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Biomedical subjects

A Petersen

Publications and source records attributed to A Petersen.

At least 19 recordsLinked to original sources

Laparoscopic partial nephrectomy using the potassium titanyl phosphate laser in a porcine model.

INTRODUCTION: To evaluate the potential and feasibility of the potassium titanyl phosphate (KTP) Greenlight laser to perform partial nephrectomy in a porcine model. TECHNICAL CONSIDERATIONS: A total of 15 laparoscopic partial nephrectomies were performed in 4 Danish land-raised pigs under anesthesia. Transperitoneal access was obtained, and using a total of four ports, the 80-W KTP laser was used to perform bilateral upper and lower pole partial nephrectomy. The procedures were done successfully without renal cooling or clamping of the vessels. The estimated blood loss for each procedure was less than 30 mL. Only in one operation, in which a secondary renal vein was transected, was any additional hemostasis required (a single Endoclip). The mean operating time was 42 minutes (range 31 to 59) for each partial nephrectomy. As demonstrated on video, smoke formation was, at times, a problem during the procedure, because it reduced visibility, making only intermittent application of laser energy possible. Histopathologic analysis of the specimens showed a zone of loss of substance (less than 1 mm) at the resection line and narrow adjacent zones on both sides of the resection line with minimal changes. CONCLUSIONS: We have shown for the first time that normally perfused laparoscopic partial nephrectomy using the KTP laser is feasible and efficacious in the porcine model. This represents a novel application for the KTP laser, which produced excellent renal parenchymal hemostatic ablation. We are currently working on ways to improve the visibility by reducing smoke formation before undertaking a clinical trial in humans.

Animals↗

In contrast to specific B cells, human basophils are unaffected by the toxic activity of an allergen toxin due to lack of internalization of immunoglobulin E-bound allergen.

BACKGROUND: Specific immunotherapy is the only curative therapy for type I allergies and the alarming increase in allergy prevalence emphasizes the need for additional/alternative strategies for curative treatment. Allergen toxins (AT), fusion products of an allergen with an apoptosis inducing cytotoxin, are a new kind of immunotoxin. OBJECTIVE: AT should allow allergen-specific targeting and elimination of allergy-relevant cells, with B cells being the primary target. An important question is the fate of the effector cells, e.g. mast cells and basophils, which carry allergen-specific IgE: the immunotoxin might even prove to be harmful. METHODS: We established a reliable in vitro B cell model (using two mouse hybridoma cell lines) for testing specificity and toxicity of P5-ETA', a fusion protein of the major timothy grass pollen allergen Phl p 5b and truncated Pseudomonas Exotoxin A. In a second step, we investigated the impact of the AT on human basophils. RESULTS: P5-ETA' reliably eliminated Phl p 5-specific cells in the in vitro B cell model, leaving unspecific B cells unharmed. Human basophils of grass pollen allergic donors specifically bound P5-ETA', released IL-4 and up-regulated the activation marker CD203c, but were not subject to the toxic effect because of lack of internalization of IgE-bound allergen. CONCLUSION: According to our data, basophils are pure effector cells in the context of IgE-bound allergen and not involved in classical antigen presentation.

ADP Ribose Transferases↗

Potential protective effects of NSAIDs/ASA in oxidatively stressed human lens epithelial cells and intact mouse lenses in culture.

PURPOSE: To study possible toxic effects of indomethacin, diclofenac, and celecoxib (NSAIDs) and acetylsalicylic acid (ASA) as well as potentially protective effects of these substances in oxidatively stressed human lens epithelial cells (HLEC) and in intact mouse lenses in culture. METHODS: HLEC and mouse lenses were incubated with NSAIDs or ASA alone or in the presence of H2O2. To study apoptosis the cells were then either stained with Hoechst 33342 or assayed for caspase-3 activity. Mouse lenses were studied with respect to lens transparency. RESULTS: Low concentrations of NSAIDs/ASA caused a significant protection against H2O2-induced apoptosis in HLEC whereas higher concentrations were toxic. CONCLUSION: The protective effects of NSAIDs/ASA against oxidative damage are confined to a relatively small therapeutic window.

Animals↗

Identification of an obeche (Triplochiton scleroxylon) wood allergen as a class I chitinase.

BACKGROUND: Wood dust is known to cause allergic occupational asthma and obeche (Triplochiton scleroxylon) is a prominent exponent in this field. However, the knowledge about wood allergens is still limited. The aim of this study was to identify and characterize obeche wood allergens. METHODS: Obeche extracts were prepared from freshly ground in comparison to 7 years stored wood dust and investigated by Sodium dodecyl sulfate-polyacrylamid gel electrophoresis, enzyme-linked allergosorbent test and immunoglobulin (Ig)E-immunoblot. Allergens were detected by specific IgE of seven obeche allergic patients' sera and protein analysis was performed by mass spectrometry. Cross-reactivity was demonstrated by ImmunoCAP-inhibition with sera of seven obeche and four latex-allergic patients. RESULTS: Obeche extracts showed different protein pattern and IgE-binding capacities depend on the age of the wood dust. A 38 kDa protein was identified as major obeche wood allergen, detected by six of seven (85%) obeche allergic patients' sera and was entitled as Trip s 1. Trip s 1 is homologous to plant class I chitinases and exhibited enzyme activity demonstrated by chitinolysis. Co-recognition or cross-reactivity of Trip s 1 according to structural similarity was seen in sera of latex allergic patients. IgE inhibition studies with obeche as solid phase and Trip s 1 and latex hevein as inhibitor demonstrated that Trip s 1 was a more effective inhibitor in obeche as well as in latex allergic patients' sera. CONCLUSIONS: Trip s 1 is a new obeche wood allergen of the plant class I chitinase family. This finding may explain the dominant role of obeche in sensitization against wood dust.

Adult↗

The relationship between expressive language level and psychological development in children with autism 5 years of age.

The age of detection of autism varies and may be linked to differences in the severity of disturbance and any associated retardation. Symptom intensity, overall language level, age of recognition of first disturbances and level of psychological development were examined in 222 children with pervasive developmental disorder with a mean age of 5 years. Results showed a positive correlation between language level and psychological development as well as between language level and intensity of symptoms. The central position of language in psychological development is discussed.

Age Factors↗

Activity of MMP-19 inhibits capillary-like formation due to processing of nidogen-1.

Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the basement membrane. To investigate the impact of MMP-19 activity on endothelial cells in the context of tumor extracellular matrix (ECM), we treated Matrigel matrix with an active recombinant MMP-19 and analyzed its effect on capillary-like formation. Human microvascular endothelial cells (HMEC-1) could not form capillary-like formation on Matrigel treated with recombinant MMP-19. Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates the G3 globular domain containing the binding site for the gamma1 chain of laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1 to cross-link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of nidogen-1 inhibited the capillary-like structure formation to a similar extent as MMP-19. Since nidogen-1 is thought to stabilize microvessels, MMP-19 might be one of the enzymes that interferes with stabilization or maturation of nascent vasculature.

Cell Division↗

Characterization of immunoglobulin E responses in Balb/c mice against the major allergens of timothy grass (Phleum pratense) pollen.

BACKGROUND: Grass pollen, such as that from timothy grass (Phleum pratense), represents a major cause of type I allergy. OBJECTIVE: To characterize the IgE immune response and to identify the major allergens eliciting an IgE response in a mouse model using pollen extract of P. pratense for sensitization, in order to assess analogies to human hyperreactivity and to gain information on the allergenic potential as determined by the IgE-reactivity kinetics of defined allergens. METHODS: Balb/c mice were sensitized with pollen extract or with purified natural allergens. Serum IgE levels, the induction of specific IgE antibodies and immediate hypersensitivity were monitored by ELISA, Western blot and a skin test, respectively. RESULTS: The sensitized mice mounted a strong IgE response and showed IgE-reactivity first against Phl p 5a and 5b, then Phl p 4 and 13 and lastly against Phl p 6. No IgE response was mounted against Phl p 1. However, all purified fractions examined (Phl p 5a, 5b, 6 and 1) induced specific IgE and showed similar kinetics of IgE induction as pollen extract (first Phl p 5a and 5b, then Phl p 6). Skin test experiments demonstrated positive reactivity only in sensitized mice. CONCLUSION: The IgE reactivity induced by the major allergens in Balb/c mice was very similar to that found in allergic patients, with the exception of Phl p 1. The kinetics of the specific IgE response was comparable using either pollen extract or the purified major allergens, indicating that the intrinsic properties of the allergens are of importance rather than their proportionate amounts in pollen extract. This model should prove to be suitable for investigations regarding the mechanisms of induction and manifestation of timothy grass pollen allergy and for the evaluation of therapeutic strategies.

Allergens↗

Cumulative risk assessment of the intake of organophosphorus and carbamate pesticides in the Danish diet.

The aim of the study is to evaluate the potential cumulative effects of organophosphorus and carbamate pesticides that act through a common mechanism of toxicity, and to assess the long- and short-term risks for the Danish population. The intake estimates are based on dietary intake data collected in the Danish nation-wide food consumption survey in 1995. The pesticide data are based on the Danish pesticide residue-monitoring programme from 1996-2001. The amount of 35 organophosphorus pesticides and carbamates were included in the cumulative risk assessment. Processing factors, such as reduction of pesticide levels by rinsing and peeling, were applied in the exposure assessment. The "Toxicity Equivalence Factor" (TEF) approach was used to normalise the toxicity of the different organophosphorus and carbamate pesticides. Cumulative chronic exposure of organophosphorus and carbamates pesticides via fruit, vegetables and cereals is for adults 0.8-2% of the Acceptable Daily Intake (ADI) in chlorpyrifos equivalents, and 0.03-11% of the ADI in methamidophos equivalents; and for children 2-5% of the ADI in the chlorpyrifos equivalents, and 0.07-27% of the ADI in methamidophos equivalents. Neither Acute Reference Dose (ARfD) nor ADI was exceeded for any of the compounds studied. The results indicate that the Danish population is neither exposed to any cumulative chronic risk, nor at risk of acute exposure, from consumption of organophosphorus and carbamate pesticides from fruit, vegetables and cereals.

Adolescent↗

Monitoring the content and intake of trace elements from food in Denmark.

The content of cadmium, lead, nickel, mercury and selenium in 83 foods was monitored from 1993 to 1997. In comparison with similar results from 1988 to 1992, a general decrease in lead levels had occurred, whereas the contents of cadmium, nickel, mercury and selenium were stable or declined only slightly. The distribution in dietary intake of the five trace elements was estimated by combining the mean trace element concentrations with food consumption data from 1837 Danes aged 15-80 years. The lead intake for 1993-97 showed a decrease in comparison with similar estimates from the previous monitoring cycles: 1983-87 and 1988-92. The intake of cadmium and mercury decreased to a lesser extent, whereas the intake of selenium and nickel remained unchanged in the same period. The dietary intake of trace elements was compared with the provisional tolerable weekly intake (PTWI). The 95th percentile of the distribution in cadmium intake amounts to 34% of PTWI, which is relatively high, and therefore calls for a more detailed future risk assessment. The intakes of lead and mercury were 11% of PTWI and, like the intake of nickel, did not cause any health concern in the adult population. The Danes ingest close to 100% of the Nordic Nutrition Recommendation for selenium at 50 microg day(-1), and no individuals had an intake less than the lower limit of 20 microg day(-1).

Adolescent↗

Content of ochratoxin A in paired kidney and meat samples from healthy Danish slaughter pigs.

In 1999, paired samples of kidney and meat were taken from 300 healthy Danish pigs and analysed for ochratoxin A. The concentrations of ochratoxin A in kidney ranged from 0 to 15 microg kg(-1) (mean 0.50 microg kg(-1), median 0.18 microg kg(-1)) and in meat from 0 to 2.9 microg kg(-1) (mean 0.12 microg kg(-1), median 0.03 microg kg(-1)). The data together with the Danish control data show that today the pig industry in Denmark has no problem keeping the content of ochratoxin A in pig at very low levels even in years with wet harvest conditions. The mean ratio 'content in meat/content in kidney' for paired samples was 39%. For kidney samples >1.0 microg kg(-1), the mean ratio was 22%. The Danish control system for ochratoxin A in pig kidney established in 1978 can be regarded as a success because the levels in pig have been reduced substantially, and hence for the consumer the contribution from pig products to the total intake of ochratoxin A is very small compared with other sources.

Animals↗

The peripherally inserted central catheter (PICC): a prospective study of its natural history after cubital fossa insertion.

A prospective cohort study was undertaken to describe the natural history of the cubital fossa peripherally inserted central catheter (PICC), determine which factors influenced the hazard of complication and develop a standard methodology for evaluation of a PICC service. A total of 4349 patient days of PICC observation were analysed using survival analysis techniques. The median time to PICC removal for a complication was 60 days. The most common complications were phlebitis, malposition and tip migration. Complications usually occurred during the first week. There was only one episode of line-related sepsis. Size 3 French gauge catheters had a complication rate of 7.3 per 1,000 line days compared to 14.2 for 4 French catheters (hazard rate 1.26 90% CI 1.02 to 1.55). PICCs requiring two or more attempts at insertion were more likely to develop complications than those inserted at the first attempt: 20 per 1,000 line days vs 10.5 but the confidence intervals were wide (hazard rate 1.91, 90% CI 0.90 to 4.05). Operator (amongst the four experienced operators who inserted all PICCs), arm of placement, or medial or lateral placement in the cubitalfossa did not influence PICC survivaL

Adult↗

Investigations on the carbohydrate moieties of glycoprotein allergens.

Many allergens are glycoproteins and their carbohydrate structure can contribute to the IgE reactivity. Therefore it is of great interest to study the carbohydrate structures of these particular antigens. Here, we present an overview of methods combining basic procedures in glycochemistry with various applications of electrophoresis that allow investigating single allergens in crude extracts. Various allergen extracts, e.g. from tomato, grass pollen and bacteria were analysed and the suitability of the tests are discussed.

Allergens↗

Biofantasies: genetics and medicine in the print news media.

The contemporary news media is an important site for exploring the diverse and complex cultural images of genetics and its medical possibilities, and of the mechanisms by which these images are (re) produced and sustained. This article investigates how the print news media 'frames' stories on genetics and medicine. It is based on a discourse analysis of articles appearing in three Australian newspapers in the late 1990s. Gene stories were found to be prominent in each of the newspapers, and to emphasise the medical benefits of genetic research. Stories frequently cite and quote scientists, who explain the nature and significance of the research and/or its implications for treatment or prevention. Many stories focus on new genetic discoveries, and portray genetic researchers as involved in a quest to unlock nature's secrets. Stories of hope, and depictions of geneticists as warriors or heroes, appear regularly. The positive vision of genetics is supported by the use of particular metaphors, accompanying illustrative material, 'human interest' stories, and reference to credible sources. There is rarely mention of the influence of non-genetic factors and 'multifactorial' interactions on disorders, or questioning of the goals, direction, methods, or value of genetic research. Scientists made extensive use of the media in their efforts to maintain a positive image of research in the face of public concerns about scientists 'going too far', following the announcement of the cloning of Dolly. Boundaries were drawn between 'therapeutic cloning'--implicitly defined as 'good', useful, and legitimate--and 'reproductive cloning'--seen as 'bad', dangerous, and illegitimate. By framing news stories as they do, the print news media are likely to exert a powerful influence on public responses to health problems. With new genetic technologies becoming more integrated in preventive medicine and public health, it is important to investigate how news stories help shape the agenda for public debate.

Animals↗

Discontinuous IgE-binding epitopes contain multiple continuous epitope regions: results of an epitope mapping on recombinant Hol l 5, a major allergen from velvet grass pollen.

The knowledge of IgE-binding epitopes on allergen molecules is important for better understanding allergen-antibody interactions and, thus, for developing new strategies for immunotherapy. Our purpose was to more precisely define the number and structure of IgE-binding epitopes of a paradigmatic major grass pollen allergen. We performed an IgE-binding epitope mapping of rHol l 5, a group V pollen allergen of velvet grass (Holcus lanatus), with overlapping fragments (length between 15 and 186 amino acids), which were expressed in E. coli as MBP fusion proteins. Using sera of 65 grass pollen allergic patients, the fragments were analysed by immunoblotting for IgE reactivity. Specificity of antibody binding was confirmed by competitive blot inhibition assays. At least four different continuous IgE-binding epitopes were identified on small fragments (about 30 amino acids), and at least five different discontinuous IgE-binding epitopes on larger fragments, which were destroyed by further fragmentation. The fragments were differentially recognized by individual patients' sera. By investigating IgE-binding to one of the small fragments in more detail, we found further epitope regions on this fragment. It was noteworthy that IgE reactivity to small fragments was weak compared to large fragments or to the complete molecule. Competitive blot inhibition experiments showed that binding of IgE antibodies to the small fragments was specific but with lower avidity than to the complete rHol l 5. rHol l 5 harbours multiple discontinuous as well as continuous IgE-binding epitopes spread over the whole molecule, which were individually recognized by IgE antibodies from different patients. Low avidity of IgE antibodies to small fragments suggests that the continuous epitope regions do not represent the complete epitope and are most probably parts of discontinuous epitopes.

Allergens↗

Group 13 grass allergens: structural variability between different grass species and analysis of proteolytic stability.

BACKGROUND: Determination of the allergen composition of an extract is essential for the improvement of hyposensitization therapy. Surprisingly, although grass pollen extracts have been studied intensively for 20 years, a further major allergen, Phl p 13, was detected recently in timothy grass pollen. OBJECTIVES: We sought to determine the occurrence and importance of group 13 allergens in various grass species and to investigate their proteolytic stability. METHODS: The group 13 allergens were determined by means of 2-dimensional PAGE blotting with patient sera and group 13-specific mAbs. The allergens were isolated chromatographically from several pollen extracts and analyzed by means of microsequencing. Cross-reactivity among various grass species was studied by using Western blots and immunoblot inhibition tests. The stability of the allergens was tested under defined extraction conditions. RESULTS: Group 13 allergens are detectable in all common grasses and show IgE cross-reactivity among them. The allergenic components were identified in the neutral pH range with molecular masses of 50 to 60 kd, and in the case of Phl p 13, maximal binding of the isoforms was observed at 55 kd and at an isoelectric point of 6 to 7.5. Protein sequencing clearly confirms structural identities between different grass species, although individual variations are found. If low-molecular-mass components were depleted by means of gel filtration, a rapid degradation of group 13 allergens was observed. This is in contrast to other pollen allergens described thus far. CONCLUSION: Group 13 allergens are widespread and are major allergens in the grasses. Predicted from their primary structures, these allergens are polygalacturonases. This class of enzymes is already known from microorganisms, and these enzymes are recognized as potential inducers of asthma. Our studies indicate that the group 13 allergens show a considerable microheterogeneity and degradation, especially after depletion of low-molecular-mass components. One has to be aware of this pivotal fact when soluble grass pollen extracts are prepared for diagnostics and hyposensitization therapy.

Allergens↗

Preliminary evaluation of fumonisins by the Nordic countries and occurrence of fumonisins (FB1 and FB2) in corn-based foods on the Danish market.

Experts from the Nordic countries (Denmark, Norway, Sweden, Finland and Iceland) have carried out an evaluation of fumonisins. The working group members concluded that, at that time point, it was not possible to carry out a complete risk assessment. However, it was recommended that the human daily' intake of fumonisins should be less than 1 microg/kg bw/day. Subsequently, the presence of the Fusarium mycotoxins fumonisin B1 and B2 (FB1 and FB2) in corn-based food on the Danish retail market has been determined. A total of 70 samples were analysed and 37% contained FB1 and 21% contained FB2. No fumonisins were found in sweet corn (canned or frozen), corn-on-the-cob, corn starch or gruel powder for babies. FB1 was found in about half of the corn flakes, corn snack and popcorn (not popped) samples, whereas FB2 was seen to a lesser extent. Both FB1 and FB2 were found in 75% or more of the corn flour, tacos and polenta samples. In general, the content of FB1 was in the range of 1-1000 micro/kg and the content of FB2 was in the range of 4-250 microg/kg. Corn-based foods are consumed in rather low amounts and irregularly among the Danish population and therefore it is not meaningful to calculate an average daily funonisin intake. An estimate for an 'eater' shows that the intake of fumonisins will not exceed 0.4 microg/kg bw/day.

Animals↗

Therapeutic drug monitoring of haloperidol, perphenazine, and zuclopenthixol in serum by a fully automated sequential solid phase extraction followed by high-performance liquid chromatography.

In Denmark, haloperidol, perphenazine, and zuclopenthixol are among the most frequently requested antipsychotics for therapeutic drug monitoring. With the number of requests made at the authors' laboratory, the only rational analysis is one that can measure all three drugs simultaneously. The authors therefore decided to develop an automated high-performance liquid chromatography (HPLC) method. Two milliliters serum, 2.0 mL 10 mmol/L sodium phosphate buffer (pH 5.5), and 150 microL internal standard (trifluoperazine) solution were pipetted into HPLC vials and extracted on an ASPEC XL equipped with 1 mL (50 mg) Isolute C2 (EC) extraction columns and acetonitrile-methanol-ammonium acetate buffer (60:34:6) as extracting solution. Three hundred fifty microliters was analyzed by HPLC; a 150 x 4.6-mm S5CN Spherisorb column with a mobile phase of 10 mmol/L ammonium acetate buffer-methanol (1:9), a flow rate of 0.6-1.7 mL/min, and ultraviolet detection at 256 and 245 nm were used. Reproducibility was 5-12% and the lower limit of quantitation was 10, 1, and 5 nmol/L (4, 0.4, and 2 ng/mL) for haloperidol, perphenazine, and zuclopenthixol, respectively. The method was found to be sufficiently selective and robust for routine analysis.

Antipsychotic Agents↗

Transcript-based computer animation of movement: evaluating a new tool for nonverbal behavior research.

A new approach for the use of computer animation in experimental nonverbal research is introduced. The method was evaluated in a pilot study comparing video recordings of movement in dyadic interactions with computer animations based on transcripts of the behavior, to determine whether similar impression effects could be obtained. At the core of our development is a software tool allowing for the conversion of so-called position time-series protocols of movement into animation scripts for a professional computer animation platform. Our software combines computer-assisted movement transcription and editing with state-of-the-art 3-D animation technology. We present empirical evidence indicating remarkable overall correspondence between video recordings and computer animations. Due to the lack of facial activity in the computer animations, a decline in visual attention for the face area could be observed, which did not, however, affect the impression ratings.

Adolescent↗