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Biomedical subjects

P Persson

Publications and source records attributed to P Persson.

At least 19 recordsLinked to original sources
PubMed2006

Mapping and partial characterization of proteases expressed by a CHO production cell line.

The proteolytic activities expressed by a Chinese hamster ovary (CHO) cell line in the cultivation supernatant during the production of recombinant factor VIII were mapped with a broad spectrum protease assay and a series of different types of protease inhibitors. The destabilizing effect on the product emanated from a metalloproteinase, which could be effectively blocked by chelating agents to lead to product stabilization. Amino acid sequences of the isolated metalloproteinase were found to have sequence homology with matrix metalloproteinases (MMPs) MMP3, MMP10, and MMP12. Several species with metalloproteinase activity were characterized and found to be related to each other. The results indicate that an MMP pro-enzyme of >/=200 kDa was released from the CHO cells during the production phase. The enzyme expressed collagenase/gelatinase activity when activated. Due to autoproteolysis, a number of smaller, less specific MMPs were formed with the smallest form, a 19.4 kDa protein, being the most active. These results may be of particular relevance for other production processes using CHO cells for the expression of recombinant proteins.

Animals↗
PubMed2006

High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

Adaptation, Physiological↗
PubMed2006

Psychological wellbeing after laparoscopic and abdominal hysterectomy--a randomised controlled multicentre study.

OBJECTIVE: To compare laparoscopic hysterectomy and abdominal total hysterectomy regarding influence on postoperative psychological wellbeing and surgical measures. DESIGN: A prospective, open, randomised multicentre trial. SETTING: Five hospitals in the South East of Sweden. POPULATION: Hundred and twenty-five women scheduled for hysterectomy for benign conditions were enrolled in the study, and 119 women completed the study. Fifty-six women were randomised to abdominal hysterectomy and 63 to laparoscopic hysterectomy. METHODS: Psychometric tests measuring general wellbeing, depression and anxiety preoperatively and 5 weeks and 6 months postoperatively. MAIN OUTCOME MEASURES: Effects of operating method on the psychological wellbeing postoperatively. Analysis of data regarding operating time, peroperative and postoperative complications, blood loss, hospital stay and recovery time. RESULTS: No significant differences in the scores were observed between the two groups in any of the four psychometric tests. Both the surgical methods were associated with a significantly higher degree of psychological wellbeing 5 weeks postoperatively compared with preoperatively. The operating time was significantly longer for the laparoscopic hysterectomy group, but the duration of the stay in hospital and sick-leave were significantly shorter for laparoscopic hysterectomy group compared with the abdominal hysterectomy group. CONCLUSIONS: General psychological wellbeing is equal after laparoscopic and abdominal hysterectomy within 6 months after the operation. The advantages of the laparoscopic hysterectomy are the shorter stay in hospital and shorter sick-leave, but these issues must be balanced by a longer duration of the operation.

Adult↗
PubMed2005

Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia.

Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n=49) and male patients with schizophrenia (n=90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM+/-0.10 vs. 1.06 nM+/-0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM+/-0.19, n=37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM+/-0.17, n=34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM+/-0.10, n=19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.

Adolescent↗
PubMed2001

Routine analysis of alcohol and nonylphenol polyethoxylates in wastewater and sludge using liquid chromatography-electrospray mass spectrometry.

A wide range of alcohol and nonylphenol polyethoxylates was determined by separation on a reversed-phase liquid chromatographic column, followed by electrospray ionisation-mass spectral analysis. The compounds were separated chromatographically according to their aliphatic chain length. The mass spectral analysis functioned as a second separation step during which homologues of the ethoxylates were separated according to their polyethoxylate chain length. In this manner a truly orthogonal separation was obtained. The compounds were detected as ammonium complexes. The analysis presented is capable of qualitative and quantitative determination of a large number of ethoxylates as well as their metabolites in a single run. The method was applied to many different sample types, ranging from primary and treated wastewater to sludge. Batches of 50 real samples were routinely analysed without the need for cleaning the mass spectrometer or regeneration of the column. By utilising the extracted mass chromatograms, detection limits of 1 to 10 microg/l could be obtained for individual compounds in water samples, while the detection limits were around 100 microg/kg in sludge, depending on the degree of pollution.

Alcohols↗
PubMed2001

IR and EXAFS spectroscopic studies of glyphosate protonation and copper(II) complexes of glyphosate in aqueous solution.

The varying degrees of protonation of N-(phosphonomethyl)glycine (PMG, glyphosate) were investigated with infrared (IR) spectroscopy and ab initio frequency calculations. The zwitterionic nature of PMG in solution was confirmed, and intramolecular hydrogen bonding was identified. Successive protonation of the PMG molecule follows the order amine, phosphonate, carboxylate. Intramolecular hydrogen bonding is indicated to exist at all stages of protonation: between both RCO(2-) and RNH(2)(+) and RPO(3)(2-) and RNH(2+) in HL(2)(-) (where L represents the ligand PMG); between RCO(2)(-) and RNH(2)(+) in H(2)L(-); predominantly between RPO(3)(2-) and RNH(2)(+) in H(3)L. There are strong indications that the zwitterion is intact throughout the pH range investigated. Results from IR and extended X-ray absorption fine structure (EXAFS) spectroscopies provide new evidence for structures of N-(phosphonomethyl)glycinecopper(II) complexes. The structures of 1:1 complexes, CuL(-) and CuHL, are essentially the same, differing only in protonation of the phosphonate group. Copper(II) lies at the center of a Jahn-Teller distorted octahedron with all three donor groups (amine, carboxylate, phosphonate) of PMG chelating with copper(II) to form two five-membered chelate rings oriented in the equatorial plane. EXAFS indicates that oxygen (most likely a water molecule) is a fourth ligand, which would thus occupy the fourth corner in the equatorial plane of the elongated octahedron. CuL(2)(4-) most probably forms an isomeric mixture in solution, and there are indications that this mixture is dominated by complexes where two PMG ligands are bound to copper(II) via equatorial and axial positions, with both phosphonate and carboxylate donor groups responsible for chelation at axial positions.

Journal Article↗
PubMed2001

New class of oligonuclear platinum-thallium compounds with a direct metal-metal bond. 5. Structure determination of heterodimetallic cyano complexes in aqueous solution by EXAFS and vibrational spectroscopy.

The structures of three closely related heterodimetallic cyano complexes, [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) (n = 1-3), formed in reactions between [Pt(II)(CN)(4)](2)(-) and Tl(III) cyano complexes, have been studied in aqueous solution. Multinuclear NMR data ((205)Tl, (195)Pt, and (13)C) were used for identification and quantitative analysis. X-ray absorption spectra were recorded at the Pt and Tl L(III) edges. The EXAFS data show, after developing a model describing the extensive multiple scattering within the linearly coordinated cyano ligands, short Pt-Tl bond distances in the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) complexes: 2.60(1), 2.62(1), and 2.64(1) A for n = 1-3, respectively. Thus, the Pt-Tl bond distance increases with increasing number of cyano ligands on the thallium atom. In all three complexes the thallium atom and five cyano ligands, with a mean Pt-C distance of 2.00-2.01 A, octahedrally coordinate the platinum atom. In the hydrated [(NC)(5)Pt-Tl(CN)(H(2)O)(4)](-) species the thallium atom coordinates one cyano ligand, probably as a linear Pt-Tl-CN entity with a Tl-C bond distance of 2.13(1) A, and possibly four loosely bound water molecules with a mean Tl-O bond distance of about 2.51 A. In the [(NC)(5)Pt-Tl(CN)(2)](2)(-) species, the thallium atom probably coordinates the cyano ligands trigonally with two Tl-C bond distances at 2.20(2) A, and in [(NC)(5)Pt-Tl(CN)(3)](3)(-) Tl coordinates tetrahedrally with three Tl-C distances at 2.22(2) A. EXAFS data were reevaluated for previously studied mononuclear thallium(III)-cyano complexes in aqueous solution, [Tl(CN)(2)(H(2)O)(4)](+), [Tl(CN)(3)(H(2)O)], and [Tl(CN)(4)](-), and also for the solid K[Tl(CN)(4)] compound. A comparison shows that the Tl-C bond distances are longer in the dinuclear complexes [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) (n = 1-3) for the same coordination number. Relative oxidation states of the metal atoms were estimated from their (195)Pt and (205)Tl chemical shifts, confirming that the [(NC)(5)Pt-Tl(CN)(n)()](n)()(-) complexes can be considered as metastable intermediates in a two-electron-transfer redox reaction from platinum(II) to thallium(III). Vibrational spectra were recorded and force constants from normal-coordinate analyses are used for discussing the delocalized bonding in these species.

Chemical Phenomena↗
PubMed2001

(26)Al investigations at the AMS-laboratory in Lund.

At the accelerator mass spectrometry (AMS) laboratory in Lund, a facility for (26)Al analysis is under development. The sensitivity is expected to be several orders of magnitude higher than with standard mass spectrometry. The planned biomedical program includes studies of aluminium uptake, distribution and retention in man. The initial work has been concentrated on the construction and testing of a new dedicated injector for the accelerator and on the preparation of biological samples for aluminium analysis. The current quality of the facility is presented and the first experimental results reported.

Aluminum↗
PubMed2001

The DD5 gene of the decapod crustacean Penaeus japonicus encodes a putative exoskeletal protein with a novel tandem repeat structure.

A gene, named DD5, was identified in the penaeid prawn Penaeus japonicus and its cDNA cloned and sequenced. DD5 is expressed in the epidermal cells underlying the exoskeleton and the transcripts are detected specifically during the postmolt stage of the molt cycle. Sequence analysis of the conceptual protein product suggests that the DD5 protein is a component of the exoskeleton. The bulk of the protein consists of tandem repeats of a unit sequence of approximately 100 amino acids. The repeated sequences are highly homologous to one another and each of them includes a variant of the Rebers--Riddiford consensus sequence.

Amino Acid Sequence↗
PubMed2001

Speech recognition in background noise: monaural versus binaural listening conditions in normal-hearing patients.

HYPOTHESIS: Patients with unilateral conductive hearing impairment often experience a great advantage in improved hearing thresholds after reconstructive ear surgery because the binaural hearing leads to increased speech recognition in competing noise. The aim of this study was to develop a clinical audiometric test to quantify the ability of speech recognition in background noise preoperatively and postoperatively. METHODS: A model consisting of phonetically balanced (PB) monosyllabic words and/or a just-follow-conversation test (JFC) was used in 16 normal-hearing listeners. In 8 of the participants, JFC at two levels of background noise (60 and 40 dB sound pressure level) was used as the only method. The tasks were performed in an anechoic chamber with varying spatial separations of speech and noise sources under free field conditions. The tests were made binaurally and monaurally; the latter condition was achieved by occluding one ear with a hearing protector. In PB word tests, the percent of correctly repeated words was scored. In the JFC task, the speech signal was adjusted by the listener to a level where he or she could just understand what was being said. This was expressed as a signal-to-noise (S/N) ratio. RESULTS: In both types of tests, the subjects achieved significantly better speech recognition scores in the binaural situations. In summary, compared with monaural conditions, the subjects achieved 17% to 18% better speech recognition in PB tests, and in JFC tests a 2-to 3-dB lower S/N ratio in binaural conditions. CONCLUSION: These free field tests can be developed further as a clinical tool preoperatively and postoperatively to evaluate the effect of binaural hearing after ear surgery.

Audiometry, Pure-Tone↗
PubMed2001

Shake-up and shake-off excitations with associated electron losses in X-ray studies of proteins.

Photoionization of an atom by X-rays usually removes an inner shell electron from the atom, leaving behind a perturbed "hollow ion" whose relaxation may take different routes. In light elements, emission of an Auger electron is common. However, the energy and the total number of electrons released from the atom may be modulated by shake-up and shake-off effects. When the inner shell electron leaves, the outer shell electrons may find themselves in a state that is not an eigen-state of the atom in its surroundings. The resulting collective excitation is called shake-up. If this process also involves the release of low energy electrons from the outer shell, then the process is called shake-off. It is not clear how significant shake-up and shake-off contributions are to the overall ionization of biological materials like proteins. In particular, the interaction between the outgoing electron and the remaining system depends on the chemical environment of the atom, which can be studied by quantum chemical methods. Here we present calculations on model compounds to represent the most common chemical environments in proteins. The results show that the shake-up and shake-off processes affect approximately 20% of all emissions from nitrogen, 30% from carbon, 40% from oxygen, and 23% from sulfur. Triple and higher ionizations are rare for carbon, nitrogen, and oxygen, but are frequent for sulfur. The findings are relevant to the design of biological experiments at emerging X-ray free-electron lasers.

Chemical Phenomena↗
PubMed2000

Molecular cloning of the crustacean DD4 cDNA encoding a Ca(2+)-binding protein.

A cDNA, named DD4, was identified in the prawn Penaeus japonicus in a search for genes that were expressed during calcification of the crustacean exoskeleton. DD4 transcripts were detected in the epidermal cells underlying the exoskeleton specifically during the postmolt stage, when the calcification takes place. In the DD4 cDNA an open reading frame of 542 amino acids was found. The deduced protein was acidic and proline-rich, and exhibited similarity to the Drosophila Ca(2+)-binding protein calphotin in the amino acid sequence and composition. The DD4 cDNA was expressed in Escherichia coli to characterize Ca(2+)-binding of the encoded protein, and Ca(2+) was found to bind to a central segment of 186 amino acids. The DD4 protein is suggested to play a role in the calcification of the crustacean exoskeleton.

Amino Acid Sequence↗
PubMed2000

Metal Ion Coordination at the Water-Manganite (gamma-MnOOH) Interface.

The local structure of Cd(II) surface complexes adsorbed onto manganite (gamma-MnOOH) has been investigated by extended X-ray absorption fine structure (EXAFS) spectroscopy. Adsorption experiments were carried out within the pH range 7.4-9.8 and with surface coverage from 2.2 to 8.9 µmol/m(2). Quantitative analysis of the EXAFS spectra shows little difference in the local coordination environment of Cd regardless of the coverage. Analysis of the first shell required a third cumulant in an asymmetric distribution model (i.e., non-Gaussian distribution), indicating distorted CdO(6) octahedra with an average Cd-O distance of 2.31 Å. A single second shell of Mn neighbors at a constant distance of 3.33 Å was detected. This comparatively short distance shows that inner-sphere complexes are formed. No Cd neighbor was found which means that cadmium hydroxide precipitation or cluster formation does not occur at the surface at the experimental conditions probed in this study. We assign the Cd-Mn distance to edge sharing between CdO(6) and MnO(6) octahedra, with a geometry similar to that in the mixed solid Cd(2)Mn(3)O(8). This adsorption mode is possible on the {110} and {010} cleavage planes of manganite. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Metal Ion Coordination at the Water-Manganite (gamma-MnOOH) Interface.

The local structure of Zn(II) adsorbed at the water-manganite (gamma-MnOOH) interface has been investigated by extended X-ray absorption fine structure (EXAFS) spectroscopy. Adsorption experiments were carried out within the pH range 6.17-9.87 and surface coverages of 0.9 to 9.7 µmol/m(2)cZn(II) coordination was observed to change from six to four as pH was increased. This was indicated by a change in Zn-O distance from 2.04 to 1.96 Å and by a decrease in the obtained coordination numbers. Two higher shells were detected at about 3.08 and 3.33 Å, at all pH values and surface coverage investigated. As the backscattering phase and amplitude functions of Mn and Zn are similar, we used structural and chemical considerations to assign the backscattering at 3.08 Å to Mn neighbors, and the one at 3.33 Å to Zn atoms. Indeed the size of the Zn polyhedra, especially of ZnO(4), does not quite match the structure of the manganite surface. We conclude that Zn(II) forms multinuclear hydroxo-complexes or a zinc hydroxide phase at the surface, as it might be easier for an additional Zn(II) to bond to an already sorbed Zn. These results were compared to our previous EXAFS study of Cd(II) adsorption onto manganite, where mononuclear inner-sphere complexes bound to the surface via edges were found. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex.

The basic helix-loop-helix (bHLH) transcription factor mammalian achaete-scute homolog-1 (MASH-1 in mouse and HASH-1 in human) is essential for proper development of olfactory and most peripheral autonomic neurons, and for the formation of distinct neuronal circuits within the central nervous system. We have previously shown that HASH-1 is expressed in neuroblastoma tumors and cell lines, and in this study we have used the yeast two-hybrid system to isolate HASH-1 interacting proteins from a human neuroblastoma cDNA library. Two of the isolated clones contained cDNA from the E2-2 gene (also known as ITF2/SEF2-1). We show that E2-2 interacts with HASH-1 in both yeast and mammalian cells. The HASH-1/E2-2 complex binds an E-box (CACCTG) in vitro, and transactivates an E-box containing reporter construct in vivo. Furthermore, E2-2 seems to be one of the major HASH-1 interacting proteins in extracts from neuroblastoma cells. In conclusion, E2-2 forms a functional complex with HASH-1, and might therefore be involved in the development of specific parts of the central and peripheral nervous systems.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2000

Benzenecarboxylate Surface Complexation at the Goethite (alpha-FeOOH)/Water Interface.

A surface complexation model describing the adsorption of three benzenecarboxylates (phthalate, trimellitate, and pyromellitate) on goethite (alpha-FeOOH) was calibrated on data using goethite particles of 37 and 43 m(2)/g surface area. The models predict potentiometric titration and batch adsorption data with the multisite complexation model coupled with the three-plane model to account for surface electrostatics. The modeling parameters were found to be similar to those calibrated on benzenecarboxylate adsorption data on goethite particles of 90 m(2)/g (Boily et al. Geochim. Cosmochim. Acta, in press). The significance of the benzenecarboxylate-dependent values of the modeling parameters is also discussed. The values of the capacitances of the inner- and outer-Helmholtz planes were shown to be important modeling parameters to model the benzenecarboxylate-dependent slopes of the adsorption edges. It was shown that the larger the charge of the ligand, the larger the capacitance of the outer-Helmholtz plane. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

The presence of high-affinity, low-capacity estradiol-17beta binding in rainbow trout scale indicates a possible endocrine route for the regulation of scale resorption.

High-affinity, low-capacity estradiol-17beta (E(2)) binding is present in rainbow trout scale. The K(d) and B(max) of the scale E(2) binding are similar to those of the liver E(2) receptor (K(d) is 1.6 +/- 0.1 and 1.4 +/- 0.1 nM, and B(max) is 9.1 +/- 1.2 and 23. 1 +/- 2.2 fmol x mg protein(-1), for scale and liver, respectively), but different from those of the high-affinity, low-capacity E(2) binding in plasma (K(d) is 4.0 +/- 0.4 nM and B(max) is 625.4 +/- 63. 1 fmol x mg protein(-1)). The E(2) binding in scale was displaced by testosterone, but not by diethylstilbestrol. Hence, the ligand binding specificity is different from that of the previously characterized liver E(2) receptor, where E(2) is displaced by diethylstilbestrol, but not by testosterone. The putative scale E(2) receptor thus appears to bind both E(2) and testosterone, and it is proposed that the increased scale resorption observed during sexual maturation in both sexes of several salmonid species may be mediated by this receptor. No high-affinity, low-capacity E(2) binding could be detected in rainbow trout gill or skin.

Ammonium Sulfate↗