, what are the benefits and challenges to physicians, health systems, and communities from this type of investment?

Community Health Services↗

PubMed1997

Activation of CD95 (APO-1/Fas) signaling by ceramide mediates cancer therapy-induced apoptosis.

We report here that anticancer drugs such as doxorubicin lead to induction of the CD95 (APO-1/Fas) system of apoptosis and the cellular stress pathway which includes JNK/SAPKs. Ceramide, which accumulates in response to different types of cellular stress such as chemo- and radiotherapy, strongly induced expression of CD95-L, cleavage of caspases and apoptosis. Antisense CD95-L as well as dominant-negative FADD inhibited ceramide- and cellular stress-induced apoptosis. Fibroblasts from type A Niemann-Pick patients (NPA), genetically deficient in ceramide synthesis, failed to up-regulate CD95-L expression and to undergo apoptosis after gamma-irradiation or doxorubicin treatment. In contrast, JNK/SAPK activity was still inducible by doxorubicin in the NPA cells, suggesting that activation of JNK/SAPKs alone is not sufficient for induction of the CD95 system and apoptosis. CD95-L expression and apoptosis in NPA fibroblasts were restorable by exogenously added ceramide. In addition, NPA fibroblasts undergo apoptosis after triggering of CD95 with an agonistic antibody. These data demonstrate that ceramide links cellular stress responses induced by gamma-irradiation or anticancer drugs to the CD95 pathway of apoptosis.

Apoptosis↗

PubMed1997

Endocytosis, storage, and release of IgE by human platelets: differences in patients with type I allergy and nonatopic subjects.

Platelets of atopic individuals differ in alpha-granular contents and in the amount of biologically active mediators released compared with platelets of nonatopic subjects. Because platelets carry the low-affinity IgE receptor (CD23), they may contribute to long-lasting IgE sensitivity by serving as a storage pool for IgE. We compared 45 atopic individuals with immediate-type allergies and 25 nonatopic control subjects with respect to storage and release of IgE by their platelets. Platelets of atopic individuals were characterized by a 10-fold higher median IgE content compared with those of nonatopic control subjects. The platelet IgE content correlated with the serum IgE level in the four atopic individuals with seasonal allergies who were followed up monthly over 1 year. Platelet stimulation with platelet activating factor, but not with thrombin or adenosine diphosphate, resulted in a release of 65% of the stored IgE. Conversely, platelet stimulation with monoclonal IgE/kappa resulted in the release of the chemokine RANTES. Platelet alpha-granules were identified as the main storage compartment for IgE by postembedding immunocytochemistry. Although more than half of the alpha-granules showed gold labeling for IgE, additional labeling was found on the external face of the plasma membrane and within the open canalicular system, indicating endocytosis and exocytosis of IgE. Moreover, the detection of CD23 not only on the plasma membrane but also on membranes of the alpha-granules further supports the existence of an exchange of IgE between the blood plasma and an internal storage compartment. Endocytosis could be confirmed by the uptake of an IgE myeloma protein coupled to colloidal gold. We conclude that platelets of atopic individuals may contribute to allergic inflammation by serving as a storage pool for IgE and by their increased capacity to liberate further mediators of allergy in response to IgE stimulation.

Blood Platelets↗

PubMed1997

ICAM-1, soluble-CD23, and interleukin-10 concentrations in serum in renal-transplant recipients with Epstein-Barr virus reactivation.

Primary and reactivated Epstein-Barr virus (EBV) infections after organ transplantation are associated with the development of posttransplant lymphoproliferative malignancies. Since viral reactivation frequently stays asymptomatic, early diagnosis and treatment are challenges during posttransplant patient monitoring. Both soluble-CD23 (sCD23) and intercellular adhesion molecule 1 (ICAM-1) cell surface expression as well as interleukin-10 (IL-10) production are closely associated with viral gene expression. Therefore, immunoglobulin M (IgM), IgG, IgA, sCD23, ICAM-1, and IL-10 concentrations were measured in serum samples from patients during EBV reactivation (n = 14) and were compared with those in samples from patients without EBV reactivation (n = 10) following renal transplantation. In addition, serum sCD23, ICAM-1, and IL-10 concentrations were measured longitudinally in weekly to biweekly samples from 10 patients with EBV reactivation for at least 20 weeks following transplantation. A significant elevation of sCD23 was found during viral reactivation (P < 0.05), whereas ICAM-1 levels showed a nonsignificant increase. The finding of a highly significant elevation of the serum IL-10 concentration during EBV reactivation (P < 0.001) may support speculations about its role in EBV-induced lymphoproliferation and in the development of opportunistic infections and secondary malignancies. Maximum serum IL-10 levels at the time of EBV reactivation were found in 7 of 10 patients. Well-defined ICAM-1 and sCD23 concentration peaks were found in 9 of 10 and 8 of 10 patients, respectively. Although both markers are not specific for EBV reactivation and therefore may not be useful for primary diagnosis, sCD23 and ICAM-1 might be potent tools for the clinical monitoring of EBV activity and virus-induced lymphoproliferation.

Antibodies, Viral↗

PubMed1997

The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents.

Monofunctional alkylating agents like methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are potent inducers of cellular stress leading to chromosomal aberrations, point mutations, and cell killing. We show that these agents induce a specific cellular stress response program which includes the activation of Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPKs), p38 mitogen-activated protein kinase, and the upstream kinase SEK1/MKK4 and which depends on the reaction mechanism of the alkylating agent in question. Similar to another inducer of cellular stress, UV irradiation, damage of nuclear DNA by alkylation is not involved in the MMS-induced response. However, in contrast to UV and other inducers of the JNK/SAPKs and p38 pathways, activation of growth factor and G-protein-coupled receptors does not play a role in the MMS response. We identified the intracellular glutathione (GSH) level as critical for JNK/SAPK activation by MMS: enhancing the GSH level by pretreatment of the cells with GSH or N-acetylcysteine inhibits, whereas depletion of the cellular GSH pool causes hyperinduction of JNK/SAPK activity by MMS. In light of the JNK/SAPK-dependent induction of c-jun and c-fos transcription, and the Jun/Fos-induced transcription of xenobiotic-metabolizing enzymes, these data provide a potential critical role of JNK/SAPK and p38 in the induction of a cellular defense program against cytotoxic xenobiotics such as MMS.

Acetylcysteine↗

PubMed1997

[Cytokines and chemokines as inducers of nonhemolytic transfusion reactions after thrombocyte transfusion].

Recently, the leukocyte-derived cytokines interleukin (IL)-1 beta, IL-6, IL-8, and tumor necrosis factor(TNF)-alpha were found in considerable concentrations in platelet concentrates (PC) involved in nonhemolytic transfusion reactions (NHTR). We investigated transfusion reactions in two study periods over the last 3 years. In the 1st period, PC were leukocyte-depleted by bedside filtration. In the 2nd period we performed prestorage leukocyte filtration of PC. Recipients who experienced a transfusion reaction were tested for total and specific IgE, and reactions were analyzed with regard to the main symptoms. In the supernatant of platelets involved, we analyzed concentrations of IL-1 beta, IL-6, IL-8, TNF-alpha, macrophage inflammatory protein(MIP)-1 alpha, and RANTES. The incidence for NHTR did not change with the kind of PC transfused (n = 44, 1.63% and n = 46, 1.56%; p = 0.84), but allergic reactions were reduced in the 2nd observation period (0.92% versus 0.51%; p = 0.02). IL-1 beta, IL-6, IL-8, TNF-alpha, and MIP-1 alpha were not detectable in the majority of all products. PC involved in allergic reactions contained significantly higher concentrations of RANTES. We found evidence that the proinflammatory chemokine RANTES, stored in the platelet alpha-granules, is involved in allergic transfusion reactions. In contrast, leukocyte-derived inflammatory cytokines were of minor relevance in the onset of NHTR.

Blood Group Incompatibility↗