The proposed synovitis score is based on well-defined, reproducible histopathological criteria and may contribute to diagnosis in rheumatic and non-rheumatic joint diseases.
Mammalian retinae have rod photoreceptors for night vision and cone photoreceptors for daylight and colour vision. For colour discrimination, most mammals possess two cone populations with two visual pigments (opsins) that have absorption maxima at short wavelengths (blue or ultraviolet light) and long wavelengths (green or red light). Microchiropteran bats, which use echolocation to navigate and forage in complete darkness, have long been considered to have pure rod retinae. Here we use opsin immunohistochemistry to show that two phyllostomid microbats, Glossophaga soricina and Carollia perspicillata, possess a significant population of cones and express two cone opsins, a shortwave-sensitive (S) opsin and a longwave-sensitive (L) opsin. A substantial population of cones expresses S opsin exclusively, whereas the other cones mostly coexpress L and S opsin. S opsin gene analysis suggests ultraviolet (UV, wavelengths <400 nm) sensitivity, and corneal electroretinogram recordings reveal an elevated sensitivity to UV light which is mediated by an S cone visual pigment. Therefore bats have retained the ancestral UV tuning of the S cone pigment. We conclude that bats have the prerequisite for daylight vision, dichromatic colour vision, and UV vision. For bats, the UV-sensitive cones may be advantageous for visual orientation at twilight, predator avoidance, and detection of UV-reflecting flowers for those that feed on nectar.
The topographical distribution of cones and rods in the tree shrew retina was analysed quantitatively in whole-mounted retinae and horizontal semithin sections stained with cresyl violet or toluidine blue. The outer nuclear layer consists of a single layer of photoreceptor nuclei with the rod nuclei slightly displaced towards the outer plexiform layer. This facilitated quantification of the photoreceptor populations. The density of cones ranges from 12,000/mm2 in the peripheral retina to a maximum of 36,000/mm2 in the inferior retina. Unlike ganglion cell density, the density of cones does not peak in the temporal retina. Rod density, between 500/mm2 and 3,500/mm2, also peaks in the inferior retina, but not in the same region as cone density. Rods constitute from 1 to 14% of the photoreceptor population, depending on retinal location, and have a local minimum at the central area. Amongst the cones a regularly arrayed subpopulation of presumed blue-sensitive cones is distinguished by its special staining properties. These cones constitute between 4 and 10% of the cone population depending on retinal location. A second, irregularly spaced, subpopulation of possibly pathological cones is also described.
These results point to an association between the IL-1beta polymorphism and the TNFalpha(high) phenotype and between the IL-1Ra polymorphism and the TNFalpha(low) phenotype found in OA. Both associations suggest that IL-1beta may be more important than TNFalpha for the regulation of cytokine and growth factor expression in articular chondrocytes.
Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case-control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-alpha)-308, TNF-beta-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I degrees -III degrees ), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group, P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases [odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01-2.75; P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47-4.41; P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease.
Older studies have claimed that bats including the Megachiroptera (fruit bats or flying foxes) have pure-rod retinas and possess no cone photoreceptors. We have determined the presence and the population densities of spectral cone types in six megachiropteran species belonging to four genera: Pteropus rufus, P. niger, P. rodricensis, Rousettus madagascariensis, Eidolon dupreanum, and Epomophorus gambianus. Spectral cone types and rods were assessed immunocytochemically with opsin-specific antibodies. All six species have rod-dominated retinas but possess significant cone populations. The high rod densities (range 350,000–800,000/mm2, depending on species and retinal location) provide good scotopic sensitivity in these predominantly nocturnal animals. With the cones (density range 1,300–11,000/mm2, corresponding to 0.25–0.6% of the photoreceptors, depending on species and retinal location) the retinas also possess the prerequisite for vision at photopic light levels. The three Pteropus species have two spectral cone types, a majority of middle-to-long-wave sensitive (L-) cones, and a minority of short-wave sensitive (S-) cones, indicating the potential for dichromatic color vision. This conforms to the pattern found in most mammals. In contrast, Rousettus, Eidolon and Epomophorus have L-cones but completely lack S-cones, indicating cone monochromacy and color blindness. The discussion relates these findings to the visual behavior of fruit bats.
Recently, we demonstrated an association of the IL-6 promoter polymorphism at position -174 (G→C) with kidney allograft survival whereby carriers of the −174GG genotype were identified as having superior graft survival. As two additional polymorphisms were discovered in the neighborhood at positions −572 (G→C) and −597 (G→A), respectively, and as functional studies revealed a cooperative impact of all three on the IL-6 gene transcription, we investigated whether there is a combined effect on kidney transplant outcome. We determined IL-6 promoter haplotypes −597 (G→C)/−572 (G→A)/−174 (G→C) ( −597/−572/−174 haplotype) using a PCR system with sequence-specific primers in 158 patients after primary cadaveric kidney transplantation. We here show that the −597 and −174 polymorphism are in tight-linkage disequilibrium and that homozygous carriers of the GGG −597/−572/−174 haplotype (GGG/GGG genotype) have superior 3-year graft survival rates compared with the 8.0-fold increased risk of premature graft loss in all other patients. Interestingly, patients carrying the GGG/GCG genotype had the lowest allograft survival rate. Thus determination of the combined −597/−572/−174 genotype allows for further differentiation of −174GG patients into subgroups and consequently for a more accurate identification of patients at risk. Our results indicate that the three polymorphisms act in a cooperative fashion and we provide evidence for an exceptional clinical impact of the IL-6 −597/−572/−174 genotype on the success of kidney transplantation.
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