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Biomedical subjects

M Ericsson

Publications and source records attributed to M Ericsson.

At least 19 recordsLinked to original sources

Depression predicts disability in long-term chronic pain patients.

PURPOSE: Investigators have examined factors that predict treatment outcome and disability status in chronic pain patients, including psychopathology and personality characteristics with equivocal results. The purpose of this study was to evaluate the usefulness of personality characteristics, depression, and personality disorders in predicting disability status in pain patients with long-term follow-up. The setting was a rehabilitation hospital in Southern Sweden. METHOD: Subjects were 184 pain patients (mean age = 43.4 (10.8) years; 72.8% female) who had no more than 365 sick leave days (Mean sick leave days = 132.7 (128.2)) prior to the baseline personality and psychiatric evaluation. The baseline evaluation consisted of a psychiatric interview that included the administration of the Structured Clinical Interview for DSM-IV Screen Questionnaire (SCID-II), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Karolinska Scales of Personality (KSP). Disability status was assessed by insurance record review a minimum of two-and-a-half years after baseline evaluation. RESULTS: Multivariate logistic regression suggests that age (OR = 1.09, 95% CI = 1.02-1.18; p = 0.013), number of sick leave days prior to evaluation (OR= 1.01, 95% CI= 1.01-1.02; p = 0.018), and baseline diagnosis of depression significantly predicted subsequent disability status (OR = 7.04, 95% CI = 1.15-42.93; p = 0.034). Baseline personality traits and the diagnosis of a personality disorder were not useful predictors of disability status in our sample. CONCLUSIONS: These data suggest that depression, but not personality disorders characteristics, was an important disability predictor in chronic pain patients with extended follow-up.

Adult↗

Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials.

AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.

Amphetamines↗

Differences in inhibition of replication between Coxsackie B4 virus strains in various cell lines by antibodies to some cell surface proteins.

Monoclonal antibodies that interact with the decay accelerating factor (DAF, CD55), the lymphocyte homing receptor (CD44) or the intercellular adhesion molecule I (ICAM- 1) were found to inhibit the replication of different strains of Coxsackievirus serotype B4 (CBV-4) to various extent. By adding antibodies to CD55 the replication of two (V345 and VD2921) of seven strains in HeLa cells, three (V89-4557, VD2921 and T318) of seven in A549-10C cells and one (VD2921) of five strains in RD cells was blocked totally. Consequently, the replication of one strain (VD2921) was blocked in all cells indicating that this strain uses CD55 as a receptor or as a co-receptor on all cell lines and is unable to use another cell surface protein. The binding of this strain to the cell surface was inhibited by the antibodies to CD55. None of the CBV-4 strains was blocked totally by adding antibodies to CD44 to HeLa and A549-10C cells, whereas in RD cells the replication of one (T318) of the CBV-4 strains was blocked totally. The antibodies to ICAM-1 did not inhibit totally the replication of any strain in HeLa and RD cells, but it blocked totally the replication of one strain (CBV-4-E) in A549-10C cells. In HeLa and A549-10C cells the degree of replication correlated highly with the degree of cytopathic effect (CPE). In RD cells, four of the strains replicated without CPE. The adding of antibodies to the integrin alpha(v)beta(3) led to slightly enhanced replication of three of the CBV-4 strains in all cell lines. It is concluded that the receptor usage by different strains of CBV-4 varies not only within the same cells but also between different cell lines.

Animals↗

Long-lasting recall response of CD4+ and CD8+ alphabeta T cells, but not gammadelta T cells, to heat shock proteins of francisella tularensis.

Decades after recovery from tularemia, circulating alphabeta T cells are known to still recognize a variety of membrane proteins of Francisella tularensis. We studied the T cell response to 3 cytoplasmic heat shock proteins of the organism: DnaK, chaperone-60 (Cpn-60) and Cpn-10. Determination of subpopulations of responding T cells was of special interest as it has been suggested that homologs of these conserved proteins may be recognized by human gammadelta T cells. Compared with reference subjects with no history of tularemia or tularemia vaccination, subjects who had been infected with tularemia 10-30 y earlier showed a significantly (p = 0.01) higher proliferative T cell response to all 3 heat shock proteins. In general, the magnitude of responses of CD4 T cells was higher than that of CD8 T cells. By flow cytometry, blast cells were shown to express the alphabeta T cell receptor. Under conditions that allowed vigorous expansion of gammadelta T cells in response to a phosphorylated non-peptide antigen, no expansion of gammadelta T cells occurred in response to DnaK or Cpn60 of F. tularensis. In conclusion, a long-lasting recall response to heat shock proteins of F. tularensis was demonstrated in alphabeta T cells but not in gammadelta T cells. The results support the assumption that human alphabeta T cells recognize bacterial proteins irrespective of the nature or localization of the proteins in the bacterial cell and thereby contribute to the maintenance of a long-lasting broad T cell response based on a wide variety of specificities.

Bacterial Proteins↗

Geometric phases for mixed states in interferometry.

We provide a physical prescription based on interferometry for introducing the total phase of a mixed state undergoing unitary evolution, which has been an elusive concept in the past. We define the parallel transport condition that provides a connection form for obtaining the geometric phase for mixed states. The expression for the geometric phase for mixed state reduces to well known formulas in the pure state case when a system undergoes noncyclic and unitary quantum evolution.

Journal Article↗

Dynamic microwave-assisted extraction.

An apparatus for extraction of solid matrices has been constructed which utilizes a microwave technique for heating in a dynamic mode. During the extraction, fresh solvent is continuously pumped through the extraction cell, which is maintained at a slight overpressure in order to keep the solvent in a liquid state. The extraction efficiency, which can be easily monitored, has been investigated in a factorial design and validated for polycyclic aromatic hydrocarbons in a reference sediment sample (EC-1). Important parameters were found to be temperature and duration of extraction. Flow-rate had no significant first-order effect on the recovery, but interaction effects with flow-rate were found to be significant. The dynamic microwave-assisted extraction apparatus was demonstrated to yield recoveries equivalent to Soxhlet extraction, but in a much shorter time. Each extraction of EC-1 typically takes 40 min.

Chromatography, High Pressure Liquid↗

Does personality or psychopathology predict disability in chronic pain patients?

PURPOSE: The purpose of this study was to evaluate the usefulness of personality characteristics, depression and personality disorders in predicting disability status in pain patients one year later. METHOD: Subjects were 250 volunteer chronic pain patients. The baseline evaluation consisted of the Karolinska Scales of Personality and psychiatric evaluation of depression and personality disorders using standardized diagnostic instruments. Disability status was assessed by insurance record review one year after the evaluation. RESULTS: The results suggest that baseline personality traits and psychopathology (i.e. depression or personality disorders) were not useful predictors of disability status in pain patients with one-year follow-up. CONCLUSIONS: These data suggest that personality characteristics and psychopathology are probably not important disability predictors in chronic pain patients.

Adult↗

Autonomic neuropathy--a complication less pronounced in patients with Type 1 diabetes mellitus who have lower blood glucose levels.

AIMS: Autonomic neuropathy is a serious diabetic complication, probably contributing to the death of many young people with Type 1 diabetes mellitus. It is often not diagnosed. METHODS: Patients with Type 1 diabetes from the Stockholm Diabetes Intervention Study were investigated with power spectral analysis (n = 88), heart rate and blood pressure reactions to tilting (n = 66), and heart rate variability during deep breathing (n = 70) a mean of 11.4 years after randomization to intensified conventional treatment (ICT) or standard treatment (ST), the treatment groups similar with regard to age, duration of diabetes and metabolic control at baseline (HbA1c 9.4 (1.3)%, mean (SD)). Blood glucose levels (mean of 29 HbA1c values) during the 10 years were lower in the patients from the ICT group (7.2 (0.6) vs. 8.3 (1.0)%, P = 0.001). RESULTS: Heart rate variability (HRV) in the high frequency range (P = 0.034), the expiration-inspiration ratio (P = 0.020), and the brake index during tilt (P = 0.044) were lower in the ST group, indicating more pronounced parasympathetic insufficiency. Systolic blood pressure fell by 10 (16) mmHg in the ST group, and by 2.5 (15) mmHg in the ICT group 8 min after rising from the supine to a 70 degrees upright position (P = 0.034). A decreased autonomic function was associated with age and higher HbA1c. CONCLUSION: Better autonomic nerve function is associated with lower HbA1c and lower age which were both the same in the intensively and the conventionally treatment groups at baseline. After a mean of 11.4 years autonomic function was better in the intensively treated group.

Adult↗

Sorting out bacterial viability with optical tweezers.

We have developed a method, using laser, optical tweezers and direct microscopic analysis of reproductive potential and membrane integrity, to assess single-cell viability in a stationary-phase Escherichia coli population. It is demonstrated here that a reduction in cell integrity, determined by using the fluorescent nucleic acid stain propidium iodide, correlated well with a reduction in cell proliferating potential during the stationary-phase period studied. Moreover, the same cells that exhibited reduced integrity were found to be the ones that failed to divide upon nutrient addition. A small but significant number of the intact cells (496 of 7,466 [6.6%]) failed to replicate. In other words, we did not find evidence for the existence of a large population of intact but nonculturable cells during the stationary-phase period studied but it is clear that reproductive ability can be lost prior to the loss of membrane integrity. In addition, about 1% of the stationary-phase cells were able to divide only once upon nutrient addition, and in a few cases, only one of the two cells produced by division was able to divide a second time, indicating that localized cell deterioration, inherited by only one of the daughters, may occur. The usefulness of the optical trapping methodology in elucidating the mechanisms involved in stationary-phase-induced bacterial death and population heterogeneity is discussed.

Escherichia coli↗

Personality and the prediction of weight loss and relapse in the treatment of obesity.

OBJECTIVE: This prospective study examined whether stable personality traits, as measured by the Karolinska Scales of Personality (KSP), predicted initial weight loss or long-term maintenance in obesity patients. METHOD: The KSP was administered to 102 obese patients prior to entering an 8-week weight loss program. Patients were weighed again at the end of treatment and at 3- and 12-month follow-up. RESULTS: The KSP did not predict initial weight loss after the 8-week program. Several of the KSP scales (Muscle Tension, Monotony Avoidance, Suspicion, and Guilt) had weak associations with 12-month relapse status. Weight gain at the 3-month follow-up was the strongest predictor of 12-month relapse status (O.R. = 0.46; 95% C.I. = 0.32, 0.66). DISCUSSION: Personality traits, as measured by the KSP, do not appear to be important predictors of initial weight loss or 12-month relapse status. Personality assessment may not substantially contribute to predicting treatment outcome in obesity research.

Adult↗

24-hour ECG frequency-domain measures in preeclamptic and healthy pregnant women during and after pregnancy.

OBJECTIVE: The aim of the present study was to evaluate the autonomic balance in women with preeclampsia and in healthy women during and after pregnancy by means of a 24-h ECG Holter recording combined with power spectral analysis. METHODS: Fifteen preeclamptic and 15 healthy women underwent 24-h Holter monitoring in the 32nd-36th week of gestation and 3-6 months postpartum. The power spectrum of the maternal electrocardiogram was analyzed with an autoregressive algorithm. MAIN OUTCOME MEASURES: The power spectrum contains two major components: a low-frequency peak, primarily attributed to sympathetic tone, and a high-frequency peak, reflecting vagal tone. RESULTS: The power spectrum of maternal heart rate variability did not differ between preeclamptic and normal women during pregnancy. After delivery, the amplitude of all components became significantly higher than those during pregnancy, with one exception: the high-frequency component in the patients who had been preeclamptic. In a comparison of the two groups, the high-frequency component after delivery was significantly lower in women who had preeclampsia than in normal healthy women (p = 0.03). CONCLUSIONS: During pregnancy, the power spectrum is reduced and cannot be used to distinguish between patients with preeclampsia and normal healthy women. Three to 6 months after delivery, the high-frequency component is still reduced in the preeclamptic group of women. This indicates an impaired vagal modulation even in the nonpregnant state in this group of women, unlike those who had a normotensive pregnancy.

Analysis of Variance↗

D4 dopamine receptor gene exon III polymorphism and obesity risk.

Many genes have been identified that may play a role in increasing individual susceptibility to obesity. Reduced dopamine function appears to play a role in dysfunctional eating patterns and may predispose some individuals to obesity. The long version of the D4 dopamine receptor gene (D4DR) has been shown to alter receptor function and reduce intracellular response to dopamine. It also has been associated with novelty-seeking-related personality traits that are found with greater frequency in obese individuals. We examined the association between the long alleles of the D4DR and obesity in a sample of 115 obese patients participating in a weight management program. No direct relationship was found between the D4DR and body mass or novelty-seeking-related personality traits. We constructed four models of increased obesity risk that included combinations of traditional risk factors (i.e., long-term history of obesity, parental obesity, a body mass index > 40) and elevations on the novelty-seeking-related scales of the Karolinska Scales of Personality. There was a significant increase in the frequency of the D4DR long alleles in individuals defined as high risk using the combination of novelty-seeking-related personality traits, severe obesity (i.e., BMI > 40), and any other traditional risk factor, but not with the traditional risk factors alone. These preliminary data suggest a potential role for the D4DR gene in increasing obesity susceptibility.

Adult↗

IL-1 beta and IL-6 in mouse parotid acinar cells: characterization of synthesis, storage, and release.

Synthesis, storage, and secretion of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) and the anti-inflammatory cytokine IL-6 have not been established in normal exocrine gland secretory cells. Parotid glands and isolated acinar cells prepared from BALB/c mice were homogenized for RNA isolation and reverse transcription-polymerase chain reaction (RT-PCR). IL-1 beta and IL-6 enzyme-linked immunosorbent assays (ELISAs) were done on supernatants prepared from mouse parotid acinar cell (MPAC) preparations unstimulated or stimulated between 0 and 10 min with 10(-5) M norepinephrine at 37 degrees C. MPACs were fixed in paraformaldehyde, frozen sectioned for light and electron microscopy, and labeled with antibodies to IL-1 beta and IL-6. Mouse specific riboprobes to IL-1 and IL-6 were used for in situ hybridization. RT-PCR yielded the expected IL-1 (336-bp) and IL-6 (614-bp) mRNA products. By ELISA, stimulated MPACs showed a significant increase in IL-1 beta (P < 0.03) and IL-6 (P < 0.01) release into supernatants by 10 min that paralleled the time course of amylase release. In situ hybridization showed the presence of transcripts for IL-1 and IL-6 in glandular epithelial cells. Gold-labeled IL-1 beta and IL-6 were significantly higher (P < 0.01) in granules than in the nucleus and cytoplasm. This study shows that MPACs synthesize IL-1 beta and IL-6 and release these cytokines from their granules after alpha- and beta-adrenergic stimulation.

Amylases↗

In vitro reconstitution of an intermediate assembly stage of vaccinia virus.

A novel method is described which facilitates the in vitro assembly of one step in the life cycle of vaccinia virus, the formation of the spherical immature virus (IV). For this, advantage was taken of the ability of rifampicin to reversibly block the assembly of the IV. Rifampicin-treated, vaccinia virus-infected HeLa cells were permeabilized with streptolysin O (SLO) and the endogenous cytosol was allowed to exit the cells at 4 degrees . Subsequently, exogenous cytosol from infected or uninfected HeLa cells as well as an ATP-regenerating system were added and the cells were incubated for different times at 37 degrees in the absence of rifampicin. The preparations were then evaluated by thin section EM. Our data show that in the presence of infected or uninfected cell cytosol and ATP a significant fraction of cells could reconstitute IV assembly in vitro. Under no conditions were we able to reconstitute any later stages of assembly. The potential of this system for the in vitro reconstitution of viral assembly in general is discussed.

Adenosine Triphosphate↗

Identification of framework residues in a secreted recombinant antibody fragment that control production level and localization in Escherichia coli.

The monoclonal antibody 5T4, directed against a human tumor-associated antigen, was expressed as a secreted Fab superantigen fusion protein in Escherichia coli. The product is a putative agent for immunotherapy of non-small cell lung cancer. During fermentation, most of the fusion protein leaked out from the periplasm to the growth medium at a level of approximately 40 mg/liter. This level was notably low compared with similar products containing identical CH1, CL, and superantigen moieties, and the Fv framework was therefore engineered. Using hybrid molecules, the light chain was found to limit high expression levels. Substituting five residues in VL increased the level almost 15 times, exceeding 500 mg/liter in the growth medium. Here, the substitutions Phe-10 --> Ser, Thr-45 --> Lys, Thr-77 --> Ser, and Leu-78 --> Val were most powerful. In addition, replacing four VH residues diminished cell lysis during fermentation. Thereby the product was preferentially located in the periplasm instead of the growth medium, and the total yield was more than 700 mg/liter. All engineered products retained a high affinity for the tumor-associated antigen. It is suggested that at least some of the identified framework residues generally have to be replaced to obtain high level production of recombinant Fab products in E. coli.

Amino Acid Sequence↗

A role for the hinge/ear domain of the beta chains in the incorporation of AP complexes into clathrin-coated pits and coated vesicles.

The clathrin-associated adaptor protein (AP) complexes drive the polymerization of clathrin in coated pits to form coated vesicles. It has previously been shown that the carboxyl-terminal hinge/ear domain of the beta 2 chain contains a binding site for clathrin and that removal of this domain from APs or from isolated beta 2 chains abrogates their ability to form clathrin coats in vitro. We show here that the hinge/ear domain is necessary for efficient incorporation of AP complexes into coated pits and coated vesicles in cells, a result that is consistent with the view that the beta chains indeed provide an important interaction between the AP complexes and clathrin.

Adaptor Proteins, Vesicular Transport↗

Characterization of the nucleotide sequence of the groE operon encoding heat shock proteins chaperone-60 and -10 of Francisella tularensis and determination of the T-cell response to the proteins in individuals vaccinated with F. tularensis.

The groE operon of Francisella tularensis LVS, encoding the heat shock proteins chaperone-10 (Cpn10) and Cpn60, was sequenced and characterized, and the T-cell response of LVS-vaccinated individuals to the two proteins and the third major chaperone, Ft-DnaK, was assayed. The cpn10 and cpn60 genes were amplified by PCR with degenerate oligonucleotides derived from the N-terminal sequence of the two proteins. The sequence analysis revealed the expected two open reading frames, encoding proteins with estimated Mrs of 10,300 and 57,400. The deduced amino acid sequences closely resembled Cpn10 and Cpn60 proteins of other prokaryotes. The genes constituted a bicistronic operon, the cpn10 gene preceding the cpn60 gene. Upstream of the cpn10 gene, an inverted repeat and motifs similar to -35 and -10 sequences of sigma70-dependent but not of sigma32-dependent promoters of Escherichia coli were found. The inverted repeat of the operon resembled so-called hairpin loops identified in other characterized prokaryotic groE operons lacking sigma32-dependent promoters. Primer extension analysis disclosed one and the same transcription start, irrespective of the presence or absence of heat or oxidative stress. After separation of lysates of the F. tularensis LVS organism by two-dimensional gel electrophoresis, DnaK, Cpn60, and Cpn10 were extracted and used as antigens in T-cell tests. When compared to those from nonvaccinated individuals, T cells from individuals previously vaccinated with live F. tularensis LVS showed an increased proliferative response to DnaK and Cpn60 but not to Cpn10. The present data will facilitate further studies of the involvement of the heat shock proteins in protective immunity to tularemia.

Antibodies, Bacterial↗