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M Espejo

Publications and source records attributed to M Espejo.

17 recordsLinked to original sources
PubMed2004

Incidence of acute cellular rejection and non-cellular rejection in cardiac transplantation.

BACKGROUND: Rejection continues to be one of the leading causes of death during the first year after cardiac transplantation. With the advent of more potent immunosuppressive therapies, the incidence of graft rejection has been reported to be decreasing. Yet, this trend has not been well established due to differences in the interpretation of and the protocols for endomyocardial biopsy specimens. Additionally, the incidence of humoral (noncellular) rejection has not been adequately addressed. METHODS: Six thousand one hundred thirty endomyocardial biopsy specimens in 487 cardiac transplant recipients during the first year posttransplantation from 1990 to 2000 were reviewed to assess the incidences of acute cellular and treated noncellular rejection episodes. Cellular rejection was defined as ISHLT grades 3-4; noncellular rejection as a 20% decrease in echo LVEF, cardiac index <2.0, and/or inotropic support associated with ISHLT grades 0-2 necessitating treatment. RESULTS: The incidence of noncellular rejection has remained relatively unchanged at approximately 20% (P=nonsignificant for all years); in contrast, there has been a significant decrease (P <.001) in the incidence of cellular rejection from 54% to 5%. CONCLUSION: The incidence of noncellular rejection in cardiac transplant recipients has remained unchanged through the 1990s despite improved immunosuppressive therapies, which have significantly decreased the incidence of acute cellular rejection. There appears to be a need for newer immunosuppressive agents to effectively treat noncellular rejection. Clinical trials using allograft rejection as a major endpoint will need to increase the enrollment of patients to achieve adequate power to demonstrate differences between study groups.

Follow-Up Studies↗
PubMed2001

CD8+ lymphocytes augment chronic rejection in a MHC class II mismatched model.

UNLABELLED: Chronic rejection, or cardiac allograft vasculopathy (CAV), remains the leading cause of late death in heart transplant recipients. The precise role and contributions of T lymphocyte subsets to CAV development remains unknown. METHODS: Donor hearts from B6.C-H2bm12 mice were transplanted into T lymphocyte subset knockout recipients and T lymphocyte-reconstituted nude recipients. No immunosuppression was used. Intimal proliferation was measured morphometrically. In vitro studies were performed to analyze the donor-specific activation status of recipient CD8+ lymphocytes by examining cellular proliferation, interleukin-2 secretion, and interleukin-2Ralpha expression. Intracellular cytokine staining assay was performed to determine both the profile and source of intragraft cytokines. RESULTS: Hearts transplanted into wild-type recipients developed severe CAV by 24 days. Intimal lesions were absent in the hearts that were transplanted into nude and CD4-/- knockout mice (containing CD8+ lymphocytes). In contrast, the donor hearts in CD8-/- knockout recipients (containing CD4+ lymphocytes) developed CAV, but significantly less than in wildtype. Adoptive transfer of T lymphocyte subset populations into nude recipients confirmed that CAV was absolutely contingent on CD4+ lymphocytes, and that CD8+ lymphocytes played an additive role in intimal lesion progression in the presence of CD4+ lymphocytes. Although CD8+ lymphocytes alone did not cause CAV in vivo, we demonstrated that MHC class II disparate alloantigens activated CD8+ lymphocytes both in vivo and in vitro. Finally, both CD4+ and CD8+ lymphocytes contributed to the intragraft IL-2 and IFN-gamma production. CONCLUSIONS: In this MHC class II mismatched murine model, CAV is a T lymphocyte dependent event, and absolutely contingent on the presence of CD4+ lymphocytes. Furthermore, CD8+ lymphocytes (1) are activated by MHC class II disparate antigens and (2) play a significant role in the progression of lesion development. Finally, both CD4+ and CD8+ lymphocytes contribute to CAV development via secretion of IFN-gamma, a known mediator of CAV in this model.

Animals↗
PubMed2000

[Orofaciodigital syndrome associated with agenesis of the pituitary gland].

UNLABELLED: Oral-facial digital syndrome (OFDS) consists of a group of heterogeneous genetic disorders with different patterns of inheritance. These disorders share facial, oral and digital abnormalities. At least 11 types of this syndrome have been described (I-IX) and the association between OFDS type II and absent pituitary has recently been reported in the case of two brothers. OBJECTIVE: 1. To describe the case of patients with OFDS associated with the absence of the hypophysis and panhypopituitarism. 2. To analyse whether the association between the agenesis of the hypophysis with OFDS represents a new type of this syndrome. PATIENT: An 11-month-old male infant presented with a malformation syndrome with oral (Gothic palate, lobulated tongue with lateral frenulae and hamartomas) facial (a small nose with flattened nasal root and hypoplastic nostrils, small facial skeleton, high forehead, low-implanted ears, stenosis of the choana) and digital malformations (poly- and clinodactyl hands and feet) typical of OFDS. In addition to these findings, at the age of 11 months he had growth retardation (length - 5.9 SD), obesity, mild psychomotor delay, a single upper incisor, micropenis and undescended testes. Endocrinologic studies showed combined GH, TSH, LH and FSH deficiency. Cranial magnetic resonance imaging showed a smooth sella turcica, lacking the pituitary gland, and the absence of the normal sign of neurohypophysis. Replacement therapy with GH and 1-thyroxine was started. SUMMARY: We report a patient with the clinical characteristics of OFDS type II, associated with the absence of hypophysis and panhypopituitarism. CONCLUSION: The infrequent association of agenesis of the pituitary gland and panhypopituitarism with OFDS, and the previous report of two brothers with this syndrome and the same association, suggests that this is a new type of OFDS.

Abnormalities, Multiple↗
PubMed1999

Exposure of foetal mesencephalic cells to bone morphogenetic protein-2 enhances the survival of dopaminergic neurones in rat striatal grafts.

The transplantation of foetal mesencephalic cells (FMC) into the brain striatal system is an emerging treatment for Parkinson's disease, despite of the relatively poor survival of implanted cells. The ability of neurotrophic factors to regulate neurone survival and differentiation suggests they could be used to enhance the success of cerebral grafts. We analyzed the effect of pre-treatment of FMC suspensions with bone morphogenetic protein-2 (BMP-2) (50 ng/ml) prior to grafting into the striatum of 6-hydroxydopamine lesioned rats. The viability of a FMC suspension was enhanced in vitro by BMP-2. Four weeks after transplantation, the number of dopaminergic neurones was higher and their morphology more developed in grafts pre-treated with BMP-2, compared with non-pre-treated grafts and rats showed a significant reduction in the turning behaviour test. Thus, the pre-treatment of FMCs with BMP-2 should be considered, together with other neurotrophic factors, as a procedure for transplantational treatment of Parkinson's disease.

Animals↗
PubMed1999

Caspase inhibition protects nigral neurons against 6-OHDA-induced retrograde degeneration.

6-Hydroxydopamine (6-OHDA) administered intrastriatally to adult rats in a single injection causes neurodegeneration of the nigrostriatal pathway and loss of > 50% of dopamine neurons in substantia nigra pars compacta 30 days after administration. The death of nigral neurons occurs, at least partially, by a caspase-mediated mechanism. The nigral loss of dopaminergic neurons could be prevented by stereotaxical administration of zVAD.fmk, a caspase inhibitor, into the substantia nigra, indicating that 6-OHDA-induced nigrostriatal degeneration involves caspase activation. These results suggest that caspases are probably involved in neurodegenerative chronic processes such as Parkinson's disease and might be considered as possible targets in the treatment of such neurological disorders.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Degeneration and gliosis in rat retina and central nervous system following 3,3'-iminodipropionitrile exposure.

3,3'-Iminodipropionitrile (IDPN) exposure causes a neurofilamentous axonopathy and olfactory, audiovestibular and visual toxicity. Many events relevant to these effects and the neurotoxic properties of nitriles as a class remain to be elucidated. We characterized the gliosis associated with the IDPN-induced retinal degeneration in comparison to other effects on the visual and central nervous systems. Gliosis was quantified using an ELISA for the intermediate filament protein, glial fibrillary acidic protein (GFAP). IDPN (0-400 mg kg-1 day-1x3 days, i.p.) caused corneal opacity and dose- and time-dependent increases in retinal GFAP, up to 26-28 fold of control values at 4 weeks post-exposure; a second peak occurred at 16 weeks. In contrast, GFAP peaked at 1 week in olfactory bulbs (OB), cingulate cortex and hippocampus. Cerebellum and striatum showed no gliosis. Retinal dopamine decreased within 2 weeks. Delayed GFAP increases occurred in superior and inferior colliculi. Retina and superior colliculi also showed increased [3H]PK-11195 binding. Histological analysis demonstrated progressive degeneration and gliosis in retina and colliculi. Taken together, the data indicate that primary and secondary degenerative events occur in the retina, and that this retinal degeneration induces GFAP increases in retina and superior colliculus. In addition, GFAP assays demonstrated that the retinal toxicity of IDPN is enhanced by CCl4 hepatotoxicity and blocked by methimazole inhibition of flavin-mono-oxygenases, similarly to its ototoxicity. GFAP assays also indicated that neither vestibulotoxic doses of crotononitrile nor olfatotoxic doses of dichlobenil damage the retina. The data support the use of GFAP assays for assessing the retinal toxicity of IDPN and other nitriles.

Animals↗
PubMed1999

Bone morphogenetic protein-2 promotes dissociated effects on the number and differentiation of cultured ventral mesencephalic dopaminergic neurons.

Bone morphogenetic proteins (BMPs) are a family of growth differentiation factors which induce bone formation from mesenchymal cells. These proteins are members of the transforming growth factor-beta super-family. The expression of BMPs in the nervous system as well as in other tissues has been reported. In this study, we show that the presence of BMP-2 resulted in a dose-dependent increase in the number of tyrosine hydroxylase-immunoreactive ventral mesencephalic cells after 7 days in serum-free medium cultures. A maximal response was elicited at 10 ng/mL. BMP-2 also increased the number of primary neurites and branch points as well as the length of the longest neurite in a dose-dependent manner, with a maximal effect at 1 ng/mL. In contrast, BMP-2 did not modify the number or the function of GABAergic neurons. On the other hand, we observed stimulation of proliferation and morphological changes in glial cells (astrocytes become more fibrous shaped) in the presence of a high BMP-2 concentration (100 ng/mL), but not with lower doses, suggesting that the neurotrophic effect in dopaminergic neurons is not mediated by astroglial cells. This is consistent with the fact that the BMP-2 effect on dopaminergic neurons was observed even when the cultures were treated with alpha-aminoadipic acid to exclude the presence of glial cells. In summary, our data indicate that BMP-2 is a potent neurotrophic factor for ventral mesencephalic dopaminergic cells in culture.

Animals↗
PubMed1998

7-Nitroindazole prevents dopamine depletion caused by low concentrations of MPP+ in rat striatal slices.

A significant loss of dopamine was found in rat striatal slices incubated with 1-methyl-4-phenylpyridinium ion (MPP+) at a concentration of 2 microM or higher. The addition of 7-nitroindazole, a specific inhibitor of neuronal nitric oxide synthase (nNOS), prevented this effect on dopamine when the concentration of MPP+ was between 2-5 microM, but not at higher concentrations. This protection was reproduced with other less specific NOS-inhibitors, such as nitro-arginine and nitro-arginine methylester. 7-nitroindazole did not protect against the dopamine depletion caused by the non-specific mitochondrial chain blocker rotenone. Neither MPP- nor rotenone significantly increased the nitrite concentration in striatal slices, measured as an index of nitric oxide production. The basal production of nitric oxide may be enough to trigger the dopamine depletion at very low concentrations of MPP+, probably acting synergistically with cytosolic calcium increase. Higher concentrations of MPP+ are toxic by themselves without the mediation of nitric oxide. The inhibition of nNOS may protect against dopamine loss at early stages of a neurodegenerative process, and it could then be considered in the treatment or prevention of neurodegenerative human processes such as Parkinson's disease.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Intrastriatal grafts of fetal mesencephalic cell suspensions in MPP+-lesioned rats: a microdialysis study in vivo.

The striatum of rats was lesioned by unilateral administration of MPP+. Two weeks later, a suspension of fetal mesencephalic cells (FMC), obtained from 14-day rat embryos, was injected into the lesioned striatum. Two weeks after grafting, the success of implantation and recovery of dopamine function were assessed by tyrosine hydroxylase immunocytochemistry (TH) and the measurement of striatal dopamine content. In addition, the extracellular concentrations of dopamine and dopamine metabolites were studied by microdialysis in vivo before and after perfusion of MPP+ to induce dopamine release from vesicular stores. TH+ cell bodies were seen in the lesioned grafted striata, indicating that fetal cells survived in these striata. In addition, there was a marked increase in TH-immunoreactivity in the neuronal fibers and terminals in the area surrounding the cell implant, suggesting a compensatory response of the host tissue which may involve fiber sprouting. Grafting induced a recovery in indices of dopamine function, including recovery in dopamine content, and basal and MPP+-induced dopamine release. Thus, grafts of FMC may provide a significant recovery of dopamine function in MPP+-lesioned striata.

1-Methyl-4-phenylpyridinium↗
PubMed1996

Early effects of basic fibroblast growth factor on foetal rat mesencephalic cell suspensions.

Mesencephalic cell suspensions are used, experimentally but also clinically, to compensate for neurological deficiencies, by implantation into the striatum. Here, we have studied the metabolism of mesencephalic cell suspensions obtained from rat embryos by measuring heat dissipation, oxygen consumption, ATP and lactate production. The effect of basic fibroblast growth factor (bFGF) at a 50 ng/ml concentration on these parameters was studied in order to assess the effect of in vitro exposure of cell suspensions to this trophic factor. Heat production and oxygen consumption were low, as could be expected from an immature nervous tissue, and they further decreased after addition of bFGF. This trophic factor decreased the total ATP concentration and increased the lactate production. The viability of the cell suspensions was reduced by nearly a half, 2 h after the addition of bFGF, and numerous fragmented nuclei were observed. It seems that, in contrast to the neuroprotective effect of bFGF on mesencephalic cultures and nigrostriatal neurons, this factor could have an initial sorting effect in the development of mesencephalic structures.

Acridine Orange↗
PubMedDate not supplied

Increased survival of dopaminergic neurons in striatal grafts of fetal ventral mesencephalic cells exposed to neurotrophin-3 or glial cell line-derived neurotrophic factor.

The transplantation of fetal mesencephalic cell suspensions into the brain striatal system is an emerging treatment for Parkinson's disease. However, one objection to this procedure is the relatively poor survival of implanted cells. The ability of neurotrophic factors to regulate developmental neuron survival and differentiation suggests they could be used to enhance the success of cerebral grafts. We studied the effects of neurotrophin-3 (NT-3) or glial cell line-derived neurotrophic factor (GDNF) on the survival of dopaminergic neurons from rat fetal ventral mesencephalic cells (FMCs) implanted into the rat striatum. Two conditions were tested: (a) incubation of FMCs in media containing NT-3 and GDNF, prior to grafting, and (b) co-grafting of FMCs with cells engineered to overexpress high levels of NT-3 or GDNF. One week after grafting into the rat striatum, the survival of TH+ neurons was significantly increased by pretreatment of ventral mesencephalic cells with NT-3 or GDNF. Similarly, co-graft of ventral mesencephalic cells with NT-3- or GDNF-overexpressing cells, but not the mock-transfected control cell line, increased the survival of graft-derived dopaminergic neurons. Interestingly, we also found that co-grafting of GDNF-overexpressing cells was less effective than NT-3 at improving the survival of fetal dopaminergic neurons in the grafts, and that only GDNF induced intense TH immunostaining in fibers and nerve endings of the host tissue surrounding the implant. Thus, our results suggest that NT-3, by strongly enhancing survival, and GDNF, by promoting both survival and sprouting, may improve the efficiency of fetal transplants in the treatment of Parkinson's disease.

3T3 Cells↗