Biomedical subjects

G Larsson

Publications and source records attributed to G Larsson.

At least 19 recordsLinked to original sources

PubMed2006

Development of a disease-specific Quality of Life questionnaire module for patients with gastrointestinal neuroendocrine tumours.

Quality of life (QoL) measurements are increasingly being used as an end point in cancer clinical trials. Standard generic QoL questionnaires may not assess symptoms produced by neuroendocrine tumours. Here we report the development of a disease-specific quality of life score questionnaire for patients with neuroendocrine tumours of the gut to supplement the EORTC core cancer questionnaire, the QLQ-C30. Phases 1-3 of the EORTC quality of life group guidelines for module development were used to design the new questionnaire. Forty-one relevant issues (questions) were generated after an extensive literature search. Following interviews of 15 health care workers and 35 patients, a 35 question provisional questionnaire was constructed. This was translated into seven European languages and pre-tested in 180 patients resulting in a 21-item module that will be validated in an international clinical trial. The EORTC QLQ-NET21 provides a site-specific module to supplement the QLQ-C30 for patients with neuroendocrine tumours.

Adolescent↗

PubMed2003

Urethral injection for stress urinary incontinence: long-term results with dextranomer/hyaluronic acid copolymer.

Urethral injection is a convenient, minimally invasive means of treating stress urinary incontinence (SUI). We present long-term follow-up data from 20 patients originally recruited in 1994-95 (mean age 67 years) to receive urethral injection with dextranomer/hyaluronic acid (Dx/HA) copolymer. The majority of patients had failed previous therapy for SUI. If the first injection was unsuccessful, up to two further injections were offered. Only 3 patients (15%) failed to show a response to treatment. Sixteen women were reassessed during 2001 (4 had died of causes unrelated to the study treatment). A sustained response throughout the follow-up period was reported in 9/16 patients (57%), with incontinence recurring in just 4 (25%). None of the 7 patients with persistent or recurrent incontinence were cured by subsequent treatments, including surgery. In conclusion, urethral injection with Dx/HA copolymer offers promising long-term efficacy in the treatment of SUI, regardless of old age or failure to respond to previous therapy.

Adult↗

PubMed2003

Medium and copy number effects on the secretion of human proinsulin in Escherichia coli using the universal stress promoters uspA and uspB.

The use of the uspA and uspB promoters (universal stress promoters) for heterologous protein production in Escherichia coli is described. Best results were obtained with a moderate copy number vector (15-60 copies) bearing the uspA promoter, reaching 4.6 mg/g dry cell weight (DCW) of ZZ-proinsulin secreted to the periplasm and 1.9 mg/g DCW secreted to the culture medium. These values are about 1.7-fold higher than those previously reported with the same ZZ fusion tag and the SpA leader peptide showing that these stress promoters are potentially valuable for recombinant protein secretion in E. coli. It is further demonstrated that the use of M9 minimal medium is advantageous for protein secretion as compared to LB rich medium.

Bacterial Proteins↗

PubMed2003

Distress, quality of life and strategies to 'keep a good mood' in patients with carcinoid tumours: patient and staff perceptions.

Patients with carcinoid tumours have reported a relatively good health-related quality of life (HRQoL) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, EORTC QLQ-C30), and low levels of anxiety and depression (Hospital Anxiety and Depression Scale, HADS). The aim was to test the validity of these results. Data were gathered through interviews with 19 patients and 19 staff. Participants were asked about disease and treatment related distress, important aspects of quality of life and strategies to 'keep a good mood'. Patients were interviewed about themselves and staff were interviewed about a certain patient. Data were analysed by content analysis. Identified aspects of distress and quality of life were referred to an emotional, a physical and a social dimension. Most aspects of distress were of a physical character whereas most aspects of quality of life were of a social character. Several aspects of emotional distress not included in the EORTC QLQ-C30 and/or the HADS were identified.

Adaptation, Psychological↗

PubMed2002

Cell and process design for targeting of recombinant protein into the culture medium of Escherichia coli.

This paper is a review of strategies to introduce protein into the liquid medium of Escherichia coli K-12 industrial production cells. The cell design strategies are generally based on one of two general mechanisms. The first strategy involves a two-stage translocation using active transporters in the cytoplasmic membrane followed by passive transport through the outer membrane. Passive transport is achieved through either external or internal destabilization of the E. coli structural components. The latter can be achieved by transplantation of destabilizing components (lysis proteins) that work by permeabilization of the outer membrane from the interior of the cell, or by using cells carrying mutations of structural components. Passive transport can also be achieved by a chemical, mechanical, or enzymatic permeabilization directed from outside the cell. The second strategy is realized through transplantation of proteins capable of active transport over one or both of the membranes. This involves the transplantation of secretion mechanisms into the K-12 cell from pathogenic E. coli as well as from other species. The process design strategies are dependent on environmental conditions and must take into account changes in physical parameters, medium design, and influx of limiting carbon source in fed-batch cultivation.

Bacterial Outer Membrane Proteins↗

PubMed2002

Introduction of the carbohydrate-activated promoter P(malK) for recombinant protein production.

A production protocol for the use of the malK promoter was established. The protocol includes two phases: an initial fed-batch phase on glucose to reach a high cell density and a fed-batch phase on maltose for production of the desired recombinant protein. It is suggested that this cultivation scheme could be used for all promoters that are catabolite repressed by glucose and where growth and production need to be separated. The specific feature of this system is shown by its ability to control the rate of synthesis of the product protein, ss-galactosidase. In the production phase with a constant feed or an exponential feeding of 0.1 h(-1) it took 4 h longer to reach the maximum specific production rate than with the higher dilution rates of 0.25 h(-1) and 0.4 h(-1), respectively. In the above experiments a dilution rate of 0.3 h(-1) in the growth phase was used. The volumetric production of this system could furthermore be extended to 40 h. All protocol procedures so far tested resulted in the same maximum production rate, but reached in different lengths of time. It is argued that this system is particularly well suited for the production of proteins that have a complex structure and/or need to be produced in a soluble form or to be exported to the periplasm.

ATP-Binding Cassette Transporters↗

PubMed2002

Growth rate-dependent changes in Escherichia coli membrane structure and protein leakage.

The phospholipid and fatty acid content of the Escherichia coli membrane were investigated during continuous cultivation. At low growth rates, there was an increase in cardiolipin produced at the expense of phosphatidylethanolamine. Phosphatidylglycerol had a maximum at a growth rate of 0.3 h(-1). The amount of cyclic fatty acids was markedly increased at lower growth rates, while there was an evident minimum at 0.3 h(-1). This was also the case for saturated fatty acids. At this point, the unsaturated fatty acids had a maximum depending mainly on changes in cis-vaccenic acid. The mechanical strength towards sonication and osmotic shock/enzymatic treatment showed that the cells were more rigid at low dilution rates. However, this was accompanied by a higher cell lysis, a reduced capacity for total and specific protein production and a lower yield of cells. The amount of lipid A in the medium (endotoxin) was constant and negligible at all growth rates. The leakage of periplasmic protein to the medium had an optimum at 0.3 h(-1), resulting in a transport of 20% of the total recombinant product. It is argued that this constitutes the point of highest membrane fluidity and thus an increase possibility for protein transport.

Cell Membrane↗

PubMed2002

'Satisfaction with care': associations with health-related quality of life and psychosocial function among Swedish patients with endocrine gastrointestinal tumours.

The aims of this study were to investigate 'satisfaction with care' and its possible relationships to hope, health-related quality of life, anxiety and depression. Eighty-five patients with endocrine gastrointestinal (GI) tumours responded to questionnaires a few days after a hospital visit. 'Satisfaction with care' was assessed by the Comprehensive Assessment of Satisfaction with Care (CASC), health-related quality of life by the EORTC QLQ C-30 and anxiety and depression by the Hospital Anxiety and Depression Scale (HADS). Patients' highest satisfaction scores were obtained for 'general satisfaction' and 'nurses' and doctors' technical skills'. The lowest satisfaction was expressed for 'doctors' interpersonal skills', 'nurses' communication skills' and 'care organization'. Patients reporting a clinically relevant level of anxiety were less satisfied with several care aspects than those reporting less anxiety. Satisfaction with 'nurses' communication skills' and 'doctors' interpersonal skills' was associated with several aspects of health-related quality of life, whereas satisfaction with 'doctors' information', 'nurses' technical skills' and 'general satisfaction' was not. Satisfaction with psychosocial aspects of care is related to the psychosocial function of patients with endocrine GI tumours.

Adult↗

PubMed2001

Atomic resolution structure of Escherichia coli dUTPase determined ab initio.

Cryocooled crystals of a mercury complex of Escherichia coli dUTPase diffract to atomic resolution. Data to 1.05 A resolution were collected from a derivative crystal and the structure model was derived from a Fourier map with phases calculated from the coordinates of the Hg atom (one site per subunit of the trimeric enzyme) using the program ARP/wARP. After refinement with anisotropic temperature factors a highly accurate model of the bacterial dUTPase was obtained. Data to 1.45 A from a native crystal were also collected and the 100 K structures were compared. Inspection of the refined models reveals that a large part of the dUTPase remains rather mobile upon freezing, with 14% of the main chain being totally disordered and with numerous side chains containing disordered atoms in multiple discrete conformations. A large number of those residues surround the active-site cavity. Two glycerol molecules (the cryosolvent) occupy the deoxyribose-binding site. Comparison between the native enzyme and the mercury complex shows that the active site is not adversely affected by the binding of mercury. An unexpected effect seems to be a stabilization of the crystal lattice by means of long-range interactions, making derivatization a potentially useful tool for further studies of inhibitor-substrate-analogue complexes of this protein at very high resolution.

Binding Sites↗

PubMed2001

The C-terminus of dUTPase: observation on flexibility using NMR.

The dynamics of the C-terminus of the dUTPases from Escherichia coli and equine infectious anaemia virus (EIAV) were studied by 1H-(15)N nuclear magnetic resonance spectroscopy. The two enzymes differ with regard to flexibility in the backbone of the 15 most C-terminal amino acid residues, some of which are conserved and essential for enzymic activity. In the bacterial enzyme, the residues closest to the C-terminus are highly flexible and display a correlation time in the nanosecond time range. No similar high flexibility could be detected for the C-terminal part of EIAV dUTPase, indicating a different time range of flexibility.

Escherichia coli↗

PubMed2001

Gross motor ability in Rett syndrome--the power of expectation, motivation and planning.

A main task for the physiotherapist at the Swedish Rett Center is to document and report successful treatment. This report shows the possibility to regain function, get variation and avoid contractures for several years. A thorough neurologic, orthopaedic and physiotherapeutic assessment and analysis is essential. We stress the importance of keeping the feet in good position, using surgery and well fitting orthoses when needed, making standing possible and for some persons, walking. For the effect of treatment the following factors were of vital importance: the expectations of the persons treating the girl/woman - what they believed she could do, the motivation of the girl/woman herself, a joint plan for intervention including everyone involved, and well educated personnel, well informed about Rett syndrome--its problems and possibilities.

Adolescent↗

PubMed2001

A comprehensive assessment of satisfaction with care: preliminary psychometric analysis in French, Polish, Swedish and Italian oncology patients.

Satisfaction with care may be closely related to quality of life in cancer patients. This evaluation is especially relevant when quality of care is considered. The present study assessed whether equivalent scaling properties could be found in a comprehensive assessment of satisfaction with care (CASC) administered in cancer patients from French, Polish and Swedish oncology settings, in comparison to the scaling properties previously evidenced in the CASC with an Italian sample. A total of 140, 186 and 133 oncology patients were approached in France, Poland and Sweden, respectively. Specific items in the CASC were identified as consistently omitted across country samples. Multitrait scaling analysis on an item-grouping adapted for the French, Polish, Swedish and Italian samples provided excellent internal consistencies and convergent validity estimates. Discriminant validity proved less satisfactory, evidencing overlap between hypothesised care dimensions across country samples. The identification of omitted or overlapping items will lead to the design of a revised CASC version to further test in larger cross-cultural samples.

Adult↗

PubMed2001

Acute leukaemia or highly malignant lymphoma patients' quality of life over two years: a pilot study.

The aim of this study was, first, to investigate the quality of life and sense of coherence for acute leukaemia and malignant lymphoma patients at the start of treatment and over 2 years. A second aim was to compare questionnaire responses with patients' statements in open-ended interviews. A consecutive sample of 16 patients responded to the Quality of Life Questionnaire (QLQ-C30), Lund Gerontological Centre questionnaire and the Sense of Coherence Scale at the start of treatment and after 12 and 24 months. The QLQ-C30 questionnaire was administered also after 4, 8, 16 and 20 months. Tape-recorded open-ended interviews were conducted every 4 months before the patients responded to the questionnaires. Quality of life (QoL) and sense of coherence were scored more highly at the beginning of treatment for patients who did not relapse, than for those who relapsed. This difference remained throughout the study period. There was no correspondence in responses between questionnaire and personal interviews, although the results from the interviews, in some aspects, validated the result from the QLQ-C30. Those patients who relapsed may have had different prerequisites or been in a worse position at the onset of the disease and, reasonably, they needed more compensatory nursing care. More knowledge about the correspondence between a person's perceived QoL when discussed in personal interviews compared with responses given in standardised QoL questionnaires is needed before any assumption about clinical relevance can be made.

Acute Disease↗

PubMed2001

Health-related quality of life, anxiety and depression in patients with midgut carcinoid tumours.

In earlier studies it has been reported that patients with carcinoid tumours have a relatively good health-related quality of life (HRQoL) and low levels of anxiety and depression. The aims of this study were (a) to investigate the extent to which psychosocial function changes in patients with carcinoid tumours with time from diagnosis and its possible relation to tumour markers, and (b) to compare the HRQoL of patients with carcinoid tumours with that of healthy Swedish adults. Twenty-four patients reported on HRQoL (the EORTC QLQ-C30), anxiety and depression (the Hospital Anxiety and Depression Scale) five times during their first year of treatment. After one year, improvement in nausea/vomiting, flush and anxiety was reported, but there was deterioration of physical function, an increase in muscular pain and problems with dry skin. Levels of tumour markers were not associated with psychosocial function. Patients reported a lower HRQoL compared with healthy Swedish adults. Thus, deterioration of physical function was not accompanied by a deterioration of emotional function, and levels of tumour markers were not related to patients' HRQoL.

Activities of Daily Living↗

PubMed2001

A novel target recognition revealed by calmodulin in complex with the basic helix--loop--helix transcription factor SEF2-1/E2-2.

Calmodulin is the predominant intracellular receptor for Ca(2+) signals, mediating the regulation of numerous cellular processes. It can inhibit the DNA binding of basic helix--loop--helix transcription factors by a direct interaction of a novel type. To structurally characterize this novel calmodulin-target interaction, we decided to study the complex of calmodulin with a dimeric peptide corresponding to the DNA-binding domains of the dimeric basic helix-loop-helix transcription factor SEF2-1 (SEF2-1mp) using NMR. Here, we report that the stoichiometry of the calmodulin:SEF2-1mp complex is one dimeric peptide binding two calmodulin molecules. We also report the 1H, 13C, and 15N resonance assignments and the secondary structure of calmodulin in this for NMR large (approximately 38 kD) complex, as well as the 1H assignments and secondary structure of SEF2-1mp. In addition, we determined the amide proton exchange rates of calmodulin and measured intermolecular calmodulin:SEF2-1mp and calmodulin:calmodulin NOE contacts. The isotope-filtered experiments show a large number of SEF2-1mp to calmodulin NOE contacts indicating that a tight complex is formed, which is confirmed by an intermolecular calmodulin:calmodulin NOE contact. The secondary structure and amide proton exchange data show that the binding does not occur via the classical wraparound binding mode. Instead, the data indicate that calmodulin interacts with SEF2-1mp in a more open conformation, although the hydrophobic surfaces of the N- and C-terminal domains still form the main interaction sites. Interactions involving charged residues are also identified in agreement with the known relatively high sensitivity of the binding to ionic strength. Finally, the peptide does not form an alpha-helix as in the classical wraparound binding mode.

Amino Acid Sequence↗

PubMed2001

Quality of care and service as perceived by adults with developmental disabilities, their parents, and primary caregivers.

How adults with developmental disabilities perceive quality of the care and service they receive was investigated and these perceptions compared with those of their parents and primary caregivers. The sample was 34 adults with developmental disabilities, one of their parents, and their primary caregiver, all from a small Swedish municipality. We adapted Quality From the Patient's Perspective by using simple words and fewer response choices. Results showed it was possible to assess how adults with developmental disabilities evaluated actual care and service conditions. Evaluations of the subjective importance ascribed to these conditions proved too difficult. A high degree of similarity was found in ratings of perceived reality of care and service conditions by the adults with developmental disabilities, their parents, and caregivers.

Adult↗

PubMed2001

Quality of life and seeking help in women with urinary incontinence.

BACKGROUND: The aims of this population-based study were to compare the quality of life (QoL) in; (a) women with urinary incontinence (UI) and women without urinary incontinence (wUI) in relation to age, (b) women with stress incontinence and women with urge incontinence, and (c) women who had, vs. women who had not, consulted a health care service because of UI. METHODS: Totally, 787 women who reported symptoms of UI and 787 women who did not report symptoms of UI, aged 18-72 years, were mailed the Short Form-36 QoL questionnaire (SF-36) and a question concerning professional consultation. They were also mailed the Detrusor Instability Score questionnaire, which was used to clarify the women as being stress vs. urge incontinent. RESULTS: Women with UI had significantly lower scores on all eight dimensions of the SF-36. There were low correlations between age and the QoL scores in women with or without UI. Both women with stress incontinence and women with urge incontinence had significantly lower scores on all eight QoL dimensions compared with the women without UI. However, the absolute difference was smaller for women with stress incontinence. Women with urge incontinence consult health care service more often than women with stress incontinence. Women with UI who had consulted health care had significantly lower QoL scores than women with UI who had not consulted health care in seven out of eight dimensions. CONCLUSIONS: The QoL, in this female general population, is more affected by women with urge incontinence than women with stress incontinence. Help seeking is associated with substantially lower QoL scores and with urge incontinence.

Adolescent↗

PubMed2000

Influence of scale-up on the quality of recombinant human growth hormone.

The aerobic fed-batch production of recombinant human growth hormone (rhGH) by Escherichia coli was studied. The goal was to determine the production and protein degradation pattern of this product during fed-batch cultivation and to what extent scale differences depend on the presence of a fed-batch glucose feed zone. Results of laboratory bench-scale, scale-down (SDR), and industrial pilot-scale (3-m(3)) reactor production were compared. In addition to the parameters of product yield and quality, also cell yield, respiration, overflow, mixed acid fermentation, glucose concentration, and cell lysis were studied and compared. The results show that oxygen limitation following glucose overflow was the critical parameter and not the glucose overflow itself. This was verified by the pattern of byproduct formation where formate was the dominating factor and not acetic acid. A correlation between the accumulation of formate, the degree of heterogeneity, and cell lysis was also visualized when recombinant protein was expressed. The production pattern could be mimicked in the SDR reactor for all parameters, except for product quantity and quality, where 30% fewer rhGH-degraded forms were present and where about 80% higher total yield was achieved, resulting in 10% greater accumulation of properly formed rhGH monomer.

Bioreactors↗