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Biomedical subjects

C Gustafsson

Publications and source records attributed to C Gustafsson.

At least 19 recordsLinked to original sources
PubMed2006

Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha.

Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10, transforming growth factor-beta (TGF-beta) and tumour necrosis factor-alpha (TNF-alpha) in decidual tissue with or without labour. Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n=17) or after normal vaginal delivery (n=15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E(2) synthase (mPGES). Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.

Adult↗
PubMed2002

Psychometric evaluation of a Swedish version of the Reiss Screen for Maladaptive Behavior.

BACKGROUND: People with intellectual disability (ID) are afflicted by mental health problems to a greater extent than other individuals, and the coexistence of ID and mental health problems involves diagnostic as well as treatment difficulties. METHODS: A Swedish version of the Reiss Screen for Maladaptive Behavior (RSMB), an instrument used for identification of mental health problems in people with intellectual disability (ID) was evaluated in terms of inter-rater agreement, internal consistency, item grouping and criterion validity based on a random sample and a clinical group of adults with ID. RESULTS: The Swedish version of the RSMB had moderate-to-low inter-rater agreement on specific items and good internal consistency. The total score was considered to be a fairly reliable measure of a positive or negative result on the RSMB. A principal component analysis yielded seven interpretable components. A close resemblance in sets of items between the Swedish version and the original version of RSMB was found for three subscales: Aggressive Behaviour, Avoidance Disorder and Depression (Behavioural Signs). The outcome of the criterion validity analysis indicated a higher rate of false negatives than false positives. CONCLUSIONS: The potential influence of concurrent psychopharmacological treatment is discussed. It is concluded that the Swedish version of the RSMB can be used as intended by staff as a primary screening device for the identification of mental health problems among people with ID in a Swedish setting.

Adult↗
PubMed2001

Reliability and responsiveness of three different pain assessments.

The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness.

Adult↗
PubMed2000

Directed evolution: the 'rational' basis for 'irrational' design.

The development of powerful genetic manipulation formats has revolutionized the creation of functional biological molecules. Recent advances in directed evolution demonstrate that multiple properties of proteins can be optimized simultaneously and rapidly. Improved proteins often contain multiple and dispersed substitutions that act synergistically to improve enzyme properties and function. The benefits of such multiple changes are often not predictable from a priori structural knowledge. Furthermore, alternative solutions to gaining functional change can be obtained.

Animals↗
PubMed1999

Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli.

The fmu gene product has been proposed to be an RNA methyltransferase [Koonin, E. V. (1994) Nucleic Acids Res. 22, 2476-2478]. Fmu has been cloned and expressed, and the encoded 47 kDa protein has been purified and characterized. The enzyme catalyzed specific methylation of C967 of unmodified 16S rRNA transcripts. A 16mer stem-loop structure containing C967 (nt 960-975) was also a good substrate for the enzyme in vitro. Methylation of C967 was confirmed by several methods including analysis of RNase T1 digests and nearest-neighbor analysis. Fmu did not catalyze methylation of transcripts of 23S rRNA. E. coli cells that contained kanr-disrupted fmu produced 16S rRNA that could be specifically methylated by Fmu in vitro at C967 but not C1407. Further, fmu disruption did not significantly alter the growth rate of E. coli in rich or minimal media. We propose renaming this ORF "rrmB" and the enzyme "RrmB" for rRNA methyltransferase.

5-Methylcytosine↗
PubMed1999

Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products.

The structures of complex polyketide natural products, such as erythromycin, are programmed by multifunctional polyketide synthases (PKSs) that contain modular arrangements of functional domains. The colinearity between the activities of modular PKS domains and structure of the polyketide product portends the generation of novel organic compounds-"unnatural" natural products-by genetic manipulation. We have engineered the erythromycin polyketide synthase genes to effect combinatorial alterations of catalytic activities in the biosynthetic pathway, generating a library of >50 macrolides that would be impractical to produce by chemical methods. The library includes examples of analogs with one, two, and three altered carbon centers of the polyketide products. The manipulation of multiple biosynthetic steps in a PKS is an important milestone toward the goal of producing large libraries of unnatural natural products for biological and pharmaceutical applications.

Catalytic Domain↗
PubMed1999

Characterisation of particle properties and compaction behaviour of hydroxypropyl methylcellulose with different degrees of methoxy/hydroxypropyl substitution.

The particle characteristics and compaction behaviour of hydroxypropyl methylcellulose (HPMC) powders from two different suppliers were studied regarding effects of methoxy/hydroxypropyl substitution. Samples included Methocel K4M (low substitution ratio), E4M (medium) and F4M (high) and the corresponding substitution ratios from Metolose: 90 SH 4000, 60 SH 4000, and 65 SH 4000. Characterisation of the particle properties and compaction behaviour of the pure polymers suggested that reported differences in drug release behaviour of Methocel E4M compared with the other two powders may be related to the lower powder surface area, differing particle morphology and lower fragmentation propensity during compaction. In addition, compacts of Methocel E4M were weaker when tested in both axial and radial directions and had different porosity and elastic recovery properties. There were no differences between the polymers in degree of disorder, as evaluated by solid-state nuclear magnetic resonance spectroscopy. The different behaviour of Methocel E4M could, however, be related to the overall higher total degree of substitution of this polymer and in particular the high content of methoxy groups compared to the other polymers. The methoxy substituent is hydrophobic and may, when present in sufficiently high concentrations, change the particulate and mechanical properties of the powder, thus potentially affecting the compactability. The high content of methoxy groups might also decrease the development of inter- and intraparticulate hydrogen bonds during compaction, and suppress the actions of the hydrophilic hydroxypropyl groups, both of which could affect drug release.

Compressive Strength↗
PubMed1999

Use of tablet tensile strength adjusted for surface area and mean interparticulate distance to evaluate dominating bonding mechanisms.

In this study, tablet tensile strength has been adjusted for tablet surface area and the average distance between particles in compacts of different materials. The aim of the study was to evaluate the feasibility of using this concept to assess the dominating interparticulate bonding mechanisms. Adjustment of the tensile strength for both tablet surface area and mean pore radius gave similar bonding strength values for materials bonding mainly by weak distance forces (crystalline lactose, sucrose, and microcrystalline cellulose) almost independently of compaction pressure. However, particle size and other factors may still affect the compensated strength values. The bond strength was much higher and more varied for materials bonding also with solid bridges (potassium chloride, sodium chloride, and possibly also sodium bicarbonate and amorphous lactose). For these materials, particle size and compaction pressure had a substantial effect on the bond strength. It is probably the formation of continuous bridges between adjacent particles that is important in these materials rather than the surface properties and the average distance between particles positioned at some distance from each other. Hence, adjusting the tensile strength of compacts does not necessarily reflect all the dominating factors responsible for interparticulate bonding. Nonetheless, adjustment for tablet surface area and mean pore radius allowed discrimination between different dominating interparticulate bonding mechanisms in these compacted materials.

Chemistry, Pharmaceutical↗
PubMed1998

Cellulose powder from Cladophora sp. algae.

The surface are and crystallinity was measured on a cellulose powder made from Cladophora sp. algae. The algae cellulose powder was found to have a very high surface area (63.4 m2/g, N2 gas adsorption) and build up of cellulose with a high crystallinity (approximately 100%, solid state NMR). The high surface area was confirmed by calculations from atomic force microscope imaging of microfibrils from Cladophora sp. algae.

Cellulose↗
PubMed1998

Identification of the rrmA gene encoding the 23S rRNA m1G745 methyltransferase in Escherichia coli and characterization of an m1G745-deficient mutant.

An Escherichia coli mutant lacking the modified nucleotide m1G in rRNA has previously been isolated (G. R. Björk and L. A. Isaksson, J. Mol. Biol. 51:83-100, 1970). In this study, we localize the position of the m1G to nucleotide 745 in 23S rRNA and characterize a mutant deficient in this modification. This mutant shows a 40% decreased growth rate in rich media, a drastic reduction in loosely coupled ribosomes, a 20% decreased polypeptide chain elongation rate, and increased resistance to the ribosome binding antibiotic viomycin. The rrmA gene encoding 23S rRNA m1G745 methyltransferase was mapped to bp 1904000 on the E. coli chromosome and identified to be identical to the previously sequenced gene yebH.

Chromatography, High Pressure Liquid↗
PubMed1997

The spoU gene of Escherichia coli, the fourth gene of the spoT operon, is essential for tRNA (Gm18) 2'-O-methyltransferase activity.

We have evidence that the open reading frame previously denoted spoU is necessary for tRNA (Gm18) 2'-O-methyltransferase activity. The spoU gene is located in the gmk-rpoZ-spoT-spoU-recG operon at 82 minutes on the Escherichia coli chromosome. The deduced amino acid sequence of spoU shows strong similarities to previously characterized 2'-O-methyltransferases. Comparison of the nucleoside modification pattern of hydrolyzed tRNA, 16S rRNA and 23S rRNA from wild-type and spoU null mutants showed that the modified nucleoside 2'-O-methylguanosine (Gm), present in a subset of E. coli tRNAs at residue 18, is completely absent in the spoU mutant, suggesting that spoU encodes tRNA (Gm18) 2'-O-methyltransferase. Nucleoside modification of 16S and 23S rRNA was unaffected in the spoU mutant. Insertions in the downstream recG gene did not affect RNA modification. Absence of Gm18 in tRNA does not influence growth rate under the tested conditions and does not interfere with activity of the SupF amber suppressor, a suppressor tRNA that normally has the Gm18 modification. We suggest that the spoU gene be renamed trmH (tRNA methylation).

Amino Acid Sequence↗
PubMed1997

The prevalence of people with intellectual disability admitted to general hospital psychiatric units: level of handicap, psychiatric diagnoses and care utilization.

Previous studies have stated that people with intellectual disability (ID) are more often afflicted by psychiatric disorders than the general population. In spite of the high prevalence of psychiatric disorders among people with ID, it is not known how many actually receive psychiatric in-patient care and treatment by the mental health services. In the present study, the number of people with mild and severe ID admitted to in-patient psychiatric care were compared with corresponding figures in the general population in Sweden. The results show a low frequency of psychiatric care utilization among people with ID and coexisting psychiatric disorders in comparison to the proportion of psychiatric care utilization among people with psychiatric disorders in the general population. The results are discussed in terms of how the level of ID might influence referral or diagnoses, the length of admissions, and the support provided within the special services to people with ID and psychiatric disorders.

Adult↗
PubMed1997

Effects of reduced oxygen partial pressure on cognitive performance in confined spaces.

The reduction of oxygen levels is a technique used both for fire fighting and fire protection in confined spaces. The purpose of this study was to find out if and how reduced oxygen levels affect cognitive performance in a small group of persons living in a confined space such as a submarine. In 3 separate experiments lasting for 11 to 14 days, a total of 22 men were exposed to normoxic and different levels of hypoxic normobaric atmospheres (15, 14, and 13 kPa O2). Each participant completed a cognitive test battery twice every 24-hr period in the first 2 experiments, but only once a day in the 3rd experiment. Performance in almost all tests improved with the number of test sessions performed, despite reductions of the oxygen partial pressure. Under the conditions tested, cognitive performance decrements could not be observed if inspiratory oxygen partial pressure was kept above 13 kPa.

Adult↗
PubMed1997

Effects of normobaric hypoxic confinement on visual and motor performance.

INTRODUCTION: The use of reduced oxygen levels has been suggested for fire prevention in closed spaces, such as submarines. However, if humans are to work and live in environments with reduced oxygen levels, the effect of hypoxia on human performance must be further assessed. METHODS: In 3, 11- to 14-d confinements a total of 22 subjects were exposed to different levels of normobaric hypoxia (13, 14, and 15 kPa O2), for up to 10 d, with intervening periods of normoxia. In each experiment eight subjects were divided into two teams, working in 6-h shifts around the clock. Subjects performed tests of spatial orientation, visual reaction time, parallel processing and motor skills. Performance tests and questionnaires were administered once or twice in every 24-h period. RESULTS: All of the subjects appeared to tolerate the acute reduction in oxygen partial pressure well. In many of the tests performance improved with time as a result of learning, despite reductions in the oxygen level. No reduction in performance or decrease in rate of learning was observed at any of the oxygen levels tested. CONCLUSIONS: Oxygen levels down to 14 kPa appear not to impair visual and motor performance during rest.

Adult↗
PubMed1996

Identification of new RNA modifying enzymes by iterative genome search using known modifying enzymes as probes.

The complete nucleotide sequences of the Haemophilus influenzae and Mycoplasma genitalium genomes and the partially sequenced Escherichia coli chromosome were analyzed to identify open reading frames (ORFs) likely to encode RNA modifying enzymes. The protein sequences of known RNA modifying enzymes from three families--m5U methyltransferases, psi synthases and 2'-O methyltransferases--were used as probes to search sequence databases for homologs. ORFs identified as homologous to the initial probes were retrieved and used as new probes against the databases in an iterative manner until no more homologous ORFs could be identified. Using this approach, we have identified two new m5U methyltransferases, seven new psi synthases and four new 2'-O methyltransferases in E. coli. Many of the ORFs found in E.coli have direct genetic counterparts (orthologs) in one or both of H.influenzae and M.genitalium. Since there is a near-complete knowledge of RNA modifications in E.coli, functional activities of the proteins encoded by the identified ORFs were proposed based on the level of conservation of the ORFs and the modified nucleotides.

Amino Acid Sequence↗
PubMed1994

Production of large amounts of recombinant interleukins by cDNA transfected mouse myeloma cells cultured in dialysis tubing.

Studies of interleukin function often require large quantities of these highly expensive substances. The available interleukins are generally recombinant proteins produced in bacteria or yeast and, less commonly, interleukins produced by mammalian cells, which provide appropriate glycosylation and other post-translational modifications. Due to differences in biosynthesis, difficulties in production and purification the quality of the interleukin preparations may vary. We have taken advantage of the recently developed constitutively interleukin-secreting mouse myeloma cell lines and the dialysis tubing culture technique, which permit cells to be grown at high densities, in order to establish a method for the production of large amounts of recombinant murine IL-2 and IL-4. We show that these interleukins can be produced at low cost and in concentrations 20-30-fold higher than in conventional culture flasks. A single dialysis tubing culture will produce more than 10(6) U of interleukin which may be compared with the available commercial preparations containing between 10- and a 100-fold less per vial. The IL-2 and IL-4 produced in this manner are biologically active molecules as demonstrated by the strong proliferative response of clonal T cells and the isotype-switching effect in LPS-stimulated splenic B cell cultures. The dialysis tubing culture technique is a simple and highly cost-effective means of generating large quantities of biologically active interleukins and is especially suitable for research laboratories interested in functional studies of these proteins.

Animals↗