Biomedical subjects

C Lundberg

Publications and source records attributed to C Lundberg.

At least 19 recordsLinked to original sources

PubMed2000

In vivo protection of nigral dopamine neurons by lentiviral gene transfer of the novel GDNF-family member neublastin/artemin.

The glial cell line-derived neurotrophic factor (GDNF)-family of neurotrophic factors consisted until recently of three members, GDNF, neurturin, and persephin. We describe here the cloning of a new GDNF-family member, neublastin (NBN), identical to artemin (ART), recently published (Baloh et al., 1998). Addition of NBN/ART to cultures of fetal mesencephalic dopamine (DA) neurons increased the number of surviving tyrosine hydroxylase (TH)-immunoreactive neurons by approximately 70%, similar to the maximal effect obtained with GDNF. To investigate the neuroprotective effects in vivo, lentiviral vectors carrying the cDNA for NBN/ART or GDNF were injected into the striatum and ventral midbrain. Three weeks after an intrastriatal 6-hydroxydopamine lesion only about 20% of the nigral DA neurons were left in the control group, while 80-90% of the DA neurons remained in the NBN/ART and GDNF treatment groups, and the striatal TH-immunoreactive innervation was partly spared. We conclude that NBN/ART, similarly to GDNF, is a potent neuroprotective factor for the nigrostriatal DA neurons in vivo.

Amino Acid Sequence↗

PubMed2000

Inhibition of CD11-CD18 complex prevents acute lung injury and reduces mortality after peritonitis in rabbits.

Acute lung injury is frequent after severe peritonitis. The aim of this study was to investigate whether inhibition of the adhesion molecule CD11-CD18 on polymorphonuclear leukocytes (PMNs) would have any beneficial effects on pulmonary function and mortality in an animal model reproducing these clinical conditions. Acute peritonitis was induced in 36 rabbits by intraperitoneal injection of zymosan (0.6 g/kg) suspended in mineral oil; 20 were pretreated with a murine-specific IgG2a anti-CD18 monoclonal antibody, 16 (controls) with nonspecific purified murine IgG (1 mg/kg). The animals were followed for 10 d, then killed for histologic examination of the lungs. Blood samples were taken on Days 0, 1, 3, 7, and 10 for red blood cell (RBC), white blood cell (WBC), and platelet counts, pH, PO(2), PCO(2), carbon dioxide content (HCO(3)(-)) measurements, and renal and liver tests. Treatment with the anti-CD18 monoclonal antibody reduced mortality by approximately 40% (p < 0.05). PO(2) was higher in these treated animals than in the control animals throughout the study (p < 0.05 on Day 1, 3, and 10). On Day 1 control animals had significant leukopenia, whereas anti-CD18-treated animals had a moderate increase of the number of circulating WBC compared with baseline values (p < 0.05 between groups). The lungs of the anti-CD18-treated animals showed minor signs of inflammation and PMN infiltration whereas controls had interstitial and intra-alveolar edema and a large number of granulocytes. Quantification of PMNs by morphometry showed that there were constantly less granulocytes in the lungs of the animals treated with the anti-CD18 antibody (p < 0.001). PMN infiltration correlated with the levels of PO(2) (p < 0.001). Lung tissue of anti-CD18-treated rabbits contained less malonyldialdehyde, a by-product of membrane lipid peroxidation by PMN oxygen radicals (950 +/- 120 versus 1,710 +/- 450 pM/mg of protein) and, conversely, more of the antioxidant alpha-tocopherol (136 +/- 22 versus 40 +/- 9 ng/mg of protein), than the control rabbits (p < 0.01). In this particular model of ARDS the monoclonal antibody against the CD11-CD18 complex had a beneficial effect, reducing PMN infiltration and oxygen radical release in the lungs, preventing alveolocapillary membrane damage, improving gas exchange and, finally, significantly reducing mortality.

Animals↗

PubMed2000

Nasopharyngeal tonsil's provision of the surface secretions with immunocytes, a property additional to antigen processing.

As we recently found that IgA, IgM, and IgG are produced and secreted by immunocytes present in nasopharyngeal secretions, we tested the hypothesis that B- and T-lymphocytes in the surface secretions are derived from the nasopharyngeal tonsil in an active process. By immunohistochemistry, we found that numerous B- and T-lymphocytes were often accumulated in restricted areas in the epithelium, and some of these cells were demonstrated just beneath the epithelial surface or could be observed protruding into the lumen. A portion of these cells were Ki-67+, indicating clonal expansion and/or immunoglobulin class switching. Analyses of the surface secretions by immunocytochemistry also demonstrated B- and T-lymphocytes, as well as Ki-67+ cells--a finding that indicates that immunologically active cells are transported into the surface secretions. The results imply that there is a substantial migration from the nasopharyngeal tonsil of immunologically active cells into the surface secretions.

Adenoidectomy↗

PubMed1999

Non-MHC gene regulation of nerve root injury induced spinal cord inflammation and neuron death.

Spinal ventral root avulsion leads to an inflammatory response around lesioned motoneurons and the subsequent degeneration of a large proportion of the neurons. We demonstrate here differences in the regulation of cytokine mRNAs, microglia/macrophage activation, MHC expression and nerve cell survival in the two inbred rat strains DA and ACI. These strains have similar major MHC haplotypes, but differ in their non-MHC background genes. T cells were rare in the lesioned segments and depletion of T cells did not affect the response. Thus, non-MHC gene(s) regulate the inflammation and neuron death after nerve trauma by mechanisms not involving antigen-specific immune responses.

Animals↗

PubMed1999

Immunoglobulin-secreting cells in the surface secretion on the pharyngeal tonsils.

As B-lymphocytes on the pharyngeal tonsils constitute a considerable part of the leukocytes in the surface secretion, and their biological role is obscure, we explored their possible function with respect to immunoglobulin production. Twenty children scheduled for routine adenoidectomy participated. Surface secretion from 10 children was analysed for presence of plasma cells and cells from the secretions of the other 10 children were tested in enzyme-linked immunosorbent spot assays (ELISPOT-assays) for their capacity to secrete and produce IgA, IgM and IgG. Plasma cells and cells that secreted IgA, IgM and IgG respectively were present in the secretions of all tested children. In eight of ten children the IgG immunocytes, Ig-producing blasts and plasma cells. outnumbered the IgA immunocytes. The number of immunoglobulin secreting cells (ISCs) was reduced by half or more in cell suspensions exposed to the reversible protein synthesis inhibitor cycloheximide. It is concluded that immunocytes that produce and secrete immunoglobulin are present in the surface secretion on the pharyngeal tonsils. The production represents an addition to the immunoglobulins transported to the secretion by the poly-Ig receptor and by passive diffusion. The results shed new light on the pathogenesis of mucosal infections in the upper airways.

Adenoids↗

PubMed1998

Impairments of some cognitive functions are common in crash-involved older drivers.

The relationship between limitations in different cognitive functions, measured with a neuropsychological test battery, and moving traffic violations among older drivers was investigated. Thirty-seven drivers aged 65 years or more, with temporarily suspended driving licenses (suspended drivers) were identified 23 were crash-involved and 14 were not. When compared to 31 controls with clean driving records, crash-involved suspended drivers performed less well on tests of visuoconstructive ability (p = 0.008), psychomotor speed (p = 0.019) and visuospatial memory (p = 0.036). Non-crash-involved suspended drivers did not differ from controls. A combination of three tests (of visuoconstructive ability, visuospatial memory and verbal episodic memory) succeeded in correctly classifying 65.2% of the crash-involved suspended drivers. The results support the idea of cognitive decrements as an important causal factor in crashes of older drivers.

Accidents, Traffic↗

PubMed1998

Are electrocardiographic Q-wave criteria reliable for diagnosis of perioperative myocardial infarction after coronary surgery?

OBJECTIVE: A major assumption in cardiovascular medicine is that Q-waves on the electrocardiogram indicate major myocardial tissue damage. The appearance of a new Q-wave has therefore been considered the most reliable criterion for diagnosis of perioperative myocardial infarction (PMI) in cardiac surgery. In a study, originally intended to evaluate troponin-T as a marker of PMI, analysis of our data aroused the need to address the reliability of Q-wave criteria for diagnosis of PMI. METHODS: In 302 consecutive patients undergoing coronary surgery, Q-wave and other electrocardiogram (ECG) criteria were compared with biochemical markers of myocardial injury and the postoperative course. All ECGs were analysed by a cardiologist blinded to the biochemical analyses and the clinical course. RESULTS: The incidence of positive Q-wave criteria was 8.1%. Combined biochemical (CK-MB > or = 70 microg/l) and Q-wave criteria were found in 1.0%. Patients with new Q-waves did not have CK-MB or troponin-T levels significantly different from those without Q-waves. More than 25% of the Q-waves were associated with plasma troponin-T below the reference level (< 0.2 microg/l) on the fourth postoperative day. Q-wave criteria alone did not influence the postoperative course. In contrast, biochemical markers correlated with clinical outcome. CONCLUSIONS: The majority of Q-waves appearing after coronary surgery were not associated with major myocardial tissue damage, and according to troponin-T one-fourth of the Q-waves were not associated with myocardial necrosis. Furthermore, the appearance of Q-waves had little influence on short term clinical outcome. Therefore, the use of Q-wave criteria as the gold standard for diagnosis of PMI may have to be questioned.

Aged↗

PubMed1998

Acute pharyngotonsillitis is an infection restricted to the crypt and surface secretion.

A commonly accepted hypothesis is that acute pharyngotonsillitis is caused by bacteria which first adhere to the epithelial surface and then invade the tonsillar parenchyma; however, evidence directly supporting this hypothesis is not available. In previous studies on acute pharyngotonsillitis, we found that the secretion in crypts and at the surface was infected in acute pharyngotonsillitis while no bacteria were detected in the parenchyma. Based on these results, we have proposed a new hypothesis stating that the infection is restricted to the crypt and surface secretions in acute pharyngotonsillitis. To evaluate this hypothesis further, in the present study we examined tonsillar tissue and secretion from patients with acute pharyngotonsillitis, recurrent pharyngotonsillitis and healthy tonsils. Surface secretion was studied after sampling by an imprint technique followed by routine histological preparation. Tonsillar tissue was examined by fluorescence microscopy after staining with acridine orange and by transmission electron microscopy. There were high numbers of bacteria and moderate or extensive ongoing phagocytosis in the crypt and surface secretion from patients with acute pharyngotonsillitis. Bacteria, leucocytes and phagocytosis were also present, but to less extent in the secretion from patients with recurrent pharyngotonsillitis and to even less extent in the healthy controls. In none of all the investigated tonsils were bacteria present in the parenchyma. Bacterial adherence to the epithelial surface was only very rarely observed. This study supports the hypothesis that acute pharyngotonsillitis is an infection restricted to the crypt and surface secretion and that bacterial adherence is not of significant importance in the pathogenesis of acute pharyngotonsillitis.

Adenoids↗

PubMed1998

Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation.

PURPOSE: To study lens epithelial cell (LEC) regulation after experimental cataract surgery in rabbits. The effect of aqueous humor (AqH) on LECs in vitro was investigated and the AqH concentrations of basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF-beta) were determined. METHODS: Aqueous humor was aspirated immediately before, and 1, 5, 10, 15, and 30 days after cataract surgery (n=8 each day). The effect of AqH on LEC proliferation was investigated by the incorporation of [3H]thymidine. The following concentrations were determined in AqH: bFGF, active and total TGF-beta, leukocytes, and total protein. RESULTS: Aqueous humor collected after surgery triggered LEC growth on each occasion, except on (postoperative) day 30, in contrast to the effect of normal AqH. Lens epithelial cell proliferation peaked on day 1, displaying a sixfold increase. The bFGF concentration in AqH increased 6 to 10-fold after surgery and remained high throughout the experimental period. The AqH concentration of active TGF-beta decreased sevenfold 1 day after surgery. It then returned to normal levels on day 15. Total TGF-beta in postoperative AqH was twice as high as that in normal AqH on all days. Lens epithelial cell proliferation correlated with protein (r=0.685), leukocytes (r=0.565), and active TGF-beta (r=-0.418). CONCLUSIONS: The stimulating effect of postoperative AqH on LEC proliferation may be caused by a reduction in the concentration of TGF-beta.

Animals↗

PubMed1997

Nephelometric determination of rat fibrinogen as a marker of inflammatory response.

Following tissue injury or infection, the concentrations of several plasma proteins are altered substantially. The characteristic pattern of this change is termed the acute phase response, and can be observed in many different inflammatory situations, including surgical trauma, injury, infections, tissue infarction and several immunologically mediated states such as temporalis arteritis, polymyalgia rheumatica and rheumatoid arthritis. It is often of great clinical value to monitor the acute phase response in humans but the assays used to measure the acute response in man (e.g., erythrocyte sedimentation rate and C-reactive protein) is less well suited for experimental studies in the rat. We have instead developed a nephelometric assay for determination of fibrinogen as a marker of the inflammatory response in rats. The assay was used to monitor the inflammatory response in type II collagen arthritis in rats. This model involves the induction of severe polyarthritis and is a widely used animal model for rheumatoid arthritis (RA). Fibrinogen concentrations increased from 3.1 g/l before immunization to 10.5 g/l 2 weeks after the immunization, after which they gradually declined towards normal levels. This pattern of fibrinogen alterations correlated well with the inflammatory phase of the arthritic response. Plasma fibrinogen may thus represent a rapid and sensitive marker of the acute phase response in the rat.

Acute-Phase Reaction↗

PubMed1997

Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum.

The in vivo properties of four different neural stem cell lines, generated from embryonic striatum or hippocampus by immortalization with the temperature-sensitive (s) A58/U19 allele of the SV40 Large T-antigen, have been studied with respect to their ability to survive, differentiate, and integrate after transplantation to the adult rat striatum. The cells were labeled with [3H]thymidine prior to grafting, and combined autoradiography and immunohistochemistry was used to characterize their phenotypic differentiation within the adult brain environment. The results show that all four types of cells survived well, up to at least 1.5-6 months postgrafting, without any signs of tissue perturbation or tumor formation. The cells underwent, on average, 2-3 cell divisions during the first 5 days after implantation and exhibited extensive migration over a distance of 1-1.5 mm from the injection site to become morphologically integrated with the surrounding host striatum. The cell number and tissue distribution attained by 2 weeks remained stable for up to 6 months postgrafting with the exception of one cell line, which showed a 40% loss of cells between 2 and 6 weeks. Twice the number of [3H]thymidine-labeled cells were recovered when the cells were grafted into a 1-week-old excitotoxic striatal lesion, probably due to an increased proliferation of the cells in response to the neuron-depleting depleting lesion. The immortalized cells behaved as multipotent neural progenitors. The vast majority of the cells developed a glial-like morphology, 6-14% being clearly GFAP-positive; however, a small but consistent proportion of them (1-3%) expressed MAP-2 and exhibited neuron-like morphology. In mature transplants about 75-80% of the grafted cells were located in the striatal grey matter, and 10-15% in white matter, some of which are proposed to have differentiated into oligodendrocytes. Remaining 5-10% occurred around small blood vessels (resembling pericytes) and in the subventricular zone underneath the ependyma of the lateral ventricle. It is concluded that the ts cell lines are highly suitable for intracerebral transplantation and that they allow the creation of a regionally confined cellular chimeras where the graft-derived glial cells become stably integrated with the resident glial cell matrix.

Animals↗

PubMed1997

Dementia and driving: an attempt at consensus.

The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Aged↗

PubMed1997

The 1994 International Consensus Conference on Dementia and Driving: a brief report. Swedish National Road Administration.

A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, although dementia effects cognitive functions essential for safe driving, the evaluation of driving competence in demented persons is problematic. A clear-cut policy, intended chiefly for primary care physicians, is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to review existing research and to formulate a consensus on the issue of driving and dementia. The consensus group suggested that physicians should routinely make a cursory evaluation of the mental condition of their older driving patients. When signs of cognitive impairment are detected, possible influence on visuospatial skills, attention, judgment, and memory functions should be carefully considered. Information from caregivers on past and current driving performance as well as functions relating to activities of daily living (ADL) should be taken into account. Consensus was reached that a diagnosis of moderate to severe dementia indicates sufficient cognitive impairment to preclude driving. In addition, diagnosed mildly demented individuals or nondiagnosed cognitively impaired individuals with functional deterioration should be considered for specialized assessment of driving competence.

Automobile Driving↗

PubMed1997

Do the leukocytes in the surface secretion on the adenoid have an immunological function?

To elucidate whether leukocytes in the surface secretion on the adenoid have a potential immunological function, imprint samples of surface secretion were obtained from the adenoid of 11 children and the corresponding mucosal area of 10 adults. May-Grünewald-Giemsa staining was used for evaluation of cell morphology and spatial relations, and immunohistochemical staining for identification of granulocytes, B cells, T cells and macrophages. The children's imprints showed large numbers of leukocytes, with mononuclear cells in the majority. The adults' imprints were characterized by moderate numbers of epithelial cells and few leukocytes. In six out of seven adenoid secretions successfully analysed with all four CD antigens, there was the simultaneous presence of granulocytes, B cells, 1 cells and macrophages. This was the case in one of nine analysable adult secretions. The CD-positive cells were often seen in juxtaposition, in clusters of two to 10 cells, as well as in contact with leukocytes of unknown CD antigenicity and epithelial cells. The simultaneous presence in the secretion of morphologically intact and CD antigen-presenting leukocytes in juxtaposition could indicate a potential immunological function of these cells.

Adenoids↗

PubMed1996

Conditionally immortalized neural progenitor cell lines integrate and differentiate after grafting to the adult rat striatum. A combined autoradiographic and electron microscopic study.

Neural progenitor cell lines, generated by conditional immortalization from the embryonic CNS, have previously been shown to survive and integrate after transplantation to the adult brain. The present study was designed to investigate the in vivo differentiation and morphological features of grafted neural progenitors using combined autoradiography and transmission electron microscopy of two temperature-sensitive neural progenitor cell lines, HiB5 and ST14A, labeled with 3H-thymidine prior to grafting. Two weeks after transplantation to the striatum the cells were found dispersed over an area extending about 1.5 mm from the injection site. Labeled cells located within the myelinated fiber bundles of the internal capsule were closely associated with myelinated axons and presented profiles similar to oligodendrocytes, while most of the grafted cells in the grey matter had morphological features of astroglia. Some labeled cells occurred also in close association with small blood vessels, morphologically resembling host pericytes. The results show that the immortalized neural progenitors can differentiate into mature glial cells, including astrocytes, oligodendrocytes and pericytes, after implantation into the adult striatum. The ability of the cells to become fully integrated with the resident glial population suggests that they will be highly useful as vehicles for intracerebral transgene expression in ex vivo gene transfer.

Animals↗

PubMed1996

Host regulation of glial markers in intrastriatal grafts of conditionally immortalized neural stem cell lines.

After transplantation into the adult CNS the immortalized neural stem cell lines ST14A and HiB5 differentiate preferentially into glia-like cells. After lesions of the host brain, which activate resting glial populations, the grafted cells responded with up-regulation of glial markers and a change in morphology towards a reactive state. The protein expression followed the same pattern as in the host glial population. The results show that the astrocytes formed by the grafted neural stem cells become functionally integrated in the host brain and that they may take an active part in the reactive gliosis caused by brain damage.

Analysis of Variance↗

PubMed1996

Generation of DOPA-producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene: in vitro characterization and in vivo effects in the rat Parkinson model.

Astrocytes secreting high levels of L-3,4-dihydroxyphenylalanine (DOPA) have been generated by retrovirus-mediated transfer of the human tyrosine hydroxylase (TH) gene. Immature astrocytes obtained from prenatal rat brain were cocultured with TH virus producing psi-2 cells that had been pretreated with the mitosis inhibitor mitomycin-C. During the first week of coculture DOPA production gradually increased to reach a plateau after 7-9 days. At this time point virtually all cells were GFAP positive and over 80% of them expressed TH. DOPA production in the transduced astrocytes was largely independent of exogenous cofactor, and DOPA release into the medium was not influenced by addition of either KCl or tetrodotoxin or by removal of Ca2+ from the culture medium, indicating that the newly synthesized DOPA was constitutively released from the cells. Transplantation of the TH-transduced astrocytes to the striatum in unilaterally 6-hydroxydopamine lesioned rats reduced apomorphine-induced turning by about 50% at 2 weeks postgrafting. Microscopic analysis revealed that the transduced astrocytes survived very well after transplantation and that some of the grafted cells had migrated out, partly along blood vessels, into the surrounding striatum. TH expression was observed in cells with both the appearance of mature GFAP-positive astrocytes, as well as in more immature-looking cells. However, only a few percent of all transplanted cells maintained significant expression of the transgene, as determined by TH immuno-histochemistry. The results show that primary astrocytes may be highly useful as gene carriers for ex vivo gene therapy in the CNS. With future improvement in the gene transduction procedure for more efficient, sustained expression of the TH transgene in vivo, genetically engineered DOPA-producing astrocytes hold great promise as a tool to explore the potential of ex vivo gene therapy in Parkinson's disease.

Animals↗

PubMed1996

Conditionally immortalized neural progenitor cells grafted to the striatum exhibit site-specific neuronal differentiation and establish connections with the host globus pallidus.

The cell line RN33B has been reported to differentiate into neurons in a site-specific manner when grafted to the cortex and hippocampus of adult rats. To investigate the fate of RN33B cells in a subcortical structure, we grafted RN33B cells into the intact or excitoxically lesioned striatum of adult or neonatal rats. The total number and phenotypic characteristics of the [3H]thymidine-labeled grafted cells were analyzed at different time points after transplantation. Transplanted RN33B cells were found to survive, integrate, and differentiate into both neurons and astrocytes, and a significant proportion of the cells (approx. 10%) were found to differentiate into cells with morphological and phenotypic characteristics of medium-sized striatal projection neurons. Retrograde tracing showed that at least some of the graft-derived neurons were capable of establishing connections with one of the primary striatal targets, the globus pallidus. These findings demonstrate a remarkable capacity of the RN33B cells for site-specific neuronal differentiation in both the adult and the developing striatum and suggest that the same differentiating factors that are operating during normal neurogenesis in brain development are retained, at least to some extent, also in the adult CNS.

Adult↗