Biomedical subjects

S Jander

Publications and source records attributed to S Jander.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Unstable carotid stenosis--an inflammatory disease?].

Arterioarterial thromboembolism from extracranial internal carotid artery (ICA) stenosis is an important pathogenic mechanism of ischemic stroke. However, even a high-grade ICA stenosis carries a greatly variable annual risk of stroke, as high as 13% following a recent occurrence of transient or minor cerebral ischemia or as low as 1-2% in clinically asymptomatic patients. There is increasing evidence that inflammatory processes play a central role in atherosclerosis and particularly in plaque destabilization converting chronic atherosclerosis into an acute neurological disorder. In thromboendarterectomy specimens from patients with high-grade ICA stenoses, the extent of inflammatory infiltration and the expression of matrixmetalloproteinase-9 correlated to clinical and ultrasonic features of plaque destabilization such as cerebral microembolism. Inflammation might become a new therapeutic target in symptomatic carotid artery disease.

Carotid Artery, Internal↗

PubMed2000

Treatment of Amanita phalloides poisoning: I. Retrospective evaluation of plasmapheresis in 21 patients.

Amanita phalloides poisoning is the most common cause of lethal mushroom poisoning (lethality >20% in adults). A specific antidote against the amanitin toxins is not available. This retrospective study reports results in 21 patients (12 males, 9 females; ages 9-59 years) treated for amanita phalloides poisoning between 1984 and 1993. Plasmapheresis was carried out using a commercial plasma protein solution (Biseko, Biotest, Dreieich, Germany) in 17 patients, fresh plasma in 2 patients, and human albumin/Ringer's solution in 2 patients. Ancillary drugs, including penicillin and silibinin, also were used for detoxification, correction of blood-clotting deficiencies, and hepatic protection. One patient died of acute hepatic failure. The results, assessed using mortality (4.8% overall) and frequency of complications, indicate that plasmapheresis is a safe and effective treatment for amanita phalloides poisoning but that further investigations are needed, especially involving measurements of efficacy and the efficiency of toxin removal.

Adolescent↗

PubMed2000

Plasmapheresis in the treatment of Amanita phalloides poisoning: II. A review and recommendations.

Amanita phalloides poisoning is the most common cause of lethal mushroom poisoning (lethality >20% in adults, >50% in children). However, there is no standard treatment strategy and no antidote against the ensuing hepatic failure. This review of 14 investigations published over the last 20 years shows that the introduction of detoxification techniques, in particular the use of plasmapheresis, in combination with supportive therapy to prevent the absorption of aminitine toxins into blood, produced a substantial reduction in mortality. The main complications in using these techniques include infections and coagulation disorders. Because of the latency period in the development of symptoms, treatment should begin on the first suspicion that an intoxication is present. The best therapeutic results can be expected when the detoxification techniques are applied in combination with conservative therapies within the first 36--48 h. Using this approach, mortality rates in some recent studies have been below 10%.

Amanita↗

PubMed2000

[The effects of coronary artery bypass grafting in men under the age of 45].

In Poland young and middle-aged men are a population at risk of premature development of ischemic heart disease (IHD). This prospective study was designed in order to estimate the effects of coronary artery bypass grafting (CABG) on survival and quality of life in this population. 60 men aged (mean&SD) 41 +/- 3.2 years, operated on in 1993 at the Department of Cardiosurgery, Medical University of Lódź, were enrolled into the study. The study protocol included two postoperative follow-up examinations: after 2 and 5 years. A perioperative mortality rate was 3.3%, 2-years survival rate 92% and 5-years one 87%. Asymptomatic survival rates were 75% et 44%, respectively. During the first follow-up examination a significant improvement of exercise performance compared with preoperative period, was observed. However, at the same time there was no improvement in left ventricular function, measured as its ejection fraction in echocardiography. The effects of CABG procedure on risk factors control, medical treatment and professional activity were also analysed. The long-term results of CABG operations in young men, as far as survival rates are concerned, are good. However, the longer follow-up period was analysed the less beneficial influence of the operations on patients' clinical state and quality of life was observed.

Adult↗

PubMed1999

The role of microglia and macrophages in the pathophysiology of the CNS.

Microglia are a major ghal component of the central nervous system (CNS) and are extremely sessile. Only a subtype, the perivascular microglia, are regularly replaced from the bone marrow in adult animals. Microglia respond to virtually any, even minor pathological events in the CNS. In most pathological settings microglia are aided by infiltrating hematogenous macrophages. Upon activation microglia and macrophages share most phenotypical markers and can exert similar effector functions. After transection of a CNS fibre tract microglia are insufficiently activated and hematogenous macrophages do not significantly enter the degenerating nerve stump. Thereby myelin debris that contains neurite outgrowth inhibiting activity persists for long time. This is in sharp contrast to the peripheral nervous system in which hematogenous macrophages are rapidly recruited in response to axotomy and clear myelin debris allowing regrowth of axons from the proximal stump. However, CNS lesion paradigms with breakdown of the blood-brain barrier such as cerebral ischemia, brain abscesses and stab wounds elicit prompt microglial activation, macrophage recruitment and debris clearance. There is increasing evidence that microglia play an active part in degenerative CNS diseases. In Alzheimer's disease activated microglia appear to be involved in plaque formation. In experimental globoid cell dystrophy T-cell independent induction of major histocompatibility complex class II molecules on microglia accelerates demyelination. In autoimmune diseases microglia probably have dual functions. Microglia present antigen to infiltrating T cells and exert effector functions thereby locally augmenting immune responses. On the other hand, microglia have the capacity to downregulate T cell responses. In the human acquired immunodeficiency syndrome (AIDS) virus infected macrophages probably introduce the virus to the CNS and in concert with microglia are involved in the pathophysiology of the AIDS dementia complex.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Heterogeneity of the microglial response in photochemically induced focal ischemia of the rat cerebral cortex.

This study examined microglial responses after photochemically induced focal ischemia of the rat cortex. Microglial activation exceeded by far the area of the ischemic lesion. Based on morphological criteria and expression of immunomolecules three distinct patterns could be distinguished. (1) In the infarct core and the border zone microglia transformed into phagocytes and removed debris with the aid of hematogeneous macrophages. Exclusively in this area a subpopulation of CD8+ microglia/mnacrophages was present. (2) In secondarily degenerating fibre tracts and nuclei with retrograde neuronal loss, microglia were activated with a delay of days and showed increased expression of complement receptor 3, major histocompatibility complex class II and CD4 molecules, but only low phagocytic activity. (3) In remote ipsilateral cortex devoid of neuronal damage, microglia transiently responded by increased complement receptor 3, but not by major histocompatibility complex class II and CD4 expression. Furthermore, the total number of microglia had increased. This remote response could partly be blocked by dizocilpine maleate, a non-competitive N-methyl-D-aspartate receptor antagonist, implicating a functional role of spreading depression. Taken together, our findings point to a tight and differential regulation of microglial responses in the infarct core, degenerating fibre tracts and remote brain regions without neuronal loss.

Animals↗

PubMed1998

Differential induction of interleukin-12, interleukin-18, and interleukin-1beta converting enzyme mRNA in experimental autoimmune encephalomyelitis of the Lewis rat.

Experimental autoimmune encephalomyelitis (EAE) is a model of autoimmune central nervous system (CNS) disease that is mediated by autoreactive Th1 cells secreting the proinflammatory cytokine interferon (IFN)-gamma. Interleukin (IL)-12 in its heterodimeric p35/p40 isoform and the recently described cytokine IL-18 potently induce T cell production of IFN-gamma. Interleukin-1beta converting enzyme (ICE) is required to convert IL-18 precursor protein into its biologically active mature form. In this study, we used semiquantitative reverse transciptase-polymerase chain reaction to determine steady state levels of IL-12, IL-18, and ICE mRNA in the spinal cord of Lewis rats at different stages of EAE. In control rats, we found significant IL-18, ICE, and IL-12p35, but not IL-12p40 mRNA expression. IL-18 mRNA increased during the acute stage of EAE together with a marked induction of ICE mRNA. IL-12p35 mRNA levels did not change significantly throughout the course of EAE. Surprisingly, the peak expression of IL-12p40 mRNA was delayed by several days relative to the peak of T cell infiltration and IFN-gamma mRNA synthesis. Our data implicate the IL-18/ICE pathway in the amplification of Th1-mediated immune responses in the CNS but suggest a different, so far undefined role of endogenous IL-12 in the late effector phase of EAE.

Animals↗

PubMed1998

Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demyelination and Wallerian degeneration.

This study examined the time course of mRNA levels of the proinflammatory cytokines interferon-gamma (IFNgamma), interleukin-1beta (IL1beta), interleukin-12 (IL12; p40 subunit), and the immunosuppressant interleukin-10 (IL10) by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in rats with actively induced experimental autoimmune neuritis (EAN) and in distal stumps of crushed sciatic nerves undergoing Wallerian degeneration. In EAN IFNgamma- and IL1beta-mRNA peaked at the onset and acute phase of clinical disease. IL12p40-mRNA was upregulated later than IFNgamma-mRNA in the late acute phase from days 15 to 21. IL10-mRNA appeared concomitantly with the proinflammatory cytokines at day 11, but persisted at high levels into the clinical recovery phase. After nerve crush both IL1beta- and IL10-mRNA were rapidly upregulated in the distal stump at day 1 and slowly declined over the next 2 weeks. Significant levels of mRNA for IFNgamma could be found at days 4 and 7, whereas IL12p40-mRNA showed a biphasic induction. We provide evidence for a concomitant induction of pro- and anti-inflammatory cytokines in EAN. Moreover, the rapid upregulation in Wallerian degeneration suggests a more general role of cytokines in the biology of the peripheral nerve.

Animals↗

PubMed1998

Major histocompatibility complex class II expression and macrophage responses in genetically proven Charcot-Marie-Tooth type 1 and hereditary neuropathy with liability to pressure palsies.

This study examined major histocompatibility complex (MHC) class II expression and macrophage infiltration in sural nerve biopsies from patients with genetically proven Charcot-Marie-Tooth (CMT) 1A and 1B and hereditary neuropathy with liability to pressure palsies (HNPP) by immunocytochemistry. In both young and older patients with duplication of the PMP22 gene, MHC class II expression was consistently up-regulated and not closely related to the extent of macrophage infiltration. On the other hand, MHC class II expression was more variable in CMT1A and CMT1B caused by point mutations and in HNPP. The extent of nerve pathology as assessed by teased fiber preparations or electron microscopy was not predictive for the degree of MHC class II expression in CMT1/HNPP. We conclude that MHC class II up-regulation is a common feature in hereditary neuropathies. As shown for the animal model of globoid cell dystrophy, it is conceivable that increased expression of MHC class II molecules in CMT1 and HNPP accelerates nerve pathology.

Adolescent↗

PubMed1998

Inflammation and glial responses in ischemic brain lesions.

Focal cerebral ischemia elicits a strong inflammatory response involving early recruitment of granulocytes and delayed infiltration of ischemic areas and the boundary zones by T cells and macrophages. Infiltration of hematogenous leukocytes is facilitated by an upregulation of the cellular adhesion molecules P-selectin, intercellular adhesion molecule-1 and vascular adhesion molecule-1 on endothelial cells. Blocking of the leukocyte/endothelial cell adhesion process significantly reduces stroke volume after transient, but not permanent middle cerebral artery occlusion. In the infarct region microglia are activated within hours and within days transform into phagocytes. Astrocytes upregulate intermediate filaments, synthesize neurotrophins and form glial scars. Local microglia and infiltrating macrophages demarcate infarcts and rapidly remove debris. Remote from the lesion no cellular infiltration occurs, but astroglia and microglia are transiently activated. Astrocytic activation is induced by spreading depression. In focal ischemia neurons die acutely by necrosis and in a delayed fashion by programmed cell death, apoptosis. Proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta are upregulated within hours in ischemic brain lesions. Either directly or via induction of neurotoxic mediators such as nitric oxide, cytokines may contribute to infarct progression in the post-ischemic period. On the other hand, inflammation is tightly linked with rapid removal of debris and repair processes. At present it is unclear whether detrimental effects of inflammation outweigh neuroprotective mechanisms or vice versa. In global ischemia inflammatory responses are limited, but micro- and astroglia are also strongly activated. Glial responses significantly differ between brain regions with selective neuronal death and neighbouring areas that are more resistent to ischemic damage.

Animals↗

PubMed1998

Focal ischaemia of the rat brain elicits an unusual inflammatory response: early appearance of CD8+ macrophages/microglia.

Cerebral ischaemia leads to profound glial activation and leukocyte infiltration into the infarct area. In this study, we provide evidence for a dual macrophage response in focal ischaemic lesions of the rat brain. We show that a considerable proportion of macrophages in the ischaemic lesions express the CD8alphabeta heterodimer to date only described on CD8+ T cells. As known from other lesion paradigms, CD4+ macrophages were also present. Interestingly, CD8- and CD4-expressing macrophages formed two non-overlapping subpopulations. CD8+ macrophages reached their maximum during the first week with pronounced downregulation thereafter whereas CD4+ cells persisted at high levels into the second week. In contrast to cerebral ischaemia, macrophages in the spleen and in Wallerian degeneration after optic nerve axotomy expressed CD4, but not CD8. In experimental autoimmune encephalomyelitis, CD8 was mainly associated with T cells and very weakly detectable on some ramified cells resembling activated microglia. In conclusion, we show that cerebral ischaemia triggers an unusual inflammatory response characterized by the appearance of CD8+/CD4- macrophages that might exert specific functions in the pathogenesis of ischaemic brain damage.

Animals↗

PubMed1998

Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization.

BACKGROUND AND PURPOSE: Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this study, we investigated whether the extent of inflammatory infiltration in high-grade stenoses of the internal carotid artery (ICA) correlates to clinical features of plaque destabilization. METHODS: Endarterectomy specimens from 37 consecutive patients undergoing surgery for high-grade ICA stenosis were stained immunocytochemically for macrophages (CD68) and T cells (CD3). The staining was quantified by planimetry of immunostained areas (CD68) or counting individual cells (CD3). Clinical evidence of plaque instability was provided by the preoperative assessment of recent ischemic symptoms attributable to the stenosis and of the occurrence of cerebral microembolism in transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. RESULTS: The percentage of macrophage-rich areas and number of T cells per mm2 section area were larger in recently symptomatic patients than in asymptomatic patients (macrophages: 18+/-10% versus 11+/-4%, P=0.005; T cells: 71.2+/-34.4 versus 40.5+/-31.4 mm2, P=0.005). The presence of microembolism was associated with an increase in macrophage-rich areas (P=0.011). Macrophage (19+/-10% versus 9+/-3%, P=0.0009) and T cell (71.5+/-39.0 versus 46.4+/-22 mm2, P=0.045) infiltration were more pronounced in predominantly atheromatous than in fibrous plaques, but did not correlate significantly to the presence of surface ulceration or luminal thrombosis. CONCLUSIONS: Our data suggest a role of plaque-infiltrating macrophages and T cells in the clinical destabilization of high-grade ICA stenoses. Inflammatory mechanisms may be a therapeutic target in patients with symptomatic ICA disease.

Adult↗

PubMed1998

Time course and cellular localization of interleukin-10 mRNA and protein expression in autoimmune inflammation of the rat central nervous system.

Experimental autoimmune encephalomyelitis of the Lewis rat is a T-cell-mediated autoimmune disease of the central nervous system characterized by a self-limiting monophasic course. In this study, we analyzed the expression of the anti-inflammatory cytokine interleukin (IL)-10 at the mRNA and protein level in experimental autoimmune encephalomyelitis actively induced with the encephalitogenic 68-86 peptide of guinea pig myelin basic protein. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that IL-10 mRNA expression peaked during the acute phase of the disease at days 11 and 13. IL-10 mRNA was synchronously induced with mRNA for the proinflammatory cytokine interferon-gamma. Immunocytochemistry with a monoclonal antibody against rat IL-10 showed that the peak of IL-10 mRNA was accompanied by an abundant expression of IL-10 protein during the acute stage of the disease. Both in situ hybridization and double labeling immunocytochemistry in combination with confocal microscopy identified T cells, macrophages/microglia, and astrocytes as major cellular sources of IL-10 in vivo. The early peak of IL-10 production was unexpected in light of its well-documented anti-inflammatory properties. Additional studies are required to determine whether endogenous IL-10 contributes to rapid clinical remission typical for Lewis rat experimental autoimmune encephalomyelitis or if it plays other, yet undefined, roles in central nervous system autoimmunity.

Animals↗

PubMed1997

Phagocytic response in photochemically induced infarction of rat cerebral cortex. The role of resident microglia.

BACKGROUND AND PURPOSE: In this study we assessed the relative extent to which resident microglia and blood-borne macrophages contribute to the population of phagocytes after focal infarction of the rat cortex. METHODS: Focal cerebral infarction was induced in rats by photothrombosis after hematogenous macrophages were depleted by means of liposomes containing dichloromethylene diphosphonate. The phagocytic activation of microglia and macrophages was monitored by immunocytochemistry with the antibody ED1. RESULTS: In both macrophage-depleted rats and controls, ED1+ phagocytes bordered the infarct to the same extent at day 3 after photothrombosis. By contrast, at day 6 after photothrombosis ED1+ phagocytes in control rats greatly outnumbered those in macrophage-depleted rats. With the use of the antibody Ox42 directed against the CR3 receptor on the surface of microglia, it was possible to selectively document the transition of resident microglia into stellate and ameboid phagocytic microglia during the first 6 days after photothrombosis in the absence of bloodborne macrophages. CONCLUSIONS: The initial phagocytic response after focal brain ischemia is an intrinsic property of the nervous system mainly performed by resident microglia. The majority of hematogenous macrophages are recruited secondarily to participate in the removal of necrotic tissue.

Animals↗

PubMed1996

Differential expression of interleukin-10 mRNA in Wallerian degeneration and immune-mediated inflammation of the rat peripheral nervous system.

Interleukin-10 (IL-10) is a potent immunosuppressant cytokine which downregulates MHC class II antigen expression and inflammatory cytokine production. In this study we localized mRNA for IL-10 in the rat peripheral nervous system (PNS) by nonradioactive in situ hybridization using a digoxygenin-labeled riboprobe specific for rat IL-10. IL-10 mRNA was expressed by some Schwann cells (SCs) in the normal sciatic nerve. During Wallerian degeneration, SCs strongly expressed IL-10 mRNA between days 2 and 4 after transection. By day 14 only occasional cells were positive for IL-10 mRNA. The vast majority of ED1-positive macrophages were IL-10 negative after axotomy. Contrastingly, infiltrating macrophages expressed IL-10 mRNA conincident with beginning clinical recovery in experimental autoimmune neuritis (EAN), the rat model of human Guillain-Barré syndrome. Our data suggest that SCs provide a constitutive immunosuppressant system in the PNS. In EAN additional macrophage-derived IL-10 may be important for the resolution of the T cell-mediated immune response.

Animals↗

PubMed1996

Strain-specific expression of microglial keratan sulfate proteoglycans in the normal rat central nervous system: inverse correlation with constitutive expression of major histocompatibility complex class II antigens.

We have recently demonstrated that a novel type of keratan sulfate proteoglycan (KSPG) identified by the monoclonal antibody (mAb) 5D4 is expressed on ramified microglia but downregulated coincident with T-cell-mediated autoimmune inflammation of the spinal cord in Lewis (LEW) rats. In this study we show by immunocytochemistry and Western blot analysis that various inbred rat strains differ significantly in their constitutive expression of KSPG on ramified microglia in the normal CNS. Microglial KSPG was high in LEW and Fischer 344 rats but low in DA, Brown Norway (BN), and PVG rats. The KSPG low-expressing strains exhibited constitutive expression of major histocompatibility complex (MHC) class II antigens on ramified microglia that was not detectable in the KSPG high-expressing strains. Thus, an inverse correlation between constitutive KSPG and MHC class II expression was present. The KSPG-low-/MHC class II-positive phenotype is associated with resistance to experimental autoimmune encephalomyelitis in BN and PVG, but not DA rats. These findings suggest a significant impact of genetic factors on the molecular differentiation of resident macrophages in the CNS.

Animals↗

PubMed1996

Spatiotemporal relationship of apoptotic cell death to lymphomonocytic infiltration in photochemically induced focal ischemia of the rat cerebral cortex.

In this study we examined the time course of apoptotic cell death after photochemically induced focal ischemia of the rat cerebral cortex. For unequivocal differentiation between apoptosis and necrosis two criteria of programmed cell death were used: terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and morphological evidence of fragmentation and marginalization of nuclei. After photothrombosis, many TUNEL-positive cells were found within the infarct region from 12 h to 3 days. By day 6 they were preferentially located in the boundary zone of the infarct, and by day 14 they had disappeared. A high proportion of TUNEL-positive cells displayed fragmentation or marginalization of their nuclei, indicating apoptosis. Neurons, but not T cells and macrophages, were apoptotic. Inflammatory infiltrates were in close contact to apoptotic neurons throughout the infarct areas at day 1 and in the boundary zone between days 2 and 6 after photothrombosis. In summary, our study shows that neuronal apoptosis after cerebral ischemia is a prolonged process to which leukocyte-derived cytokines may contribute. In contrast to autoimmune diseases of the nervous system, termination of the local inflammatory response after cerebral ischemia does not involve apoptosis.

Animals↗

PubMed1996

Vascular cell adhesion molecule-1 mRNA is expressed in immune-mediated and ischemic injury of the rat nervous system.

In this study we used nonradioactive in situ hybridization for the cellular localization of vascular cell adhesion molecule-1 (VCAM-1) mRNA in immune-mediated, ischemic and degenerative diseases of the rat nervous system. In the acute phase of experimental autoimmune encephalomyelitis and neuritis VCAM-1 mRNA was expressed not only on the luminal surface of inflamed vessels but also in perivascular cells suggesting a functional role of VCAM-1 in both endothelial adhesion and local restimulation of autoantigen-specific T cells. Accordingly, perivascular T cell accumulation was most pronounced at sites of local VCAM-1 mRNA expression. In addition, VCAM-1 mRNA was detected in the border zone around photochemically induced cerebral infarcts which is the predeliction site of T cell infiltration and expression of immune activation markers during the first week after ischemia. VCAM-1 mRNA was absent from the center of the infarcts as well as axotomized central and peripheral nerves undergoing Wallerian degeneration. These data indicate that VCAM-1-mediated adhesion processes are involved in immune-mediated and ischemic diseases of the nervous system but not in T cell-independent macrophage recruitment during Wallerian degeneration.

Acute Disease↗