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Biomedical subjects

C Scholz

Publications and source records attributed to C Scholz.

At least 19 recordsLinked to original sources
PubMed2006

Tracer test with As(V) under variable redox conditions controlling arsenic transport in the presence of elevated ferrous iron concentrations.

To study transport and reactions of arsenic under field conditions, a small-scale tracer test was performed in an anoxic, iron-reducing zone of a sandy aquifer at the USGS research site on Cape Cod, Massachusetts, USA. For four weeks, a stream of groundwater with added As(V) (6.7 muM) and bromide (1.6 mM), was injected in order to observe the reduction of As(V) to As(III). Breakthrough of bromide (Br(-)), As(V), and As(III) as well as additional parameters characterizing the geochemical conditions was observed at various locations downstream of the injection well over a period of 104 days. After a short lag period, nitrate and dissolved oxygen from the injectate oxidized ferrous iron and As(V) became bound to the freshly formed hydrous iron oxides. Approximately one week after terminating the injection, anoxic conditions had been reestablished and increases in As(III) concentrations were observed within 1 m of the injection. During the observation period, As(III) and As(V) were transported to a distance of 4.5 m downgradient indicating significant retardation by sorption processes for both species. Sediment assays as well as elevated concentrations of hydrogen reflected the presence of As(V) reducing microorganisms. Thus, microbial As(V) reduction was thought to be one major process driving the release of As(III) during the tracer test in the Cape Cod aquifer.

Arsenic↗
PubMed2006

Complementary and alternative therapeutic approaches in patients with early breast cancer: a systematic review.

Complementary and alternative medicine (CAM) is becoming increasingly popular, particularly among patients with breast cancer. We have done a systematic review of studies published between 1995 and February 2005, identified through a comprehensive search. CAM encompasses a wide range of treatment modalities, including dietary and vitamin supplements, mind-body approaches, acupuncture, and herbal medicines. The objectives of CAM treatments are diverse: reduction of therapy-associated toxicity, improvement of cancer-related symptoms, fostering of the immune system and even direct anticancer effects. Clinical trials have generated few or no data on the efficacy of CAM, whether regarding disease recurrence, survival, overall quality of life or safety. Some CAM methods may even have adverse effects or reduce the efficacy of conventional treatment. The primary justification for CAM is based on empirical evidence, case studies, and hypothetical physiological effects. We conclude that available data on CAM modalities in the treatment of early-stage breast cancer does not support their application.

Breast Neoplasms↗
PubMed2005

Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature.

BACKGROUND: Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed "chronic periaortitis". OBJECTIVE: To determine the optimal therapeutic and diagnostic approaches to IAAA. METHODS: The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. RESULTS: The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. CONCLUSIONS: Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment.

Adult↗
PubMed2003

[Retinal photoablation with the Erbium:YAG laser. Initial experimental results for traction-free removal of tissue].

BACKGROUND: To investigate the potential of an Er:YAG laser for precise and traction-free removal of retinal layers in vitro. MATERIAL AND METHODS: Retinal ablation in porcine retinal explants was performed using a free running Er:YAG laser focused either into a low-OH quartz fiber or a sapphire fiber. The explants were treated under air or perfluorodecaline (PFD). The ablation depth was evaluated by optical coherence tomography (OCT) and histology sections. RESULTS: A radiant exposure of 5.0 J/cm(2) under air and PFD resulted in complete transsection of the neurosensory retina. Between 3.5 and 2.0 J/cm(2) the ablation depth and the defect patterns varied markedly and adjacent thermal zones areas were seen. Below 2.0 J/cm(2) no defects could be created in air, whereas under PFD the ablation extended into the ganglion cell layer. Ablations using a sapphire fiber and 2.0 J/cm(2) showed a significantly higher reproducibility of ablation depth, and homogeneous defect patterns limited to the nerve fiber layer could be produced without thermal damage. CONCLUSIONS: The Er:YAG laser system with a low-OH quartz fiber allowed ablation of inner retinal layers in vitro, but revealed a variable ablation depth and low reproducibility.However, a sapphire fiber showed markedly improved results. Therefore its use during vitreoretinal surgery seems possible not only as a cutting device but also as a tool for the ablation of fine retinal structures.

Animals↗
PubMed2002

Adenoviral transduction of tumor cells induces apoptosis in co-cultured T lymphocytes.

Adenoviral gene transfer of immunmodulatory molecules has been employed successfully in tumor vaccination studies to induce rejection of transplanted syngeneic tumors. In contrast, the response observed when treating chemically induced murine tumors is rather limited. The same applies for human malignancies. A number of reasons including poor transduction efficiency or insufficient T cell infiltration have been held accountable for this lack of efficacy. However, little attention has been given to effects of the adenoviral transduction itself on the T cell system. Here, we show that T cells are sensitized for activation-induced cell death after co-culture with adenovirally infected tumor cells. The levels of CD95/Fas ligand or TNF-alpha, both known mediators of activation induced cell death, however were not affected by the presence of adenovirus-infected target cells. Furthermore, supernatant transfer from adenovirally transduced or non-infected tumor cell cultures did not result in increased T cell apoptosis. This suggests that cell contact rather than a soluble factor is responsible for the induction of T cell apoptosis upon co-culture with adenovirally transduced tumor cells. Interestingly, and in line with our previous observations, activation-induced cell death was partially inhibited if T cells were co-cultured with tumor cells adenovirally transduced to express IL-7 and CD80, both molecules having the capacity to prevent T cell apoptosis.

Adenoviridae↗
PubMed2001

Dynamic association of trigger factor with protein substrates.

Trigger factor is a ribosome-bound folding helper, which, apparently, combines two functions, chaperoning of nascent proteins and catalyzing prolyl isomerization in their folding. Immediate chaperone binding at the ribosome might interfere with rapid protein folding reactions, and we find that trigger factor indeed retards the in vitro folding of a protein with native prolyl isomers. The kinetic analysis of trigger factor binding to a refolding protein reveals that the adverse effects of trigger factor on conformational folding are minimized by rapid binding and release. The complex between trigger factor and a substrate protein is thus very short-lived, and fast-folding proteins can escape efficiently from an accidental interaction with trigger factor. Protein chains with incorrect prolyl isomers cannot complete folding and therefore can rebind for further rounds of catalysis. Unlike DnaK, trigger factor interacts with substrate proteins in a nucleotide-independent binding reaction, which seems to be optimized for high catalytic activity rather than for chaperone function. The synthetic lethality, observed when the genes for both DnaK and trigger factor are disrupted, might result from an indirect linkage. In the absence of trigger factor, folding is retarded and more aggregates form, which can neither be prevented nor disposed of when DnaK is lacking as well.

Amino Acid Substitution↗
PubMed2001

Cross-reactive binding of cyclic peptides to an anti-TGFalpha antibody Fab fragment: an X-ray structural and thermodynamic analysis.

The monoclonal antibody tAb2 binds the N-terminal sequence of transforming growth factor alpha, VVSHFND. With the help of combinatorial peptide libraries it is possible to find homologous peptides that bind tAb2 with an affinity similar to that of the epitope. The conformational flexibility of short peptides can be constrained by cyclization in order to improve their affinity to the antibody and their stability towards proteolysis. Two cyclic peptides which are cross-reactive binders for tAb2 were selected earlier using combinatorial peptide libraries. One is cyclized by an amide bond between the N-alpha group and the side-chain of the last residue (cyclo-SHFNEYE), and the other by a disulfide bridge (cyclo-CSHFNDYC). The complex structures of tAb2 with the linear epitope peptide VVSHFND and with cyclo-SHFNEYE were determined by X-ray diffraction. Both peptides show a similar conformation and binding pattern in the complex. The linear peptide SHFNEYE does not bind tAb2, but cyclo-SHFNEYE is stabilized in a loop conformation suitable for binding. Hence the cyclization counteracts the exchange of aspartate in the epitope sequence to glutamate. Isothermal titration calorimetry was used to characterize the binding energetics of tAb2 with the two cyclic peptides and the epitope peptide. The binding reactions are enthalpically driven with an unfavorable entropic contribution under all measured conditions. The association reactions are characterized by negative DeltaC(p) changes and by the uptake of one proton per binding site. A putative candidate for proton uptake during binding is the histidine residue in each of the peptides. Hydrogen bonds and the putative formation of an electrostatic pair between the protonated histidine and a carboxy group may contribute markedly to the favorable enthalpy of complex formation. Implications to cyclization of peptides for stabilization are discussed.

Amino Acid Sequence↗
PubMed2001

Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: an in vitro model for the assessment of tumor vaccines.

Dendritic cells (DCs) are potent antigen-presenting cells and play a pivotal role in T cell-mediated immunity. DCs have been shown to induce strong antitumor immune responses in vitro and in vivo, and their efficacy is being investigated in clinical trials. Compared with vaccination strategies directed against a single tumor antigen, tumor-cell lysate as the source of antigen offers the potential advantage of inducing a broad T-cell response against multiple known, as well as unknown, tumor-associated antigens expressed by the individual tumor. We used pancreatic carcinoma cell lines to develop an in vitro model for monitoring T-cell responses induced by lysate-pulsed DCs. Monocyte-derived DCs of HLA-A2(+) donors were pulsed with lysate generated from the HLA-A2(+) pancreatic carcinoma cell line Panc-1. In some experiments, the immunogenic protein keyhole limpet hemocyanin (KLH) was added to the lysate. Subsequently, the antigen-loaded DCs were activated with tumor necrosis factor-alpha and prostaglandin E(2). Autologous mononuclear cells were cocultured with DCs in the presence of low-dose interleukin (IL)-2 and IL-7 and were restimulated weekly with new DCs. High levels of IL-12 and IFN-gamma could be detected in the supernatants, indicating a T-helper type 1-type immune response. This cytokine profile was associated with the expression of the activation marker CD69 on both T helper and CTLs and with an antigen-induced proliferative T-cell response. After 4 weeks, CTL-mediated cytotoxicity was assessed. Tumor cell lysis was specific for Panc-1 tumor cells and was MHC class I-restricted. Cytokine secretion, CD69 expression of T cells, and antigen-induced T-cell proliferation correlated with the cytotoxic activity and were more pronounced when KLH was added to the lysate. This is the first study to show that T cells specific for pancreatic carcinoma cells can be generated in vitro by lysate-pulsed DCs and that the T-cell response can be enhanced by KLH. This in vitro model can be applied to compare different strategies in the development of DC-based tumor vaccines.

Antigen Presentation↗
PubMed2001

[Biomorphometry of corneal epithelium with slit lamp-adapted optical coherence tomography].

INTRODUCTION: The purpose of this study was to evaluate the biomorphometry of the corneal epithelium with slitlamp-adapted optical coherence tomography (OCT). PATIENTS AND METHODS: In a clinical study, slitlamp-adapted OCT of the cornea was performed in 15 patients before and immediately after therapeutic corneal abrasion. Central corneal epithelium thickness measurements were compared to the pre- and postoperative central corneal thickness. RESULTS: Preoperatively, the corneal epithelium could be visualised from the highest OCT light reflections at the interfaces air-tear film and epithelium-Bowman's membrane. The preoperative mean geometrical central epithelial thickness determined with OCT ranged from 65 +/- 12 microns to 72 +/- 14 microns (45-92 microns). The mean difference of the pre- and postoperative central corneal thickness was 48 +/- 19 microns (9-79 microns). This resulted in a deviation from the direct epithelial thickness measurements of 26-33%. The reproducibility of the geometrical epithelial thickness was +/- 9 microns. CONCLUSIONS: Slitlamp-adapted OCT enabled a noncontact evaluation of the corneal epithelium. The difference between direct and indirect corneal epithelium thickness measurements could be related to the partial optical inclusion of the precorneal tear film and the Bowman's membrane. With some restrictions the biomorphometry of the corneal epithelium with slitlamp-adapted OCT seems to be a valuable technique to monitor therapeutical and refractive procedures of the cornea.

Adult↗
PubMed2001

[Examination of the cornea using optical coherence tomography].

INTRODUCTION: This study evaluated the clinical use of optical coherence tomography (OCT) for two-dimensional representation of the cornea. PATIENTS AND METHODS: Noncontact slitlamp-adapted OCT was used in selected cases to evaluate pathologically altered corneas and to measure the central corneal thickness and curvature. RESULTS: OCT provided correlation between differences in reflection and morphological changes. Scar tissue resulted in hyper-reflective light scattering, whereas cystic lesions were hyporeflective. Precise biomorphometry also allowed representation of intrastromal and retrocorneal changes. Central corneal thickness measured by OCT yielded reproducible values and corneal curvature could be calculated from the optical signals of the corneal surface. CONCLUSIONS: OCT provides high-resolution representation of the cornea and exact evaluation of its morphology, thickness, and curvature. Due to the noncontact, simple, and rapid examination using the slitlamp the corneal OCT method is a promising additional diagnostic modality.

Adolescent↗
PubMed2001

Synthesis of microbial poly(beta-hydroxybutyrate) modified with oligo(pentaerythritol ethoxylate) by Ralstonia eutropha.

Poly(beta-hydroxybutyrate) (PHB) modified with different amounts of pentaerythritol ethoxylate (PEE) has been synthesized using Ralstonia eutropha. The growth kinetics and the synthesis of PHB in the presence of PEE were modeled using appropriate differential equations for the mass balance of the two-stage process. The influence of PEE addition on the morphology of PHB was studied by various microscopic and scattering techniques. Light microscopic and wide-angle X-ray measurements indicated that the addition of PEE had a nucleating effect on the crystallization of PHB. The spherulite growth rate was widely independent of the PEE addition. The lamellae of PHB became more disordered when PEE was added as demonstrated by atomic force microscopy. Furthermore, small-angle X-ray data indicated a decrease in the long period with increasing PEE content of the modified PHB.

Crystallization↗
PubMed2000

Changing the antigen binding specificity by single point mutations of an anti-p24 (HIV-1) antibody.

The murine mAb CB4-1 raised against p24 (HIV-1) recognizes a linear epitope of the HIV-1 capsid protein. Additionally, CB4-1 exhibits cross-reactive binding to epitope-homologous peptides and polyspecific reactions to epitope nonhomologous peptides. Crystal structures demonstrate that the epitope peptide (e-pep) and the nonhomologous peptides adopt different conformations within the binding region of CB4-1. Site-directed mutagenesis of the fragment variable (Fv) region was performed using a single-chain (sc)Fv construct of CB4-1 to analyze binding contributions of single amino acid side chains toward the e-pep and toward one epitope nonhomologous peptide. The mutations of Ab amino acid side chains, which are in direct contact with the Ag, show opposite influences on the binding of the two peptides. Whereas the affinity of the e-pep to the CB4-1 scFv mutant heavy chain variable region Tyr(32)Ala is decreased 250-fold, the binding of the nonhomologous peptide remains unchanged. In contrast, the mutation light chain variable region Phe(94)Ala reduces the affinity of the nonhomologous peptide 10-fold more than it does for the e-pep. Thus, substantial changes in the specificity can be observed by single amino acid exchanges. Further characterization of the scFv mutants by substitutional analysis of the peptides demonstrates that the effect of a mutation is not restricted to contact residues. This method also reveals an inverse compensatory amino acid exchange for the nonhomologous peptide which increases the affinity to the scFv mutant light chain variable region Phe(94)Ala up to the level of the e-pep affinity to the wild-type scFv.

Alanine↗
PubMed2000

Extracellular ATP and TNF-alpha synergize in the activation and maturation of human dendritic cells.

Extracellular ATP mediates numerous biological activities by interacting with plasma membrane P2 purinergic receptors. Recently, P2 receptors have been described on dendritic cells (DC), but their functional role remains unclear. Proposed functions include improved Ag presentation, cytokine production, chemotaxis, and induction of apoptosis. We investigated the effects of ATP and of other P2 receptor agonists on endocytosis, phenotype, IL-12 secretion, and T cell stimulatory capacity of human monocyte-derived DC. We found that in the presence of extracellular ATP, DC transiently increase their endocytotic activity. Subsequently, DC up-regulate CD86, CD54, and MHC-II; secrete IL-12; and exhibit an improved stimulatory capacity for allogeneic T cells. These effects were more pronounced when chemically modified ATP derivatives with agonistic activity on P2 receptors, which are resistent to degradation by ectonucleotidases, were applied. Furthermore, ATP and TNF-alpha synergized in the activation of DC. Stimulated with a combination of ATP and TNF-alpha, DC expressed the maturation marker CD83, secreted large amounts of IL-12, and were potent stimulators of T cells. In the presence of the P2 receptor antagonist suramin, the effects of ATP were completely abolished. Our results suggest that extracellular ATP may play an important immunomodulatory role by activating DC and by skewing the immune reaction toward a Th1 response through the induction of IL-12 secretion.

Adenosine Triphosphate↗
PubMed2000

Crystal structure of a phage library-derived single-chain Fv fragment complexed with turkey egg-white lysozyme at 2.0 A resolution.

The three-dimensional structure of the single-chain Fv fragment 1F9 in complex with turkey egg-white lysozyme (TEL) has been determined to a nominal resolution of 2.0 A by X-ray diffraction. The scFv fragment 1F9 was derived from phage-display libraries in two steps and binds both hen and turkey egg-white lysozyme, although the level of binding affinity is two orders of magnitude greater for the turkey lysozyme. The comparison of the crystal structure with a model of the single-chain Fv fragment 1F9 in complex with hen egg-white lysozyme (HEL) reveals that in the latter a clash between Asp101 in lysozyme and Trp98 of the complementarity determining region H3 of the heavy chain variable domain occurs. This is the only explanation apparent from the crystal structure for the better binding of TEL compared to HEL. The binding site topology on the paratope is not simply a planar surface as is usually found in antibody-protein interfaces, but includes a cleft between the light chain variable domain and heavy chain variable domain large enough to accommodate a loop from the lysozyme. The scFv fragment 1F9 recognizes an epitope on TEL that differs from the three antigenic determinants recognized in other known crystal structures of monoclonal antibodies in complex with lysozyme.

Amino Acids↗
PubMed2000

[Correlation of morphologic changes between optical coherence tomography and topographic angiography in a case of gyrate atrophy].

PURPOSE: To characterize ultrastrructual changes in atrophic disease of the retina, RPE and choroid as seen with gyrate atrophy using two new diagnostic modalities, optical coherence tomography (OCT) and topographic angiography. PATIENT AND METHOD: OCT images were taken in a patient with pericentral choroidal atrophy using a slit-lamp-adapted OCT system. Ophthalmoscopy, conventional and topographic angiographic findings were correlated to the reflectivity changes as seen on OCT. RESULTS: Areas of chorioretinal atrophy correlated with a loss of reflectivity in the RPE-choriocapillaris complex on OCT. Additionally OCT identified a thinning of the nerve fiber layer. Topographic angiography demonstrated an extensive defect, seen as an area of depression, consistent with a loss of choriocapillaris and larger-sized choroidal vessels. In contrast to conventional angiography, central islands were not found to demonstrate structural intensity, while the midperipheral surrounding area was clearly elevated to physiological levels. CONCLUSION: OCT and topographic angiography provide in vivo insight into morphologic changes within neurosensory retina and choroid caused by pericentral choroidal atrophy.

Choroid↗
PubMed2000

Slit-lamp-adapted optical coherence tomography of the anterior segment.

PURPOSE: To evaluate the diagnostic potential of a slit-lamp-adapted optical coherence tomography (OCT) system as an in vivo imaging device for routine clinical examination of the anterior segment of the eye. PATIENTS AND METHODS: In a pilot study, healthy volunteers and patients with different pathologies of the anterior segment were examined with a slit-lamp-adapted OCT system using 100-200 axial scans with 100-Hz line-scan frequency. The scan length is variable up to 7 mm, and the axial depth is 1.5 mm in tissue. RESULTS: The slit-lamp-adapted OCT system allowed direct biomicroscopic imaging of the measured area. Anatomic structures and morphological changes anterior to the attenuating iris pigment epithelium could be visualized with high accuracy. Biometric analyses of the cornea, the chamber angle, the iris and secondary cataract were possible. Complete demonstration of the chamber angle was difficult due to the backscattering properties of the anterior part of the sclera and the consequent shadowing of the most peripheral part of the iris. CONCLUSIONS: Slit-lamp-adapted OCT is a useful diagnostic tool which allows in vivo microscopic cross-sectional imaging of the anterior segment and precise measurement of ocular structures.

Anterior Eye Segment↗
PubMed2000

Corneal optical coherence tomography before and immediately after excimer laser photorefractive keratectomy.

PURPOSE: To investigate the representation of the corneal structure with optical coherence tomography before and immediately after excimer laser photorefractive keratectomy. METHODS: Twenty-four eyes of 24 patients with myopia and myopic astigmatism were prospectively studied. The corneal thickness and the corneal profile were assessed with slit-lamp-adapted optical coherence tomography preoperatively and immediately after excimer laser photorefractive keratectomy. RESULTS: The attempted mean spherical equivalent of the refractive corrections was -6.7 +/- 3.6 (mean +/- SD) diopters with a mean calculated stromal ablation depth of 91 +/- 38 microm. The corneal optical coherence tomography was reproducible in all patients, demonstrating a mean decrease of central corneal thickness after epithelial debridement and excimer laser photorefractive keratectomy of 118 +/- 45 microm. The comparison of the calculated stromal ablation depth and the corneal thickness changes determined by corneal optical coherence tomography revealed a significant linear relationship with a correlation coefficient of 0.88 (P <.001). The flattening of the corneal curvature was confirmed in all patients with the optical coherence tomography system and correlated with the attempted refractive correction (r =.82, P <.001). CONCLUSIONS: The slit-lamp-adapted optical coherence tomography system presented in this study allowed noncontact, cross-sectional, and high-resolution imaging of the corneal configuration. This initial clinical evaluation demonstrated that corneal optical coherence tomography could be a promising diagnostic modality to monitor corneal changes of thickness and curvature before and after excimer laser photorefractive keratectomy.

Adult↗