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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a time-dependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.
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PMID:Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia. 155 47

Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) may play an important role in the function and/or dimensions of the left ventricle. We present an autopsied case of HCM followed for 10 years. A 68-year-woman with HCM underwent trans-aortic myectomy of the interventricular septum in 1979. A significant amount of round cell infiltration, myocardial fibrosis and disarray were observed in the resected specimen. She experienced repeated admissions due to diabetes mellitus and congestive heart failure, and died of renal failure in 1989. An autopsy revealed extensive myocardial fibrosis and significant cell infiltration in the ventricular myocardium. The infiltrating cells were almost all lymphocytes, and the ratio of CD4 to CD8 was 3.8. This ratio was different from that of typical viral myocarditis. This case suggests that there may be an undefined inflammatory process causing fibrosis in HCM, in addition to the ischemia due to intramural small coronary artery stenosis.
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PMID:An autopsy case of hypertrophic cardiomyopathy with pathological findings suggesting chronic myocarditis. 820 86

The success of orthotopic liver transplantation is dependent on multiple factors including MHC tissue compatibility and ischemic/reperfusion injury. Ischemic/reperfusion (I/R) injury in the liver occurs in a biphasic pattern consisting of both acute phase (oxygen free radical mediated) and subacute phase (neutrophil-mediated) damage. Although numerous studies have given insights into the process of neutrophil recruitment after I/R injury to the liver, the exact mechanism that initiates this subacute response remains undefined. Using a T cell-deficient mouse model, we present data that suggests that T-lymphocytes are key mediators of subacute neutrophil inflammatory responses in the liver after ischemia and reperfusion. To this end, using a partial lobar liver ischemia model, we compared the extent of reperfusion injury between immune competent BALB/c and athymic nu/nu mice. Studies evaluating the extent of liver damage as measured by serum transaminases (GPT) demonstrate similar acute (3-6 h) post-I/R responses in these two mouse models. In contrast, the subacute phase (16-20 h) of liver injury, as measured by both serum GPT levels and percent hepatocellular necrosis, was dramatically reduced in T cell-deficient mice as compared with those with an intact immune system. This reduction in liver injury seen in nu/nu mice was associated with a 10-fold reduction in hepatic neutrophil infiltration. Adoptive transfer of T cell-enriched splenocytes from immune competent mice was capable of reconstituting the neutrophil-mediated subacute inflammatory response within T cell-deficient nu/nu mice. Furthermore, in vivo antibody depletion of CD4(+) T-lymphocytes in immune competent mice resulted in a reduction of subacute phase injury and inflammation as measured by serum GPT levels and neutrophil infiltration. In contrast, depletion of CD8(+) T-lymphocytes had no effect on these indexes of subacute inflammation. Kinetic analysis of T cell infiltration in the livers of BALB/c mice demonstrated a fivefold increase in the number of hepatic CD4(+) T-lymphocytes within the first hour of reperfusion with no significant change in the number of CD8(+) T-lymphocytes. In summary, these results implicate CD4(+) T-lymphocytes as key regulators in initiating I/R-induced inflammatory responses in the liver. Such findings have implications for therapy directed at the early events in this inflammatory cascade that may prove useful in liver transplantation.
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PMID:CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver. 921 4

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.
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PMID:Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS. 945 7

Lower extremity symptoms are caused by lesions at any level of the neuraxis, from cortex to muscle. HIV affects virtually every level of the nervous system, either directly or indirectly. The presence of pathology at multiple levels and by multiple processes further complicates the bedside diagnosis of a patient with AIDS and neurologic symptoms. Many neuropathies and other conditions that affect the lower extremities can be identified with careful history and physical examination, confirmed with limited testing, and can be treated successfully. Distal symmetric polyneuropathy is the most common lower extremity disorder, but it must be distinguished from similar-appearing neuropathies caused by medications, B12 deficiency, or vasculitis. Diffuse infiltrative lymphocytosis syndrome also causes a painful peripheral neuropathy that must be distinguished from distal symmetric polyneuropathy. Inflammatory demyelinating polyneuropathies are characterized by muscle weakness. They occur in early, asymptomatic HIV infection and respond to plasmapheresis or steroids. Mononeuropathies in patients with CD4 counts more than 200 often resolve on their own. Multiple mononeuropathies, which occur in patients with CD4 counts less than 50, are often associated with cytomegalovirus infection and may follow a rapidly progressive course unless treated promptly and aggressively. Progressive polyradiculopathy occurs late in the course of AIDS, is often caused by cytomegalovirus, is rapidly progressive, and generally is fatal unless recognized and treated promptly. Muscle weakness, myalgia, and fatigue are common in HIV and have multiple causes. Lower extremity spasticity may be caused by treatable etiologies such as spinal cord abscess, tumor, disc compression, B12 deficiency, or ischemia. Gait disturbances are common but nonspecific and may be caused by treatable neurologic disorders at any level of the neuraxis.
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PMID:Neurologic problems of the lower extremity associated with HIV and AIDS. 957 54

Hypoxia-ischemia induces an inflammatory response in the immature central nervous system that may be important for development of brain injury. Recent data implicate that chemoattractant cytokines, chemokines, are involved in the recruitment of immune cells. The aim was to study alpha- and beta-chemokines in relation to the temporal activation of inflammatory cells after hypoxia-ischemia in immature rats. Hypoxia-ischemia was induced in 7-day-old rats (left carotid artery occlusion + 7.7% oxygen). The pups were decapitated at different times after the insult. Immunohistochemistry was used for evaluation of the inflammatory cell response and RT-PCR to analyze the cytokine mRNA and chemokine mRNA expression. A distinct interleukin-1beta and tumor necrosis factor-alpha cytokine expression was found 0-24 h after hypoxia-ischemia that was accompanied by induction of alpha-chemokines (growth related gene and macrophage inflammatory protein-2). In the next phase, the beta2-integrin expression was increased (12 h and onward) and neutrophils transiently invaded the vessels and tissue in the infarct region. The mRNA induction for the beta-chemokines macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and RANTES preceded the expression of markers for lymphocytes [cluster of differentiation (CD)4, CD8], microglia/macrophages (MHC I), and natural killer cells in the infarct area. The activation of microglia/macrophages, CD4 lymphocytes, and astroglia persisted up to at least 42 d of postnatal age implicating a chronic component of immunoinflammatory activation. The expression of mRNA for alpha- and beta-chemokines preceded the appearance of immune cells suggesting that these molecules may have a role in the inflammatory response to insults in the immature central nervous system.
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PMID:Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. 1020 41

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.
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PMID:Heterogeneity of the microglial response in photochemically induced focal ischemia of the rat cerebral cortex. 1036 21

In unraveling the pathogenesis of chronic transplant dysfunction (CTD), non-alloantigen specific factors, as ischemia/reperfusion and renal mass have been suggested to play a role in the process. The aim of the present study was to investigate the effect of the transplantation procedure per se on the development of CTD in a syngeneic kidney transplant model in the rat. Kidney transplantation was performed with the BN rat as donor and recipient, the recipient kidneys having been removed. Unilaterally nephrectomized (UNx) and native BN rats served as controls. Renal function was determined monthly (proteinuria and glomerular filtration rate/100 g body weight; GFR). The follow-up period was until 52 weeks post-transplantation. Histomorphological analysis of CTD according to the BANFF criteria was carried out. Immunohistochemical staining was performed to identify infiltrating cells (CD4, CD8, and ED1) and the expression of MHC class II and ICAM-1. Isografts had a minor, constant proteinuria during follow-up, which did not differ from that of UNx: 27 +/- 10 vs. 29 +/- 2 mg/24 h at week 52. Unilateral nephrectomy led to a significant reduction of the GFR, which was about 80% of that of native rats. The GFR of isografts did not differ from that of UNx rats. Histomorphology of renal isografts was comparable to UNx and native kidneys; some glomerulopathy and tubular atrophy leading to a total BANFF-score of 2.6 +/- 0.5. In native BN kidneys, few CD4+ cells and ED-1+macrophages (mphi) were found; MHC class II was constitutively expressed on the proximal tubules and ICAM-1 on the glomeruli and peritubular capillaries. UNx-kidneys showed a similar pattern. Isografts had significantly more CD4+ cells and Mphi, mainly localized in the glomeruli, and a more intense ICAM-1 expression in the glomeruli and interstitium. Transplantation of one kidney in itself does not lead to CTD.
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PMID:Transplantation of a single kidney per se does not lead to late graft dysfunction. 1126 54

We have recently described a novel population of CD8+ phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent from axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8+ phagocyte response, we selectively depleted peripheral macrophages by systemic administration of dichloromethylene diphosphonate-filled liposomes prior to the induction of permanent ischemia by photothrombosis of cortical microvessels. Macrophage depletion led to a dramatic reduction but not complete abolishment of CD8+ cells in the ensuing infarcts. Systemic administration of monoclonal antibody Ox-8 eliminated CD8+ cells from peripheral lymphoid organs but had no effect on CD8+ phagocytes in the ischemic brain lesions. To further characterize the lesion conditions inducing the recruitment of CD8+ phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannecrosis surrounded by areas with selective neuronal cell death. Recruitment of CD8+ phagocytes was restricted to areas of ischemic pannecrosis. In areas undergoing selective neuronal loss microglia up-regulated complement receptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), and to some extent expressed CD4, but not CD8 antigens. In conclusion our present study shows that CD8+ phagocytes in focal brain ischemia are predominantly derived from hematogenous macrophages and selectively target to areas of ischemic pannecrosis.
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PMID:CD8+ phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis. 1148 15

To clarify the mechanism of muscle fiber destruction in sarcoid myopathy, muscle biopsy specimens were examined from patients with sarcoid myopathy, polymyositis, or dermatomyositis. In sarcoid myopathy, noncaseating granulomatous lesions were located in the perimysium or endomysium or both. Little fiber atrophy, caused by mechanical compression of the granuloma, was seen, and there was no evidence of ischemia-induced changes (i.e., perifascicular atrophy) due to microangiopathy in muscles. Immunoreactivity for membrane-associated cytoskeletal proteins such as dystrophin and merosin was detected homogeneously along the surface of many small granulomas in intrafascicular lesions. These granulomas showed a characteristic phenotypic cellular distribution: CD68(+) and CD4(+) cells were present in the center, and some CD8(+) cells were found at the periphery, indicating typical sarcoid granuloma formation in each muscle fiber. Strong expression of proteases such as cathepsin B, calpain II and ubiquitin-proteasome was observed in macrophages and epithelioid cells but not in lymphocytes in granulomas within muscle fibers or those in the endomysium or perimysium. The expression intensity was stronger in premature-stage granulomas than in late-stage granulomas. Weak expression of these proteases was detected mainly in some muscle fibers invaded by epithelioid cells and macrophages and in a few atrophic or necrotic fibers adjacent to inflammatory foci but not in fibers of fascicles without granuloma formation or in fibers in perifascicular areas. Our results suggest that muscle fiber destruction in sarcoid myopathy is caused mainly by direct invasion of granulomatous inflammatory cells into muscle fibers during the process of granuloma formation rather than by mechanical compression or ischemia. Furthermore, the proteases derived from epithelioid cells and macrophages may play an important role in muscle fiber destruction.
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PMID:Cellular distribution of proteolytic enzymes in the skeletal muscle of sarcoid myopathy. 1207 Jun 62


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