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Biomedical subjects

B Simmen

Publications and source records attributed to B Simmen.

17 recordsLinked to original sources

S100A4 is expressed at site of invasion in rheumatoid arthritis synovium and modulates production of matrix metalloproteinases.

The metastasis-associated protein S100A4 promotes the progression of cancer by regulating the remodelling of the extracellular matrix. The expression of S100A4 in vivo is shown and the functional role of S100A4 in the pathogenesis of osteoarthritis and rheumatoid arthritisis is explored. The expression of S100A4 in rheumatoid arthritis, osteoarthritis and normal synovial tissues was determined by immunohistochemistry. The expression of matrix metalloproteinase (MMP) mRNA was measured in rheumatoid arthritis and osteoarthritis synovial fibroblasts treated and untreated with S100A4 oligomer by real-time polymerase chain reaction. Levels of released MMPs were confirmed by ELISA in cell culture supernatants. S100A4 protein was expressed in rheumatoid arthritis and osteoarthritis synovial tissues, in contrast with normal synovium. S100A4 up regulated MMP-3 mRNA in rheumatoid arthritis synovial fluid, with a peak after 6 h. This resulted in release of MMP-3 protein. MMP-1, MMP-9 and MMP-13 mRNA were also up regulated in synovial fluid, but with different kinetics. MMP-14 mRNA showed no change. Thus, S100A4 protein is expressed in synovial tissues of patients with rheumatoid arthritis and osteoarthritis in contrast with healthy people. It induces the expression and release of MMP-3 and other MMPs from synovial fluid. The data suggest that S100A4-producing cells could be involved in the pathogenesis of osteoarthritis and rheumatoid arthritis, including pannus formation and joint destruction.

Arthritis, Rheumatoid↗

Discrepancy between mRNA and protein expression of tumour suppressor maspin in synovial tissue may contribute to synovial hyperplasia in rheumatoid arthritis.

OBJECTIVE: To investigate the expression of maspin in RA synovial tissue and compare it with the expression in osteoarthritis (OA) and normal synovial tissue (NS). METHODS: Using specific primers for maspin, a 237 bp fragment was amplified from cDNA obtained from cultured RA, OA, and normal synovial fibroblasts (SF) by RT-PCR. Additionally, mRNA expression levels were determined quantitatively by real time PCR. mRNA expression of maspin was investigated on snap frozen and paraffin embedded synovial tissue sections by in situ hybridisation. Immunohistochemistry was used to identify the cell type expressing maspin. SDS-PAGE and western blotting were performed to evaluate the protein expression in cultured SF. To confirm protein synthesis in situ, immunohistochemistry with specific anti-maspin antibodies was performed in synovial tissue sections of patients with RA. RESULTS: RT-PCR showed expression of maspin in all cDNA samples from cultured SF. Maspin mRNA was found to be decreased in RA SF twofold and 70-fold compared with OA SF and NS SF, respectively. Maspin mRNA was expressed in RA, OA, and normal synovial tissue. Importantly, maspin transcripts were also found at sites of invasion into cartilage and bone. At the protein level, maspin could be detected in RA and, less prominently, OA SF. In RA synovial tissue, maspin protein was detected in only a few synovial lining cells. CONCLUSION: Maspin is expressed intensively in RA SF at the mRNA level, but only slightly at the protein level, possibly owing to down regulation of maspin; this may contribute to the hyperplasia of synovial tissue in RA.

Adult↗

New perspectives on taste and primate evolution: the dichotomy in gustatory coding for perception of beneficent versus noxious substances as supported by correlations among human thresholds.

In various environments where primates are presently observed, as well as in forests and savannas which have been inhabited by australopithecines and early hominids, there are (or there have been presumably) categories of substances eliciting taste signals associated with stereotyped responses. Such is the case for various soluble sugars of fruits and nectars, attracting consumers, and for several plant compounds in which bitter or strongly astringent properties have a repulsive effect. The occurrence of such classes of tasty substances among natural products appears to be related to the evolutionary trends that shaped primate sensory perception (for detecting either beneficent or potentially noxious substances) in the context of a long history of coevolution between animals and plants. Here, we present original psychophysical data on humans (412 individuals aged 17-59 years) as an analogy with which to test recent evidence from electrophysiology in nonhuman primates (Hellekant et al. [1997] J. Neurophysiol. 77:978-993; Danilova et al. [1998] Ann. N.Y. Acad. Sci. 855:160-164) that taste fibers can be grouped into clusters of "best-responding fibers" with two more specific clusters, one for sugars and one for quinine and tannins. The collinearity found between human taste responses (recognition thresholds) for fructose and sucrose, as well as for quinine and tannins, is presented and discussed as another evidence of the two-direction evolutionary trend determining taste sensitivity. Salt perception appears to be totally independent of these trends. Accordingly, the appreciation of a salty taste seems to be a recent culturally learned response, and not a primary taste perception. The very existence of primary tastes is discussed in the context of evolutionary trends, past and present.

Adolescent↗

Taste thresholds and suprathreshold responses to tannin-rich plant extracts and quinine in a primate species (Microcebus murinus).

Theories of plant chemical defenses discriminate between quantitative digestibility reducers (e.g., tannins) and qualitative toxins (e.g., alkaloids). Since the differential effect on taste of these compounds is poorly known, we recorded ingestive responses of a primate species, Microcebus murinus, to four tannin-rich plant extracts and to quinine, by using the behavioral method of the "two-bottle test." The efficiency of tannic extracts at precipitating protein was measured with the blue BSA method. Inhibition taste thresholds for tannins added to a moderately sweet solution varied between 0.25 and 2 g/l. The threshold for quinine hydrochloride was 0.32 g/l. The profiles of the response/concentration curves established for these astringent and bitter substances were similar, with maximal inhibition of consumption occurring for near-threshold concentrations. The large amounts of quinine required to deter this small-bodied species from feeding were unexpected, given its unspecialized frugivorous/insectivorous diet. We propose that the taste responses of Microcebus to tannins have been shaped in relation to the widespread occurrence of efficient polyphenols in food plants, while low responsiveness to quinine reflects a low risk of ingesting toxic alkaloids when feeding on ripe fruits and insects.

Animals↗

Fruits, foliage and the evolution of primate colour vision.

Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines.

Animals↗

Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis.

OBJECTIVE: To study the expression of messenger RNA (mRNA) for different membrane-type matrix metalloproteinases (MT-MMPs) and compare their expression pattern in rheumatoid arthritis (RA) and normal synovium. METHODS: Polymerase chain reaction (PCR) with specific primers was performed to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synovial tissue and synovial fibroblasts from 10 patients with RA and 4 subjects without arthritis. In addition, in situ hybridization with digoxigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the synovium of these subjects. MT-MMP-expressing cells were characterized by immunohistochemical double labeling with anti-CD68 monoclonal antibodies. RESULTS: Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, in situ hybridization showed considerable differences in the expression pattern of the different MT-MMPs in RA synovium. MT1- and MT3-MMP mRNA were highly expressed in both the lining and the sublining layer, with more intense staining in the lining. Immunohistochemical double labeling demonstrated the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining. Normal synovial samples showed only limited staining for all MT-MMPs. CONCLUSION: Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.

Arthritis, Rheumatoid↗

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Journal Article↗

Frugivory and colour vision in Alouatta seniculus, a trichromatic platyrrhine monkey.

It is a long-standing hypothesis that primate trichromacy evolved to help fruit-eating primates find fruits amongst leaves. We measured the reflectance spectra of fruits eaten by a trichromatic primate, Alouatta seniculus, in the rainforest of French Guiana, as well as those of the leaves that form the natural background to fruits. We develop a method of specifying these natural colour signals in a chromaticity diagram appropriate for A. seniculus. By treating the task facing frugivorous monkeys as a signal detection task, we show that the spectral tuning of the L and M cone pigments in A. seniculus is optimal for detecting fruits amongst leaves.

Alouatta↗

Sweet and bitter taste discrimination in primates: scaling effects across species.

The adaptive nature of taste discrimination has been questioned on the basis that marked differences in taste thresholds for soluble sugars across mammals may not correspond to distinct dietary tendencies and further imply inaccurate prediction of the energetic value of food. Appropriate models of the evolution of taste, however, require not only consideration of adaptations to diet but also recognition of phylogenetic and allometric effects. Here, we analyse these factors in primates exhibiting various diets and covering a wide range of body weights. Taste thresholds for sucrose and fructose are negatively related to body weight overall but are commonly similar in closely related species irrespective of dietary specialisations. By contrast, major interspecific differences in the discrimination of quinine hydrochloride are observed in the absence of any allometric effect. We propose that this asymmetrical differentiation of sweet and bitter taste discrimination reflects divergent evolutionary trends for meeting energy requirements and for avoiding noxious substances.

Animals↗

[Taste thresholds and above-threshold responses to fructose solution in relation to diet in Callitrichidae primates].

Taste thresholds and consumption responses to above-threshold concentrations of fructose solutions were determined in eight callitrichid primate species using the "two-bottle preference test". Although taste thresholds are relatively similar across species, above-threshold responses may differ considerably between marmosets and tamarins. As fructose concentration increases, the rate of consumption increases less for most marmoset species (Cebuella and Callithrix spp.) than for Goeldi's monkey (Callimico) and tamarins (Saguinus and Leontopithecus spp.). It is proposed that distinct shapes of the curves illustrating these responses characterize species in terms of global taste system adaptations to different diets.

Animals↗

[The thumb saddle joint].

In the management of patients with osteoarthritis of the carpometacarpal joint of the thumb, good to very good results can be achieved both subjectively and objectively by surgical intervention. In young patients who do manual hard work and have isolated post-traumatic osteoarthritis of the trapeziometacarpal joint, the treatment method of choice is still arthrodesis. However, in women with postclimacteric osteoarthritis, which is very frequent, we prefer arthroplasty. Resection of the trapezium is a technique only used in selected cases, as it results in considerable loss of stability and strength. We prefer Silastic interposition arthroplasty to cemented total replacement. In patients with major involvement of the joints at the trapezium (especially where it connects with the scaphoid), the treatment of choice is implantation of a Swanson trapezium prosthesis, accompanied by surgical stabilization of the soft tissue. The good results we have achieved with this method, as reported in this paper, also justify its application in the future. In patients with isolated osteoarthritis of the carpometacarpal joint of the thumb we shall use the modified Swanson prosthesis more frequently in the future.

Adult↗

[Recurrence frequency following traumatic shoulder dislocation].

99 cases of primary traumatic shoulder dislocation were evaluated in regard of the influence of the time of immobilization on recurrency. 3 weeks of strict immobilization gave a recurrency rate as low as 6.4% whereas a shorter immobilization resulted in 12% of recurrency within 1--6 years. A survey from 46 other clinics as well as the literature has given no evidence of clear rules of treatment and thus the discussion of treatment remains open.

Adult↗

[Results of surgical treatment of acute knee joint injuries after winter sport accidents].

From 1974 to 1976 140 patients with knee joint injuries required immediate surgical treatment. 119 of these patients have been reexamined 1 to 3 years after operation, 83 by the authors. Clinical findings, indication for operation, operative procedures and the criteria for analysis of the late results are discussed. Good and satisfactory results were found in 96% of the cases. The results after reconstruction of the medial collateral ligament are excellent, 39 of 41 operatively treated patients showing a good result. After combined reconstruction of collateral and cruciate ligaments in 2/3 of the cases good results were obtained. Complications occurred in two cases requiring further surgery. The importance of intensive physiotherapeutical training until full rehabilitation of the injured joint was stressed.

Athletic Injuries↗