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Biomedical subjects

M Larsson

Publications and source records attributed to M Larsson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Antibiotic medication and bacterial resistance to antibiotics: a survey of children in a Vietnamese community.

OBJECTIVE: To investigate antibiotic use and antibiotic susceptibility of respiratory tract pathogens in children aged 1-5 years in Bavi, Vietnam. METHOD: Nasopharynx and throat specimens were collected from 200 children from randomly selected households in a demographically defined population. Respiratory isolates were tested for antibiotic susceptibility according to the standard disk diffusion method. A questionnaire survey of carers elicited information on type of antibiotic used, duration of treatment, where the antibiotics had been purchased, type of treatment information retained by carers and episodes of illness preceding the study. RESULTS: 82% of the children had at least one symptom of acute respiratory tract infection (ARI) in the 4 weeks prior to the study, and of these 91% were treated with antibiotics. The most commonly used antibiotics were ampicillin (74%), penicillin (12%), amoxicillin (11%), erythromycin (5%), tetracycline (4%) and streptomycin (2%). Ampicillin was used for 3.3 days on average (SD:1.8) and penicillin for 2.6 days (SD:0.7). When deciding which antibiotic to use, 67% of the carers consulted the pharmacy seller, 11% decided themselves and 22% followed the doctor's prescription. The carrier rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis was 50%, 39% and 17%, respectively. Isolates from 145 children were susceptibility tested, and 74% were found to carry resistant pathogens. Of the tested isolates, 90% of S. pneumoniae, 68% of H. influenzae and 74% of M. catarrhalis were resistant to at least one antibiotic. The mean number of antibiotics (susceptible strains excluded) to which resistance was found was 2.0 (SD:1.2), 2.5 (SD:1.8) and 2.1 (SD:0.9), respectively. S. pneumoniae and H. influenzae showed high resistance to tetracycline (88% and 32%, respectively), trimethoprim/sulphonamide (32% and 44%), and chloramphenicol (25% and 24%). 23% of S. pneumoniae were erythromycin-resistant and 18% of H. influenzae isolates were resistant to ampicillin. There was a significant difference in ampicillin and penicillin resistance between the group of children previously treated with beta lactam antibiotics and the group of children who did not receive antibiotics. CONCLUSION: As reported by the carers, children in Bavi are treated with antibiotics frequently. Most antibiotics were obtained without consulting a doctor. High levels of antibiotic resistance and high prevalence of multidrug-resistant strains were found among respiratory pathogens. The existence of a large reservoir of resistance genes among children in low-income countries represents a threat to the success of antibiotic therapy throughout the world. Multi-faceted programmes to improve rational use of antibiotics in Vietnam are urgently needed.

Adult↗
PubMed2000

The spatial and temporal expression of Tekt1, a mouse tektin C homologue, during spermatogenesis suggest that it is involved in the development of the sperm tail basal body and axoneme.

Tektins comprise a family of filament-forming proteins that are known to be coassembled with tubulins to form ciliary and flagellar microtubules. Recently we described the sequence of the first mammalian tektin protein, Tekt1 (from mouse testis), which is most homologous with sea urchin tektin C. We have now investigated the temporal and spatial expression of Tekt1 during mouse male germ cell development. By in situ hybridization analysis TEKT1 RNA expression is detected in spermatocytes and in round spermatids in the mouse testis. Immunofluorescence microscopy analysis with anti-Tekt1 antibodies showed no distinct labeling of any subcellular structure in spermatocytes, whereas in round spermatids anti-Tekt1 antibodies co-localize with anti-ANA antibodies to the centrosome. At a later stage, elongating spermatids display a larger area of anti-Tektl staining at their caudal ends; as spermiogenesis proceeds, the anti-Tekt1 staining disappears. Together with other evidence, these results provide the first intraspecies evidence that Tekt1 is transiently associated with the centrosome, and indicates that Tekt1 is one of several tektins to participate in the nucleation of the flagellar axoneme of mature spermatozoa, perhaps being required to assemble the basal body.

Animals↗
PubMed2000

Odor identification: influences of age, gender, cognition, and personality.

The aim of this study was to examine the influences of age, gender, cognitive abilities, and personality styles on odor identification. Participants (N = 532) aged 45-87 years from the Swedish Adoption/Twin Study of Aging were assessed with a Swedish version of the National Geographic Smell Survey. Both detection and identification of olfactory information were impaired with age. Gender had no effect on detection or identification. Hierarchical regressions revealed that proficiency in semantic memory, intensity perception, and personality style (i.e., neuroticism, impulsivity, and lack of assertiveness) were potent predictors for successful odor identification, even when individual variations in chronological age, sex, education, and global cognitive functioning were taken into account.

Age Factors↗
PubMed2000

Pharmaceutical sector in transition--a cross sectional study in Vietnam.

Increasing efforts are being made to improve pharmaceutical sector performance in low- and middle-income countries. An essential tool for such work is an objective and standard method of assessment which can be used to promote evidenced based National Drug Policy development and implementation. The average drug expenditure per capita has steadily increased in Vietnam and at the time of this study a National Drug Policy was being developed. This study assessed the Vietnamese pharmaceutical sector 1991-1994, focusing on the standard of the drug quality control system, availability of drugs and rational use of essential drugs in the private and public sectors by means of standardised indicators. The results from this study show that the quality control system is impaired and does not have capacity to quality control all drugs on the market. The availability of essential drugs is good whereas essential drugs are poorly prescribed, injections common and there is a high average number of drugs per prescription, both in the public and private sectors. Violations are common and enforcement of regulations weak. On top of this there is an active commercial advertising and marketing of drugs. These findings identify priorities for action to improve the present situation where the development and implementation of the Vietnamese National Drug Policy will be of major importance.

Cross-Sectional Studies↗
PubMed1999

Vaccinia virus inhibits the maturation of human dendritic cells: a novel mechanism of immune evasion.

Vaccinia virus employs multiple mechanisms to evade the immune system, yet is highly immunogenic. We studied the interaction between vaccinia and human dendritic cells (DCs), potent APCs. DCs develop from precursor cells in two stages: an immature stage in which Ag uptake and processing occur, and a mature stage in which there is up-regulation of costimulatory and HLA molecules and efficient T cell activation. Vaccinia virus undergoes an abortive replication in both stages of DCs and induces apoptotic cell death. Furthermore, maturation of immature DCs and consequently T cell activation are inhibited. Obstruction of DC maturation may constitute a novel mechanism by which vaccinia attempts to evade the immune response.

Antigen-Presenting Cells↗
PubMed1999

A recombinant vaccinia virus based ELISPOT assay detects high frequencies of Pol-specific CD8 T cells in HIV-1-positive individuals.

OBJECTIVES: HIV-1-specific CD8 T cells are considered to be critical in anti-HIV responses. It is important to quantify these cells and to determine their antigenic targets. Here quantification of interferon (IFN)-gamma secreting, virus-specific cells was achieved with an enzyme linked immuno spot (ELISPOT) assay. METHODS: Peripheral blood mononuclear cells (PBMC) were infected with recombinant vaccinia vectors expressing HIV-1 genes (gag, pol, env or nef) and added to wells precoated with anti-IFN-gamma monoclonal antibodies. Spot forming cells (SFC), i.e. antigen-specific T cells were detected 24 h later by the addition of biotinylated anti-IFN-gamma monoclonal antibodies, followed by avidin-bound biotinylated horseradish peroxidase. RESULTS: In a cohort of 19 patients, of whom 15 were on highly active antiretroviral therapy, 18 had primed T cells directed against one or more HIV-1 antigens (P < 0.0001). Pol-specific T cells routinely dominated the CD8 response with frequencies up to 2000 SFC per 10(6) PBMC. In HLA A*0201-positive patients, the vaccinia vectors detected much higher frequencies of SFC than haplotype-restricted peptides. Elimination of CD8 T cells resulted in > 90% loss of antigen-specific SFC when vaccinia virus was used as a vector. The number of CD8 SFC exceeded the number of memory cells detected in limiting dilution assays by > 1 log10, whereas a correlation was found between the frequency of effector cells detected by both ELISPOT and MHC class I peptide tetramer assays. CONCLUSIONS: Vaccinia virus vectors used in ELISPOT assays are useful for determining the frequency and specificity of CD8 T cells for individual HIV-1 gene products. The dominance of cytolytic T lymphocytes (CTL) recognizing pol proteins suggests that this antigen should be considered in vaccine strategies.

Adult↗
PubMed1999

Effects of extracellular calcium on the subcellular translocation of bovine parathyroid PKC isozymes.

The release of parathyroid hormone is regulated by the extracellular concentration of Ca2+ through a sensor(s) on the surface of the parathyroid cells, but few details are known on the further relay of the signal inside the cell. Activation of protein kinase C (PKC) isozymes is associated with their translocation from the cell soluble fraction to the particulate fraction of the cell. Therefore, identification of a subcellular localization of a PKC isozyme in parathyroid cells as a response to changes in extracellular Ca2+ should be an indication for its putative role in signal transduction coupled to the Ca2+ sensor. We have determined the subcellular localization of six PKC isozymes (alpha, betaI, betaII, epsilon, zeta, and iota) in nonstimulated parathyroid cells and in those treated with low (0.5 mM) and high (3.0 mM) extracellular Ca2+ by confocal microscopy. At the physiological concentration of serum Ca2+, all PKC isozymes studied were localized mainly to the cytosol, although to different extents. Low extracellular Ca2+ caused a redistribution of PKCalpha to the periphery of the cells. In contrast, PKCbetaI, -epsilon, -zeta, and -iota were translocated to the periphery of the cells at high extracellular Ca2+. These results indicate that PKCalpha, -betaI, -epsilon, -zeta, and -iota are involved in the response of parathyroid cells to changes in extracellular Ca2+.

Animals↗
PubMed1999

Characterization of a molten globule state of bovine carbonic anhydrase III: loss of asymmetrical environment of the aromatic residues has a profound effect on both the near- and far-UV CD spectrum.

Bovine muscle carbonic anhydrase (isoenzyme III; BCAIII) exhibited a three-state unfolding process at equilibrium upon denaturation in guanidine hydrochloride (GuHCl). The stable folding intermediate appeared to be of molten globule type. The stability towards GuHCl in terms of mid-point concentrations of denaturation were very similar for BCAIII and human CAII (HCAII). It was further demonstrated that the aromatic amino acid residues contributed significantly to the circular dichroism (CD) spectrum in the far-UV wavelength region during the native-->molten globule state transition. Thus, the ellipiticity change at 218 nm was shown to monitor the loss of tertiary interactions of aromatic side chains at the first unfolding transition as well as the rupture of secondary structure at the second unfolding transition. Similar aromatic contributions to the far-UV CD spectrum, but with varying magnitudes, were also noted for BCAII and HCAII, further emphasizing that interference of aromatic residues should not be neglected at wavelengths that normally are assigned to secondary structural changes.

Animals↗
PubMed1999

Presentation of epstein-barr virus latency antigens to CD8(+), interferon-gamma-secreting, T lymphocytes.

Epstein-Barr virus (EBV) infects more than 95 % of the human population and causes an asymptomatic life-long infection in the majority of EBV carriers. Cell-mediated immunity provides resistance to EBV, as demonstrated by the occurrence of EBV-induced post-transplant lymphoproliferative disease in immunosuppressed patients. Here we looked for IFN-gamma-producing T lymphocytes in the blood of healthy donors with a rapid enzyme-linked immunospot (ELISPOT) assay, comparing as antigen presenting cells monocytes and dendritic cells (DC) infected with recombinant vaccinia virus (rVV). We found a strong CD8(+) ELISPOT response to one or more of the EBNA 3A, 3B and 3C antigens in the PBMC from 14 / 18 donors. The sensitivity of the overnight ELISPOT assay was increased using DC as antigen-presenting cells, including 3 / 3 individuals who lacked ELISPOT in PBMC. In addition, DC could markedly expand EBV-specific spots after a 7-day culture. In a smaller number of donors, we documented recognition of the subdominant LMP 1, LMP 2 and EBNA 1 antigens that are expressed in a variety of EBV-associated malignancies. Therefore our data provide more evidence for the efficacy of DC in eliciting rapid responses to EBV latency antigens in circulating CD8(+) T cells.

Antigen Presentation↗
PubMed1999

Solid-phase differential display and bacterial expression systems in selection and functional analysis of cDNAs.

Differential gene expression can be expected during activation and differentiation of cells as well as during pathological conditions, such as cancer. A number of strategies have been described to identify and understand isolated differentially expressed genes. The differential display methodology has rapidly become a widely used technique to identify differentially expressed mRNAs. In this chapter we described a variant of the differential display method based on solid-phase technology. The solid-phase procedure offers an attractive alternative to solution-based differential display because minute amounts of sample can be analyzed in considerably less time than previously. The employed solid support, monodisperse super paramagnetic beads, which circumvents precipitation and centrifugations steps, has also allowed for optimization of the critical enzymatic and preparative steps in the differential display methodology. We also described how bacterial expression can be used as a means to elucidate gene function. An efficient dual-expression system was presented, together with a basic concept describing how parallel expression of selected portions of cDNAs can be used for production of cDNA-encoded proteins as parts of affinity-tagged fusion proteins. The fusion proteins are suitable both for the generation of antibodies reactive to the target cDNA-encoded protein and for the subsequent affinity enrichment of such antibodies. Affinity-enriched antibodies have proved to be valuable tools in various assays, including immunoblotting and immunocytochemical staining, and can thus be used to localize the target cDNA-encoded protein to certain cells in a tissue section or even to a specific cell compartment or organelle within a cell. High-resolution localization of a cDNA-encoded protein would provide valuable information toward the understanding of protein function.

Animals↗
PubMed1999

Dendritic cells generated from blood monocytes of HIV-1 patients are not infected and act as competent antigen presenting cells eliciting potent T-cell responses.

The CTL response to HIV-I can be vigorous, but antigen presenting cell requirements have not been studied in detail. To approach this question, we have examined the dendritic cell populations that can be obtained from the blood of HIV-1 infected individuals. We studied 13 asymptomatic patients, who spanned a wide range of plasma viremia and CD4 counts. We show here that sizeable numbers of mature dendritic cells can be generated from nonproliferating progenitors in the blood of HIV + patients using a recently developed approach. The procedure involves two steps. The first step or 'priming' phase is a 7 day culture of T-cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4. The second step or 'differentiation' phase requires the exposure to monocyte conditioned medium. The yields of DCs from HIV + individuals were comparable to normal blood donors, 0.4 - 3 x 10(6) mature dendritic cells from 50 ml of blood. Strong APC function was evident for both the proliferation of allogeneic T-cells in the MLR, and the generation by syngeneic T-cells of class I restricted, CTL responses to influenza virus. A panel of dendritic cell restricted markers are expressed, including CD83, p55, and perinuclear CD68. By semi-quantitative PCR analysis, the cytokine derived cells did not express HIV-1 DNA. We suggest that these blood derived dendritic cells will be effective for studies of immune responses to HIV-1 antigens and may be considered as adjuvants for active immunotherapy.

Antigen-Presenting Cells↗
PubMed1999

Characterization of a novel nucleolar protein that transiently associates with the condensed chromosomes in mitotic cells.

We report the isolation and characterization of a murine gene encoding a conserved mammalian nucleolar protein. The protein, called Tsg118, has a predicted molecular mass of 59.4 kDa and a high content of basic amino acids. A homologous human gene was localized to chromosome 16p12.3. The Tsg118 protein is predominantly expressed in proliferating somatic cells and in male germ cells. Indirect immunofluorescence microscopy analysis using an affinity-purified anti-Tsg118 serum shows colocalization of Tsg118 and a known nucleolar protein, fibrillarin, to the dense fibrillar component of the nucleolus. The nucleolar localization of the Tsg118 protein appears to be temporally restricted to the interphase stages of the somatic cell cycle and to the meiotic phase of spermatogenesis. We find that the Tsg118 protein localizes to the nucleolus in both proliferating and serum-starved cells. Interestingly, as the nucleolar signal disappears in mitotic cells, the Tsg118 protein instead becomes associated with the surface of the condensed chromosomes.

Amino Acid Sequence↗
PubMed1999

Chemical and sensory properties of liquid beet sugar.

Sensory analysis and headspace gas chromatography-flame ionization detection (GC-FID) analysis of liquid sugars (sucrose) designated for food-industrial use were performed in order to elucidate which compounds are responsible for perceived off-odors and off-flavors in liquid sugar. The liquid sugar samples investigated had various kinds of off-odors and off-flavors that might influence the quality of any food product in which they might be used, such as a jam or a soft drink. The sensory scores for the different attributes and the levels of different volatile compounds as measured by GC were analyzed for correlation using partial least-squares (PLS) analysis. A link between sensory analysis and GC analysis was thereby established, and compounds critical for the odor and flavor were identified using MS (mass spectrometry). Approximately 10 compounds were found to be correlated with the defined sensory attributes. Among these compounds associated with the sensory attributes were dimethyl disulfide, 2,6-dimethylpyrazine, 4-methoxyphenol, and 2, 5-dimethylfuran.

Chenopodiaceae↗
PubMed1999

Odor identification in normal aging and early Alzheimer's disease: effects of retrieval support.

Odor sensitivity and identification were examined in normal aging and early Alzheimer's disease (AD). The aims were to investigate AD as associated with lower odor sensitivity, odor identification as a function of retrieval support, and the relationship between global cognitive functioning (Mini-Mental State Exam [MMSE]; M. F. Folstein, S. E. Folstein, & P. R. McHugh, 1975) and olfactory performance. Results indicated intact odor sensitivity but deficient odor identification in AD. Both groups benefited from cues in identification, and the size of the gains was equally large in AD patients and controls. The finding of no selective benefit from retrieval support in AD suggests that a degradation of olfactory knowledge contributes to the odor identification deficits in these patients. MMSE and identification were positively related, whereas MMSE and olfactory sensitivity were unrelated. These findings suggest that the AD-related olfactory impairment stems from lesions in cortical rather than peripheral structures.

Aged↗
PubMed1999

Changes in frequency of HIV-1-specific cytotoxic T cell precursors and circulating effectors after combination antiretroviral therapy in children.

Combination antiretroviral therapy has had a major role in reducing human immunodeficiency virus type 1 (HIV-1) plasma viral loads in HIV-1-infected adults but a variable effect in infants, in whom complete viral suppression appears to be less readily achieved. In adults, after the reduction in plasma viremia, there is a decrease in the numbers of circulating cytotoxic T cell (CTL) effectors and precursors in the majority of patients. This longitudinal study assessed the effect of combination drug therapy on the frequency of HIV-1-specific CTL responses in 8 HIV-1-infected children. Following treatment, the frequency of HIV-1-specific CTL responses initially increased, especially in children with incomplete viral suppression but with increasing CD4+ cell counts. In children with complete viral suppression, the frequency of HIV-1-specific CTL responses decreased, suggesting that viral replication is required to maintain CTL responses in the systemic circulation.

Anti-HIV Agents↗