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Biomedical subjects

M Soares

Publications and source records attributed to M Soares.

At least 37 records · Page 2Linked to original sources
PubMed1998

The purloined Ladder: its place in lesbian history.

This essay traces The Ladder from its initial publication in October 1956 as the official vehicle of the lesbian rights group the Daughters of Bilitis to its final issue as a privately published magazine in August 1972. By excerpting quotes from key lesbian figures of the time, it seeks to trace The Ladder's history from amateur newsletter to a more polished literary magazine--a reflection of the shift in the culture's perspective of itself from "variant" to "lesbian."

Female↗
PubMed1998

[Anticardiolipin antibodies in patients with cerebral vascular accident].

Through a prospective controlled study of 81 non-selected patients with acute cerebral ischemia, admitted to the hospital over the period of one year, anticardiolipin antibodies (IgG and IgM) were compared to a control group with the objective of evaluating their place as independent risk factors for stroke. Stroke patients' anticardiolipin antibodies (ACA) were again measured at 6 months and compared to the initial values. At the time of the acute ischemic event, the patients' mean ACA IgM was significantly higher than that of the controls and, at 6 months, the patients' mean ACA IgG and IgM were significantly lower than at the time of stroke. Furthermore, through logistic regression analysis and taking into account all other stroke risk factors present in the patient population, ACA IgM's association with stroke was statistically significant. We conclude that ACA may have a role in the pathogenesis of acute cerebral ischemia. Their cross-reactivity with anti-oxidised LDL antibodies may constitute a link between atherosclerosis and thrombosis.

Adult↗
PubMed1997

Xenogeneic endothelial cells activate human prothrombin.

BACKGROUND: Delayed xenograft rejection is characterized by platelet activation and fibrin deposition and is thought to occur independently of complement activation. We have therefore investigated the potential for xenogeneic endothelial cells (EC) to regulate the conversion of prothrombin to thrombin, a central component of the final common pathway of coagulation and an important platelet agonist. METHODS AND RESULTS: Quiescent porcine aortic EC (PAEC) were found to convert high levels of human prothrombin to thrombin (0.234+/-0.019 IU/ml) when compared with human aortic EC (0.017+/-0 IU/ml, 30-min time point, chromogenic assay; P<0.001). PAEC activation by human complement resulted in comparable levels of thrombin generation. Prothrombin conversion by PAEC as determined by generation of F1+2 (1.909+/-0.119 nmol/L) and formation of thrombin-antithrombin III complexes (125.611+/-6.373 microg/L) was significantly greater than the matched human aortic EC values (F1+2: 1.539+/-0.03 nmol/L, P<0.001; thrombin-antithrombin III: 1.833+/-0.104 microg/L, P<0.001). Sequential analysis of prothrombin activation by PAEC indicated generation of the intermediate meizothrombin followed by autolytically accelerated thrombin formation. Subsequent experiments established important cross-species' incompatibilities with respect to porcine thrombomodulin interaction with human thrombin and protein C in that PAEC had a reduced capacity to generate activated human protein C in vitro. CONCLUSION: These observations indicate a potentially important molecular barrier involving blood coagulation that may impact on the planned clinical application of porcine transgenic organs.

Animals↗
PubMed1997

Effects of leflunomide and deoxyspergualin in the guinea pig-->rat cardiac model of delayed xenograft rejection: suppression of B cell and C-C chemokine responses but not induction of macrophage lectin.

BACKGROUND: If complement (C) activation is prevented or the host is C depleted, discordant vascularized xenografts undergo delayed xenograft rejection (DXR), characterized by graft infiltration by macrophages (MO) and natural killer (NK) cells, endothelial cell activation, and widespread fibrin deposition. Given a lack of effect of T cell-directed therapies on development of DXR, we evaluated two novel agents, 15-deoxyspergualin (DSG) and leflunomide (LEF), with reported anti-B-cell and/or anti-MO actions. METHODS: DSG and LEF were administered to C-depleted, splenectomized rat recipients of guinea pig cardiac xenografts, and their effects on graft survival and production of anti-guinea pig antibodies were determined. Serial intragraft events were studied by immunohistology using monoclonal antibodies to rat leukocytes, cytokines, and novel proteins, including rat MO lectin, which in other systems is important to MO binding, activation, and target cell killing. RESULTS: Median graft survival was 62 hr in cobra venom factor (CVF)-treated controls versus 108 hr (DSG), 129 hr (LEF), and 120 hr (DSG and LEF; all groups P<0.01 vs. CVF alone). LEF and DSG each decreased (immunoglobulin M [IgM]) or abrogated (IgG) posttransplant production of anti-guinea pig antibodies. Immunohistologic studies showed that each agent also inhibited graft infiltration by NK and T cells, and expression of various cytokines, including the chemokine monocyte chemoattractant protein-1 (MCP-1), but did not affect the tempo or extent of MO infiltration. Consistent with this, the rapid induction of MO lectin postxenografting, and induction of MO lectin by rat MO exposed to guinea pig cells in vitro, were unaffected by therapy with DSG and/or LEF. CONCLUSIONS: LEF or DSG along with CVF can result in the longest prolongation of xenograft survival yet reported in this model, in conjunction with a dampening of host mononuclear cell responses, including suppression of B cell activation. However, the persistent influx of MO in this model, despite lack of C-, Fc receptor- or apparent chemokine-dependent mechanisms, suggests the presence of additional mechanisms for cell recruitment and activation. It was of importance that, in this regard, although MO depletion is technically difficult and can lead to undesired effects, the demonstration of rapid MO lectin induction postxenografting indicates opportunities for blockade of MO recruitment and functions during DXR by use of anti-MO lectin monoclonal antibodies or administration of competing sugars.

Animals↗
PubMed1997

A collaborative approach to the diagnosis of a lethal short limb skeletal dysplasia.

We report a male infant with a lethal short limb Skeletal Dysplasia, born in a District Hospital in the South of Portugal. Local paediatricians investigated clinical and radiographical data. At the Perinatal Pathology Unit of the Egas Moniz hospital the diagnosis of Atelosteogenesis type II was proposed by the Clinical Geneticist and was supported by histopathological findings. Only a collaborative approach turned possible the diagnosis of this unusual entity. Atelosteogenesis type II and Diastrophic Dysplasia are closely related diseases, with similarities in phenotypic and histopathological presentation. Recently, these similarities were extended to molecular levels. The DNA analysis, in progress, will be able to establish a final diagnosis for this affected family.

Abnormalities, Multiple↗
PubMed1996

Glucocorticoid-mediated repression of NFkappaB activity in endothelial cells does not involve induction of IkappaBalpha synthesis.

Repression of NFkappaB-dependent gene expression is one of the major elements of immunosuppression by glucocorticoids. Protein-protein interactions between the glucocorticoid receptor and NFkappaB have been characterized and shown to be a possible mechanism of mutual inhibition of transactivation properties. More recently, glucocorticoid-mediated induction of IkappaBalpha, an inhibitor of NFkappaB, has been described in monocytes and lymphocytes; an increase in IkappaBalpha mRNA and protein resulted in inactivation and cytosolic retention of NFkappaB. Thus, rather than the physical interaction between the glucocorticoid receptor and NFkappaB, the up-regulation of IkappaBalpha was presented as the key element in immunosuppression by glucocorticoids. In contrast, we show that the IkappaBalpha pathway is not involved in glucocorticoid-mediated inhibition of NFkappaB activity in endothelial cells. Although transcriptional activation by NFkappaB was significantly reduced in the presence of glucocorticoids, we did not detect induction of IkappaBalpha protein that could prevent nuclear translocation of NFkappaB upon stimulation with lipopolysaccharide or tumor necrosis factor alpha. Furthermore, treatment with glucocorticoids did not seem to affect the transcription rate or mRNA stability of IkappaBalpha. We therefore conclude that, although induction of IkappaBalpha expression by glucocorticoids seems to be of importance in monocytes and lymphocytes, it cannot explain inhibition of NFkappaB-dependent gene expression in endothelial cells. Our results emphasize the relevance of physical interaction between the glucocorticoid receptor and NFkappaB in endothelial cells and thus in suppression of inflammation by glucocorticoids.

Animals↗
PubMed1996

Modulation of rat B cell differentiation in vivo by the administration of an anti-mu monoclonal antibody.

We have previously described that the administration of an anti-mu mAb to adult rats results in the total depletion of circulating IgM. In the present study we analyzed the cellular mechanisms involved in the depletion of circulating IgM by the administration of an anti-mu mAb to adult rats. Administration of an anti-mu mAb to adult rats led to the cross-linking and internalization of membrane IgM (mIgM) but not mIgD on the surface of B cells. This correlated with the depletion in spleen and bone marrow of immature and short-lived Thy-1+ CD45RB+ B cells and with the specific depletion of the number of IgM but not IgA-, IgG1-, IgG2a-, and IgG2b-secreting cells in the spleen, which paralleled the depletion of circulating IgM but not IgA, IgG1, IgG2a, and IgG2b. In contrast to the other IgG subclasses, IgG2c-secreting cells as well as circulating IgG2c were increased by 10-fold in anti-mu-treated rats as compared with controls. Finally, anti-mu-treated rats showed an inhibition in the generation of primary thymus-dependent as well as thymus-independent Ab responses as compared with controls. In conclusion, the data presented suggests that anti-mu administration in adult rats results in the early arrest of B cell differentiation in the bone marrow, which causes the down-regulation of IgM production. Furthermore, anti-mu mAb administration directly or indirectly activates a particular subset of mature B cells, which differentiates into IgG2c-secreting cells.

Animals↗
PubMed1996

Patterns of nitric oxide synthase expression in the developing superior colliculus.

Nitric oxide (NO) is synthesized in cells of both the central and peripheral nervous system and has been implicated in several forms of synaptic plasticity. The enzyme that produces NO, nitric oxide synthase (NOS), can be visualized in the brain by the reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry technique (NADPH-d). We have used NADPH-d activity to detect the presence of NOS-positive cells in the developing rat superior colliculus. Our results showed that NOS is present in cells and neuropil in the developing and adult rat superior colliculus. The first NOS-positive cells appeared at postnatal day 7 and were weakly stained. The number and intensity of the NOS-positive cells increased progressively during the following days reaching a maximum at postnatal day 15. By the end of the third postnatal week, both the number and intensity of stained cells showed an adult-like pattern. The NOS-positive cells showed a Golgi-like morphology and we have found that all cell types present in the superior colliculus express the enzyme. The expression of NOS by tectal cells parallels the functional development of the retino-collicular and cortico-tectal projections and suggest that nitric oxide synthase-positive cells might be involved in this process. In this review we highlighted some of the recent descriptions of the expression of NOS in the mammalian visual system with emphasis in the superior colliculus and correlate these findings with several developmental events taking place in this structure.

Animals↗
PubMed1994

In vivo IgM depletion by anti-mu monoclonal antibody therapy. The role of IgM in hyperacute vascular rejection of discordant xenografts.

Xenoreactive natural antibodies (XNA) and complement activation are thought to be the 2 main factors responsible for the hyperacute vascular rejection (HVR) of discordant xenografts. The aim of this work was to study the role of IgM XNA in the HVR of guinea pig to rat cardiac xenografts, a discordant model. Adult LOU/C rats were depleted of circulating IgM and therefore of IgM XNA using an anti-mu mAb (mouse anti-rat IgM mAb 7 [MARM-7]). Rats were injected with 10 mg and 5 mg of MARM-7 at days -3 and -1, respectively, and guinea pig cardiac xenografts were performed on day 0. Control animals were injected on the same days with 10 mg and 5 mg of anti-alpha mAb (MARA-1) or equivalent volumes of PBS. Xenografts were performed on day 0. Guinea pig cardiac xenograft survival time was significantly prolonged in IgM-depleted animals (62 min, P < 0.01) compared with controls using PBS (18 min) or MARA-1 mAb (12 min). This prolongation was not due to a decrease in the complement activity in IgM-depleted rats, since no significant variation of the C1q, C4, C3, and C5 complement hemolytic activity was observed between control and treated animals before HVR. Prolongation of the xenograft survival time in the MARM-7-treated group was correlated with an undetectable serum level of IgM and IgM XNA and a lack of IgM XNA deposits on the rejected xenograft vascular endothelium. Contrarily, both IgM-depleted and control animals showed C3 deposits on the rejected xenograft vascular endothelium and myocardium, as well as diffuse deposits of IgG2a XNA. Although HVR was not abrogated by the depletion of IgM XNA, our data indicate that IgM is implicated in the HVR and that the anti-mu approach is a potential therapeutic treatment for discordant xenografts. Finally, we suggest that other factors such as IgM-independent activation of complement might be one of the mechanisms responsible for the pathogenesis of HVR in the guinea pig to rat xenograft model.

Animals↗
PubMed1994

Preformed antibody and complement rebound after plasma exchange: analysis of immunoglobulin isotypes and effect of splenectomy.

UNLABELLED: Splenectomy (Sx) has been proposed to attenuate post-PE (plasma exchange) rebound of isoagglutinins and xenogenic (XG) antibody (Ab) in both ABO-incompatible allografts and discordant xenografts. This study analyses the qualitative nature and kinetics of serum immunoglobulins as well as complement resynthesis after PE in sham-operated (PE) and splenectomized (PE+Sx) syngeneic LOU/C rats; non-PE sham-operated or splenectomized animals were used as controls. PE was performed in unanesthetized, unheparinized rats. Immunoglobulin isotypes and subclasses (IgM, IgG1, IgG2 alpha, IgG2b) of total circulating Ab were measured pre-PE and up to 21 days post-PE, using ELISA (enzyme-linked immunosorbent assay) and specific mouse antirat monoclonal Ab. Antiguinea-pig (GP) XG Ab (IgM, IgG2a) serum levels were measured using cellular ELISA with cultured GP endothelial cells as targets. Sx alone significantly reduced XG IgM serum levels (p < 0.0001). Maximal rebound of total and XG IgM was observed on day 3 post-PE, reaching 674% and 187% of the pre-PE levels, respectively; these overshoots were entirely suppressed by Sx (p < 0.005 for total IgM; p < 0.0001 for XG IgM). Total IgG2a, IgG2b and IgG1 as well as XG IgG2a serum levels did not show significant overshoot post-PE. The activity of the complement classical pathway (mean +/- SD), assessed by CH50, was decreased at 51 +/- 19% of basal value 15 minutes after PE, and had returned to baseline level by day 2 post-PE with or without Sx. IN CONCLUSION: (1) Six alone significantly reduced XG IgM serum levels; (2) early post-PE Ab rebound was mainly observed for IgM; (3) both total and XG IgM rebound was inhibited by Sx. This suggests that Sx probably removes a significant proportion of IgM producing cells undergoing post-PE stimulation. These data provide a rationale for combining PE with Sx in ABO-incompatible and discordant XG transplantation.

Animals↗
PubMed1994

Depletion of IgM xenoreactive natural antibodies by injection of anti-mu monoclonal antibodies.

It is believed that IgM xenoreactive natural antibodies (XNA) and activation of complement are the two main effectors involved in the hyperacute rejection (HAR) of discordant xenografts, such as pig-to-primate kidney, liver or heart transplants. We have hypothesized that long-term depletion of circulating IgM XNA might be able to overcome HAR and induce the "accommodation" of pig-to-primate vascular discordant xenografts. Several techniques have been described to eliminate circulating XNA in primates but, up to now, none has been able to totally deplete these antibodies for a sufficiently long period of time in order to test the hypothesis of discordant xenograft "accommodation". Previous reports from our laboratory have shown that, in rodents, B-cell immunosuppression could be achieved by neonatal administration of anti-mu antibodies. Recently we have shown that administration of an anti-mu mAb, in adult rats, was able to totally deplete circulating IgM and IgM XNA, without immune complex disease. Furthermore, we have used different methods such as splenectomy, plasma exchange and an anti-B cell immunosuppressive agent mycophenylate mophetil (RS61443, Syntex, Palo Alto, USA) to pre-deplete circulating IgM before administration of anti-mu mAb (MARM-7) and showed that the effectiveness of anti-mu mAb to deplete circulating IgM was increased by 100-fold. Depletion of circulating IgM in adult rats by anti-mu mAb (MARM-7) was used as an experimental model to study the role of IgM XNA in the pathogenesis of HAR in guinea pig-to-rat cardiac xenografts. Our data show that IgM XNA play a major role in HAR, even if in this discordant combination direct activation of complement, probably through the alternative pathway, seems to be the main effector involved in HAR. We have analyzed the mechanisms of anti-mu depletion of circulating IgM in adult animals and shown that, besides anti-mu/IgM immune complex formation, depletion of circulating IgM results from the very significant inhibition of B-cell differentiation and secretion of IgM following in vivo crosslinking and internalization of surface IgM on B cells. As well, we provide evidence demonstrating that anti-mu mAb blocks B cells at an early stage of maturation, probably in the bone marrow. Furthermore, we have developed several rat anti-human and anti-baboon IgM mAb and tested their ability to deplete circulating IgM and IgM XNA in baboons, after splenectomy or splenectomy and plasma exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Counselling following diagnosis of fetal abnormality: a comparison between German, Portuguese and UK geneticists.

The principle of non-directiveness in genetic counselling is embraced by all relevant professional bodies. Little is known about the extent to which it is endorsed by geneticists, or incorporated into their clinical practice. The aim of the current study is to document how geneticists in three European countries, Germany, Portugal and the UK, report counselling women at risk for having children with a range of conditions. While geneticists in all three countries reported counselling in a largely non-directive style, this varied both across genetic conditions and between countries. German and Portuguese geneticists were significantly more directive than UK geneticists, although they differed in the way in which they were directive. German geneticists were more likely to encourage continuation of pregnancies, while Portuguese geneticists were more likely to encourage termination of affected pregnancies. There was no strong consensus on approaches to counselling for any of the genetic conditions, defined as agreement between 70% of all three groups of geneticists. Despite strong professional codes of non-directiveness, geneticists report being somewhat directive in some counselling situations. Future research needs to focus on what geneticists are trying to achieve in genetic counselling, how they actually counsel, and with what effects.

Abortion, Induced↗