Atypical left paraduodenal hernia.
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Abdominal Pain↗
Biomedical subjects
M Bustos
Publications and source records attributed to M Bustos.
[Headache caused by cerebral angiopathy during labor with epidural analgesia].
A 29-year-old woman presented projectile vomiting followed by frontal headache, immediately upon receiving epidural analgesia for labor. The clinical picture persisted until expulsion. Although no leaking of spinal fluid into the needle or epidural catheter had been observed, post-dural puncture headache was diagnosed. The postpartum persistence of symptoms and the patient's generally worsening condition indicated the need for more thorough physical examination, which revealed signs of neurological involvement. Those findings and imaging studies (computed tomography of the brain, transcranial Doppler and magnetic resonance angiography) established a final diagnosis of postpartum cerebral angiopathy. Although epidural analgesia is increasingly requested by women entering labor, it is not a risk-free procedure. We describe a relatively unknown clinical entity, postpartum cerebral angiopathy, that developed during epidural analgesia for labor and that was initially believed to be a complication of the analgesic technique.
Adult↗
[Tattoos along the lumbar median line and epidural anesthesia].
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Analgesia, Obstetrical↗
Platelet-mediated activation of endothelial cells: implications for the pathogenesis of transplant rejection.
BACKGROUND: Platelets exert their normal functions at sites of endothelial disruption by plugging discontinuities in blood vessels and secreting products that promote thrombosis, inflammation, and the healing of wounds. Whether platelets might induce these changes in xenograft blood vessels, leading to development of acute vascular rejection, has been uncertain. METHODS: To examine the role of human platelets in modulation of xenograft endothelium, pig endothelial cells were treated with human platelets. RESULTS: Treatment of quiescent porcine endothelial cells with human platelets modulated the endothelial cells. Whereas resting human platelets caused little change in normal porcine endothelial cells, platelets activated with small amounts of thrombin induced striking changes in the endothelial cells, including the induction of tissue factor activity, the expression of E-selectin, and the secretion of endothelin-1. These changes were induced, at least in part, by interleukin-1 (IL-1) associated with the platelet surface and were modified by the secretion of transforming growth factor-beta (TGF-beta). CONCLUSION: These findings may explain how the activation of platelets at an early point in the rejection of vascularized organ xenografts or in chronic diseases might contribute to thrombotic, ischemic, and inflammatory changes characteristic of an organ xenograft undergoing rejection.
Animals↗
Alpha(v)beta(3) integrin-mediated adenoviral transfer of interleukin-12 at the periphery of hepatic colon cancer metastases induces VCAM-1 expression and T-cell recruitment.
We previously reported that systemic injection of recombinant adenovirus resulted in a rim of gene transduction around experimental liver tumor nodules. This zone of higher infection is dependent on the alpha(v)beta(3) integrin, acting as an adenovirus internalization receptor, which is overexpressed in tissues surrounding liver metastases. When a recombinant adenovirus encoding interleukin-12 (AdCMVIL-12) is given into a subcutaneous tumor nodule in mice also bearing concomitant liver tumors, a fraction of AdCMVIL-12 reaches the systemic circulation and infects liver tissue, especially at the malignant/healthy tissue interface. As a result of the expression at this location of the interleukin-12 transgenes, VCAM-1 is induced on vessel cells and mediates the recruitment of adoptively transferred anti-tumor cytolytic T-lymphocytes. These studies provide mechanistic explanations for the potent therapeutic synergy observed between interleukin-12 gene transfer and adoptive T-cell therapy.
Adenoviridae↗
Immune complex formation after xenotransplantation : evidence of type III as well as type II immune reactions provide clues to pathophysiology.
Rejection of renal and cardiac xenografts is initiated when natural antibodies of the recipient bind to donor endothelium, activating complement on the surface of endothelial cells. Pulmonary xenotransplants, however, reveal less evidence of antibody binding and complement activation and, in contrast to other xenografts, fare worse when the complement of the graft recipient is depleted. Accordingly, we asked whether distinct immunochemical reactions might occur after xenotransplantation of the lung and what implications such reactions might have for pulmonary pathophysiology. Analysis of serum from baboons after transplantation with porcine lungs revealed complexes containing baboon IgM and porcine von Willebrand factor. The baboon IgM in these complexes was specific for Galalpha1-3Gal. Immune complexes were also seen, albeit to a lesser extent, in the serum of kidney and heart xenotransplant recipients. Deposits of porcine von Willebrand factor and baboon C3 were detected in livers and spleens of transplanted baboons. These results indicate pulmonary xenotransplantation eventuates in formation of immune complexes and in the deposition of those complexes at distant sites. Immune complex formation could explain the peculiar fate of xenoreactive antibodies after pulmonary xenotransplantation and might contribute to the pathophysiology of the lung and systemic changes not previously considered a complication of xenotransplantation.
Animals↗
The irreplaceable image: A patient with subacute degeneration of the spinal cord secondary to pernicious anemia.
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Aged↗
CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is a lung inflammatory disorder characterized by accumulation of T lymphocytes. However, the mechanisms implicated in this process remain undefined. We examined the expression of dendritic cell (DC)-derived CC chemokine 1 (CK1)/CCL18, a chemokine putatively involved in naive T cell recruitment, in lungs from 10 patients with HP, 9 patients with idiopathic pulmonary fibrosis (IPF), and 20 healthy lungs. CCL18 was measured by real-time quantitative PCR and localized in lungs by in situ hybridization and immunohistochemistry. CCL18 expression was significantly increased in lungs affected by HP in comparison with lungs affected by IPF (2,085+/-393 vs. 1,023+/-110; P<0.05) and controls (2,085+/-393 vs. 467+/-94; P<0.01). Macrophages, DCs, and alveolar epithelial cells were the main sources of CCL18. There was a direct correlation between the levels of tissue CCL18 and the number of lymphocytes in the bronchoalveolar lavage fluids. High levels of CCL18 were detected in the subacute rather than the chronic phase of HP. These findings suggest a role for CCL18 in the pathogenesis of HP.
Alveolitis, Extrinsic Allergic↗
Altered intragraft immune responses and improved renal function in MHC class II-deficient mouse kidney allografts.
BACKGROUND: During renal allograft rejection, expression of MHC class II antigens is up-regulated on the parenchymal cells of the kidney. This up-regulation of MHC class II proteins may stimulate the intragraft alloimmune response by promoting their recognition by recipient CD4+ T cells. In previous studies, absence of donor MHC class II antigens did not affect skin graft survival, but resulted in prolonged survival of cardiac allografts. METHODS: To further explore the role of MHC class II antigens in kidney graft rejection, we performed vascularized kidney transplants using donor kidneys from A(beta)b-deficient mice that lack MHC class II expression. RESULTS: At 4 weeks after transplant, GFR was substantially depressed in control allografts (2.18+/-0.46 ml/min/kg) compared to nonrejecting isografts (7.98+/-1.62 ml/min/kg; P<0.01), but significantly higher in class II- allografts (4.38+/-0.60 ml/min/kg; P<0.05). Despite the improvement in renal function, class II- allograft demonstrated histologic features of acute rejection, not unlike control allografts. However, morphometric analysis at 1 week after transplantation demonstrated significantly fewer CD4+ T cells infiltrating class II- allografts (12.8+/-1.2 cells/mm2) compared to controls (25.5+/-2.6 cells/mm2; P=0.0007). Finally, the intragraft profile of cytokines was altered in class II- allografts, with significantly reduced expression of Th2 cytokine mRNA compared to controls. CONCLUSIONS: These results support a role of MHC class II antigens in the kidney regulating immune cells within the graft. Further, effector pathways triggered by class II antigens promote renal injury during rejection.
Animals↗
Liver damage using suicide genes. A model for oval cell activation.
Liver regeneration from the facultative hepatic stem cells, the oval cells, takes place in situations in which liver regeneration from pre-existing hepatocytes is prevented. Different models have been used to stimulate oval cell response. Many of them involve the use of carcinogenic agents with or without partial hepatectomy. In this study we show that adenovirus-mediated gene transfer of the suicide gene thymidine kinase followed by ganciclovir administration caused hepatotoxicity of variable intensity. Rats with moderate elevation in serum transaminases recovered normal liver architecture few weeks after adenovirus injection. In contrast, rats with severe liver damage exhibited a marked and persisting activation of oval cells accompanied by ductular hyperplasia. In some rats, such lesion eventually evolved to cholangiofibrosis and in one rat to cholangiocarcinoma. Deposition of fibronectin and increased number of hepatic stellate cells were found in association with oval cells and cholangiofibrotic lesions. Hepatocyte growth factor was hyperexpressed in the livers with intense oval cell response or ductular proliferation, suggesting a participation of this factor in those lesions. In summary, our data demonstrate activation of oval cell response after gene transfer of thymidine kinase followed by ganciclovir administration. These findings indicate that high doses of this therapy causes liver damage together with an impairment in hepatocellular regeneration.
Adenoviridae↗
Evidence of immunocomplex formation in pulmonary xenografts.
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Animals↗
A blood-tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds.
We have evaluated gene transfer efficiency to tumor nodules in diethylnitrosoamine (DENA)-induced hepatocellular carcinoma (HCC) in rats using adenoviral vectors administered by three different routes: intraportal, intra-arterial and intratumoral injection. Our results showed that intraportal infusion could not transduce tumor nodules greater than 1 mm in diameter while the intra-arterial route allowed transduction of nodules up to 2-5 mm in diameter. Tumors greater than this size were resistant to transduction by intravascular route, but could be transduced by direct intratumoral injection, indicating that the obstacle preventing gene transfer to tumor cells was mainly at the level of tumor vasculature and not at the level of neoplastic cells. We have studied the extracellular matrix in tumoral lesions to assess whether nodules with different size and histological pattern have different profiles in relation to transduction efficacy. Immunohistochemical detection showed a high expression of fibronectin (FN), laminin (LN) and alpha-smooth muscle actin (alpha-SMA) in those large HCC, which were resistant to adenoviral infection. Intra-arterial infusion of vasoactive compounds (histamine, angiotensin II or nitric oxide donor nitroglycerin) before vector administration enhanced gene transfer to tumor nodules that were poorly transduced without pre-treatment. Nitroglycerin was active to enhance transduction of large tumors with trabecular or pseudoglandular histological pattern, which were impermeable to adenoviral vectors even after histamine or angiotensin treatments. Our data indicate the presence of a physical barrier between blood and neoplastic cells, which prevents transduction of the tumor by vectors given by the intravascular route. The thickness and impermeability of the barrier increases as the tumor nodule grows. Vasoactive compounds may be of value in gene therapy of liver cancer by increasing transduction efficiency by intravascularly administered vectors.
Actins↗
Extracorporeal shockwave lithotripsy of 2000 urinary calculi with the modulith SL-20: success and failure according to size and location of stones.
PURPOSE: We analyzed the successes and failures of SWL in the treatment of 2016 urinary calculi stratified according to size and position in the urinary tract. METHODS: All the patients were treated with a Modulith SL-20 (Storz Medical). RESULTS: The overall stone-free rate, regardless of the size and position of the stone, was 87.4%. The rate was different for kidney and ureteral stones. The stone-free rate observed for the different positions of the calculi within the kidney was upper calix 89.2%, middle calix 90.5% lower calix 84.8%, and renal pelvis 86.0%. For staghorn calculi, the stone-free rate was 60.0%. The stone-free rate for the different positions of calculi within the ureter was: upper ureter 84.3%, iliac ureter 82.4%, and pelvic ureter 91.0%. For calculi >24 mm, the retreatment rate increased, and the success rate dropped sharply. CONCLUSION: Extracorporal shockwave lithotripsy should be the first therapeutic option for urinary calculi of <24 mm regardless of their position in the urinary tract.
Adolescent↗
Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis.
Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis.
Animals↗
Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas.
Stimulation of the antitumor immune response by dendritic cells (DC) is critically dependent on their tightly regulated ability to produce interleukin-12 (IL-12). To enhance this effect artificially, bone marrow (BM)-derived DC were genetically engineered to produce high levels of functional IL-12 by ex vivo infection with a recombinant defective adenovirus (AdCMVIL-12). DC-expressing IL-12 injected into the malignant tissue eradicated 50-100% well established malignant nodules derived from the injection of two murine colon adenocarcinoma cell lines. Successful therapy was dependent on IL-12 transfection and was mediated only by syngeneic, but not allogeneic BM-derived DC, indicating that compatible antigen-presenting molecules were required. The antitumor effect was inhibited by in vivo depletion of CD8+ T cells and completely abrogated by simultaneous depletion with anti-CD4 and anti-CD8 mAbs. Mice which had undergone tumor regression remained immune to a rechallenge with tumor cells, showing the achievement of long-lasting systemic immunity that also was able to reject simultaneously induced concomitant untreated tumors. Tumor regression was associated with a detectable CTL response directed against tumor-specific antigens probably captured by DC artificially released inside tumor nodules. Our results open the possibility of similarly treating the corresponding human malignancies.
Adenocarcinoma↗
Chronic rejection of mouse kidney allografts.
BACKGROUND: Chronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined. METHODS: To explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and examined the effects of altering the expression of donor major histocompatibility complex (MHC) antigens on the development of chronic rejection. RESULTS: We found that long-surviving mouse kidney allografts develop pathological abnormalities that resemble chronic rejection in humans. Furthermore, the absence of MHC class I or class II antigens did not prevent the loss of graft function nor alter the pathological characteristics of chronic rejection. Expression of transforming growth factor-beta (TGF-beta), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-beta up-regulation was significantly blunted in MHC-deficient grafts. Nonetheless, these differences in TGF-beta expression did not affect the character of chronic rejection, including intrarenal accumulation of collagens. CONCLUSIONS: Reduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-beta expressed in the allograft. This suggests that the severity of chronic rejection is independent of the level of MHC disparity between donor and recipient and the level of TGF-beta expression within the allograft.
Animals↗
Fate of antigen in xenotransplantation: implications for acute vascular rejection and accommodation.
Antigen down-modulation plays a critical role in xenotransplants involving humoral responses against the Forssman antigen and may play a role in the long-term survival of ABO-incompatible allografts. The present study investigates the fate of porcine antigens in pig-to-primate xenotransplantation. Human antibodies bound to the glycocalyx of cultured porcine aortic endothelial cells as judged by electron microscopy and were shed from the cell surface in a complex with fibronectin, a glycoprotein that is found in the apical membrane glycocalyx of cultured cells. Antibody was shed in a metabolically dependent process with a t(1/2) of 2 to 3 hours. However, the amount of antigen on the cell surface did not change appreciably within 24 hours, suggesting that antigen modulation did not occur. Over the ensuing days, antigen expression decreased, although the change was always less than 50% of baseline. Changes in antigen expression were due for the most part to changes in expression of alpha-galactosyl residues. Consistent with results obtained in vitro, antigen expression in porcine organ transplants remained at approximately the baseline level as determined by immunofluorescence analysis of IgM binding to graft endothelium. If, as these results suggest, antigen is not down-modulated in pig-to-primate xenotransplantation, then therapies aimed at prolonged xenograft survival must focus on antibody or genetic manipulation of antigen expression.
Animals↗
Modulation of eicosanoid metabolism in endothelial cells in a xenograft model. Role of cyclooxygenase-2.
Lipid inflammatory mediators are thought to play a critical role in the pathogenesis of vascular injury. Among the events which might cause the synthesis of eicosanoids in blood vessels is activation of the complement. To evaluate how complement might influence eicosanoid metabolism, we investigated endothelial cells exposed to xenoreactive antibodies and complement, as might occur in rejecting xenografts where severe vascular injury is a typical feature. While resting porcine aortic endothelial cells released only prostaglandin (PG) I2, endothelial cells stimulated with xenoreactive antibodies and complement released PGE2 and thromboxane A2 (TXA2), in addition to increased amounts of PGI2. This alteration in eicosanoid metabolism was associated with induction of cyclooxygenase (Cox)-2 and thromboxane synthase, but not Cox-1. Unlike results seen in other systems, the upregulation of Cox-2 and the subsequent release of eicosanoids by endothelial cells was not directly induced by complement but rather required production of IL-1alpha, which acted on endothelial cells as an autocrine factor. Since eicosanoids have a potent effect on inflammation, vascular tone and platelet aggregation, we postulated that the abnormalities in eicosanoid release induced by xenoreactive antibodies and complement might provide one explanation for the vascular injury, focal ischemia, and thrombosis observed in acute vascular rejection and other vasculitides mediated by complement.
Animals↗