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Behcet's disease (BD) was first described by Hippocrates in ancient Greece, and the disease is named after Hulusi Behcet, a Turkish dermatologist. It is a multisystem disorder with oral and genital ulcers, uveitis, and cutaneous, arthritic, and neurological manifestations. The rationale for investigating stress proteins in the pathogenesis of BD is that the diverse microbial and possibly autoimmune manifestations might be accounted for by stress proteins. This chapter reviews the evidence that the mycobacterial 65-kDa heat shock protein (hsp) and the homologous human mitochondrial 60-kDa hsp are involved in the pathogenesis of BD. Defibnnated blood samples from eight patients with BD were separated by Ficoll-Triosil density gradient centrifugation and monocyte-enriched cells were obtained by adherence to plastic dishes. T- and B-cell epitopes of the 65-kD mycobacterial and the 60-kD human mitochondrial hsp were mapped in patients with BD.

Two new species of the lampeye genus Hylopanchax are described from the Ivindo River basin in the Ogowe River drainage. Hylopanchax multisquamatus, new species, and Hylopanchax thysi, new species differ from congeners by the presence of a hyaline urogenital male papilla with small black spots and a dark brown reticulate pattern on the flanks of both males and females in preserved specimens. Hylopanchax multisquamatus, new species, is distinguished from congeners by the number of scales on the mid-longitudinal series (27-30 vs. 19-26, respectively) and by the relative anterior/posterior flank scale depth ratio (140-150% vs. 170-220%). Hylopanchax thysi, new species, is distinguished from all other congeners, except H. paucisquamatus, by having (30 vs. 31-33 vertebrae) and is further distinguished from H. multisquamatus, new species, by having a deeper caudal peduncle and much larger anterior flank scales. It is distinguished from H. paucisquamatus by the presence of a hyaline urogenital male papilla with small black spots and a dark brown reticulate pattern on the flanks of both males and females in preserved specimens. Osteological data of Hylopanchax are presented for the first time and an updated diagnosis is provided based on external morphology, colouration pattern, and osteology. An osteological comparison with closely related species belonging to the genera Procatopus, Hypsopanchax and 'Hypsopanchax' is presented. The presence of (i) a truncate and slightly downwards directed anterior process of the angulo-articular and (ii) a guitar-shaped lachrymal with both its anterior and posterior margins sharply curved are herein considered as diagnostic features of Hylopanchax. This article is protected by copyright. All rights reserved.

Three new ‘ Aphyosemion ’ species are described from the upper Louesse River in the Massif du Chaillu, Republic of the Congo, based on a combination of DNA, habitat preference, male colour pattern, and morphological data. ‘ Aphyosemion ’ cyanoflavum , new species, is a member of the ‘ A ’ . ogoense group. It differs from its congeners by a unique colour pattern and cephalic sensory system which contains a wide supra-orbital groove with large, densely pigmented anterior neuromasts and dark frontal neuromasts housed in one pit with one central anterior lobe. ‘ Aphyosemion ’ mandoroense , new species, and ‘ A ’ . cryptum , new species, are members of the ‘ A ’ . coeleste group. ‘ Aphyosemion ’ cryptum , new species, is in appearance very similar to ‘ A ’ . coeleste , but lacks the typical post opercular metallic green blotch and is generally larger in body size. Initial DNA analyses demonstrate that ‘ A ’ . cryptum, new species , is more closely related to ‘ A ’ . mandoroense , new species, than to ‘ A ’ . coeleste, despite similarity in appearance . ‘ Aphyosemion ’ cryptum, new species, and ‘ A ’ . coeleste occur syntopic in several locations in a sub-catchment of the upper Louesse system, however differ in microhabitat preference. ‘ Aphyosemion ’ mandoroense, new species, differs by male body and fin colour pattern from all species of the ‘ A ’ . coeleste group except ‘ A ’ . citrineipinnis . From the latter, it can be distinguished by the absence of red pigmentation and a dark grey to black margin in the unpaired fins.

A new procatopodid, assigned to the genus Poropanchax, is described from a wetland habitat located adjacent to the Inga Falls in Lower Congo. Poropanchax pepo, new species, is distinguished from all congeners by a combination of characters including a higher D/A ratio, rounded anal and dorsal fins, a humeral blotch in males, and the absence of a sharp ventral process on the basipterygium. The finding of a Poropanchax species in Lower Congo was unexpected, since the closest known congeneric population is located in northwestern Gabon, some 700 kilometers to the north. As recognized herein the genus Poropanchax is a clade comprised of five species geographically restricted to humid coastal regions of west and west-central Africa.

Aphyosemion teugelsi is described from specimens collected in a small creek in the upper Wamba River basin in the southwest of the Democratic Republic of the Congo not far from the Angolan border. This is ~400 km outside the known distribution area of the genus. It is distinguished from all other members of the genus Aphyosemion by the combination of broad black margins on all fins in males, a robust lower jaw, a more convex back, a large head with large eyes, a more anterior position of the dorsal fin relative to anal fin, and absence of extensions on the upper and lower caudal fin.

Objective— HSP60-specific T cells contribute to the development of the immune responses in atherosclerosis. This can be dampened by regulatory T cells activated via oral tolerance induction, and we explored the effect of oral tolerance induction to HSP60 and the peptide HSP60 (253 to 268) on atherosclerosis. Methods and Results— HSP60 and HSP60 (253 to 268) were administered orally to LDLr −/− mice before induction of atherosclerosis and resulted in a significant 80% reduction in plaque size in the carotid arteries and in a 27% reduction in plaque size at the aortic root. Reduction in plaque size correlated with an increase in CD4 + CD25 + Foxp3 + regulatory T cells in several organs and in an increased expression of Foxp3, CD25, and CTLA-4 in atherosclerotic lesions of HSP60-treated mice. The production of interleukin (IL)-10 and transforming growth factor (TGF)-β by lymph node cells in response to HSP60 was observed after tolerance induction. Conclusion— Oral tolerance induction to HSP60 and a small HSP60-peptide leads to an increase in the number of CD4 + CD25 + Foxp3 + regulatory T cells, resulting in a decrease in plaque size as a consequence of increased production of IL-10 and TGF-β. We conclude that these beneficial results of oral tolerance induction to HSP60 and HSP60 (253 to 268) may provide new therapeutic approaches for the treatment of atherosclerosis.

Fundulopanchax kamdemi, new species, is described from small swampy pools and rivulets of the Ndian and Akpa-Yafe River systems, Cameroon. F. kamdemi is distinguished from all other known Fundulopanchax species by a unique male coloration and from most congeners by a higher number of rays in dorsal and anal fins.Key words: Nothobranchiidae, Fundulopanchax kamdemi sp. nov., Western Central Africa, systematics

Three new species of the lampeye genus Hylopanchax are described from the central Congo basin: H. leki, new species, H. ndeko, new species, and H. moke, new species. These differ considerably in body shape from the two previously de- scribed species, H. stictopleuron and H. silvestris, with two deep bodied and one small and slender species. A redefinition of the diagnostic characters of the genus Hylopanchax is presented, including pronounced sexual dimorphism.

Immunosterilization is an attractive alternative to surgical castration. Gonadotropin-releasing hormone (GnRH) controls the production of the gonadotropins thereby having an orchestrating effect on the reproductive hormone cascade and spermatogenesis. Induction of neutralizing antibody can abrogate the effect of the hormone. Current GnRH-based vaccines often require strong adjuvants and/or multiple injections of the vaccines to overcome variability in the response. Heat shock proteins (hsp) have been used as carrier molecules because of their powerful intrinsic ability to enhance an immune response to associated antigens. A GnRH-analogue, GnRH-d6-Lys, was conjugated to recombinantMycobacterium tuberculosishsp70. Male BALB/c mice were immunized i.p. with GnRH-hsp70 in the mild adjuvant Ribi or in incomplete Freund’s adjuvant (IFA). The initial immunizations were done on pre-pubertal 3-week-old mice, with boosts at 5 and 8 weeks of age. The mice were killed at 10 weeks of age and GnRH-specific antibodies and serum testosterone levels measured. All the immunized mice mounted GnRH-specific antibody responses, with no difference in the mice immunized with GnRH-hsp70/Ribi or with GnRH-hsp70/IFA. There was substantial atrophy of the urogenital complex and significantly (P< 0.0005) reduced levels of testosterone-dependent testicular relaxin-like factor mRNA expression. Mice immunized with GnRH-hsp70/Ribi showed substantially reduced (P< 0.001) serum testosterone levels. These results indicate that hsp70 may serve as a particularly advantageous carrier for GnRH-based vaccines.

A new deep-bodied Hylopanchax species is described from the northwestern Congo basin. Hylopanchax paucisquamatus, new species, was collected in the Odzala-Kokoua National Park in the Likouala River drainage of the Republic of Congo. It differs from its congeners, including the deep-bodied H. leki and H. ndeko, by a unique combination of morphological characters, including low number of mid-longitudinal and transverse scales, number of dorsal-fin rays, and position of dorsal-fin origin in relation to anal-fin. It is the only deep-bodied species currently known outside the Kasaï River drainage.

Objective: To obtain more insight in the role of IGF-1 in cardiac remodeling and function after experimental myocardial infarction. We hypothesized that cardiac remodeling is altered in IGF-1 deficient mice, which may affect cardiac function. Methods: A myocardial infarction was induced by surgical coronary artery ligation in heterozygous IGF-1 deficient mice. One week after surgery, left ventricular function was analyzed, and parameters of cardiac remodeling were measured. Results: No significant difference in cardiac function was found between infarcted wildtype and knock-out animals, despite a marked reduction in capillarization and blunting of the hypertrophic response of the interventricular septum in the IGF-1 deficient group. Furthermore, decreased DNA synthesis and increased apoptosis rates were observed in the IGF-1 knock-out mice. Conclusion: IGF-1 deficient mice show preservation of cardiac function 1 week after MI, despite an altered cardiac remodeling process.

Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as a possible autoantigen. It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not from patients with other arthritides. Mice with established collagen- or pristane-induced arthritis developed IgG Abs to BiP. Although BiP injected in CFA failed to induce arthritis in several strains of rats and mice, including HLA-DR4+/−- and HLA-DR1+/+-transgenic animals, it completely inhibited the development of arthritis when given i.v. 1 wk before the injection of type II collagen arthritis. Preimmunization with BiP suppressed the development of adjuvant arthritis in Lewis rats in a similar manner. This is the first report of a mammalian chaperone that is an autoantigen in human RA and in experimental arthritis and that can also prevent the induction of experimental arthritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.

Background —Nebivolol is a β 1 -selective adrenergic receptor antagonist with proposed nitric oxide (NO)–mediated vasodilating properties in humans. In this study, we explored whether nebivolol indeed induces NO production and, if so, by what mechanism. We hypothesized that not nebivolol itself but rather its metabolites augment NO production. Methods and Results —Mouse thoracic aorta segments were bathed in an organ chamber. Administration of nebivolol did not affect NO production. When nebivolol was allowed to metabolize in vivo in mice, addition of plasma of these mice caused a sustained 2-fold increase in NO release. Interestingly, coadministration of a selective β 2 -adrenergic receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and Western blot analysis demonstrated the presence of β 2 - but not β 1 -adrenergic receptors on endothelial cells. In the absence of calcium, metabolized nebivolol failed to increase NO production, suggesting a role for calcium-dependent NO synthase. With digital fluorescence imaging, a rapid and sustained rise in endothelial cytosolic free Ca 2+ concentration was observed after administration of metabolized nebivolol, which also was abrogated by butoxamine pretreatment. Conclusions —In vivo metabolized nebivolol increases vascular NO production. This phenomenon involves endothelial β 2 -adrenergic receptor ligation, with a subsequent rise in endothelial free [Ca 2+ ] i and endothelial NO synthase–dependent NO production. This may be an important mechanism underlying the nebivolol-induced, NO-mediated arterial dilation in humans.