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K Kristensson

Publications and source records attributed to K Kristensson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Sorting signals and targeting of infectious agents through axons: an annotation to the 100 years' birth of the name "axon".

A brief review is given on mechanisms by which axons may be initiated during development and by which the polarity of neurons is maintained by selective sorting and delivery of molecules to axons and dendrites. The use of viruses as tools to study targeting of newly synthesized proteins to axons is described. Emphasis is then given to the hazards that are presented to the individual by the retrograde transport of infectious agents in axons to the brain. Borna disease virus, prions, and Listeria monocytogenes are examined briefly as examples of these mechanisms. These agents have attracted interest previously in veterinary medicine for the most part, but they may present potential and substantial threats to human health. Such infectious agents also represent a new type of virus, a new principle for disease transmission, and a new mechanism for intracellular transport, respectively.

Animals↗
PubMed1996

Lipid composition in scrapie-infected mouse brain: prion infection increases the levels of dolichyl phosphate and ubiquinone.

The neutral and phospholipid composition of mouse brain infected with scrapie prions was investigated. During the later stages of this disease, the level of dolichol decreased by 30% whereas the level of dolichyl phosphate increased by 30%. In terminally ill mice, there was also a 2.5-fold increase in both total ubiquinone and its reduced form. Furthermore, alpha-tocopherol was elevated at this stage by 50%. In contrast, no changes were observed in phospholipid amount, in phospholipid composition, and in phosphatidylethanolamine plasmalogen content during the entire disease process. The fatty acid and aldehyde composition of individual phospholipids remained unaltered as well. No modifications could be detected in cholesterol content. Thus, the majority of membrane lipids in scrapie-infected mouse brain are modified in neither quantity nor structure, but specific changes occur to a few polyisoprenoid lipids. This specificity indicates that, although prions accumulate in lysosomes, the infection process is not associated with a general membrane destruction caused by lysosomal enzyme leakage.

Animals↗
PubMed1996

Induction of interferon-gamma, transforming growth factor-beta, and interleukin-4 in mouse strains with different susceptibilities to Trypanosoma brucei brucei.

A Trypanosoma brucei brucei-derived lymphocyte triggering factor (TLTF) induced CD8+ T cells to produce IFN-gamma, which in turn stimulates parasite growth. This parasite-host interaction was studied in mouse strains that are either relatively susceptible (C3H/He) or resistant (C57Bl/6J) to infection, as well as in athymic nude mice. In all mouse strains, T. b. brucei infection caused a strong induction of IFN-gamma production by spleen mononuclear cells (MNC). In vivo blocking of IFN-gamma by intraperitoneal injection of mouse monoclonal anti-IFN-gamma antibody suppressed parasite growth and increased survival of both C3H/H3 and C57Bl/6J animals, suggesting that, irrespective of strain-related disease susceptibility, IFN-gamma is a growth-promoting stimulus for T. b. brucei. Spleen MNC from noninfected mice of all strains were in vitro like-wise strongly induced to IFN-gamma production when exposed to TLTF. This suggests that CD8+ expressing T cell receptor (TCR) alpha/beta, gamma/delta-bearing T cells and NK cells may all be triggered to IFN-gamma production by TLTF. In all mouse strains, TLTF also caused an increase in the number of cells expressing mRNA for TGF-beta in vitro. However, significant triggering to IL-4 mRNA expression only occurred in the relatively disease-resistant C57Bl/6J strain. As IL-4 is required for the synthesis and class switches of immunoglobulins, which are essential host immune defenses against T. b. brucei, the degree of resistance may be related to inherent strain ability to produce IL-4 in response to TLTF.

Animals↗
PubMed1996

Rabies: interactions between neurons and viruses. A review of the history of Negri inclusion bodies.

The first clear-cut description of a virus-nerve cell interaction was made by Adelchi Negri in 1903 with the detection of cytoplasmic bodies (Negri bodies) in subsets of neurons in the brain from rabies-infected animals. A biographical sketch of Negri is given here; he was born in Perugia, Italy, in 1875 and died in Pavia in 1912. In 1900 Negri became assistant to Camillo Golgi, who encouraged him to study rabies-infected brains with histological techniques. The report of intraneuronal bodies described by Negri as specific for rabies stimulated an intense debate both concerning their diagnostic value and their nature. The diagnostic value was finally determined in a study by Negri's wife, Lina Negri-Luzzani, in 1913, while the viral nature of the bodies had to await the introduction of electron microscopy and immunohistochemistry. However, the true significance of the Negri bodies is still mysterious, since they only develop in subsets of infected neurons and occur mainly after infection with wild, so-called 'street', virus strains and not after infection with strains passaged in the laboratory, so-called 'fixed' strains.

Animals↗
PubMed1995

Mimicking the humoral immune response in vitro results in antigen-specific isotype switching supported by specific autologous T helper cells: generation of human HIV-1-neutralizing IgG monoclonal antibodies from naive donors.

Molecular and cellular requirements for antigen-specific isotype switch of human B cells have been investigated by mimicking signaling occurring in germinal centers. Peripheral blood mononuclear cells from healthy seronegative blood donors were first primary immunized in vitro, using a synthetic immunogen containing both a T and B cell epitope, which generated specific IgM-secreting B cells. We used the apex of the V3 loop of gp120 as B cell epitope linked to a promiscuous T helper epitope from tetanus toxin. In parallel, CD4+ T helper cell clones specific for the T epitope of the immunogen were established. In a secondary in vitro stimulation period, we co-cultured the antigen-specific T and B cells on CD32-transfected fibroblasts, together with an anti-CD40 monoclonal antibody. This resulted in isotype switching and human antigen-specific, IgG-secreting B cells were detected. This response was strictly dependent upon the presence of autologous T helper cells and the immunogen. Antigen-specific human B cells derived from this primary and secondary in vitro immunization were subsequently subjected to electrofield-induced somatic cell hybridization and hybridomas secreting human anti-V3 IgG monoclonal antibodies were isolated. One human antibody was further characterized and shown to be specific for the immunizing antigen with an affinity constant of 24 nM. This antibody also effectively neutralized different isolates of HIV-1, achieving a 50% neutralization at 0.46 microgram/ml.

Amino Acid Sequence↗
PubMed1995

Sleep fragmentation, and changes in locomotor activity and body temperature in trypanosome-infected rats.

The rest-activity and body temperature 24 h cycles, as well as the structure of spontaneous sleep, were studied in rats 3 weeks after infection with monomorphic Trypanosoma brucei brucei. This parasite belongs to the species of trypanosomes that causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves alterations of endogenous biological rhythms. In the infected rats, entrained to a 12 h:12 h photoperiod, a considerable hypokinesia was detected during the hours of darkness. A significant oscillation of the body temperature during 24 h was lost in some infected animals. In the other infected animals, the body temperature cycle displayed a lower amplitude and a phase advance. The mean temperature was slightly higher in the infected than in control rats during the period of light. A detailed analysis of the structure of spontaneous sleep, based on daytime electroencephalographic recordings, revealed during trypanosome infection an increased relative proportion of wake, and a decreased percent value of synchronized sleep. A marked reduction of the mean REM latency and a fragmented pattern of synchronized sleep, resulting in a considerable alteration of the REM-non-REM sleep sequences, were also observed in the infected animals. These findings indicate that trypanosomiasis in the rat results in a striking sleep fragmentation, as well as in changes of locomotor activity and body temperature rhythm. Thus, trypanosome infection in the rat provides an experimental model of sleep dysregulation in a structurally intact brain, and may provide an animal model of endogenous rhythm changes documented in African sleeping sickness.

Analysis of Variance↗
PubMed1995

Increased levels of antibodies to IFN-gamma in human and experimental African trypanosomiasis.

In African trypanosomiasis the occurrence of antibodies to interferon-gamma (IFN-gamma) was studied in both humans and experimental rats. Sera from patients infected with Trypanosoma brucei gambiense showed increased levels of antibodies to IFN-gamma as compared with controls from the same regions in Africa. In Sprague-Dawley rats infected with Trypanosoma brucei brucei an early appearance of IFN-gamma-producing spleen cells was observed, followed by an increase in levels of antibodies against IFN-gamma in the sera. Previously, IFN-gamma has been found to play a crucial role in trypanosome infections in rats by promoting proliferation of Trypanosoma brucei brucei. The appearance of antibodies to IFN-gamma in humans, as in rats, indicates that this cytokine is produced also in the human infection. Its parasitic growth-stimulating and pathophysiological effects on the organism may be reduced by the antibodies.

Animals↗
PubMed1994

Neuronal IFN-gamma in tuberomammillary neurones.

Neuronal interferon-gamma (N-IFN-gamma), recently isolated from the nervous system, has a molecular weight distinct from that of lymphocyte-derived IFN-gamma, but crossreacts immunologically and shares certain bioactivities with this cytokine. In the rat brain N-IFN-gamma-immunoreactive perikarya were concentrated in the hypothalamic tuberomammillary nuclei; some immunostained neurones were also detected in the dorsal pontine tegmentum. Immunopositive nerve fibres were profusely distributed through the periventricular hypothalamus and midline thalamus. Scattered fibres occurred diffusely through the brain, ramified in the subpial layer and also surrounded intrathecal vessels. A dense concentration of puncta was detected in the suprachiasmatic nuclei and in the molecular layer of the hippocampal dentate gyrus. A role of N-IFN-gamma in immunological reactions and in modulation of selective brain functions is suggested.

Animals↗
PubMed1994

Intrathecal interferon-gamma facilitates the spinal nociceptive flexor reflex in the rat.

The effect of intrathecal (i.t.) injection of the cytokine interferon-gamma) (IFN-gamma) on the spinal nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats. IFN-gamma elicited an initial intense, brief facilitation of the flexor reflex followed by a sustained reflex facilitation lasting 40 +/- 5 min (range 20-65 min). The initial and prolonged reflex facilitations by IFN-gamma were partially and totally blocked, respectively, by i.t. pretreatment with nitro-L-arginine-ester, an inhibitor of nitric oxide synthase, at doses which did not influence spinal cord blood flow. Spinal application of IFN-gamma produced powerful and prolonged facilitation of the flexor reflex, possibly reflecting a hyperalgesic action of this cytokine. The facilitatory effect of IFN-gamma was mediated, at least in part, by the activation of the L-arginine-nitric oxide pathway. Thus, IFN-gamma released in the CNS may participate in eliciting pain and hyperalgesia in infectious or neuroinflammatory diseases where there is increased production of this cytokine.

Animals↗
PubMed1994

Dysregulation of photic induction of Fos-related protein in the biological clock during experimental trypanosomiasis.

The mammalian suprachiasmatic nuclei of the hypothalamus (SCN) serve as pacemaker for circadian rhythms and the immediate-early gene c-fos is known to be induced by photic stimulation in the SCN of rodents. We studied the induction of Fos-related protein following a light pulse in rats infected with Trypanosoma brucei. This parasite causes in humans African sleeping sickness, a neuropsychiatric syndrome that involves changes of endogenous biological rhythms. Fos-like immunoreactivity after photic stimulation was dramatically reduced in the SCN of trypanosome- infected rats during the subjective night. These findings indicate that the photic entrainment of the biological clock may be altered during the infection.

Animals↗
PubMed1994

Interferon-gamma and a factor derived from trypanosomes cause behavioural changes in the rat.

A newly isolated interferon-gamma (IFN-gamma) immunoreactive molecule, "neuronal IFN-gamma", and recombinant lymphocyte-derived IFN-gamma were injected intracerebroventricularly (i.c.v.) through a previously implanted cannula into adult male rats during both the light and the dark phases of the light/dark cycle. The two molecules caused a reduction in both frequency and duration of rearing and locomotion during the dark, but not the light, phase. A molecule isolated from Trypanosoma brucei brucei, a parasite of the same subspecies of trypanosomes which causes African sleeping sickness, can induce production and release of IFN-gamma and "neuronal IFN-gamma" from lymphocytes and neurons, respectively. I.c.v. injection of this factor also reduced rearing during the dark period, but to a less extent. Thus, "neuronal IFN-gamma" appears to have effects on animal behaviour in common with lymphocyte-derived IFN-gamma. This study highlights the potential role of these cytokines in behaviour disturbances.

Animals↗
PubMed1994

Trypanosomes cause dysregulation of c-fos expression in the rat suprachiasmatic nucleus.

Rats infected with the parasite Trypanosoma brucei brucei showed selective changes of c-fos expression in the suprachiasmatic nucleus of the hypothalamus (SCN) during spontaneous sleep (S) and wakefulness (W) under a basal 12 h/12 h light-dark (L-D) cycle. In the vast majority of W (D phase) control animals the SCN was devoid of cells displaying Fos-related immunopositivity, while Fos-like-immunoreactive (ir) neurones were detected in most S (L phase) control rats. In most infected animals, on the other hand, Fos-ir neurones were detected in the SCN during W, but not during the S period, with a significant difference between control and infected S rats. Thus, these data indicate that the basal c-fos expression in the SCN during the L-D and S-W cycles is considerably altered in experimental trypanosomiasis. This is the first observation of a selective change in the SCN in trypanosome-infected rat brains. Since the SCN plays an important role as a pace-maker for biological rhythms, this finding may provide a basis for understanding the pathogenesis behind endogenous rhythm dyregulation and changes in sleeping pattern in human trypanosomiasis (African sleeping sickness).

Animals↗
PubMed1994

Neuronal interferon-gamma immunoreactive molecule: bioactivities and purification.

An interferon (IFN)-gamma immunoreactive molecule, localized to small neurons in peripheral sensory ganglia (N-IFN-gamma), has been detected with two mouse monoclonal antibodies (DB1 and DB16) directed against different epitopes of rat IFN-gamma. To define N-IFN-gamma with regard to its protein characteristics and bioactivities, DB1 and DB16 were used to purify N-IFN-gamma from rat trigeminal ganglia in a two-step sequential antibody-affinity procedure. Sodium dodecylsulfate polyacrylamide gel electrophoresis (PAGE) and silver staining of purified N-IFN-gamma displayed three bands with an approximate molecular mass of 66, 62 and 54 kDa. The N-IFN-gamma bioactivity was confined to the protein stained on gel when native material was run on PAGE. Biological effects of pure N-IFN-gamma were examined and compared with those of lymphocyte-derived recombinant IFN-gamma. N-IFN-gamma had antiviral effects in vitro and induced major histocompatibility complex class I and II antigens on macrophages and in cells in skeletal muscle cell cultures. N-IFN-gamma also stimulated myoblast proliferation and affected cholinergic receptor distribution on myotubes similar to recombinant IFN-gamma. Both molecules potently stimulated Trypanosoma brucei brucei growth. These data suggest that, although N-IFN-gamma is a protein distinct from lymphocyte-derived IFN-gamma, the two molecules have enough structural similarities to allow for antibody recognition of at least two epitopes, and action on similar target structures on both parasite and mammalian cells.

Animals↗
PubMed1994

Increased brain quinolinic acid production in mice infected with a hamster neurotropic measles virus.

In order to examine the status of quinolinic acid (QUIN) metabolism in a model of delayed excitotoxic neurodegeneration, the de novo production of QUIN from 3-hydroxyanthranilic acid was assessed in brain homogenates and brain slices of mice injected with hamster neurotropic measles virus. In the hippocampus, which presents exclusive nerve cell loss in this model, the activity of 3-hydroxyanthranilic acid oxygenase, an astrocytic enzyme responsible for the biosynthesis of QUIN, was increased 3.3-fold by 7 days after virus inoculation. Less dramatic increases were observed in the cerebral cortex and the striatum, while cerebellar enzyme activity was not different from control values. In the same brain homogenates, no changes occurred in the activities of kynurenine aminotransferase, the biosynthetic enzyme of the neuroprotectant kynurenic acid, and of the astrocytic marker glutamine synthetase. At 7 days postinoculation, hippocampal slices from virus-treated animals, when exposed to 3-hydroxyanthranilic acid, produced 18 times more QUIN than slices from control animals. Notably, a significant increase was also seen 3 days postinoculation, i.e., at a time when astrocytes had started to proliferate but prior to the onset of neurodegeneration (Eur. J. Neurosci. 3:66-71, 1991). These data suggest that astrocyte-derived QUIN may play a causative role in the occurrence of hippocampal nerve cell loss in measles virus-infected mice.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1994

Co-induction of neuronal interferon-gamma and nitric oxide synthase in rat motor neurons after axotomy: a role in nerve repair or death?

Induction of an interferon-gamma-like molecule, previously isolated from neurons (N-IFN-gamma), and of the neuronal isoform I of the synthetic enzyme of the free radical nitric oxide, nitric oxide synthase I, as well as of NADPH-diaphorase, were examined in axotomized dorsal motor vagal and hypoglossal neurons. Unilateral transection of the vagal and hypoglossal nerves was performed in the same rat and an induction of N-IFN-gamma and nitric oxide synthase I immunostaining as well as NADPH-diaphorase histochemical positivity was observed in the ipsilateral motoneurons after 2-4 days. The immuno- and enzyme-histochemical positivities were much stronger in the dorsal motor vagal neurons than in hypoglossal neurons. Two and 4 weeks after axotomy N-IFN-gamma immunoreactivity and NADPH-diaphorase positivity persisted in the former, but started to decrease in the latter neurons. Previous data have shown that 23 weeks after nerve transection the majority of the dorsal motor vagal neurons are lost, while the majority of the hypoglossal neurons survive. The high and persistent expression of N-IFN-gamma and nitric oxide synthase I after axotomy in the dorsal motor vagal neurons, that are largely destined to die, indicates that the co-induction of these two molecules may be implicated in the pathogenesis of neuronal degeneration.

Amino Acid Oxidoreductases↗
PubMed1994

From trypanosomes to the nervous system, from molecules to behavior: a survey, on the occasion of the 90th anniversary of Castellani's discovery of the parasites in sleeping sickness.

The observation of Trypanosomes in patients affected by sleeping sickness has been reported in 1903 by Aldo Castellani. On the occasion of the 90th anniversary of this discovery, we here present the findings recently obtained in and experimental model of African trypanosomiasis in the rat. The molecular and cellular mechanisms of the interplay between the parasite and the host have been largely clarified: a bidirectional signalling occurs between trypanosomes and CD8+ T cells of the host animal. This new pathogenetic mechanism of infection involves a lymphocyte triggering factor released by the parasite and interferon-gamma. A recently isolated neuronal interferon-gamma could also play a role in the disease. The selective induction of major histocompatibility antigens class I has revealed the involvement of the hypothalamic paraventricular and supraoptic nuclei in trypanosomiasis. Finally, studies based on the expression of the immediate early gene c-fos have pointed out during the infection a selective dysregulation of the suprachiasmatic nucleus of the hypothalamus, that plays the role of biological clock. The latter finding could account for the disruption of endogenous rhythms in sleeping sickness.

Animals↗
PubMed1994

Activation of human CD4+45RA+ T cells using B cells as accessory cells.

Human naive CD4+ T cells, as defined by expression of CD45RA and lack of CD45R0, can be activated in vitro using B cells as accessory cells. CD4+CD45RA+ T cells proliferate, as determined by [3H]thymidine or bromodeoxyuridine (BrdU) incorporation, after activation with the superantigen staphylococcal enterotoxin A (SEA) presented by major histocompatibility complex class II-expressing B cells. The identity of the responding cells as being CD45RA+ and not contaminating CD45R0+ T cells was determined by FACS analysis, showing that purified CD45RA-expressing T-helper cells went into S phase and progressively acquired expression of the CD45R0 isoform while simultaneously losing expression of the CD45RA isoform. Cultivation of the CD4+ T-cell subsets under limiting dilution conditions supported these findings and revealed that (i) the frequency of responding cells in the CD45RA+ population was equal to or higher than in the CD45R0+ subset and (ii) that the number of CD45R0+ cells possibly contaminating the CD45RA population was too low to be able to account for the response observed.

Antigen-Presenting Cells↗