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Biomedical subjects

J Kopp

Publications and source records attributed to J Kopp.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Sentinel lymph node diagnosis in prostatic carcinoma: II. Biokinetics and dosimetry of 99mTc-Nanocolloid after intraprostatic injection].

AIM: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. METHODS: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLN-localisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. RESULTS: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 microSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. CONCLUSION: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.

Biological Transport↗
PubMed2002

[Sentinel lymph node diagnosis in prostatic carcinoma: I: Method and clinical evaluation].

AIM: Evaluation of the significance of lymphoscintigraphy and intraoperative probe measurement for the identification of the sentinel lymph node (SLN) in prostate cancer. PATIENTS AND METHOD: In 117 patients with prostate cancer scintigrams in various projections were acquired till approximately 6 hours p.i. after ultrasound guided transrectal intraprostatic injection of 99mTc-Nanocoll. On the following day the SLNs were identified in the operation theatre with a gamma probe and removed. Pelvic standard lymph node dissection followed SLNE. RESULTS: In three of 117 patients with preoperative lymphoscintigraphy no SLN was scintigraphically detectable. These three patients had antecedent transurethral resection of the prostate. In 113 of the residual 114 patients SLN could be intraoperatively localized. In the mean four SLNs per patient were removed. 28 of 117 patients had pelvic lymph node metastases. In 25 cases SLN were right-positive, in one false-negative and in one intraoperatively not detectable. In one patient we found macrometastasis of up to 4 cm diameter (one SLN was tumour positive). In 15 cases only the SLN was bearing tumour. CONCLUSION: The SLNE with preoperative lymphoscintigraphy and intraoperative gamma probe measurement is suitable for detecting lymph node metastasis in prostate cancer. SLNE is superior to the surgical techniques commonly used in pelvic lymphadenectomy.

Aged↗
PubMed2001

Transient prenatal expression of NPY-Y1 receptor in trigeminal axons innervating the mystacial vibrissae.

Using immunohistochemistry in combination with confocal laser scanning microscopy, we studied the ontogeny of neuropeptide Y-Y1 receptor (Y1-R) expression in the trigeminal system of the rat. The study was limited to the nerve fibers innervating the mystacial pad and the trigeminal ganglia. In the trigeminal ganglia, Y1-R-immunoreactive (IR) neurons were first observed at E16.5. At this same stage some nerve fibers in the trigeminal ganglia also exhibited Y1-R-like immunoreactivity (LI). Strongly Y1-R-IR nerve fibers innervating the follicles of the mystacial vibrissae were first observed at E18. After double labeling, the Y1-R-LI was found to be colocalized with the neuronal marker protein gene product 9.5. At P1 only weak labeling for the Y1-R was found around the vibrissae follicles, whereas the neurons in the trigeminal ganglia were intensely labeled. The same was true for the adult rat, but at this stage no Y1-R labeling at all was observed in nerve fibers around the vibrissal follicles. These results strongly support an axonal localization of the Y1-R at this developmental stage. The transient expression of the Y1-R during prenatal mystacial pad development suggests a role for the Y1-R in the functional development of the vibrissae.

Animals↗
PubMed2001

Granulocyte/macrophage-colony-stimulating-factor plus interleukin-2 plus interferon alpha in the treatment of metastatic renal cell carcinoma: a pilot study.

Granulocyte/macrophage-colony-stimulating factor (GM-CSF) plays a central role in the differentiation and function of dendritic cells, which are crucial for the elicitation of MHC-restricted T cell responses. Preclinical and the first clinical data provide a rationale for the application of GM-CSF in immunotherapy of cancer. Ten patients with renal cell carcinoma stage IV (Holland/ Robson) were treated in this pilot study. Therapy was started with GM-CSF alone (2 weeks). Interleukin (IL-2) and interferon alpha (IFNalpha) were added sequentially (3 weeks GM-CSF plus IL-2 or IFNalpha, 3 weeks GM-CSF plus IL-2 plus IFNalpha). Therapy was performed on an outpatient basis. The cytokine regimen was evaluated for toxicity, clinical response and immunomodulatory effects [fluorescence-activated cell sorting analysis of peripheral blood mononuclear cells (PBMC), mixed-lymphocyte reaction and cytotoxicity of PBMC]. GM-CSF treatment caused a significant increase in the number of PBMC expressing costimulatory molecules. Addition of IL-2 and IFNalpha led to an increase in CD3 , CD4+, CD8+ and CD56+ PBMC in week 9. In an autologous mixed-lymphocyte reaction a 2.1-fold increase in T cell proliferation was observed after 2 weeks of GM-CSF treatment, and cytotoxicity assays showed changes in natural-killer-(NK)- and non-NK-mediated cytotoxicity in some patients. Two patients achieved partial remission, one patient had a mixed response. The toxicity of the regimen was mild to moderate with fever, flu-like symptoms and nausea being observed in most patients. Severe organ toxicity was not observed. We conclude that GM-CSF might be useful for immunotherapy of renal cell carcinoma, especially in combination with T-cell-active cytokines. Further studies are warranted.

Adolescent↗
PubMed2001

Fast track as a routine for open heart surgery.

OBJECTIVE: Evaluation of thoracic epidural analgesia (TEA), normothermic cardiopulmonary bypass (CPB) and normothermic blood cardioplegia as a routine procedure for fast track open heart surgery. METHODS: Consecutive patients (n=250, age 36--81 years, mean 63, M/F, ratio=4) were subjected to the combination of general anaesthesia using ultra-short acting opiates, TEA, normothermic CBP, normothermic whole blood cardioplegia. Operative procedures included coronary artery bypass grafting (CABG), valve replacement, combined CABG and valves, aortic aneurysm and Maze III. LVEF ranged 20--76%. Eighty percent were in Tuman score 0--5 and 20% in score >5. RESULTS: All patients were extubated within 10 min after skin closure. There was one myocardial infarction. Four percent were shortly treated with cathecholamines. Postoperative atrial fibrillation was noticed in 9.6%. Four transient cerebral ischemic events were encountered. No neurological disturbance related to the use of TEA was seen. Seven patients were reoperated because of bleeding. Blood transfusion was given to 6.4% of the patients. Mortality was 0.8%. CONCLUSIONS: The combined methods provides a way for routine immediate postoperative extubation, with low morbidity and short hospital stay.

Adult↗
PubMed2001

Estimation of neutron and other radiation exposure components in low earth orbit.

The interaction of high-energy space radiation with spacecraft materials generates a host of secondary particles, some, such as neutrons, are more biologically damaging and penetrating than the original primary particles. Before committing astronauts to long term exposure in such high radiation environments, a quantitative understanding of the exposure and estimates of the associated risks are required. Energetic neutrons are traditionally difficult to measure due to their neutral charge. Measurement methods have been limited by mass and weight requirements in space to nuclear emulsion, activation foils, a limited number of Bonner spheres, and TEPCs. Such measurements have had limited success in quantifying the neutron component relative to the charged components. We will show that a combination of computational models and experimental measurements can be used as a quantitative tool to evaluate the radiation environment within the Shuttle, including neutrons. Comparisons with space measurements are made with special emphasis on neutron sensitive and insensitive devices.

Astronauts↗
PubMed2001

Prediction of full-scale dewatering results of sewage sludges by the physical water distribution.

The dewaterability of sewage sludge can be described by the total solids concentration of the sludge cake and the polymer-demand for conditioning. The total solids concentration of the sludge cake depends on the physical water distribution. The various types of water in sewage sludge are mainly distinguished by the type and the intensity of their physical bonding to the solids. In a sewage sludge suspension four different types of water can be distinguished. These are the free water, which is not bound to the particles, the interstitial water, which is bound by capillary forces between the sludge flocs, the surface water, which is bound by adhesive forces and intracellular water. Only the share of free water can be separated during mechanical dewatering. It can be shown, that by thermo-gravimeteric measurement of the free water content, an exact prediction of full-scale dewatering results is possible. By separation of all free water during centrifugation the maximum dewatering result is reached. Polymer conditioning increases the velocity of the sludge water release, but the free water content is not influenced by this process. Furthermore it is not possible, to replace the measuring of the water distribution by other individual parameters such as ignition loss.

Calibration↗
PubMed2001

Influence of the free water content on the dewaterability of sewage sludges.

Dewaterabilty of sewage depends on the physical water distribution. The various types of water in sewage sludge are mainly distinguished by type and intensity of their physical bonding to the solids. In a sewage sludge suspension different types of water can be distinguished. These are free water, which is not bound to the particles, interstitial water, which is bound by capillary forces between the sludge flocs, surface water, which is bound by adhesive forces and intracellular water. Only free water can be separated during mechanical dewatering. It can be shown, that thermo-gravimteric measurement of the free water content leads to an exact prediction of full-scale dewatering results. Maximum dewatering results are reached by separating all free water during centrifugation. Furthermore on the basis of the drying curve an estimation of water binding energies can be achieved. The binding energy for free water is less than 0,28 kJ/kg water. The binding energy for bound water (sum of surface and intracellular water) is higher than 5 kJ/kg water.

Centrifugation↗
PubMed2000

Functional and structural characterization of synthetic HIV-1 Vpr that transduces cells, localizes to the nucleus, and induces G2 cell cycle arrest.

Human immunodeficiency virus (HIV) Vpr contributes to nuclear import of the viral pre-integration complex and induces G(2) cell cycle arrest. We describe the production of synthetic Vpr that permitted the first studies on the structure and folding of the full-length protein. Vpr is unstructured at neutral pH, whereas under acidic conditions or upon addition of trifluorethanol it adopts alpha-helical structures. Vpr forms dimers in aqueous trifluorethanol, whereas oligomers exist in pure water. (1)H NMR spectroscopy allows the signal assignment of N- and C-terminal amino acid residues; however, the central section of the molecule is obscured by self-association. These findings suggest that the in vivo folding of Vpr may require structure-stabilizing interacting factors such as previously described interacting cellular and viral proteins or nucleic acids. In biological studies we found that Vpr is efficiently taken up from the extracellular medium by cells in a process that occurs independent of other HIV-1 proteins and appears to be independent of cellular receptors. Following cellular uptake, Vpr is efficiently imported into the nucleus of transduced cells. Extracellular addition of Vpr induces G(2) cell cycle arrest in dividing cells. Together, these findings raise the possibility that circulating forms of Vpr observed in HIV-infected patients may exert biological effects on a broad range of host target cells.

Amino Acid Sequence↗
PubMed2000

Comparative structural analysis and substrate specificity engineering of the hyperthermostable beta-glucosidase CelB from Pyrococcus furiosus.

The substrate specificity of the beta-glucosidase (CelB) from the hyperthermophilic archaeon Pyrococcus furiosus, a family 1 glycosyl hydrolase, has been studied at a molecular level. Following crystallization and X-ray diffraction of this enzyme, a 3.3 A resolution structural model has been obtained by molecular replacement. CelB shows a homo-tetramer configuration, with subunits having a typical (betaalpha)(8)-barrel fold. Its active site has been compared to the one of the previously determined 6-phospho-beta-glycosidase (LacG) from the mesophilic bacterium Lactococcus lactis. The overall design of the substrate binding pocket is very well conserved, with the exception of three residues that have been identified as a phosphate binding site in LacG. To verify the structural model and alter its substrate specificity, these three residues have been introduced at the corresponding positions in CelB (E417S, M424K, F426Y) in different combinations: single, double, and triple mutants. Characterization of the purified mutant CelB enzyme revealed that F426Y resulted in an increased affinity for galactosides, whereas M424K gave rise to a shifted pH optimum (from 5.0 to 6.0). Analysis of E417S revealed a 5-fold and a 3-fold increase of the efficiency of hydrolyzing o-nitrophenol-beta-D-galactopyranoside-6-phosphate, in the single and triple mutants, respectively. In contrast, their activity on nonphosphorylated sugars was largely reduced (30-300-fold). The residue at position E417 in CelB seems to be the determining factor for the difference in substrate specificity between the two types of family 1 glycosidases.

Amino Acid Sequence↗
PubMed2000

Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.

In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by constitutive expression of bcr/abl and possibly other yet undefined leukemia-associated antigens, since these DC share a common progeny with leukemic cells. Induction of anti-leukemic T cell responses has been described in vitro. For a phase I vaccination study, autologous bcr/abl+ DC are generated under GMP conditions mainly from monocyte precursors in chronic phase CML patients. Lin-, CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c. vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC-based vaccination strategies are a promising clinical approach, particularly as postremission immunotherapy in the setting of autologous stem cell transplantation.

Cytotoxicity, Immunologic↗
PubMed2000

[Gene therapy perspectives in modulation of wound healing].

A variety of reasons can afflict wound healing. Current research is focussed on the acceleration of wound healing by stimulating molecular processes. Gene therapy may offer completely new ways to treat chronic wounds. Possible advantages of gene therapeutic modulation of wound healing might be a long term efficiency, systemic or local regulation of gene expression and low side-effects. Current goals comprise the improvement of transfection efficiency and specificity. In vivo applications are therefore focussed on optimized inducible or even cell-type specific promotors, as well as on improved local application techniques. Studies from our laboratory demonstrate the possibility to combine modern cell culture techniques with different types of gene transfer. This enables the simultaneous grafting of manipulated cells to the wound with the continuous delivery of specific proteins of interest. Experimentally, this lead to accelerated closure of partial and full thickness animal wounds. Clinically, gene therapy for the treatment of chronic wounds seems to be a realistic goal within the next years and might be applicable for a variety of novel indications.

Animals↗
PubMed2000

Effects of disintegration on anaerobic degradation of sewage excess sludge in downflow stationary fixed film digesters.

The effects of mechanical disintegration on anaerobic digestibility of sewage excess sludge in downflow stationary fixed film (DSFF) digesters were investigated on laboratory scale. Mechanical pretreatment using a high pressure homogenizer led to significantly enhanced concentrations of soluble proteins and carbohydrates in the feed sludge. Using DSFF digesters with two different tubular plastic media as support material it was shown that a stable digestion process could be achieved at hydraulic retention times (HRT) down to 5 days. Compared to conventional digesters at 10 d and 15 d HRT respectively, the degradation of volatile solids was enhanced up to 25%, also resulting in a higher specific biogas production. Further investigations on degradation of soluble proteins and carbohydrates showed that a slowly degradable fraction of carbohydrates was released via disintegration. Using the distribution of chain length and the concentrations of volatile fatty acids as process parameters, the dependability on the HRT and the degree of disintegration (the release of soluble COD) predominated the effects of specific surface area of the support media.

Bacteria, Anaerobic↗
PubMed1999

Recent European measurements inside Biorack.

The dosimetric package used inside Biorack on board STS76, STS81 and STS84 comprises passive detector stacks built from plastic nuclear track detectors (PNTDs), thermoluminescence detectors (TLDs) and one or two active DOSTEL (DOSimetric TELescope) units using planar silicon detectors. Five passive detector stacks were exposed at different places inside the BIORACK incubators and in different stowage positions. DOSTEL units were exposed inside the 22 degrees C incubator in all flights. Mission integrated dose measurements, particle fluence rates and neutron doses are obtained from the passive detector stacks. These results are complemented by time resolved particle counts and dose rates and linear energy transfer (LET) spectra separately for the contribution of the trapped particles and the galactic cosmic rays (GCR) as a result of the DOSTEL measurements. In addition, it was possible to investigate the anisotropy of the radiation field inside Biorack by the use of a second DOSTEL unit on STS84. Since all exposures are during a solar minimum period, the total radiation exposure is of a similar extent for all flights, although position differences in dose rate up to a factor of two are observed. Particle fluence rates show lower variations. Mission averaged mean quality factors (Q) determined from the LET spectra are 2.0+/-0.1; the deduced dose equivalent rates range from 631 to 716 microSv/day.

Analog-Digital Conversion↗
PubMed1999

Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis.

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and piriform and entorhinal cortices. Gene expression had returned to control level in the dentate granule cell layer at 48 h but remained high in the other areas, reaching baseline at 1 week. Transient decreases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions, amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R mRNA levels were reduced at 2-4 h in the CA3 region and piriform cortex, but exhibited marked increases at 48 h and 1 week post-seizure in the dentate gyrus, amygdala and piriform and entorhinal cortices. At 3 weeks, Y2-R mRNA expression had virtually returned to baseline. Elevated Y5-R mRNA levels were only detected at 2-4 h and confined to dentate granule cell layer and piriform and entorhinal cortices. These results demonstrate a cell- and region-specific, differential regulation of mRNA expression for NPY and Y1-R, Y2-R, and Y5-R in the limbic system following recurring seizures. Because the gene changes were transient, it seems unlikely that the presumed alterations of the corresponding proteins are involved in the maintenance of the epileptic syndrome, which develops up to 4 weeks post-seizure in the present model and is stable thereafter. Our data provide further support for the hypothesis that the changes of NPY and its receptors act to dampen seizure susceptibility, and suggest that the cascade of gene changes is orchestrated to optimize this anticonvulsant effect.

Amygdala↗
PubMed1999

Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice.

Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated alpha-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of alpha-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease.

Aging↗
PubMed1999

An immunohistochemical marker for Wallerian degeneration of fibers in the central and peripheral nervous system.

This work was prompted by the accidental observation that a newly developed, affinity purified polyclonal antibody against the C-terminus of the neuropeptide tyrosine (NPY) Y1-receptor protein decorates degenerating fibers in the central nervous system (CNS). This staining did not appear in control animals in which the antibody marked perikarya and dendrites at previously described locations [X. Zhang, L. Bao, Z.-Q. Xu, J. Kopp, U. Arvidsson, R. Elde, T. Hökfelt, Localization of neuropeptide Y Y1-receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurons, Proc. Natl. Acad. Sci. USA 91 (1994) 11738-11742]. Three models of experimental lesions were studied: sciatic nerve transection, spinal cord transection and parietal cortex thermocoagulation. In each model, animals were divided in groups (n=2) and processed for indirect immunofluorescence at different time intervals up to 28 days post-lesion (PL) (see below). All three experimental lesions produced a very intense immunolabeling of fibers in the projection pathways of the lesioned structures, strongly reminding of Wallerian degeneration (WD). In the sciatic nerve, the staining first appeared on day 1 PL, was strongly increased on day 3 PL, then declined after 7 days and had almost completely disappeared after 14 days. In the CNS, the staining appeared later and was first observed on day 3 PL and remained for a longer period, thus showing different time courses in the brain and spinal cord as compared to the sciatic nerve. The labeling was completely abolished, both in the CNS and in the sciatic nerve, by pre-incubation of the Y1-R antibody with the immunogenic peptide at a dilution of 10-6 M. The appearance of the staining and its time course strongly suggest that the process was related to degenerating axons. Although the protein actually detected remains to be determined, it is suggested that the staining ability of this antibody could be used as a positive marker of axonal degeneration following experimental or naturally occurring lesions of the nervous system.

Animals↗