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Biomedical subjects

A Peter

Publications and source records attributed to A Peter.

At least 19 recordsLinked to original sources

Combined application of conservative transport modelling and compound-specific carbon isotope analyses to assess in situ attenuation of benzene, toluene, and o-xylene.

In recent years, compound specific isotope analyses (CSIA) have developed into one of the most powerful tools for the quantification of in situ biodegradation of organic contaminants. In this approach, the calculation of the extent of biodegradation of organic contaminants in aquifers is usually based on the Rayleigh equation, and thus neglects physical transport processes such as dispersion that contribute to contaminant dilution in aquifers. Here we combine compound specific isotope analyses with a conservative transport model to study the attenuation of aromatic hydrocarbons at a former gasworks site. The conservative transport model was first used to simulate concentration reductions caused by dilution at wells downgradient of a BTEX source. In a second step, the diluted concentrations, together with the available stable carbon isotope ratios and carbon fractionation factors for benzene, toluene and o-xylene were applied in the Rayleigh equation to quantify the degree of biodegradation at each of those wells. At the investigated site, where other attenuation processes such as sorption and volatilisation were proven to be negligible, the combined approach is recommended for benzene, which represents a compound for which the effect of biodegradation is comparable to or less than the effect of dilution. As demonstrated for toluene and o-xylene, the application of the Rayleigh equation alone is sufficient if dilution can be proved to be insignificant in comparison to biodegradation. The analysis also suggests that the source width and the position of the observation wells relative to the plume center line are significantly related to the degree of dilution.

Benzene↗

Spectroscopic investigation of the deeply buried Cu(In,Ga)(S,Se)2/Mo interface in thin-film solar cells.

The Cu(In,Ga)(S,Se)(2)Mo interface in thin-film solar cells has been investigated by surface-sensitive photoelectron spectroscopy, bulk-sensitive x-ray emission spectroscopy, and atomic force microscopy. It is possible to access this deeply buried interface by using a suitable lift-off technique, which allows us to investigate the back side of the absorber layer as well as the front side of the Mo back contact. We find a layer of Mo(S,Se)(2) on the surface of the Mo back contact and a copper-poor stoichiometry at the back side of the Cu(In,Ga)(S,Se)(2) absorber. Furthermore, we observe that the Na content at the Cu(In,Ga)(S,Se)(2)Mo interface as well as at the inner grain boundaries in the back contact region is significantly lower than at the absorber front surface.

Journal Article↗

Assessing microbial degradation of o-xylene at field-scale from the reduction in mass flow rate combined with compound-specific isotope analyses.

In recent years, natural attenuation (NA) has evolved into a possible remediation alternative, especially in the case of BTEX spills. In order to be approved by the regulators, biodegradation needs to be demonstrated which requires efficient site investigation and monitoring tools. Three methods--the Integral Groundwater Investigation method, the compound-specific isotope analysis (CSIA) and a newly developed combination of both--were used in this work to quantify at field scale the biodegradation of o-xylene at a former gasworks site which is heavily contaminated with BTEX and PAHs. First, the Integral Groundwater Investigation method [Schwarz, R., Ptak, T., Holder, T., Teutsch, G., 1998. Groundwater risk assessment at contaminated sites: a new investigation approach. In: Herbert, M. and Kovar, K. (Editors), GQ'98 Groundwater Quality: Remediation and Protection. IAHS Publication 250, pp. 68-71; COH 4 (2000) 170] was applied, which allows the determination of mass flow rates of o-xylene by integral pumping tests. Concentration time series obtained during pumping at two wells were used to calculate inversely contaminant mass flow rates at the two control planes that are defined by the diameter of the maximum isochrone. A reactive transport model was used within a Monte Carlo approach to identify biodegradation as the dominant process for reduction in the contaminant mass flow rate between the two consecutive control planes. Secondly, compound-specific carbon isotope analyses of o-xylene were performed on the basis of point-scale samples from the same two wells. The Rayleigh equation was used to quantify the degree of biodegradation that occurred between the wells. Thirdly, a combination of the Integral Groundwater Investigation method and the compound-specific isotope analysis was developed and applied. It comprises isotope measurements during the integral pumping tests and the evaluation of delta13C time series by an inversion algorithm to obtain spatially integrated mean isotope values at the control planes. It was shown that the Rayleigh equation is applicable to spatially integrated mean isotope values in order to obtain the mean biodegradation between the consecutive control planes. All three approaches yielded consistently a 98-99% degradation of o-xylene.

Biodegradation, Environmental↗

Proliferation and death of conditionally immortalized neural cells from murine neocortex: p53 alters the ability of neuron-like cells to re-enter the cell cycle.

Neurons are distinctive in that they are generally considered to be permanently post-mitotic cells. The oncoprotein p53 is a key regulator in neuronal development, notably in cell proliferation and neuronal death. We hypothesize that p53 maintains the post-mitotic characteristic of differentiated neurons. New lines of conditionally immortalized cortical cells were generated to test this hypothesis. Populations of cells were obtained from the neocortices of dual transgenic mice that were null for p53 and expressed a temperature-sensitive SV40 large T antigen. At a permissive temperature (32 degrees C), the cells continued to proliferate and most expressed nestin and proteins associated with glia. At a non-permissive temperature (39 degrees C), the cells expressed cytoskeletal proteins associated with differentiated neurons such as microtubule associated protein 2 and neurofilament 200. Under permissive conditions, both p53(+/-) and p53(-/-) cells exhibited similar cycling behaviors; the length of the cell cycle was 13-15 h and >85% of the cells were actively cycling. In non-permissive conditions, most p53(+/-) cells stopped dividing, whereas the p53(-/-) cells continued to proliferate. The survival of the cells also differed. In the non-permissive conditions, many p53(+/-) cells died following treatment with a neurotoxin (ethanol, 400 mg/dl), whereas the p53(-/-) cells did not. After re-introduction to the permissive conditions, both cell lines expressed neuron-like characteristics, but only the p53(-/-) cells retained their ability to cycle. Therefore, p53-mediated activities appear to be involved in the proliferation, survival, and post-mitotic nature of neuron-like cells.

Animals↗

Visual and spectrophotometric shade analysis of human teeth.

Due to interhuman differences in the perception of color, visual shade assessment of human teeth is lacking standardization that may be improved by the use of a spectrophotometer. In this study, we tested the hypothesis that spectrophotometric assessment of tooth color is comparable with human visual determination. On 30 patients, three operators with unreported visual color deficiency independently selected the best match to the middle third of unrestored maxillary central incisors, using a Vita Classical Shade Guide. The same teeth were measured by means of a reflectance spectrophotometer. In the human group, all 3 visual shade selections matched in only 26.6%. In the spectrophotometric group, all 3 shade selections matched in 83.3%. In 93.3%, Delta E values of visually assessed tooth shades were higher than spectrophotometrically assessed Delta E values (p < 0.0001). The results suggest that spectrophotometric shade analysis is more accurate and more reproducible compared with human shade assessment.

Adolescent↗

Osteoarthritis of the scaphoidtrapezium joint: an early sign of calcium pyrophosphate dihydrate disease.

The aim of this study was to determine the value of scaphoidtrapezium osteoarthritis (ST osteoarthritis) as an early sign of calcium pyrophosphate dihydrate disease (CPDD) in a cohort of patients undergoing surgery for osteoarthritis of the first carpometacarpal joint. We examined whether patients with cartilage calcification of the wrist at the time of operation had ST osteoarthritis, indicating CPDD at an earlier time (retrospective study), and whether patients with ST osteoarthritis but without cartilage calcification at the time of surgery develop radiological or clinical signs of CPDD at a later time (prospective study). From 1 January 1989 to 31 December 1995 a total of 169 patients (from an orthopaedic clinic) with a diagnosis of osteoarthritis of the first carpometacarpal joint were included in the study; 167 underwent surgery and two were treated without. Of the 16 patients showing calcification on surgery and therefore included in the retrospective study, 12 had prior radiographs, of which eight showed ST osteoarthritis. Among these, four had no concomitant cartilage calcification in the prior radiographs. Of the 32 patients in the prospective group having ST osteoarthritis but no calcifications at the time of surgery, 27 could be clinically examined. Of these, two showed cartilage calcifications on the follow-up radiographs of the hands. The presence of ST osteoarthritis is a helpful diagnostic finding for the diagnosis of CPDD, especially in cases without radiographic cartilage or fibrocartilage calcification of the wrist. ST osteoarthritis may then point to the correct diagnosis.

Aged↗

Measurement of torsion angles of long finger bones using computed tomography.

OBJECTIVE: Rotational dislocation at the fracture site is a complication of long finger bone fractures of the metacarpals and phalanges. To evaluate such deformities, we performed CT of the articular surfaces of these bones to demonstrate the torsion angles. DESIGN: We evaluated 10 pairs of cadaver hands. These were placed flat, with the bones of interest perpendicular to the gantry to acquire axial images. The torsion of the long bone axes was defined as the angle between a tangent positioned parallel to the proximal articular surface and a tangent parallel to the distal articular surface of individual bones. RESULTS: The maximum difference between repeated measurements was 4 degrees. Intraobserver differences measured between right and left hands are less than 3 degrees. CONCLUSION: Side differences in torsion angles exceeding 3 degrees are strongly suspicious of a malrotation after fracture. These measurements might help to plan derotational osteotomy and assess the results of therapy.

Cadaver↗

From first base: the sequence of the tip of the X chromosome of Drosophila melanogaster, a comparison of two sequencing strategies.

We present the sequence of a contiguous 2.63 Mb of DNA extending from the tip of the X chromosome of Drosophila melanogaster. Within this sequence, we predict 277 protein coding genes, of which 94 had been sequenced already in the course of studying the biology of their gene products, and examples of 12 different transposable elements. We show that an interval between bands 3A2 and 3C2, believed in the 1970s to show a correlation between the number of bands on the polytene chromosomes and the 20 genes identified by conventional genetics, is predicted to contain 45 genes from its DNA sequence. We have determined the insertion sites of P-elements from 111 mutant lines, about half of which are in a position likely to affect the expression of novel predicted genes, thus representing a resource for subsequent functional genomic analysis. We compare the European Drosophila Genome Project sequence with the corresponding part of the independently assembled and annotated Joint Sequence determined through "shotgun" sequencing. Discounting differences in the distribution of known transposable elements between the strains sequenced in the two projects, we detected three major sequence differences, two of which are probably explained by errors in assembly; the origin of the third major difference is unclear. In addition there are eight sequence gaps within the Joint Sequence. At least six of these eight gaps are likely to be sites of transposable elements; the other two are complex. Of the 275 genes in common to both projects, 60% are identical within 1% of their predicted amino-acid sequence and 31% show minor differences such as in choice of translation initiation or termination codons; the remaining 9% show major differences in interpretation.

Animals↗

Development of diabetes mellitus in aging transgenic mice following suppression of pancreatic homeoprotein IDX-1.

Monogenic forms of diabetes can result from mutations in genes encoding transcription factors. Mutations in the homeodomain transcription factor IDX-1, a critical regulator of pancreas development and insulin gene transcription, confer a strong predisposition to the development of diabetes mellitus in humans. To investigate the role of IDX-1 expression in the pathogenesis of diabetes, we developed a model for the inducible impairment of IDX-1 expression in pancreatic beta cells in vivo by engineering an antisense ribozyme specific for mouse IDX-1 mRNA under control of the reverse tetracycline transactivator (rtTA). Doxycycline-induced impairment of IDX-1 expression reduced activation of the Insulin promoter but activated the Idx-1 promoter, suggesting that pancreatic beta cells regulate IDX-1 transcription to maintain IDX-1 levels within a narrow range. In transgenic mice that express both rtTA and the antisense ribozyme construct, impaired IDX-1 expression elevated glycated hemoglobin levels, diminished glucose tolerance, and decreased insulin/glucose ratios. Metabolic phenotypes induced by IDX-1 deficiency were observed predominantly in male mice over 18 months of age, suggesting that cellular mechanisms to protect IDX-1 levels in pancreatic beta cells decline with aging. We propose that even in the absence of Idx-1 gene mutations, pathophysiological processes that decrease IDX-1 levels are likely to impair glucose tolerance. Therapeutic strategies to attain normal glucose homeostasis by restoring normal IDX-1 levels may be of particular importance for older individuals with diabetes mellitus.

Aging↗

[Haemodialysed, hemiparetic patient operated on for aortic aneurysm followed by successful renal transplantation].

The authors present the case of a 58 years old male patient. According to his preceding record in 1991 he suffered speech disturbance and left-side hemiparesis due to multiplex vascular lesions. A fresh cerebral ictus caused a right side hemiparesis mainly in the upper limb in 1993 and sensomotororic aphasia has also been developed. In 1995 the patient was begun acute haemodialysis treatment due to his gravis uremic state, then his dialysis was continued 3 times 4 hours weekly. In 1997 the then 56 years old inveterate right-sided hemiparetic patient, treated with chronic haemodialysis requested to be put on the transplantation waiting list. The first thing that had to be done in case of this high-risk patient was the resection of the abdominal aortic aneurysm (38 mm x 67 mm x 115 mm in size) noticed at the ultrasound examination which was carried out in January 1997. The continuity of the vessel was secured by graft-interposition where the arteria mesenterica was also implanted. Following the successful operation, the patient was qualified for the transplantation list and in the February of 1998 a successful kidney-transplantation was carried out. Following the temporary, post-transplantation difficulties (post-operative 5th day acute rejection well-reacting to 3 steroid-shots; the two re-operations due to partial necrosis in the uretero-ureteralis anastomosis and successfully overcoming the Pseudomonas aeruginosa uroinfection) the patient is currently doing well and has no complaint.

Aortic Aneurysm, Abdominal↗

Defective signaling to Fyn by a T cell antigen receptor lacking the alpha -chain connecting peptide motif.

A key role in the communication between the alphabetaTCR and the CD3/zeta complex is played by a specific motif within the connecting peptide domain of the TCR alpha chain (alpha-CPM). T cell hybridomas expressing an alpha-CPM-mutated TCR show a dramatic impairment in antigen-driven interleukin-2 production. This defect can be complemented by a calcium ionophore, indicating that activation of the calcium pathway is impaired. Several lines of evidence implicate Fyn in the regulation of calcium mobilization, at least in part through the activation of phospholipase Cgamma. Here we have investigated the potential involvement of Fyn in the TCR alpha-CPM signaling defect. Using T cell hybridomas expressing either a wild-type TCR or an alpha-CPM mutant, we show that Fyn fails to be activated by the mutant receptor following SEB binding and fails to generate tyrosine-phosphorylated Pyk2, a member of the focal adhesion kinase family. This defect correlated with an impairment in phospholipase Cgamma phosphorylation. Production of interlukin-2 and activation of the transcription factor NF-AT in response to triggering of the TCR alpha-CPM mutant with SEB were fully restored in the presence of constitutively active Fyn. Hence the signaling defect generated by the TCR alpha-CPM mutation results at least in part from an impaired coupling of the TCR.CD3 complex to Fyn activation.

Adaptor Proteins, Signal Transducing↗

From sequence to chromosome: the tip of the X chromosome of D. melanogaster.

One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.

Animals↗

Characterization of antibodies to prostate-specific antigen.

Antibodies submitted to the ISOBM TD-3 PSA Workshop were tested for reactivity with free prostate-specific antigen (PSA) and the PSA alpha1-antichymotrypsin (ACT) complex, inhibition of proteolytic activity, recognition of continuous epitopes, and epitope specificity based on complete cross-inhibition studies. The antibodies could be separated into two categories: those recognizing hidden epitopes specific for free PSA, and those recognizing epitopes in both free PSA and the PSA-ACT complex. A large number of distinct antigenic domains were identified both in free PSA and the PSA-ACT complex.

Antibodies, Monoclonal↗

[Left branch portal vein thrombosis associated with hyperhomocysteinemia].

A 34 year-old man, who was a smoker, was hospitalised because of severe epigastric and right upper quadrant pain. An isolated left branch portal vein thrombosis was diagnosed using ultrasonography and arteriography. Two thrombogenic pathologies were found: i) a latent myeloproliferative syndrome with spontaneous presence of erythroid colony forming unit (CFU-E) in bone marrow culture, normal blood cell count, platelet count and medullogram; ii) a hyperhomocysteinemia associated with low serum folate levels and a methyl tetrahydrofolate reductase mutation. The association of these two factors probably resulted in portal vein thrombosis. This is the first adult case of a portal vein thrombosis associated with hyperhomocysteinemia. Increased homocysteine serum levels could be a previously unrecognized factor for portal vein thrombosis. Homocysteinemia should be systematically investigated in patients with idiopathic portal vein thrombosis since folate supplements could prevent deleterious vascular effects of hyperhomocysteinemia.

Adult↗

Semenogelin I and semenogelin II, the major gel-forming proteins in human semen, are substrates for transglutaminase.

The major seminal vesicle secreted proteins in human semen, semenogelin I and semenogelin II, interact non-covalently and via disulphide bridges to instantly form a coagulum upon ejaculation. The coagulum is liquefied after a few minutes due to the action of a prostatic serine protease, prostate-specific antigen (PSA). In contrast to rat semen, which forms an insoluble plug within minutes of expulsion, no transglutaminase-mediated cross-linking has been demonstrated in ejaculated human semen. However, we here show that semenogelin I and semenogelin II, both in seminal vesicle fluid and purified from semen, are substrates for factor XIIIa, the fibrin cross-linking transglutaminase. The cross-linking of the semenogelins, which was conformation-dependent, and the incorporation of a fluorescence-labelled amine, were visualised by SDS/PAGE and Western blot. Purified semenogelin I and semenogelin II could be cross-linked separately into complexes. Moreover, digestion of semenogelin with PSA produced fragments, some of which were cross-linked into complexes by factor XIIIa. We also found that PSA was unable to release any semenogelin fragments during exposure of the high molecular-mass complexes of cross-linked semenogelin to active PSA.

Cadaverine↗