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Biomedical subjects

K Kristensson

Publications and source records attributed to K Kristensson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Interferon-gamma-like immunoreactivity in sensory neurons may influence the replication of Sendai and mumps viruses.

Rat dorsal root ganglia in tissue culture, which contain an interferon-gamma (IFN-gamma)-like immunoreactive subpopulation of neurons, were infected with paramyxoviruses. Sendai virus caused a substantial neuronal lysis, while the RW strain of mumps virus caused a much less pronounced nerve cell loss. Early during infection, the subpopulation of IFN-gamma-like immunoreactive neurons was less susceptible to mumps virus. Virus antigen was rapidly lost from surviving IFN-gamma-like positive neurons infected with Sendai virus, while this remarkable self-curing effect occurred in both nerve cell populations at later time points after mumps virus infection. By quantitative enzyme-linked immunosorbent assay (ELISA) technique, increased levels of "neuronal IFN-gamma" were recorded at 10 hr and 30 hr after infection with Sendai and mumps virus, respectively. This study indicates a role for the neuronal IFN-gamma-like molecule in determining the outcome of a viral infection in sensory ganglia.

Animals↗
PubMed1992

Bidirectional signals between Trypanosoma brucei brucei and dorsal root ganglion neurons.

The extracellular haemoflagellate Trypanosoma brucei brucei releases a factor, which can induce CD8+ T-cells to produce interferon-gamma. Interferon-gamma derived from these cells promotes proliferation of the trypanosomes. We now report that these trypanosomes can interact with small neurons in cultures of rat dorsal root ganglia, which contain an interferon-gamma like immunoreactive molecule. Cultures of dorsal root ganglia were able to promote the proliferation and survival of the trypanosomes and this growth promoting effect was blocked by monoclonal antibodies against the trypanosome-derived lymphocyte triggering factor, interferon-gamma and CD8+ and by Fab-fragments of these antibodies. Living trypanosomes and the factor induced an increase in expression of major histocompatibility complex class I antigens in the cultures; this induction was blocked by Fab fragments of the interferon-gamma antibody, indicating that it is mediated by release of the neuronal interferon-gamma-like immunoreactive molecule. These data suggest, that the interferon-gamma-like immunoreactive molecule in small dorsal root ganglion neurons mimics certain physiological effects of lymphocyte derived interferon-gamma. Furthermore, the trypanosomes and small sensory neurons seem to interact bidirectionally by release of the trypanosome-derived lymphocyte triggering factor and the neuronally derived interferon-gamma-like molecule, whereby, perhaps, neuronal disturbances may be elicited and trypanosome proliferation regulated.

Animals↗
PubMed1992

Epstein-Barr virus-induced transformation of human B lymphocytes: the effect of L-leucyl-L-leucine methyl ester on inhibitory T cell populations.

Epstein-Barr virus-mediated transformation of human B lymphocytes is inhibited by human T lymphocytes as well as by interferon-gamma. Removal of the inhibitory cell populations is essential in order to achieve successful transformation in vitro. Cells with the capacity to inhibit outgrowth of lymphoblastoid cell lines can be removed by pretreatment of peripheral blood mononuclear cells with L-leucyl-L-leucine methyl ester. This treatment eliminates monocytes, NK-cells and a CD8+ T cell subpopulation. We now show that such treatment also has toxic effects on other human T cell populations. In addition, CD4+ and/or CD8+ lymphocytes are demonstrated to contain effector cell activities which inhibit outgrowth of EBV-transformed B cells. This inhibitory activity is abolished after treatment of peripheral blood mononuclear cells or purified CD4+ T cells with L-leucyl-L-leucine methyl ester. No evidence was found for a selective toxicity against any subset within the CD4+ or CD8+ T cell populations. However, the capacity of the treated cells, both peripheral blood mononuclear cells and purified CD4+ T lymphocytes, to produce mRNA encoding IFN-gamma, a protein previously shown to downregulate outgrowth of EBV-transformed B cells, was selectively impaired. The results obtained suggest a role for CD4+ T cells to inhibit EBV-induced transformation of B cells.

Antibodies, Monoclonal↗
PubMed1992

Interactions between Trypanosoma brucei and CD8+ T cells.

The mechanisms for several important features o f African trypanosomiasis are still largely unexplained. These include (1) the occurrence of parasite growth-promoting molecules provided by the host, (2) polyclonal T- and B-cell activation and the development of immunosuppression and (3) neuropsychiatric signs. Here Tomas Olsson, Moiz Bakhiet and Krister Kristensson focus on interactive events between Trypanosoma brucei and CD8(+) T cells, and the release of a diffusible molecule from T. brucei that triggers CD8(+) T cells to produce interferon-gamma (IFN-gamma). This cytokine provides a growth stimulus for the parasite and modulates events in the host's immune and nervous systems.

Journal Article↗
PubMed1992

Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type.

The lipid compositions of 10 different brain regions from patients affected by Alzheimer's disease/senile dementia of Alzheimer's type were analyzed. The total phospholipid amount decreased somewhat in nucleus caudatus and in white matter. The cortical areas that are morphologically affected by Alzheimer's disease, i.e., frontal and temporal cortex and the hippocampus, showed elevated contents of lipid solvent-extractable phosphatidylinositol. Sphingomyelin content was decreased in regions rich in myelin. There was a 20-50% decrease in dolichol amount in all investigated parts of the brain, but no change was seen in the polyisoprenoid pattern. Levels of alpha-unsaturated polyprenes were decreased in Alzheimer brains. Dolichyl-phosphate content increased in most regions, up to 100%. In both control and Alzheimer tissue almost all of the dolichyl-phosphate was covalently bound, apparently through glycosylation. Cholesterol amounts were highly variable but mostly unchanged, whereas ubiquinone concentrations increased by 30-100% in most regions in brains affected by Alzheimer's disease. These results demonstrate that both phospholipids and neutral lipids are modified in brains affected by Alzheimer's disease/senile dementia of Alzheimer's type.

Aged↗
PubMed1992

Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease.

The lipid compositions of various regions of the human brain were investigated during aging and in Alzheimer's disease. The phospholipid amounts and compositions remained unchanged during aging. There were, however, considerable differences both in phospholipid composition and amount when the various regions were compared. The level of dolichol increased severalfold in all regions up to the age of 70, but there was no further elevation thereafter. The ubiquinone level decreased significantly in all parts of the brain upon aging. In Alzheimer's disease, the dolichol level was decreased in all regions, and particularly, in those affected by the disease. In contrast, the dolichyl-P concentration increased in those regions that exhibited morphological changes. There was no modification in cholesterol distribution, but a significant elevation in ubiquinone content was observed in most regions. The only phospholipid whose level was elevated was phosphatidylinositol, and only in those parts of the brain that were affected. The content of polyunsaturated fatty acids in phosphatidylethanolamine was greatly decreased in connection with the disease, with a parallel increase in the saturated portion. The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain.

Aged↗
PubMed1992

Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus.

Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump.

Animals↗
PubMed1992

Human CD4+ T cells expressing CD45RA acquire the lymphokine gene expression of CD45RO+ T-helper cells after activation in vitro.

CD4+ T cells were separated into subpopulations according to their expression of different isoforms of the CD45R molecule, i.e. CD45RA and CD45RO. The separated cells were activated with staphylococcal enterotoxin A (SEA) in the presence of formalin fixed Raji cells. Each set of cells was activated twice with a 6-day interval, and the lymphokine gene expression during the first 3 days after initiation of each stimulation was followed by use of polymerase chain reaction (PCR) technology. The lymphokine messenger RNA (mRNA) profiles were found to differ between the subsets, since after the first stimulation the CD45RA+ cells produced mRNA encoding interleukin-2 (IL-2) and IL-1 alpha, whereas the CD45RO+ cells transcribed genes for IL-1 alpha, IL-2, IL-4, IL-5 and interferon-gamma (IFN-gamma). After 6 days of SEA stimulation both populations were mainly CD45RO reactive, and when restimulated displayed the lymphokine mRNA profile restricted to this subset. These results indicate that the CD45RA subset is a precursor of the CD45RO and further strengthen the hypothesis that the former cell population represents naive whereas the latter subset represents memory T cells within the CD4 subset.

Antigens, CD↗
PubMed1991

[Prions and Trypanosoma as a source of knowledge of the brain].

Recent research on prions and trypanosomes is reviewed as they constitute examples of how infectious agents can cause degenerative diseases or functional disturbances in the nervous system. Prions are novel, transmissible pathogens causing degenerative diseases of the central nervous system both in humans and in animals. Kuru, Creutzfeldt-Jakob's disease and Gerstmann-Sträussler-Scheinker's (GSS) syndrome illustrate the acquired, sporadic and genetic manifestations of the human prion diseases, respectively. Prions are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is a normal cellular protein occurring at high concentrations in the central nervous system. Specific mutations in the prion gene may cause the sporadic and hereditary human disease. S B Prusiner's group at the University of California has used genetic engineering techniques to recreate GSS syndrome by transplanting the mutated prion gene into mice in which the effects of the prion protein genes can then be studied. Trypanosomes are extracellular parasites which cause distinct functional disturbances of the nervous system, although they do not penetrate the blood-brain barrier. Factors are now being isolated in the interactions between the parasites and the immunesystem, and the effects of such factors on the functional properties of neurons are studied.

Animals↗
PubMed1991

Paramyxovirus infections alter certain functional properties in cultured sensory neurons.

Functional properties of cultured mouse dorsal root ganglion cells infected with paramyxoviruses have been studied using intracellular recording techniques. Mumps virus, which causes a persistent non-lytic infection, and Sendai virus, which causes an infection that leads to cell lysis after about a week were used. In the early phase of the infection (24-48 h) both viruses caused a reduction in the influx of calcium ions during the action potential, but did not alter resting membrane potential, action potential amplitude or input resistance. At later times functional properties became normal in mumps infected neurons. In contrast, Sendai virus infected neurons showed a reduction of action potential amplitude and input resistance at 48-72 h after infection, and finally there was also a reduction of membrane potential before the cells disintegrated. These results show that different paramyxovirus infections may cause different types of alterations in the functional properties of neurons. The reduced calcium influx resulting from mumps infection suggests that a non-lytic viral infection may have selective effects on important regulators of neuronal functions. Moreover, a lethal viral infection (Sendai) may influence specific membrane properties, such as calcium channel activation, several days prior to general structural and functional degeneration.

Action Potentials↗
PubMed1991

Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth.

The hemoflagellate Trypanosoma brucei (T.b.) is the cause of African sleeping sickness. T. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (MNC). Co-cultivation in vitro of rat or human MNC and T.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (IFN-gamma) which was dependent on CD8+ lymphoid cells. The parasites triggered MNC proliferation if IFN-gamma was blocked by a specific antibody in vitro. Separate cultures of parasites and MNC in a two-chamber system allowing exchange of soluble mediators showed CD8+ cell-dependent MNC triggering, indicating that a diffusable factor released by trypanosomes acts on the MNC. Gel filtration according to molecular mass of disrupted parasites and assay of the fractions revealed a peak activity at an approximate molecular mass of 185 kDa for the trypanosome-derived lymphocyte-triggering factor (TLTF). Conversely, there was a CD8+ cell-dependent action of MNC on the trypanosomes. MNC released a diffusable factor that in short-term experiments caused a striking increase in number of parasites. This effect was inhibited by antibodies against rat IFN-gamma. The increase in number of trypanosomes was promoted by rat MNC or rat IFN-gamma but not human MNC or human IFN-gamma suggesting a species-restricted recognition of IFN-gamma. An in vivo uptake of IFN-gamma by the parasites was suggested by immunohistochemical staining of T.b. brucei with an mAb against rat IFN-gamma and Western blot of the parasites showing a band with a molecular mass corresponding to IFN-gamma. The bidirectional signals we define here may explain certain features of trypanosomiasis, i.e. T cell activation, immunosuppression and host-range restriction. The seemingly important role of the TLTF indicates that it should be purified and explored as target for immune-specific intervention.

Animals↗
PubMed1991

Interferon-gamma-like immunoreactivity in developing rat spinal ganglia neurons in vivo and in vitro.

Interferon-gamma-like immunoreactivity was observed in a subpopulation of 16-day-old embryonic rat spinal ganglion neurons using two monoclonal antibodies directed against different epitopes of recombinant interferon-gamma. During ontogenesis both in vivo and in vitro, it was found that the strong immunoreactivity was confined to small neurons when neurons become morphologically distinct on the basis of size. In vivo, the interferon-gamma-immunoreactive neurons started to express major histocompatibility complex class I antigens after the first postnatal week, while in vitro no such antigen could be detected. A quantitative Elisa method was developed to determine the levels of major histocompatibility complex class I and interferon-gamma in vitro, whereby increased amounts of major histocompatibility complex class I antigen was detected after exposing the cultures to recombinant interferon-gamma and Sendai virus. Sendai virus also caused a small increase in interferon-gamma with a peak about 12 hours after infection. The in vitro system will be used to study further the role of the putative neuronal interferon-gamma-like molecule in the regulation of cell growth, for induction of major histocompatibility complex antigens and in virus infection of sensory neurons.

Animals↗
PubMed1991

Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease.

The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain, i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18:1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer's disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18:1, is not significantly altered in Alzheimer's disease, but there is a substantial increase in the relative amounts of the saturated components 14:0, 16:0 and 18:0. This is paralleled by a decrease in the polyunsaturated FA 20:4, 22:4 and 22:6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process.

Adult↗
PubMed1991

Studies of hyperalgesia induced by Trypanosoma brucei brucei infection in rats.

Sprague-Dawley rats were infected by intraperitoneal injections of a strain of Trypanosoma brucei brucei. This parasite spreads early to areas in the nervous system which lack a so-called blood-brain or blood-nerve barrier including spinal ganglia. Signs of sensory disturbance in the form of hyperalgesia were observed already seven days post infection, using a hot plate analgesimeter. The sensory disturbances progressed and the rats started to lose weight about 3 weeks post infection, and died about one week later. Immunohistochemistry showed no reduction in density of calcitonin gene-related peptide or substance P immunoreactive fibres in the skin or spinal cord. It is suggested that the sensory disturbances are mediated via release of kinin or interleukin-1 which are known as potent hyperalgesic agents. The hot plate analgesimeter is a simple and reliable method and may be useful in experimental trypanosomiasis to test drugs developed to combat this disease.

Analysis of Variance↗
PubMed1991

A monoclonal antibody against HSV type 1 ribonucleotide reductase cross-reacts with the P0 protein of peripheral nerve myelin.

An epitope on peripheral nerve myelin was detected by the use of a mouse monoclonal antibody directed against the 38 kDa subunit of herpes simplex virus (HSV) type 1 ribonucleotide reductase. Immunohistochemistry showed reactivity solely in PNS myelin. In nerve roots there was a sharp border in transitional zones to the negative CNS myelin. The immunoreactivity was found in rat, guinea pig, bovine and human peripheral nerves. Western blot analysis of peripheral nerve myelin as well as purified P0 revealed a distinctly stained band corresponding to a molecular weight of approximately 29 kDa. The present finding of a shared antigenic determinant between HSV ribonucleotide reductase and peripheral nerve P0 may be of pathogenetic relevance in virus induced demyelinating diseases in the peripheral nervous system.

Animals↗
PubMed1991

Gamma interferon expression and major histocompatibility complex induction during measles and vesicular stomatitis virus infections of the brain.

Lymphocytic interferon gamma (IFN-gamma) production and major histocompatibility complex (MHC) antigen induction were studied in experimental measles and vesicular stomatitis virus infections in the brain. Fifteen-day-old Sprague-Dawley rats injected intracerebrally with the HNT strain of measles virus showed already within 1 day after infection an increased number of cells producing IFN-gamma in the spleen, cervical lymph nodes and leptomeninges. These rats recovered after a transient neuronal infection in the brain. Rats infected intracerebrally with vesicular stomatitis virus, on the other hand, all succumbed after 2 days and showed no IFN-gamma production in lymphoid cells. Immunohistochemically MHC class I antigen appeared in infected and uninfected cells in the brain during replication of both viruses. A role for the recently discovered nerve fibres with IFN-gamma-like immunoreactivity, which are normally present in the brain, in the MHC antigen induction is discussed.

Animals↗
PubMed1991

A calcium-channel antagonist can prevent paramyxovirus-induced neurodegeneration.

Mumps virus caused a partially lytic infection in cultivated rat embryonic dorsal root ganglion neurons with a restricted formation of viral components. The neuronal degeneration was markedly enhanced by increasing the calcium concentration of the medium and could be almost totally inhibited by the dihydropyridine calcium channel antagonist nifedipine. The drug had no effect on a productive and completely lytic Sendai virus infection of the neurons. A previous neurophysiological study has shown that a reduced calcium influx occurs during the action potential early during the infection. The present study suggests a crucial role of calcium in neurodegeneration induced by certain viruses.

Animals↗