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Biomedical subjects

X Havaux

Publications and source records attributed to X Havaux.

26 records · Page 2Linked to original sources
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

Neovascularization in human coronary atherosclerotic lesions.

Neovessels within human coronary atherosclerotic lesions are frequently observed, but their pathophysiological significance is still subject to debate. Also, the origin of these vessels and their pathways in the arterial wall are not well-known. In this study, we describe the transmural pathway and the frequency of neovessels both in vivo and in autopsy cases. Atherosclerotic coronary arteries were obtained during autopsy in 10 subjects without previous cardiovascular symptoms. In 25 patients undergoing percutaneous intervention for either stable or unstable angina, plaque fragments were retrieved by directional coronary atherectomy. In the autopsy study, at least one coronary artery in each case showed some degree of neointimal proliferation, characterized by smooth muscle cells in a dense extracellular matrix. A neovascularization process was seen in 17.5% of the 40 samples analyzed. In 2 cases, the transmural pathway of the neovessels could be tracked: serial sections revealed the emergence of an arteriole from the adventitia of the coronary artery, its transmedial course as a capillary, and its opening into the coronary arterial lumen. In symptomatic patients who underwent atherectomy, neovessels were found in 1 of 9 patients with stable angina (11%) and in 8 of 16 patients with unstable angina (50%, P < 0.05). Mostly, the neovessels appeared as capillaries cut in their short axis. In 2 cases, however, the capillary was seen in its longitudinal axis, and its pathway could be traced through the atherosclerotic lesion to its opening in the coronary lumen, as in the autopsy study. Therefore, neovessels frequently develop in the atherothrombotic plaque, both in asymptomatic and anginal patients. In the latter group, the proliferation of neovessels is more frequent in acute coronary syndromes. These findings have several implications, in particular for percutaneous coronary angioplasty and related procedures, such as local drug delivery.

Adult↗
PubMed1995

Is acoustic shadowing at intracoronary ultrasound always the marker of intramural calcium accumulation?

Intracoronary ultrasound (ICUS) is increasingly used at catheterization to assess more precisely the severity of luminal narrowing, to delineate the composition of the atherosclerotic plaque, and to select the optimal therapeutic strategy. With this technique, a drop in signal intensity, known as acoustic shadowing, is usually equated with the presence of calcium in the plaque. We report the study of an atherosclerotic coronary artery showing intense acoustic shadowing at ICUS, but in which no calcium deposition could be evidenced at postmortem pathological analysis. This observation suggests a word of caution with regard to considering acoustic shadowing at ICUS as the reflection of superficial calcium deposition within a vessel wall.

Calcinosis↗
PubMed1995

A rat monoclonal anti-(human CD2) and L-leucine methyl ester impacts on human/SCID mouse graft and B lymphoproliferative syndrome.

The transfer of human peripheral blood mononuclear cells (hu-PBMC) from adult Epstein-Barr-virus(EBV)-seropositive donors in SCID (severe combined immunodeficiency) mice frequently leads to the development of a human B lymphoproliferative syndrome (hu-BLPS). Therefore, as 90% of adult potential donors are EBV-seropositive, efforts have to be made to avoid the occurrence of this B lymphoproliferative disorder. McCune et al. [Science 241:1632 (1988)] used human fetal organs for a human SCID graft. This system does not give rise to hu-BLPS but human fetal organs are much less available than peripheral blood leucocytes. The experiments reported in this paper show how crucial is the presence of functional T lymphocytes for a graft to take and for development of hu-BLPS in hu-PBMC-reconstituted SCID mice, since inhibition of T lymphocyte by a rat anti-(human CD2) monoclonal antibody (LO-CD2a) during the first 10 days of the graft prevents successful engraftment of human normal lymphocytes as well as hu-BLPS in SCID mice. The transfer of B cells alone or B cells plus monocytes in SCID mice does not permit either long-term engraftment or development of hu-BLPS. We also demonstrate that hu-PBMC treated with L-leucine methyl ester are less susceptible to the development of hu-BLPS after engraftment in SCID mice than are untreated hu-PBMC. The mechanism of action of L-leucine methyl ester on these cells is discussed.

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

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

A new method for rat accessory hepatic transplantation--the cervical approach.

Current methods for accessory liver transplantation in the rat require a high degree of microsurgical expertise and long training before success is achieved. We present a simpler method of arterialized accessory liver transplantation using the cervical vessels for revascularization of the transplanted liver with the cuff technique, which is useful for studies of liver preservation, reperfusion injury, and liver regeneration. After classical 70% hepatectomy is performed on the graft, the right common carotid artery is anastomosed to the donor aorta, the distal right external jugular vein is anastomosed to the donor portal vein, and the proximal right external jugular vein is anastomosed to the donor supradiaphragmatic inferior vena cava. The skin is not closed over the cervically transplanted liver (CTL). This method was used 30 times for periods of up to 6 h with a 90% success rate. CTL structure and function, as revealed by histology, bile flow rates, biliary bilirubin concentrating capacity, membrane potential, enzyme activity and distribution, have shown the CTL to be a structurally normal and metabolically active graft. In conclusion, the cervical approach to arterialized accessory liver transplantation is simple, and should prove useful for studies of liver preservation, reperfusion, regeneration, physiology, and toxicology.

Animals↗