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C Lundberg

Publications and source records attributed to C Lundberg.

At least 19 recordsLinked to original sources
PubMed2006

Efficient transduction of neurons using Ross River glycoprotein-pseudotyped lentiviral vectors.

Lentiviral vectors are promising tools for CNS gene transfer since they efficiently transduce the cells of the nervous system in vivo. In this study, we have investigated the transduction efficiency of lentiviral vectors pseudotyped with Ross River virus glycoprotein (RRV-G) (RRV-G-pseudotyped lentiviral vectors (RRV-LV)). The RRV is an alphavirus with an extremely broad host range, including the cells of the central nervous system. Previous studies have shown that lentiviral vectors can be efficiently pseudotyped with this envelope protein and have demonstrated promising features of such vectors, including the possibility to establish stable producer cell lines. After injection of RRV-LV expressing green fluorescent protein into different structures in the rat brain we found efficient transduction of both neurons and glial cells. By using two cell-type-specific promoters, neuron-specific enolase and human glial fibrillary acidic protein, we demonstrated cell-specific transgene expression in the desired cell type. Ross River virus glycoprotein-pseudotyped lentiviral vectors also transduced human neural progenitor cells in vitro, showing that receptors for the RRV-G are present on human neural cells.

Animals↗
PubMed2004

Regionalization and fate specification in neurospheres: the role of Olig2 and Pax6.

Neurosphere cultures are widely used to propagate multipotent CNS precursors, but their differentiation into neurons or oligodendrocytes is rather poor. To elucidate fate determination in this system, we examined the expression and function of candidate transcription factors in neurospheres derived from different CNS regions during development and adulthood. We observed prominent down-regulation of most transcription factors present in telencephalic precursors upon growth factor exposure in neurosphere cultures while Olig1 and Olig2 expression was strongly up-regulated. Interference with Olig2 in neurospheres revealed its role in self-renewal during expansion and for the generation of neurons and oligodendrocytes during differentiation. We further show that neurogenesis becomes fully Pax6-dependent in the neurosphere culture system, independent of the region of origin, and that Pax6 overexpression is sufficient to direct almost all neurosphere-derived cells towards neurogenesis. Thus, a pathway combining transcription factors of dorsal and ventral regions is activated in the neurosphere culture model.

Animals↗
PubMed2002

An evaluation of the usefulness of two terminology models for integrating nursing diagnosis concepts into SNOMED Clinical Terms.

OBJECTIVES: We evaluated the usefulness of two models for integrating nursing diagnosis concepts into SNOMED Clinical Terms (CT). METHODS: First, we dissected nursing diagnosis term phrases from two source terminologies (North American Nursing Diagnosis Association Taxonomy 1 (NANDA) and Omaha System) into the semantic categories of the European Committee for Standardization (CEN) categorical structure and ISO reference terminology model (RTM). Second, we critically analyzed the similarities between the semantic links in the CEN and ISO models and the semantic links used to formally define diagnostic concepts in SNOMED CT. RESULTS: Our findings demonstrated that focus, bearer/subject of information, and judgment were present in 100% of the NANDA and Omaha term phrases. The Omaha term phrases contained no additional descriptors beyond those considered mandatory in the CEN and ISO models. The comparison among the semantic links showed that SNOMED CT currently contains all but one of the semantic links needed to model the two source terminologies for integration. In conclusion, our findings support the potential utility of the CEN and ISO models for integrating nursing diagnostic concepts into SNOMED CT.

Classification↗
PubMed2002

Evaluation of Tet-on system to avoid transgene down-regulation in ex vivo gene transfer to the CNS.

Ex vivo gene transfer to the CNS has so far been hampered by instability of transgene expression. To avoid the phenomenon of transgene down-regulation, we have employed strong, constitutive promoters and compared this expression system with the inducible Tet expression system incorporated in a single plasmid vector or in lentiviral vectors. Plasmid-based transgene expression directed by the constitutive, human ubiquitin promoter, UbC, was stable in transfected HiB5 cells in vitro and comparable in strength to the CMV promoter. However, after transplantation of UbC and CMV HiB5 clones to the rat striatum, silencing of the transgene occurred in most cells soon after implantation of transfected cells. The Tet-on elements were incorporated in a single plasmid vector and inducible HiB5 clones were generated. Inducible clones displayed varying basal expression activity, which could not be ascribed to an effect of cis-elements in the vector, but rather was due, at least in part, to intrinsic activity of the minimal promoter. Basal expression activity could be blocked in a majority of cells by stable expressing the transrepressor tTS. Fully induced expression levels were comparable to CMV and UbC promoters. Similar to the constitutive promoters transgene expression was down-regulated soon after grafting of inducible HiB5 clones to the rat striatum. Lentiviral vectors can direct long-term stable in vivo transgene expression. To take advantage of this quality of the lentiviral vector, the Tet-on elements were incorporated in two lentiviral transfer vectors followed by transduction of Hib5 cells. Interestingly, all HiB5 clones established by lentiviral transduction showed very similar expression patterns and tight regulatability that apparently was independent of transgene copy number and integration site. Nevertheless, transgene expression in all lentiviral HiB5 clones was down-regulated shortly after transplantation to the rat striatum. These results confirm the general phenomenon of transgene down-regulation. Moreover, the results suggest that the considerable advantages offered by lentiviral vectors for direct gene delivery cannot necessarily be transferred directly to ex vivo gene delivery. This emphasizes the need for alternative vector strategies for ex vivo gene transfer.

Animals↗
PubMed2002

Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis.

Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63-88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-gamma and TNF-alpha, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, alphabeta+/T-cell receptor (TCR)BV8S2+, but not alphabeta+/TCRBV8S2-, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in alphabeta+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in alphabeta+/TCRBV8S2- cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.

Amino Acid Sequence↗
PubMed2002

Activated T cells in the surface secretion on the adenoid--a flow cytometric study.

We previously demonstrated the presence of leucocytes in the adenoid surface secretion with the ability of immunoglobulin A (IgA), IgM and IgG production as well as production of cells with phagocytic capacity. In the present study, we investigated the presence of activated T cells in the secretion. Adenoid surface secretion from 12 children subjected to adenoidectomy was obtained with an imprint method. From six children, peripheral blood was also obtained. By flow cytometry, the number of lymphocytes, granulocytes, epithelial cells and red blood cells was analysed as well as the expression on lymphocyte subsets of the following antigens: CD3, CD4, CD8, CD19, CD25, CD38, CD45RO, CD45RA, HLA-DR, TcRgd, CD161 and l-selectin. The majority of T cells were activated and to a significantly higher degree were CD45RO+, CD161+ and l-selectin-, as compared with the corresponding peripheral blood. The median percentage of B cells and T cells in the secretion were 81 and 13%, respectively. In conclusion, the proportion of B and T cells in the adenoid surface secretion is significantly different as compared with the peripheral blood. The T cells in the adenoid surface secretion are to a high degree activated. The results suggest that the leucocytes in the surface secretion are part of the mucosal defence.

Adenoids↗
PubMed2001

Neurodegeneration and glial activation patterns after mechanical nerve injury are differentially regulated by non-MHC genes in congenic inbred rat strains.

Ventral root avulsion in the rat leads to a retrograde response, with activation of glia and up-regulation of immunologic cell surface molecules such as major histocompatibility complex (MHC) antigens, and the subsequent degeneration of a large proportion of the lesioned motoneurons. Herein, we examined several inbred congenic rat strains previously known to react differently to experimentally induced autoimmune diseases and demonstrate a substantial genetic diversity in the regulation of glial activation and neuron death in this injury model. The panel of examined inbred rat strains included DA(RT1AV1), PVG.1AV1, LEW.1AV1, LEW.1N, BN(RT1N) and E3(RT1U), and the following parameters were determined: (1) MHC class II expression on glia; (2) expression of glial fibrillary acidic protein, C3 complement, and microglial response factor-1 mRNAs in glia; (3) levels of the tumor necrosis factor-alpha and interleukin-1beta cytokine mRNAs; (4) degree of motoneuron loss. The findings of considerable strain-dependent differences in all parameters studied demonstrate important polymorphisms in the genetic regulation of these events. Furthermore, some of the studied features segregated from each other, suggesting independent regulatory mechanisms. Genes outside of the MHC complex are mainly implicated as being of importance for the phenotypic differences, as significant differences were recorded between the MHC congenic strains differing in the non-MHC genes but not vice versa. These results contribute new important insights into the genetic regulation of glial reactivity and neuron death after mechanical nerve injuries. In addition, the finding of conspicuous strain-dependent differences makes it necessary to consider the genetic background when designing and interpreting animal experiments involving noxious insults to the central nervous system resulting in glial activation and nerve cell loss.

Animals↗
PubMed2001

Mechanisms of resistance to imipenem in imipenem-resistant, ampicillin-sensitive Enterococcus faecium.

Enterococcus faecium has six penicillin-binding proteins (PBP), where PBP5 seems to be the main target for beta-lactam antibiotics. The PBP profiles of three imipenem-resistant, ampicillin-sensitive E. faecium strains, isolated from the same patient, were studied using biotinylated ampicillin and chemiluminescence detection. Imipenem resistance in these strains was found to be associated with hyperproduction of PBP5 compared to the ampicillin- and imipenem-susceptible strain ATCC 19434. PBP5 in the imipenem-resistant strains (S1, B2) exhibited a selectively decreased affinity for imipenem. An 854 bp DNA fragment, corresponding to the penicillin-binding domain of pbp5fm, was studied in the resistant strains and the reference strain. Four amino acid substitutions were observed in the resistant strains compared to the susceptible one. The contribution of these substitutions to the increased production of PBP5 in these strains is unclear since the substitution was observed also in a strain without increased production of PBP5. Our results suggest that the moderate imipenem resistance observed in these strains is associated with increased production of PBP5 with relatively decreased affinity for imipenem, and that evolution of imipenem resistance in E. faecium is dinstinct from that of the other beta-lactams such as ampicillin.

Ampicillin↗
PubMed2001

Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy.

The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin across the blood-brain barrier may be saturable. Taken together, these results suggest that therapeutic approaches to deliver leptin through the circulation may prove to be problematic. Although recent clinical trials have suggested that peripherally administered leptin might lead to a reduction in body weight in humans, it is likely that the more effective delivery of leptin to cellular targets within the central nervous system will be necessary in order to fully reveal the therapeutic potential of the gene product. In an effort to provide a means for the delivery of leptin that obviates the need for the gene product to traverse the blood-brain barrier, we have evaluated the use of recombinant adeno-associated vectors to deliver leptin intraventricularly or directly to the hypothalamus.

Animals↗
PubMed2001

The staff's satisfaction with the hospital bed.

AIM: To determine how nurses experience the functions of hospital beds and the bedside equipment when performing specified common nursing tasks. BACKGROUND: The hospital bed is an important working tool for the nursing staff but few studies have focused on hospital beds at acute wards. METHOD: Data was collected with questionnaires answered by 74 registered and enrolled nurses from three Departments. FINDINGS: The bed was frequently used when performing nursing tasks with patients in bed, but the manoeuvring features were difficult to adjust, resulting in unsatisfactory working postures. Transporting the patient in bed and cleaning of the bed were the most troublesome tasks. The bed clothes were often experienced as unsatisfactory for their patients. CONCLUSIONS: The beds have serious deficiencies. It is imperative to improve them, as a good physical milieu positively influences the working conditions of the staff.

Adult↗
PubMed2001

Ultrasound for diagnosis of infection in revision total hip arthroplasty.

Eighty consecutive patients (85 hips; 43 women; median age, 74 years [range, 33-90 years]) underwent a revision total hip arthroplasty. Preoperatively and guided by ultrasound, biopsy specimens of the joint pseudocapsule were taken, and joint fluid was aspirated for culture. Capsule morphology was investigated with light microscopy. When septic loosening was defined as 2 intraoperative cultures yielding the same microorganism, the prevalence was 12%. Sensitivity of the capsule biopsy cultures was 67%; specificity, 68%; positive predictive value, 22%; and negative predictive value, 94%. Joint fluid was often sparse and always falsely sterile. One specimen from a hip with septic loosening showed histologic changes (> or =3 foci, each with > or =3 plasma cells/high-power field) consistent with chronic infection. The remaining 8 septic loosenings eluded histologic detection, yielding 11% sensitivity. All aseptic loosenings were classified correctly (specificity 100%). Positive and negative predictive values were 100% and 89%. Ultrasound-guided aspiration and capsule biopsy with cultures and histology does not seem to be sufficiently accurate in the preoperative diagnosis of infected total hip arthroplasty.

Adult↗
PubMed2001

Phagocytosis in the nasopharyngeal secretion by cells from the adenoid.

The aim of this study was to elucidate whether granulocytes and macrophages in surface secretion on the adenoid emanate from the adenoid and whether these cells participate in the control of the nasopharyngeal bacterial flora. Samples of the adenoid and its surface secretion were obtained during adenoidectomy from 12 children with recurrent acute otitis media, secretory otitis media or enlarged adenoids causing obstruction. Immunochemistry was used to examine the location of granulocytes and macrophages in the adenoid as well as the presence of IgA, IgM, IgG and plasma cells in the secretion. Phagocytosis in the secretion was examined in imprints stained with May Grünwald Giemsa. Acridine Orange and Gram staining were used to demonstrate the presence and location of bacteria in the secretion and mucosa. As a control, surface secretions were obtained from 12 children without any history of recurrent airway problems. Granulocytes and macrophages were observed in the epithelium of the adenoid and some of these cells penetrated the epithelial surface. Positive staining for IgA, IgM and IgG was observed in all secretions. In 10 of 12 children plasma cells were present in the secretion. Bacteria were observed in all imprints. With the exception of I child in each group phagocytosis of bacteria in the surface secretion was demonstrated from imprints in all children. We conclude that granulocytes and macrophages leave the adenoid and enter the surface secretion, where constant phagocytic activity takes place. The spatial relations between mononuclear and polymorphonuclear cells imply a possible cooperation between these cells in the overall control of the nasopharyngeal bacterial flora.

Adenoids↗
PubMed2001

An evaluation of the utility of the CEN categorical structure for nursing diagnoses as a terminology model for integrating nursing diagnosis concepts into SNOMED.

We evaluated the utility of the CEN Categorical Structure for Nursing Diagnoses as a terminology model for integrating nursing diagnosis concepts into SNOMED. First, we dissected nursing diagnosis term phrases from two source terminologies (North American Nursing Diagnosis Association (NANDA) Taxonomy 1 and Omaha System) into the semantic categories of the CEN categorical structure. Second, we critically analyzed the similarities between the semantic links in the CEN model and the semantic links used to formally define diagnostic concepts in SNOMED RT and SNOMED CT. Our findings demonstrated that focus, bearer, and judgment were present in 100% of the NANDA and Omaha term phrases. The Omaha term phrases contained no additional descriptors beyond those considered mandatory in the CEN model. In contrast, at least 3% of NANDA diagnoses included a term in each semantic category of the categorical structure. The comparison among the semantic links showed that neither SNOMED RT and SNOMED CT currently contain all the semantic links needed to model the two source terminologies for integration. In conclusion, our findings support the potential utility of the CEN categorical structure as a terminology model for dissecting nursing diagnostic concepts for integration into SNOMED RT and SNOMED CT. However, in order to accomplish this task, appropriate semantic links must be added to SNOMED RT and SNOMED CT.

Nursing Diagnosis↗
PubMed2001

Neural transplantation: restoring complex circuitry in the striatum.

During the last 30 years, the promise of neural transplantation as a therapeutic strategy for neurodegenerative disease has been slowly recognised. Across the world, clinical transplants of embryonic primary dopamine neurones have been shown to ameliorate some of the motor deficits in Parkinson s disease (PD) patients, and more recently, systematic clinical trials have been initiated for the replacement of striatal projection neurones lost in Huntington's disease (HD). Clinical transplantation as a prospective therapy for HD poses a particular set of difficulties. The hallmarks of this neurodegenerative disease include extensive loss of medium spiny long-distance projection neurones of the caudate and putamen, affecting downstream target nuclei, the globus pallidus and substantia nigra, leading to dysregulation of motor control. In addition, extensive loss of cortical neurones that form the afferent systems to the basal ganglia leads to widespread cognitive decline. If transplantation therapy is to succeed in replacing degenerating neurones in HD and reinstating controlled function of complex basal gan-glia circuitry, the new neurones must be able to develop specific long-distance projections that can form accurate and functional connections with neurones in precise target regions. Our ongoing studies are aimed at addressing how we can improve the function of striatal transplants, in particular to optimise the reformation of precise long-distance connections and to re-establish normal motor and cognitive function. In particular, we have investigated optimal requirements for embryonic primary tissue to achieve these aims, and also the potential of other cell sources to provide long-distance projection neurones and reconnect complex circuitry. This review describes current progress of experiments to optimise the reconstruction of neuronal circuitry using primary embryonic tissue transplants, as well as our current initiatives to use neural stem cells or precursors to replace long distance projection neurones in the degenerating basal ganglia.

Animals↗
PubMed2000

The use of a recombinant lentiviral vector for ex vivo gene transfer into the rat CNS.

A major obstacle in ex vivo gene transfer has been the loss of transgene expression soon after implantation of the grafted transduced cells. Recently, a lentiviral vector system has been developed which has proven to express high levels of transgenes in vivo after direct injection into the tissue. In this study, we have investigated the use of such a vector for ex vivo gene transfer to the brain. A number of neural cell types were found to be permissive to transduction by the lentiviral vector in vitro and a majority of them expressed the transgene after transplantation to the rat brain. Transgene expression was detected up to 8 weeks post-grafting. These findings suggest that recombinant lentiviral vectors may be used for further development of ex vivo gene therapy protocols to the CNS.

Animals↗
PubMed2000

Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model.

During the last few years, recombinant viral vectors derived from adenovirus (Ad), adeno-associated virus (AAV) or lentivirus (LV) have been developed into highly effective vehicles for gene transfer to the adult central nervous system. In recent experiments, in the rat model of Parkinson's disease, all three vector systems have been shown to be effective for long-term delivery of glial cell line-derived neurotrophic factor (GDNF) at biologically relevant levels in the nigrostriatal system. Injection of the GDNF encoding vectors into either striatum or substantia nigra thus makes it possible to obtain a regionally restricted over-expression of GDNF within the nigrostriatal system that is sufficient to block the toxin-induced degeneration of the nigral dopamine neurons. Injection of GDNF vectors in the striatum, in particular, is effective not only in rescuing the cell bodies in the substantia nigra, but also in preserving the nigrostriatal projection and a functional striatal dopamine innervation in the rat Parkinson model. Long-term experiments using AAV-GDNF and LV-GDNF vectors show, moreover, that sustained GDNF delivery over 3-6 months can promote regeneration and significant functional recovery in both 6-OHDA-lesioned rats and MPTP-lesioned monkeys. The impressive efficacy of the novel AAV and LV vectors in rodent and primate Parkinson models suggests that the time may now be ripe to explore these vector systems as tools for neuroprotective treatments in patients with Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells.

In experimental autoimmune encephalomyelitis (EAE), CD4(+) self-reactive T cells target myelin components of the CNS. However, the consequences of an autoaggressive T cell response against myelin for neurons are currently unknown. We herein demonstrate that EAE induced by active immunization with an encephalitogenic myelin basic protein peptide dramatically reduces the loss of spinal motoneurons after ventral root avulsion in rats. Both brain-derived neurotophic factor (BDNF)- and neurotrophin-3 (NT-3)-like immunoreactivities were detected in mainly T and natural killer (NK) cells in the spinal cord. In addition, very high levels of BDNF, NT-3, and glial cell line-derived neurotrophic factor mRNAs were present in T and NK cell populations infiltrating the CNS. Interestingly, bystander recruited NK and T cells displayed similar or higher neurotrophic factor levels compared with the EAE disease-driving encephalitogenic T cell population. High levels of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were also detected, and both these cytokines can be harmful to several types of CNS cells, including neurons. However, treatment of embryonic motoneuron cultures with TNF-alpha or IFN-gamma only had a deleterious effect in cultures deprived of neurotrophic factors. These results suggest that the potentially neurodamaging consequences of severe CNS inflammation are curbed by the production of several potent neurotrophic factors in leukocytes.

Animals↗