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C Metz

Publications and source records attributed to C Metz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regulation of macrophage migration inhibitory factor by endogenous glucocorticoids in rat adjuvant-induced arthritis.

OBJECTIVE: To explore the regulation of macrophage migration inhibitory factor (MIF) by endogenous glucocorticoids in adjuvant-induced arthritis (AIA). METHODS: Adrenalectomy or sham operation was performed 2 days prior to adjuvant arthritis induction. Synovial explant supernatant levels of MIF and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay (ELISA). Synovial MIF immunostaining was detected by 3-layer immunohistochemistry. Serum MIF levels were measured by Western blotting. Pituitary MIF release was measured by ELISA. Anti-MIF monoclonal antibody (mAb) or isotype-matched control antibody was administered to adrenalectomized (ADX) animals throughout AIA development. RESULTS: Compared with sham operation, adrenalectomy was associated with significant exacerbation of clinical disease parameters (P < 0.05). Adrenalectomy was associated with significantly reduced levels of synovial MIF, but not TNFalpha. In contrast, adrenalectomy was associated with increased serum MIF levels. Concomitant increased pituitary MIF levels were observed in ADX rats, consistent with the pituitary being the principal source of this increase. The administration of specific anti-MIF mAb conferred 100% protection from lethality during arthritis development and decreased arthritis disease expression. CONCLUSION: These findings provide the first in vivo confirmation of the observation that endogenous glucocorticoids are involved in the regulation of MIF in a site of inflammation, and that local and systemic MIF production are differentially regulated in this setting. The reversal of disease in ADX rats by anti-MIF mAb suggests that balance between glucocorticoids and MIF may influence the expression of inflammatory disease.

Adrenalectomy↗
PubMed2000

[Head-brain injury and cerebral hypoxia. Diagnosis--monitoring--therapy].

The main reason for posttraumatic secondary brain damage is cerebral hypoxia. Both, severity and duration of hypoxia are crucial in determining wether irreversible cerebral infarction will occur or not. For the clinical routine, the diagnosis of hypoxia is indirectly made by low CPP, low jugular-venous oxygen saturation (SjO2) or low tissue PO2. To minimize misleading false negative SjO2, the CT-Approach for the side of monitoring and calculation of arterial-jugular-venous lactate content for detection of anaerobic metabolism is recommended. Targeted treatment of hypoxia according to the underlying cause is mandatory. Primary goal is to increase cellular oxygen delivery by correction of low arterial oxygen content and elevation of regional CBF. Within the autoregulatory range decreasing CPP causes vasodilation and increasing CPP vasoconstriction with increasing or decreasing cerebral blood volume respectively. Initially elevation of the lower autoregulatory threshold often requires CPP 70 mmHg. Targeted treatment of intracranial hypertension must avoid decreasing CPP. In the early posttraumatic phase prevention of cerebral hypoxia relies on management of CBF by means of CPP and cerebral vascular resistance. Thereafter targeted treatment of intracranial hypertension caused by cerebral edema and hypervolemia are increasingly important.

Brain Injuries↗
PubMed2000

Functional neocortical microcircuitry demonstrated with intrinsic signal optical imaging in vitro.

Intrinsic signal optical imaging was used to record the changes in light transmittance evoked by electrical stimulation in slices prepared from sensorimotor cortex of young adult rats. The spatial characteristics of the optical signal evoked by stimulation of layer II/III, IV, V, or VI were clearly different. Layer IV and V stimulation elicited a radially-oriented region of increased light transmittance which was "hourglass" shaped: its tangential extent was greatest in layers II/III and layer V, and least in layer IV. Layer VI stimulation also elicited a radially-oriented signal but the tangential extent of this signal was the same across layers II-VI--that is, it was column-shaped. Upper layer stimulation produced a signal whose tangential extent was much greater in the upper layers than its radial extent to the deeper layers. The spatial form of the stimulus-evoked intrinsic signal was not dependent on the cytoarchitectonic area in which it was elicited. The tangential and radial distribution of the signal evoked by stimulation of different layers appears to reflect the connectivity of cortex, particularly the horizontal connectivity present in layers II/III, V, and VI, and the interlaminar connections that exist between layers II/III and V and from layers VI to IV. The spatial characteristics of the intrinsic signal were independent of the strength of stimulation used. The idea that inhibitory mechanisms restrict the tangential extent of the signal was evaluated in experiments in which the intrinsic signal was recorded before and after the addition of 10 microM bicuculline methiodide. In all slices studied in this way (n = 12), bicuculline methiodide drastically increased the tangential extent of the signal. In 4/12 slices, the tangential spread of the signal was asymmetric with respect to the stimulus site. Asymmetric spread of the signal occurred for both layer V and layer VI stimulation and, in 2/4 of those cases, could be attributed to a cytoarchitectonic border whose presence appeared to restrict the spread of the signal across the border. Although increasing stimulation strength did not change the spatial characteristics of the radially-oriented signal evoked by layer V or VI stimulation, at maximal stimulus intensity the signal evoked from these layers was often accompanied by a band of decreased light transmittance in the most superficial layers (layers I and II). It is concluded that in vitro intrinsic optical signal imaging allows one to image a response attributable to activation of local subsets of cortical connections. In addition, the opposite effects of high-intensity deep layer stimulation on the superficial layers vs layers III-VI of the same column raise the possibility that the most superficial layers may respond differently to repetitive input drive than the rest of the cortical column.

Animals↗
PubMed2000

Pharmacokinetics of human cerebral opioid extraction: a comparative study on sufentanil, fentanyl, and alfentanil in a patient after severe head injury.

BACKGROUND: The pharmacodynamic differences in time to onset and dissipation of effect of sufentanil, fentanyl, and alfentanil probably result from different rates of blood-brain equilibration. The authors investigated this hypothesis in humans. METHODS: After simultaneous central venous bolus application of sufentanil (10 microg), fentanyl (100 microg), and alfentanil (1,000 microg), arterial and jugular bulb blood samples were drawn simultaneously at 20, 30, 45, 60, 75, 90, 105, 120, 140, 160, 180, 210, 240, 300, 360, and 420 s from 19 patients during the postacute stage of head injury with normal intracranial pressure, cerebral perfusion pressure, and cerebral oxygen metabolism during normocapnia. RESULTS: Peak brain concentration, indicated by equilibrium between arterial and jugular bulb opioid concentrations, was achieved for alfentanil at 45 s, for sufentanil at 5 min, and for fentanyl at 6 min. The corresponding median time intervals (fifth and ninety-fifth percentiles) to reach 50% of peak brain concentration were 15 (14-18), 25 (18-38) and 35 (25-45) s, respectively. Uptake was highest 20 s after bolus and decreased continuously for fentanyl and sufentanil, whereas alfentanil uptake was biphasic. The ratio of the relative amounts of sufentanil, fentanyl, and alfentanil retained in the brain at peak brain concentration was 1x:x6x:x90. CONCLUSIONS: The differences in the time lag between changes in serum concentrations and drug effect after bolus application of nearly equipotent doses of sufentanil, fentanyl, and alfentanil originate from the different times required to reach blood-brain equilibration, mainly depending on different levels and different time profiles of arterial blood concentrations caused by the different tissue distribution volumes.

Adolescent↗
PubMed2000

The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle.

Severe infection or tissue invasion can provoke a catabolic response, leading to severe metabolic derangement, cachexia, and even death. Macrophage migration inhibitory factor (MIF) is an important regulator of the host response to infection. Released by various immune cells and by the anterior pituitary gland, MIF plays a critical role in the systemic inflammatory response by counterregulating the inhibitory effect of glucocorticoids on immune-cell activation and proinflammatory cytokine production. We describe herein an unexpected role for MIF in the regulation of glycolysis. The addition of MIF to differentiated L6 rat myotubes increased synthesis of fructose 2,6-bisphosphate (F2,6BP), a positive allosteric regulator of glycolysis. Increased expression of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) enhanced F2,6BP production and, consequently, cellular lactate production. The catabolic effect of TNF-alpha on myotubes was mediated by MIF, which served as an autocrine stimulus for F2, 6BP production. TNF-alpha administered to mice decreased serum glucose levels and increased muscle F2,6BP levels; pretreatment with a neutralizing anti-MIF mAb completely inhibited these effects. Anti-MIF also prevented hypoglycemia and increased muscle F2,6BP levels in TNF-alpha-knockout mice that were administered LPS, supporting the intrinsic contribution of MIF to these inflammation-induced metabolic changes. Taken together with the recent finding that MIF is a positive, autocrine stimulator of insulin release, these data suggest an important role for MIF in the control of host glucose disposal and carbohydrate metabolism.

Animals↗
PubMed2000

Increased expression of c-rel, from the NF-kappaB/Rel family, in T cells from patients with systemic lupus erythematosus.

OBJECTIVE: To explore the role of the NF-kappaB/Rel transcription factor family in autoimmunity, we investigated whether peripheral blood mononuclear cells (PBMC) and T cells from the blood of patients with systemic lupus erythematosus (SLE) exhibit abnormal expression of c-rel, both when recently isolated and/or during in vitro activation. METHODS: Total RNA and protein extracts were prepared from PBMC and T cells isolated by immunoadsorption with magnetic beads. The relative concentrations of c-rel mRNA and of c-Rel protein were determined by semiquantitative assays of competitive reverse transcriptase-polymerase chain reaction and chemiluminescent immunoblots, respectively. Activity of NF-kappaB/Rel was studied by electrophoretic mobility shift assay of nuclear extracts. RESULTS: Significantly increased levels of c-rel mRNA were found (1) in PBMC from SLE patients (n = 48; p<0.0000001), even during inactive disease (n = 11; p<0.001), compared to controls (n = 54), and (2) in T cells isolated from a subgroup of these patients (n = 11; p<0.00002) and controls (n = 12). c-Rel protein was found increased in the cytosol but not in the nucleus of PBMC of patients with SLE (n = 12; p<0.02) compared to controls (n = 12). No evidence of NF-kappaB/Rel nuclear activity was detected. In vitro stimulation of T cells by incubating PBMC with concanavalin A showed that less c-Rel entered the nucleus in lupus cells than healthy cells, correlating with lower interleukin 2 production. However, the same stimulating conditions provoked an increase in c-rel mRNA to higher levels in lupus cells from 2 patients compared with 2 controls. Increased levels of both IkappaB alpha and IkappaB beta could account for c-Rel cytosolic retention. CONCLUSION: Our data suggest that T cells from patients with SLE possess altered regulatory mechanisms of c-rel expression and nuclear import that might potentially determine conditions for developing autoimmunity. Other cells present in the PBMC could also be affected.

Adolescent↗
PubMed2000

Involvement of macrophage migration inhibitory factor (MIF) in experimental uric acid nephropathy.

BACKGROUND: Deposition of uric acid in the kidney can lead to progressive tubulointerstitial injury with granuloma formation. We hypothesized that uric acid crystal deposition may induce granuloma formation by stimulating local expression of macrophage migration inhibitory factor (MIF), which is a known mediator of delayed type hypersensitivity (DTH). MATERIALS AND METHODS: A model of acute uric acid nephropathy was induced in rats by the administration of oxonic acid (an inhibitor of uricase), together with uric acid supplements. MIF expression and local cellular response were examined by in situ hybridization and immunohistochemistry. RESULTS: Kidney tissue examined at 35 days posttreatment showed widespread tubulointerstitial damage with intratubular uric acid crystal deposition and granuloma formation. Tubules within the areas of granuloma showed a six-fold increase in MIF mRNA, compared with uninvolved areas by in situ hybridization. Moreover, the areas of increased MIF mRNA expression correlated with sites of dense accumulation of macrophages and T cells, and these cells were activated when assessed by the expression of interleukin-2R (IL-2R) and (MHC) class II. Interestingly, cytoplasmic staining for MIF protein in the uric acid (UA) crystal-associated granulomatous lesions was reduced, indicating a rapid MIF secretion by damaged tubules and macrophages secondary to uric acid crystal stimulation. This was confirmed by the demonstration of a marked increase in urinary MIF protein by Western blot analysis. Control rats fed either a normal diet or only oxonic acid had no discernible evidence of renal disease by routine light microscopy and minimal tubular expression of MIF mRNA and protein. CONCLUSIONS: These data suggest that intrarenal granulomas in urate nephropathy may be the consequence of a crystal induced DTH reaction mediated by MIF.

Animals↗
PubMed1999

An inducible gene product for 6-phosphofructo-2-kinase with an AU-rich instability element: role in tumor cell glycolysis and the Warburg effect.

Cancer cells maintain a high glycolytic rate even in the presence of oxygen, a phenomenon first described over 70 years ago and known historically as the Warburg effect. Fructose 2,6-bisphosphate is a powerful allosteric regulator of glycolysis that acts to stimulate the activity of 6-phosphofructo-1-kinase (PFK-1), the most important control point in mammalian glycolysis. The steady state concentration of fructose 2,6-bisphosphate in turn depends on the activity of the enzyme 6-phosphofructo-2-kinase (PFK-2)/fructose-2, 6-bisphosphatase, which is expressed in several tissue-specific isoforms. We report herein the identification of a gene product for this enzyme that is induced by proinflammatory stimuli and which is distinguished by the presence of multiple copies of the AUUUA mRNA instability motif in its 3'-untranslated end. This inducible gene for PFK-2 is expressed constitutively in several human cancer cell lines and was found to be required for tumor cell growth in vitro and in vivo. Inhibition of inducible PFK-2 protein expression decreased the intracellular level of 5-phosphoribosyl-1-pyrophosphate, a product of the pentose phosphate pathway and an important precursor for nucleic acid biosynthesis. These studies identify a regulatory isoenzyme that may be essential for tumor growth and provide an explanation for long-standing observations concerning the apparent coupling of enhanced glycolysis and cell proliferation.

3' Untranslated Regions↗
PubMed1999

Macrophage migration inhibitory factor in rheumatoid arthritis: evidence of proinflammatory function and regulation by glucocorticoids.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine whose involvement in tumor necrosis factor alpha (TNFalpha) synthesis and T cell activation suggests a role in the pathogenesis of rheumatoid arthritis (RA). Antagonism of MIF is associated with marked inhibition of animal models of RA. Uniquely, MIF is inducible by low concentrations of glucocorticoids. We sought to investigate the expression of MIF in RA synovial tissue. METHODS: MIF was demonstrated in human RA synovium by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR). Regulation of MIF expression was investigated by treatment of cultured fibroblast-like synoviocytes (FLS) with interleukin-1beta (IL-1beta), TNFalpha, or interferon-gamma (IFNgamma), and dexamethasone (DEX). Mononuclear cell TNFalpha release after exposure to FLS-conditioned medium was measured by ELISA. RESULTS: MIF was present in RA synovial lining CD14+ macrophages and FLS. Constitutive MIF messenger RNA (mRNA) expression was demonstrated by RT-PCR of RNA from unstimulated cultured RA FLS, which also released abundant MIF. Serum, synovial fluid, and FLS intracellular MIF were significantly higher in RA patients than in controls. Synoviocyte MIF was not increased by IL-1beta, TNFalpha, or IFNgamma. In contrast, DEX 10(-7)M significantly reduced synoviocyte MIF, while DEX 10(-10)-10(-12)M induced a significant increase in MIF and MIF mRNA. Peripheral blood mononuclear cell TNFalpha release was induced by culture in RA FLS-conditioned medium, and this induction was significantly abrogated by monoclonal anti-MIF antibody, suggesting that MIF is an upstream regulator of TNFalpha release. CONCLUSION: These data represent the first demonstration of the cytokine MIF in human autoimmune disease and suggest MIF as a potential therapeutic target in RA.

Aged↗
PubMed1999

Up-regulation of macrophage migration inhibitory factor in acute renal allograft rejection in the rat.

Recent studies have identified a key role for macrophage migration inhibitory factor (MIF) in a number of immune cell-mediated diseases. The current study investigated the potential role of MIF in acute allograft rejection. Lewis rats underwent bilateral nephrectomy and then received an orthotopic DA renal allograft or an orthotopic Lewis renal isograft. Groups of six animals were killed at day 1 or 5 after transplantation. No immunosuppression was used. Animals receiving a renal allograft exhibited severe rejection on day 5, as shown by high levels of serum creatinine, very low rates of creatinine clearance, and severe tubulitis with a dense macrophage and T cell infiltrate. In contrast, isografts had normal renal function on day 5 with no histological evidence of rejection. Northern blotting showed that renal MIF mRNA expression was unchanged at day 1, but was increased 3.5-fold on day 5. In situ hybridization showed a marked increase in MIF mRNA expression by tubular cells and MIF mRNA expression by many infiltrating mononuclear cells in day 5 allografts. Immunostaining confirmed an increase in tubular MIF protein expression, particularly in areas of severe tubular damage with prominent leucocytic infiltration. Double staining showed that many infiltrating macrophages and T cells expressed the MIF protein in day 5 allografts. There was only a minor increase in MIF expression in day 5 isografts, demonstrating that neither surgical injury nor stress cause significant up-regulation of MIF expression in allograft rejection. In conclusion, this study has demonstrated that local MIF production is specifically increased in acute renal allograft rejection. These results suggest that MIF may play an important role in the cellular immune response mediating acute allograft rejection.

Acute Disease↗
PubMed1999

Rapid evaluation of S-100 serum levels. Case report and comparison to previous results.

The aim of this case report is to describe the time course of S-100 serum levels of a patient, after severe head injury, whose blood sample could be drawn very soon after injury. The results were compared to a group of patients in which a correlation between S-100 serum levels and outcome after traumatic brain injury could be demonstrated. Blood samples were taken on admission (mean 2.3 hours), 6, 12 and 24 hours after trauma and then every 24 hours up until and including the fifth day. The outcome was estimated on discharge using the Glasgow Outcome Scale. The S-100 serum level of the patient described in the case report with a favourable outcome had initially risen to 10.0 micrograms/l and showed a rapid decline. In the previous group, patients with unfavourable outcome had a S-100 serum level of 7 micrograms/l mean concerning the first probe (after 2.3 hours mean) compared to 1.5 micrograms/l mean (after 2.23 hours mean) in patients with favourable outcome (p < 0.05). In comparison to the literature, there seems to be differences regarding the enzyme liberation in stroke and head injury. Therefore, S-100 serum levels need to be interpreted with regard to collection time and underlying pathology.

Adult↗
PubMed1999

Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury.

BACKGROUND: S-1OOB, a protein of astroglial cells, is described as a marker for neuronal damage. Reliable outcome prediction from severe head injury is still unresolved. Clinical scores such as the Glasgow Coma Scale score (GCS) and diagnostic scores such as the Marshall Computed Tomographic Classification are well established and investigated, but there are still some concerns about these tools. The aim of this study was to investigate the predictive value of the initial serum level of S-100B compared with the predictive value of the GCS score and the Marshall Computed Tomographic Classification to outcome after severe head injury. METHODS: Forty-four patients with severe head injury (GCS score < 9) were included. Blood samples were drawn within 1 to 6 hours of injury. After a period of 11 months, their outcome was correlated by using the Glasgow Outcome Scale. Patients with an S-100B serum level above 2 microg/L, a GCS score between 3 and 5, and a computed tomographic scan in the categories 4 to 6 are predicted to have an unfavorable outcome. The predictive values of these tools were calculated according to these definitions. RESULTS: The protein S-100B had with 17% the lowest total misclassification rate. When compared with the GCS score and Marshall Computed Tomographic Classification the S-100B serum level calculated on admission had the highest positive predictive value (87%) and negative predictive value (77%). CONCLUSION: The serum level of S-100B calculated within 1 to 6 hours of a severe head injury is a useful additional outcome predictor.

Adolescent↗
PubMed1999

An essential role for macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma.

BACKGROUND: Macrophage migration inhibitory factor (MIF) has been shown to counterregulate glucocorticoid action and to play an essential role in the activation of macrophages and T cells in vivo. MIF also may function as an autocrine growth factor in certain cell systems. We have explored the role of MIF in the growth of the 38C13 B cell lymphoma in C3H/HeN mice, a well-characterized syngeneic model for the study of solid tumor biology. MATERIALS AND METHODS: Tumor-bearing mice were treated with a neutralizing anti-MIF monoclonal antibody and the tumor response assessed grossly and histologically. Tumor capillaries were enumerated by immunohistochemistry and analyzed for MIF expression. The effect of MIF on endothelial cell proliferation was studied in vitro, utilizing both specific antibody and antisense oligonucleotide constructs. The role of MIF in angiogenesis also was examined in a standard Matrigel model of new blood vessel formation in vivo. RESULTS: The administration of anti-MIF monoclonal antibodies to mice was found to reduce significantly the growth and the vascularization of the 38C13 B cell lymphoma. By immunohistochemistry, MIF was expressed predominantly within the tumor-associated neovasculature. Cultured microvascular endothelial cells, but not 38C13 B cells, produced MIF protein and required its activity for proliferation in vitro. Anti-MIF monoclonal antibody also was found to markedly inhibit the neovascularization response elicited by Matrigel implantation. CONCLUSION: These data significantly expand the role of MIF in host responses, and suggest a new target for the development of anti-neoplastic agents that inhibit tumor neovascularization.

Animals↗
PubMed1999

Spermine inhibition of monocyte activation and inflammation.

The innate immune system functions as a defensive front line against pathogenic invasion, but the proinflammatory products of activated monocytes and macrophages (e.g., TNF and NO) can also injure normal cells. Anti-inflammatory mediators restrain the innate immune response and prevent excessive collateral tissue damage. Spermine, a ubiquitous biogenic polyamine, specifically and reversibly suppresses the synthesis of monocyte proinflammatory cytokines. This may provide a counterregulatory mechanism to restrain monocyte activation in injured or infected tissues and in tumors where spermine levels are significantly increased. Here we show that monocyte spermine uptake was significantly increased following lipopolysaccharide stimulation. The polyamine analogue 1, 4-bis(3-aminopropyl)-piperazine (BAP) inhibited LPS-stimulated monocyte spermine uptake via the "nonselective" polyamine transporter. BAP fully restored macrophage TNF synthesis despite the presence of spermine, indicating that the mechanism of monocyte deactivation by spermine is dependent on spermine uptake. Administration of BAP in vivo significantly augmented the development of carrageenan-induced paw edema and nitric oxide release. Thus, endogenous spermine normally inhibits the innate inflammatory response by restraining macrophages.

Animals↗
PubMed1998

Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes.

We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of these cells in vivo, we examined the expression of type I collagen and cytokine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but not CD14+ monocytes or CD90+ T cells expressed mRNA for type I collagen. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1, and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-alpha. By contrast, IL-1beta decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1beta may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.

Animals↗
PubMed1998

Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis.

OBJECTIVE: Recent studies have established an essential role for macrophage migration inhibitory factor (MIF) in T cell and macrophage activation, both of which are characteristics of rat adjuvant arthritis. This study investigated the role of MIF in early adjuvant arthritis. METHODS: MIF was detected in rat synovium by immunohistochemistry and enzyme-linked immunosorbent assay using specific monoclonal antibodies (MAb). Anti-MIF MAb treatment was administered, and the effects on clinical aspects of adjuvant arthritis were assessed. RESULTS: MIF was absent from normal rat synovium prior to adjuvant injection, but was detectable on day 4 after injection (6 days before the onset of clinical disease) and was colocalized with ED-1+ macrophages throughout the evolution of the disease. Levels of MIF were increased in established adjuvant arthritis sera, and adjuvant arthritis synovial macrophages released MIF at a mean +/- SEM concentration of 607.9 +/- 201.5 pg/ml. Anti-MIF treatment led to profound, dose-dependent inhibition of the adjuvant arthritis clinical score, paw swelling, and synovial lavage leukocyte numbers (P < 0.001), and also resulted in reduced synovial macrophage and T cell accumulation. CONCLUSION: These findings demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.

Animals↗
PubMed1998

Brain ischemia detected by tissue-PO2 measurement and the lactate-oxygen index in head injury.

The aim of the study was to find out whether there is a correlation between the tissue-pO2 (ti-pO2) measurement and the lactate-oxygen index (mLOI). Both methods are to be considered as methods to detect brain ischemia. We studied 7 patients after severe head injury (GCS < 8) with a jugular bulb catheter and a tissue pO2 probe. Possible ischemia was defined with ti-pO2 below 10 mm Hg and mLOI above 0.08. 67 pairs of ti-pO2 and corresponding mLOI were found. In 5 cases out of the 7 cases with a ti-pO2 below 10 we found a pathological mLOI above 0.08. In 11 cases with pathological mLOI values, however, we found only 6 cases of decreased ti-pO2. The absolute values did not correlate. The sensitivity to predict normal values is above 85% with both methods. The specifity to predict ischemia is low (< 72%). The reason is the fact, that ti-pO2 is a local method in contrast to the mLOI values. In cases of diffuse brain injury without major contusions there should be a correlation between ti-pO2 and the mLOI.

Brain↗