Biomedical subjects

C S Chung

Publications and source records attributed to C S Chung.

At least 19 recordsLinked to original sources

PubMed2001

A linear cyclic oximate-bridged tetracopper(II) complex.

The crystal structure of the title complex, tetrakis[mu-6-amino-3-methyl-4-azahex-3-en-2-one oximato(1-)-kappa4N,N',N":O]tetracopper(II) tetraperchlorate 0.6-hydrate, [Cu4(C6H12N3O)4](ClO4)4*0.6H2O, shows the cation to be an oximate-bridged tetramer composed of four 6-amino-3-methyl-4-azahex-3-en-2-one oxime ligands and four copper(II) ions and to have crystallographically imposed 4 symmetry. Each Cu(II) atom is four-coordinated by the three N atoms of one oxime ligand and by the O atom of another oxime ligand in a distorted square-planar geometry.

Journal Article↗

PubMed2001

IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis.

Recent studies suggest that increased activation-induced lymphocyte apoptosis (AICD) is detected in mouse splenocytes during polymicrobial sepsis which may contribute to lymphocyte immune dysfunction [i.e., decreased interleukin (IL-)2 and interferon-gamma (IFN-gamma) production] leading to the associated morbidity seen in those animals. Thus, we wanted to examine the hypothesis that immune suppressive agents, such as IL-4, IL-10 or prostaglandin E2(PGE2), known to be elevated in septic animals, also contribute to this increase in AICD. Here we demonstrate that the inclusion of monoclonal antibody (mAb) to IL-10, but not anti-IL-4 or ibuprofen (IBU), blunted this sepsis induced increase in splenocyte AICD. Additionally, septic mice deficient in the IL-10 gene product (-/-) showed neither an increase in AICD nor a loss of IL-2/IFN-gamma release capacity. Interestingly, mAb to IL-10 did not altered the extent of AICD in a Th2-cell line, but exogenous IL-10 did potentiate Th1-like cell line AICD. This was consistent with the finding that the increased AICD seen in septic mouse splenocytes was restricted largely to the CD4+ cells producing IL-2 (Th1-cells) and that mAb to IL-10 treatment suppressed this change. Furthermore, IL-10 appears to mediate its AICD effect by upregulation of the Fas receptor and Fas receptor signaling protein components, but not by altered expression of Bcl/Bax/Bad family members, in septic mouse splenocytes. To the extent that these processes contribute in a pathological fashion to the animal's capacity to survive sepsis we have previously observed that in vivo post-treatment of mice with mAb IL-10 markedly attenuated septic mortality. Collectively, these data indicate that in the septic mouse the Th2 cytokine IL-10 not only serves to actively induce Th1 lymphocyte immune dysfunction but also plays a role in their apoptotic depletion. These processes in turn appear to contribute to the animal's inability to ward off lethal septic challenge.

Animals↗

PubMed2001

Inhibition of Fas signaling prevents hepatic injury and improves organ blood flow during sepsis.

BACKGROUND: Fas/Fas ligand (FasL) system is one of the major pathways triggering apoptosis that has been shown to play an important role in development and pathogenesis of various diseases including liver and gastrointestinal diseases. Studies indicate that FasL deficiency provides a survival advantage in mice subjected to polymicrobial sepsis. However, the extent to which Fas/FasL contributes to organ injury during sepsis is unclear. Thus, the aim of this study was to determine whether in vivo administration of a Fas-signaling inhibitor during sepsis preserves organ function. METHODS: Male adult C3H/HeN mice were subjected to cecal ligation and puncture (CLP) or sham CLP (sham). Twelve hours after CLP, mice received either Fas-receptor fusion protein (FasFP) (200 microg/kg body weight) or the saline vehicle. Twenty-four hours after the onset of sepsis, cardiac output and organ blood flow were measured with radioactive microspheres. Plasma levels of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase were assessed as indexes of liver damage. Changes in systemic cytokines were measured by enzyme-linked immunosorbent assay. RESULTS. The data indicate that although cardiac output and organ blood flow in the liver, intestine, kidneys, spleen, and heart decreased markedly at 24 hours after CLP, treatment with FasFP maintained the measured hemodynamic parameters and improved hepatic, intestinal, and heart blood flow (P <.05) and partially restored spleen and renal blood flow. Moreover, FasFP treatment markedly attenuated the systemic rise in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and interleukin 10 (P <.05). CONCLUSIONS: These results not only indicate that there is a role for Fas/FasL-mediated processes in the induction of organ injury but suggest that inhibition of Fas/FasL pathway may represent a novel therapeutic modality for maintaining organ perfusion and preventing liver injury during sepsis.

Alanine Transaminase↗

PubMed2001

Evolution of an immune suppressive macrophage phenotype as a product of P38 MAPK activation in polymicrobial sepsis.

Studies indicate that polymicrobial sepsis in humans and animals is characterized by a biphasic response, which is dominated early by proinflammation, but over time develops into a state of generalized anti-inflammation (depressed Th1 cell response and decreased macrophage (M0) capacity to release proinflammatory cytokines). However, with respect to the macrophage, it remains unknown what mechanism(s) controls this change. In this regard it is well documented that the p38 mitogen activated protein kinase pathway (MAPK) plays a central role in the regulation of Mphi functions. However, the contribution of p38 MAPK activation to the loss of these Mphi functions in polymicrobial septic animals remains unknown. To determine this we induced polymicrobial sepsis in C3H/HeN male mice using cecal ligation and puncture (CLP). Twenty-four hours post-CLP, during the late, immune-suppressed stage of sepsis, splenic and peritoneal Mphi were harvested, stimulated with lipopolysaccharide (LPS), and the activation of p38 MAPK assessed. In Mphi from CLP mice, p38 MAPK activity was markedly increased. To determine the extent that these changes in p38 MAPK had an impact on Mphi immune function, cells were pretreated with 10 microM of the p38 MAPK inhibitor, SB203580, or with DMSO vehicle, and subsequently stimulated with LPS. IL-10, IL-6, IL-12, and nitric oxide release was determined. Our results indicate that with LPS stimulation alone, there was a marked increase in the release of the anti-inflammatory mediator, IL-10 after CLP. Alternatively, proinflammatory IL-12 and IL-6 release was suppressed. Treatment with SB203580 suppressed the increase in IL-10 release seen after CLP, while partially restoring IL-12 secretion. IL-6 release was partially restored only in splenic macrophages treated with SB203580. To the extent that these in vitro findings could be translated to an in vivo setting, we assessed the in vivo effects of p38 MAPK inhibition on survival. Mice were given 100 mg of SB203580/kg body weight or saline vehicle (intraperitoneal) either immediately post-CLP or 12 h post-CLP. Delayed administration of SB203580 significantly improved survival, while also preventing the increased NO and IL-10 release and improving IL-12 release by macrophages. These results suggest that p38 MAPK pathway plays a critical role in the induction of an immune-suppressive macrophage phenotype, and that inhibition of p38 MAPK markedly improves survival following polymicrobial sepsis.

Animals↗

PubMed2001

MAPK p38 antagonism as a novel method of inhibiting lymphoid immune suppression in polymicrobial sepsis.

Although studies indicate that a shift from a Th1 to a Th2 response contributes to a marked suppression of cell-mediated immunity during sepsis, the mechanism by which this occurs remains unknown. Given that the mitogen-activated protein kinase (MAPK) p38 plays a critical role in the activation and function of immune cells, the aim of this study was to determine the contribution of MAPK p38 activation to the immune dysfunction seen in polymicrobial sepsis. To study this, polymicrobial sepsis was induced in C3H/HeN male mice by cecal ligation and puncture (CLP). Splenic lymphocytes and purified T cells were harvested 24 h post-CLP, pretreated with the specific MAPK p38 inhibitor SB-203580, and then stimulated with a monoclonal antibody against the T cell marker CD3. The results indicate that interleukin (IL)-2 release is markedly depressed while the release of the immunosuppressive mediator, IL-10, as well as mRNA levels of IL-10 and IL-4, are augmented after CLP. Inhibition of MAPK p38 suppressed in vitro IL-10 levels as well as IL-10 and IL-4 gene expression while restoring the release of IL-2. To determine whether these in vitro findings could be translated to an in vivo setting, mice were given 100 mg of SB-203580/kg body wt or saline vehicle (intraperitoneal) at 12 h post-CLP. Examination of ex vivo lymphocyte responsiveness indicated that, as with the in vitro finding, septic mouse Th1 responsiveness was restored. In light of our recent finding that delayed in vivo SB-203580 treatment also improved survival after CLP, we believe that these results not only illustrate the role of MAPK p38 in the induction of immunosuppressive agents in sepsis but demonstrate that SB-203580 administration after the initial proinflammatory state of sepsis significantly prevents the morbidity from sepsis.

Animals↗

PubMed2001

Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated.

Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows evidence of increased apoptosis after sepsis that is associated with localized inflammation/activation. The mechanism for this is poorly understood. Endotoxin as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis; however, their contribution to the increase of apoptosis in LP B-cells during sepsis is not known. To study this, sepsis was induced by cecal ligation and puncture (CLP) in endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasL(gld) (FasL(-)) mice and LP lymphocytes were isolated 24 h later. Phenotypic, apoptotic, and functional indexes were assessed. The number of LP B cells decreased markedly in C3H/HeJ mice but not in FasL-deficient animals at 24 h after CLP. This was associated with comparable alteration in apoptosis and Fas antigen expression in the B cells of these mice. Septic LP lymphocytes also showed increased IgA production, which was absent in the FasL-deficient CLP mice. Furthermore, Fas ligand deficiency appeared to improve survival of septic challenge. These data suggest that the increase in B cell apoptosis in septic animals is partially due to a Fas/FasL-mediated process but not endotoxin.

Animals↗

PubMed2001

Molecular cloning of the porcine acid-labile subunit (ALS) of the insulin-like growth factor-binding protein complex and detection of ALS gene expression in hepatic and non-hepatic tissues.

The acid-labile subunit (ALS) is an approximately 85 kDa N-glycoprotein that is known primarily as a component of the systemic insulin-like growth factor-binding protein (IGFBP) complex. We have amplified, using a PCR, three overlapping porcine ALS genomic DNA fragments that together encode the distal region of the signal peptide through to the COOH-terminus. The compiled sequence of 1775 nucleotides of the three overlapping DNAs and the deduced amino acid sequence of the mature porcine ALS (pALS) protein exhibited 84/81%, 79/77%, 79/78% and 84/79% identities with respect to those of the human, the rat, the mouse and the baboon respectively. Four conserved cysteine residues in the NH(2)-terminal domain and 20 leucine-rich repeats in the central domain also were identified at identical positions in the porcine ALS. By using Northern blot analysis, with a genomic DNA fragment as the probe, it was determined that a 2.2 kb ALS mRNA was induced in the liver during the late fetal stage, and hepatic ALS mRNA abundance was increased post-natally. Moreover, hepatic ALS mRNA abundance was increased by daily injection of porcine somatotropin (100 microg/kg body weight) in cross-bred market pigs each weighing approximately 100 kg. The ALS mRNA was not detected by Northern analysis in any non-hepatic tissue examined. However, results of a more sensitive solution hybridization/RNAse protection assay indicated that low levels of ALS mRNA were also present in adult muscle, spleen, ovary and uterus, but not in lung, kidney, oviduct and placenta. Taken together, the present results suggest that although liver is the primary organ that expresses the ALS gene under somatotropin stimulation, some non-hepatic tissues also express the gene at low levels in the pig.

Amino Acid Sequence↗

PubMed2000

Immune suppression in polymicrobial sepsis: differential regulation of Th1 and Th2 responses by p38 MAPK.

BACKGROUND: Studies have indicated that a shift from a Th1 to a Th2 response occurs that contributes to the late immunosuppression seen during sepsis. However, the mechanism by which this occurs is unknown. In this regard, mediators released in response to sepsis are thought to upregulate a family of stress-induced mitogen-activated protein kinases (MAPKs), such as JNK, ERK, and p38 MAPK, which may play a role in this process. MATERIALS AND METHODS: To determine the role of MAPK in immune suppression, we induced polymicrobial sepsis in C3H/HeN male mice using cecal ligation and puncture (CLP). Splenic lymphocytes were harvested 24 h post-CLP and stimulated with the T-cell mitogen concanavalin A, and the expression and activation of these MAPKs were assessed by Western analysis. To determine the extent to which these MAPKs may have an impact on splenic immune function, cells were pretreated with a 10 microM concentration of the p38 MAPK inhibitor SB203580 or the MEK inhibitor PD98059 or with DMSO vehicle. The cells were then stimulated with 2.5 microg/ml of the T-cell mitogen concanavalin A, and cytokine release was then determined (by ELISA). RESULTS: In the lymphocytes from CLP mice no JNK signal was detected, however, p38 expression and activation were markedly (P < 0.05, n = 6) increased. In contrast, the expression of activated ERK markedly decreased following septic challenge. The results indicate that p38 MAPK inhibition with SB203580 suppressed the sepsis-induced augmentation of interleukin-10 release while restoring the suppressed Th1 cytokine interleukin-2 release typically encountered following sepsis. Inhibition of ERK had no effect on cytokine release. Neither PD98059 nor SB203580 had an effect on interferon gamma release or on proliferative capacity. CONCLUSION: This would indicate that the induction of p38 MAPK activation in splenocytes contributes to the immunosuppression seen in late sepsis.

Animals↗

PubMed2000

Neither Fas ligand nor endotoxin is responsible for inducible peritoneal phagocyte apoptosis during sepsis/peritonitis.

Regulation of the phagocyte apoptotic response appears to play a significant role in the pathophysiology of sepsis. In this regard, prior studies have shown that the onset of phagocyte apoptosis, as well as those agents that regulate it at the nidus of infection, differ significantly from those seen in circulation. The aim of this study therefore was to determine if the increase in inducible phagocyte apoptosis and caspase activities seen in the peritoneum during sepsis is due to endotoxin or Fas ligand. To study this, male C3H/HeN (endotoxin-sensitive), C3H/HeJ (endotoxin-tolerant), and C3H/HeJ-FasL(gld) (endotoxin-tolerant/FasL-deficient) mice were subjected to cecal ligation and puncture or sham operation. Twenty-four hours later, phagocytes were collected and cultured with lipopolysaccharide (LPS), then harvested for apoptosis (propidium iodide cell cycle or cell death ELISA analysis), cytokine release (ELISA), and caspase activity (fluorogenic assay) determination. The data indicate that there was a marked increase in apoptosis in LPS-stimulated phagocytes which was associated with a significant increase in caspase 3, 8, and 9 activities but a decrease in caspase 1 activity from C3H/HeN and C3H/HeJ-FasL(gld) septic mice and an increase in caspase 3 and 8 activities in phagocytes from C3H/HeJ septic mice. Furthermore, cells from septic mice, including all three strains, lost their ability to produce IL-1beta and IL-6 in response to LPS stimulation. The inability to completely suppress these changes suggests that neither endotoxin (via signaling through TLR-4 pathway) nor Fas ligand regulates the peritoneal phagocyte apoptotic responses seen during the late phase of polymicrobial sepsis/peritonitis.

Animals↗

PubMed2000

Diffusion-weighted MRI in vascular dementia.

OBJECTIVE: To examine the ability of diffusion-weighted MRI (DWI) to detect ongoing cerebral ischemia in patients with vascular dementia (VaD). BACKGROUND: VaD due to small-vessel disease results from the cumulative impact of recurrent cerebral ischemia. Cerebral ischemia may produce clinical manifestations, producing the "stepwise" decline characteristic of VaD. Conventional MRI can detect small regions of ischemic damage but cannot determine when injury developed. In contrast, DWI shows sensitivity in detecting ischemia of recent onset. DESIGN/METHODS: Patients with VaD (n = 30) underwent DWI in addition to standard MRI sequences. Patients were divided into two groups according to the presence of new focal deficits or mental change within 10 days before MRI. In 10 patients of positive group, symptomatic neurologic decline occurred an average of 4.2 days before the imaging procedure. RESULTS: Seven (70%) of 10 patients with a recent neurologic event showed 15 new regions of signal abnormality on DWI. The anatomic distribution of signal change could account for the patients' new symptoms or signs in all but one patient. Similar signal abnormality was detected in 4 (20%) of 20 patients without a recent neurologic event. New foci of altered signal intensity were distinguishable from prior injuries only with DWI. No significant difference was found between patients with and without DWI abnormalities in gender, age, Mini-Mental State Examination score, Hachinski Ischemic Score, vascular risk factors, or severity of increased signal on T2-weighted MRI scans. CONCLUSION: Small foci of abnormal signal on diffusion-weighted MRI (DWI), presumably representing recent small infarcts, occur often in vascular dementia (VaD) from small-vessel disease, even in patients without a recent "stepwise decline." The results suggest that DWI might be used to monitor VaD progression in future observational and interventional studies of this disorder.

Aged↗

PubMed2000

Aspiration subsequent to a pure medullary infarction: lesion sites, clinical variables, and outcome.

BACKGROUND: Aspiration as a symptom of dysphagia and its apparent sequela, aspiration pneumonia, are common consequences of a stroke in the medulla. Previous reports that focused on dysphagia due to a medullary lesion were studies of single cases or a relatively small number of patients with multiple lesion loci. Moreover, the interval between the onset of stroke and the evaluation time of swallowing was not controlled and varied largely among patients. Thus, prediction of the swallowing status of patients with a medullary lesion has not been tenable. OBJECTIVES: To investigate the relation between the loci of pure medullary lesions and aspiration, to examine swallowing function over time, and to explore clinical variables that can predict aspiration. METHODS: We investigated 23 patients with pure medullary infarctions using the videofluoroscopic swallowing study and compared the airway status findings with the lesion location as determined with magnetic resonance imaging. The patients were classified by 6 medullary lesion-level categories (lower, lower-middle, middle, lower-middle-upper, middle-upper, and upper) and by 5 intralevel lesion loci (inferior-dorsal, large inferior-dorsolateral, para-median, midlateral, and dorsolateral). From the results of the videofluoroscopic swallowing studies, 2 patient groups were formed: one with aspiration and the other without aspiration. The clinical variables related to aspiration and outcome measures were also explored. RESULTS: Ten (44%) of the 23 patients manifested aspiration on swallowing: 9 (69%) of 13 with only middle-level lesions or lesions in multilevels, including the middle level; 1 (33%) of 3 with only upper-level lesions; and 0 (0%) of 7 with only lower-level medullary lesions. A lesion running the length of the middle and the lower medullary levels always resulted in aspiration. When an upper-level lesion was additionally involved, the incidence of aspiration depended on the horizontal extension of the lesion. We were able to discriminate the 2 patient groups with 95.7% accuracy using such variables as dysphonia, soft palate dysfunction, and facial hypesthesia. Most of the patients with aspiration symptoms due to a pure medullary infarction recovered rather quickly. CONCLUSIONS: Medullary infarctions often cause aspiration, but the occurrence may depend on the levels along the neuraxis and intralevel lesion loci. When different lesion levels and loci and their related clinical findings are considered as possible variables, aspiration becomes predictable. The outcome data prove that systematic control of evaluation time of swallowing was critical as we engaged in this study, since many aspirators with pure medullary infarctions resolve their swallowing difficulties rather quickly.

Adult↗

PubMed2000

Usefulness of triphasic perfusion computed tomography for intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke has been investigated in several clinical trials without enough information on collateral blood flow and perfusion deficit in the ischemic areas. The therapeutic time window varies from patient to patient depending on these factors. Triphasic perfusion computed tomography (TPCT) can provide this information as reliably as conventional angiography. OBJECTIVE: To assess the safety and efficacy of thrombolysis within 3 or 7 hours of stroke onset according to the extent of perfusion deficit on TPCT. METHODS: In 46 patients with acute middle cerebral artery (MCA) territory stroke, TPCT was performed with power injector-controlled, intravenous administration of contrast media after taking precontrast CT scans. Sequential scans of early, middle, and late phases were performed. The entire procedure took 5 minutes. Depending on collateral blood flow, the perfusion deficit on TPCT was graded as "severe perfusion deficit" or "moderate perfusion deficit." Twenty-nine patients were excluded based on clinical, laboratory, and TPCT findings. Seventeen patients were treated with an intravenous recombinant tissue-type plasminogen activator, 0.9 mg/kg. The 17 treated patients were divided into 2 groups: group 1 with small severe perfusion deficit (</=33% of the presumed MCA territory) and group 2 with medium-sized severe perfusion deficit (>33% but </=50% of the presumed MCA territory). The 13 patients in group 1 were treated within 7 hours of onset and the 4 patients in group 2 were treated within 3 hours. RESULTS: Initial mean National Institutes of Health Stroke Scale score was 12.1 (range, 6.0-20.0) in group 1 and 19.0 (range, 18.0-21. 0) in group 2. The initial score correlated better with the total extent of moderate perfusion deficit and severe perfusion deficit than that of severe perfusion deficit alone. Mean time lapse to thrombolysis was 4.2 hours (range, 1.5-7.0 hours) in group 1 and 2.2 hours (range, 1.9-2.5 hours) in group 2. Eight patients (47%), 7 from group 1 and 1 from group 2, improved by 4 points or more from baseline Stroke Scale score within 24 hours of thrombolysis. Patients with moderate perfusion deficit of 50% or more of MCA territory (n = 4) had a better chance of early improvement than did those (n = 13) with moderate perfusion deficit of less than 50% (4 of 4 vs 4 of 13). No fatal hemorrhage occurred. Only 1 patient (6%) had symptomatic small basal ganglia hemorrhage after thrombolysis. CONCLUSIONS: Thrombolysis can be safely performed within 3 or 7 hours of stroke onset according to the extent of severe perfusion deficit on TPCT. A larger extent of moderate perfusion deficit on TPCT may predict early improvement after thrombolysis.

Adult↗

PubMed2000

Triphasic perfusion computed tomography in acute middle cerebral artery stroke: a correlation with angiographic findings.

OBJECTIVE: To evaluate the usefulness of triphasic perfusion computed tomography (TPCT) in diagnosing middle cerebral artery (MCA) occlusion and in assessing the perfusion deficit and collateral circulation in patients with acute ischemic stroke. BACKGROUND: Conventional angiography is the criterion standard for the diagnosis of MCA occlusion and for the assessment of perfusion deficit and collateral blood supply. The risk of hemorrhagic transformation after recanalization of occluded arteries by thrombolytic therapy is considered high when pretherapeutic residual flow is markedly reduced. PATIENTS AND METHODS: In 8 patients within 3 hours of onset of acute MCA stroke, precontrast computed tomographic scans were taken, and then TPCT was performed after power-injector controlled intravenous administration of contrast media. Sequential images of early, middle, and late phases were obtained. The whole procedure took 5 minutes. Perfusion deficit on TPCT was graded as "severe" or "moderate," depending on the state of collateral flow. Digital subtraction angiography (DSA) was performed in all patients within 6 hours of acute stroke. Direct intra-arterial urokinase infusion was begun immediately after the angiographic superselection of the MCA occlusion site in 6 of the 8 patients within 7 hours of onset (range, 4.3-6.2 hours). RESULTS: The DSA findings showed occlusion of the MCA stem (n = 1) and at the bifurcation (n = 4). The sites of proximal MCA occlusion could be identified on the early and middle images of TPCT in all 5 patients. On DSA findings, all 8 patients had a zone of perfusion deficit with markedly slow leptomeningeal collaterals and a zone of perfusion deficit with no collaterals. The zone of severe perfusion deficit on TPCT corresponded to the zone of perfusion deficit with no or few collaterals on angiography, and the zone of moderate perfusion deficit on TPCT corresponded to that of perfusion deficit with markedly slow leptomeningeal collaterals. Early parenchymal hypoattenuation on precontrast computed tomography was confined to the zone of severe perfusion deficit on TPCT. The initial National Institutes of Health Stroke Scale score correlated better with the total extent of severe perfusion deficit and moderate perfusion deficit on TPCT than that of severe perfusion deficit alone. After direct intra-arterial thrombolysis within 7 hours of onset, symptomatic hemorrhagic transformation did not develop in 4 patients with small severe perfusion deficit (33% or less of the presumed MCA territory). However, the remaining 2 patients with large severe perfusion deficit (more than 50% of the presumed MCA territory) deteriorated to death with hemorrhagic transformation. CONCLUSIONS: Triphasic perfusion computed tomography is useful for diagnosing proximal MCA occlusion and assessing perfusion deficit and collateral circulation as reliably as DSA. The zone of severe perfusion deficit on TPCT may be presumed to be the ischemic core, and that of moderate perfusion deficit, the penumbra zone. Triphasic perfusion computed tomography may be used as a rapid and noninvasive tool to make thrombolysis safer.

Acute Disease↗

PubMed2000

The relationship between the angiographic findings and the clinical features of carotid artery plaque.

The purpose of this study was to investigate the histological characteristics of atheromatous carotid plaque, and to analyze the relationship between the angiographic findings and the clinical features. We retrospectively reviewed 55 cases of carotid endarterectomy for extracranial internal carotid artery stenosis, who were treated at our institute from January 1995 to December 1997. The histological examination included hematoxylin-eosin staining, Masson-trichrome staining, and immunostaining for antismooth muscle antibody and anti-CD68 antibody. The main compositions of the carotid plaque included synthetic type vascular smooth muscle cells and extracellular matrix. The histological findings showed ulceration in 49 (89.1%) cases, calcium deposits in 42 (76.4%) cases, and an inflammatory reaction in 44 (80.0%) cases. Neurological abnormalities were strongly associated with plaque ulceration (P = 0.045) and an inflammatory reaction (P = 0.013), whereas no correlation existed regarding calcium deposits (P = 0.173). The angiographic findings showed ulceration in 46 (83.6%) cases. Plaque ulceration in the angiography findings showed no statistically significant correlation with the histologic findings (P = 0.410) and preoperative neurologic abnormalities (P = 0.059). All of the atherosclerotic risk factors such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and myocardial infarction had no statistically significant correlation with the histological features of the carotid plaque. In conclusion, the main compositions of carotid plaque were synthetic-type vascular smooth muscle cells and extracellular matrix. The histological ulceration and inflammatory reaction of the plaque showed a statistically significant correlation with the preoperative neurologic symptoms, whereas no correlation was seen in the calcium deposits. Angiographic ulceration showed no correlation with the histological findings or preoperative neurologic abnormalities. In addition, the histological findings showed no correlation with the atherosclerotic risk factors.

Aged↗

PubMed2000

Synthesis and structural characterization of a Re(V) complex with a 2N1S donor and the radiochemical behavior of its Tc analog.

A rhenium(V) complex with 2-(2-pyridylmethylthio)-aniline has been synthesized and characterized by UV-VIS absorption, IR, MS and X-ray crystallography. The complex contains a ReO3+ moiety and the amine compound, acting as a monobasic tridentate(NSN) ligand. The chemical behavior of its technetium analog has been studied radioanalytically by solvent extraction, TLC, electrophoresis and HPLC using 99mTc tracer.

Crystallography, X-Ray↗

PubMed2000

IL-4-induced activation of the Stat6 pathway contributes to the suppression of cell-mediated immunity and death in sepsis.

BACKGROUND: Although studies have shown that there is a marked depression in cell-mediated (T(H)(1)) immunity after the onset of sepsis, the mechanism by which this occurs remains unknown. In this regard, the T(H2) cytokine IL-4 is known to regulate T(H1) and T(H2) cell responsiveness primarily through the activation of the signal transducer and activation of transcription factor-6 (Stat6) pathway. METHODS: We hypothesized that IL-4 may contribute to the suppression of cell-mediated immunity and to death seen in sepsis and that IL-4 may be acting through the Stat6 pathway. To determine this, we induced cecal ligation and puncture (CLP) or sham-CLP in male BALB/c mice. Mice received 2 mg of monoclonal antibody against IL-4 or IgG control at 12 hours after CLP (ie, at the onset of immune suppression). Splenic T cells were then isolated 24 hours after CLP and stimulated with monoclonal antibody to CD3. Cytokine release and Stat6 phosphorylation (activation) were determined. In a separate group of animals, survival was assessed over 10 days. RESULTS: The results indicate that after CLP, T cells are suppressed in their ability to release the T(H1) cytokines, IL-2 and IFN-gamma. Alternatively, the release of T(H2) cytokines IL-10 and IL-4 is markedly increased after CLP. This was associated with an increase in phosphorylated Stat6 protein. In vivo treatment of mice with monoclonal antibody to IL-4 at 12 hours after CLP restores T(H1) responsiveness while preventing the increase in T(H2) cytokine release and Stat6 phosphorylation. Furthermore, neutralization of IL-4 markedly increased the survival rates in septic animals. CONCLUSIONS: Taken together, these data indicate that the T(H2) cytokine IL-4 contributes to the suppression of cell-mediated immunity and death associated with polymicrobial sepsis and suggest that IL-4 may be acting through the Stat6 pathway in septic animals.

Animals↗

PubMed2000

Striatocapsular haemorrhage.

Haemorrhages in the striatocapsular area, or striatocapsular haemorrhages (SCHs), have been regarded as a single entity, although the area is composed of several functionally discrete structures that receive blood supply from different arteries. We analysed the morphological and clinical presentations of 215 cases of SCHs according to a new classification method we have designed on the basis of arterial territories. SCHs were divided into six types: (i) anterior type (Heubner's artery); (ii) middle type (medial lenticulostriate artery); (iii) posteromedial type (anterior choroidal artery); (iv) posterolateral type (posteromedial branches of lateral lenticulostriate artery); (v) lateral type (most lateral branches of lateral lenticulostriate artery); and (vi) massive type. The anterior type (11%) formed small caudate haematomas, always ruptured into the lateral ventricle, causing severe headache, and mild contralateral hemiparesis developed occasionally. The outcome was excellent. The middle type (7%) involved the globus pallidus and medial putamen, frequently causing contralateral hemiparesis and transient conjugate eye deviation to the lesion side. About 50% of the patients recovered to normal. The posteromedial type (4%) formed very small haematomas in the posterior limb of the internal capsule and presented with mild dysarthria, contralateral hemiparesis and sensory deficit, with excellent outcome in general. The posterolateral type (33%) affected the posterior half of the putamen and posterior limb of the internal capsule and presented with impaired consciousness and contralateral hemiparesis with either language dysfunction or contralateral neglect. The outcome was fair to poor but there were no deaths. The lateral type (21%) formed large elliptical haematomas between the putamen and insular cortex. Contralateral hemiparesis with language dysfunction or contralateral neglect developed frequently but resolved over several weeks. The clinical outcome was relatively excellent except when the haematoma size was very large. The massive type (24%) formed huge haematomas affecting the entire striatocapsular area. Marked sensorimotor deficits and impaired consciousness, ocular movement dysfunctions including the 'wrong-way' eyes were observed quite frequently. The outcome was very poor with a case fatality rate of 81%. The clinico-radiological presentations suggested its origin was the same as the posterolateral type.

Adult↗

PubMed2000

Immune depression in polymicrobial sepsis: the role of necrotic (injured) tissue and endotoxin.

OBJECTIVE: Recent studies suggest immune dysfunction seen after the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP), is not caused by endotoxin (ETX) alone, but may be caused by the combined effect of the necrotic tissue (cecal ligation, [CL]) and other microbial components. Thus, the objective of this study was to assess the ability of necrotic tissue, in the presence or absence of low-dose endotoxin, to induce changes in the capacity of immune cells to produce proinflammatory or anti-inflammatory cytokines approximating those seen in CLP. DESIGN: Experimental, prospective study. SETTING: A hospital laboratory in the Center for Surgical Research. SUBJECTS: Male C3H/HeN mice. INTERVENTIONS: Mice were subjected to a CL and saline infusion (CL/Sal), CL in combination with low-dose ETX infusion (CL/ETX) (0.025 mg ETX/25 g body weight/24 hrs by a peritoneally implanted osmotic mini-pump), ETX infusion alone, saline infusion alone (Sal), CLP, or sham-CLP (Sham). Splenocytes, splenic macrophage and peritoneal macrophage were harvested from these animals 24 hrs (late) after being subjected to the above protocols. Splenocyte and macrophage inducible cytokine release was assessed by ELISA/bioassay. Survival over a 7-day period was also examined in additional groups. MEASUREMENTS AND MAIN RESULTS: Our results indicate a marked decrease in splenic interleukin (IL)-2. In addition, peritoneal or splenic macrophage IL-6 productive capacity was depressed in cells from animals subjected to CL/ETX or CLP. Alternatively, CL, in the presence or absence of ETX, induced a marked change in macrophage cytokine release capacity comparable to that seen in CLP, ie, decreased IL-12 release and increased IL-10 secretion. To the extent these cellular alterations contribute to an increase in mortality rate, we observed in subsequent survival studies that neither CL alone nor ETX produced mortality. However, the combination of CL/ETX markedly increased 7-day mortality rate (approximately 33%), although not to the same extent as CLP (80%). CONCLUSIONS: These results collectively suggest that the response to devitalized tissue produced by cecal ligation may predispose the host to the induction of a suppressive macrophage phenotype. The subsequent exposure of these animals to microbial agents induces immune dysfunction, as well as mortality seen after such a polymicrobial septic challenge.

Animals↗