Progression of cochlear and retinal degeneration in the tubby (rd5) mouse

Various molecules expressed on the surface of platelets have been shown to mediate the protective or deleterious role of these cells in immuno-inflammatory mechanisms. Increasing evidence points to the involvement of the cell adhesion molecules, gpIIb-IIIa, P-selectin, CD31, LFA-1, and CD36 in the interaction between platelets and endothelial cells as well as other cell types. The possible role of these molecules in the ability of platelets to support endothelium and to protect against tumour necrosis factor mediated cytolysis or parasitic invasion are reviewed. The involvement of platelets as effectors of tissue damage in cerebral malaria, lipopolysaccharide induced pathology, and pulmonary fibrosis is also discussed. This has then been extended to include the intercellular mechanisms underpinning their pathogenic role in metastasis, transplant rejection, stroke, brain hypoxia, and related conditions. A better understanding of the complex regulation and hierarchical organisation of these various platelet adhesion molecules may prove useful in the development of new approaches to the treatment of such diseases.     

Expression of alphaB-crystallin in a mouse model of inherited retinal degeneration

AlphaB-crystallin, which is abundantly expressed in the lens but also in a diversity of other tissues, functions as a stress-inducible molecular chaperone and is increased in brain neurodegenerative diseases. We compared retinal alphaB-crystallin expression in a model of inherited retinal degeneration, the rd mouse, and controls. Northern and in situ hybridization analysis showed alphaB-crystallin mRNA to have an altered spatio-temporal pattern with increased levels localized to glial cells in the degenerative state. Immunocytochemistry confirmed increased expression at Müller cells and astrocytes, together with transiently increased localization to the degenerating photoreceptors. These findings suggest that increased alphaB-crystallin expression is associated with glial cell reaction to neuronal damage in the retina, and may comprise part of the retina's overall defensive response to the stress of apoptotic photoreceptor cell death.     

Retinal degeneration in the rd mouse in the absence of c-fos

PURPOSE: Apoptosis is the final common death pathway of photoreceptors in light-induced retinal degeneration and in several animal models for retinal dystrophy. To date, little is known about gene regulation of apoptosis in the retina. The expression of the immediate early gene c-fos is upregulated concomitant with apoptosis in light-induced photoreceptor degeneration and in the rd mouse, an animal model for inherited retinal degeneration. In a recent study it was shown that c-Fos is essential for light-induced apoptosis of photoreceptors in vivo. To determine whether c-Fos is also involved in the apoptotic pathway of inherited retinal degeneration, rd/rd, c-fos -/- double-mutant mice have been generated. METHODS: Double-mutant mice (rd/rd, c-fos -/-) were crossbred from c-fos+/- mice and rd/rd mice. Their genotype was determined by polymerase chain reaction analysis of genomic DNA. Wild-type control mice and homozygous rd mice were killed at 2-day intervals from postnatal day (P)9 through P21. Double-mutant mice were killed at postnatal days P9, P11, P13, P15, and P21. To determine levels of apoptosis in the retina, eyes were enucleated and processed for light microscopy and in situ nick-end labeling. Total retinal DNA was extracted from isolated retinas for DNA fragmentation analysis. RESULTS: Morphologic, histochemical, and biochemical analyses showed that the time course of apoptosis and the outcome of photoreceptor degeneration in rd/rd, c-fos-/- double-mutant mice was indistinguishable from that in rd mice carrying functional c-fos. CONCLUSIONS: These data suggest that in contrast to its role in light-induced photoreceptor degeneration, c-Fos is not essential for apoptosis in the rd mouse.     

An 85-kb tandem triplication in the slow Wallerian degeneration (Wlds) mouse

Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wlds) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wlds among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences ("illegitimate" or "nonhomologous" recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wlds mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.     

Primary retinal degeneration: evidence of normal phagocytosis in the retinal pigment epithelium

In rats with primary retinal degeneration, lens extraction combined with total retinal detachment provided a model for injection of a tracer of colloidal carbon into the subretinal space. Electron microscopy and acid phosphatase cytochemistry were subsequently used to analyze the ingestion of tracer by the retinal pigment epithelium. It was found that the attachment, ingestion, and digestion phases of the phagocytic process were apparently preserved. From this evidence it is suggested that there is no lack of phagocytic power in the retinal pigment epithelium of affected rat strains.     

Neurophysiology of central retinal degeneration in cat

Receptive fields of ganglion cells have been studied in cats possessing a chronic, arrested lesion of central retinal degeneration. Lesions were characterized by an ophthalmoscopically sharp border separating apparently normal retina from the region of the lesion. Under direct ophthalmoscopic guidance, a succession of recordings was obtained from ganglion cells having cell bodies at various positions relative to the lesion. Cells located more than 1 deg outside the ophthalmoscopic border had normal visual sensitivity as assessed by area-threshold experiments. Inside the lesion cells within 1 deg of the border had reduced sensitivity which often precluded functional classification by the usual visual tests. Ganglion cells located more than 1 deg inside the border of large lesions were blind and some had abnormal patterns of maintained discharge of action potentials. Nevertheless, the antidromic latencies of these blind cells fell into the familiar conduction groups (T1/T2/T3). Receptive-field maps of cells near the border of the lesion often appeared truncated, with the missing portion of the field covered by the lesion. These observations were consistent with the abnormal form of area-threshold curves. Although the responsiveness of cells near the lesion was abnormally low for grating stimuli, cutoff spatial frequency and orientation bias of these cells were within normal limits.     

Hyperplastic neuroretinopathy and disorder of pigment epithelial cells precede accelerated retinal degeneration in the SJL/N mouse

We have found a complex eye disease in the SJL/N mouse. This animal is closely related to the SJL/J mouse, which is homozygous for retinal degeneration (rd) and which also suffers from extraocular reticulum cell sarcomas at around 200 days of age. In the SJL/N animal, a high incidence of subretinal tumor is present at 9 days after birth. Furthermore, we have observed an extensive neuroretinal hyperplasia, a phenomenon that is termed "hyperplastic neuroretinopathy", and that is probably the consequence of elevated levels of cytokines in the animals. In addition to these anomalies, the SJL/N mouse shows progressive dystrophy of the retinal pigment epithelium (RPE) from day 4 onwards, and accelerated photoreceptor cell degeneration is completed by day 16. The early RPE dystrophy appears to be a secondary autoimmune disease, since cells in this structure and in the choroid develop MHC class II antigens, whereas we suspect that the accelerated photoreceptor cell loss is induced by a soluble toxic agent. The F1 progeny derived from cross-breeding the SJL/N and Balb/c +/+ strains also shows a high incidence of subretinal tumor and hyperplastic neuroretinopathy, but neither the RPE dystrophy nor retinal degeneration.     

Expression of the BCL6 gene in the pre- and postnatal mouse

Langerhans cell histiocytosis may be seen with goiter and histiocytic infiltration of the thyroid. We report a 2 1/2-year-old boy who had goiter and primary hypothyroidism develop, later had pulmonary disease, and died of neurologic involvement. Autopsy lesions suggested a transitional dendritic cell precursor of the epidermal Langerhans cell. Of the reported cases of Langerhans cell histiocytosis with goiter in children and adolescents, 82% were male when the relative incidence of Langerhans cell histiocytosis is two males to one female.     

Expression of the peroxisome proliferator-activated receptor (PPAR) in the mouse colonic mucosa

The peroxisome proliferator-activated receptor (PPAR), a member of the steroid nuclear receptor superfamily, has been shown to be activated by various compounds such as fibrates, thiazolidinediones, prostaglandins, and fatty acids. Here we demonstrate expression of PPAR in mouse colonic and small intestinal mucosa by Western blot analysis and immunohistochemistry, indicating a higher expression level in the differentiated colonic epithelial cells facing the intestinal lumen. Quantification of PPAR mRNA by ribonuclease protection assay revealed relatively high expression of PPAR gamma and Nuc1 in the colon as compared to the small intestine. In contrast, PPAR alpha expression was higher in the small intestine as compared to the colon. These results demonstrate the presence of PPAR in the intestinal mucosa; however, the physiological roles of the various isoforms in the intestine remain to be established.     

Reproduction of progressive retinal degeneration (bright blindness) in sheep by administration of ptaquiloside contained in bracken

The process of occurrence of bright blindness, progressive retinal degeneration (PRD), in sheep was observed using two Suffolk ram lambs fed on a diet containing bracken powder. The first sign of the bright blindness was detected 4 months after the start of experiment. Based on these preliminary results, the amount of bracken powder necessary to induce PRD was estimated (experiment I). In the following experiment, ptaquiloside (PT), a norsesquiterpene glucoside of the illudane type isolated from bracken, which is a bracken carcinogen and a causative principle of cattle bracken poisoning was administered to two Suffolk ram lambs. It was clearly demonstrated in this experiment (experiment II) that PT present in bracken is also a causative principle of PRD.     

Optokinetic nystagmus in progressive retinal degeneration.

Studied optokinetic nystagmus (OKN) in normally pigmented and delayed amelanotic (DAM) strains of domestic chickens (N?=?18). The DAM line is characterized by postnatal feather and ocular depigmentation accompanied by progressive retinal degeneration that occurs, initially and most severely, in the central retina. Results indicate a close association between the extent of ocular pigment loss and relative reduction in OKN responsiveness in DAMs. The directional asymmetry of OKN responses, which normally occurs with monocular temporal-to-nasal (T–N) but not with N–T stimulation, was altered in relation to the extent of ocular amelanosis among DAMs. In particular, T–N OKN responses were progressively reduced as amelanosis of the central retina increased in severity. In DAMs with moderate to severe reductions in T–N responsiveness, relatively little reduction occurred in N–T responsiveness. The central retina, therefore, appears to play a major role in mediating responses to T–N stimulation, whereas the peripheral retina mediates both directions of response. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of substance P (NK1) receptor mRNA in human nose

A capillary zone electrophoretic method (CZE) was developed using an uncoated fused silica capillary for the separation and determination of the main tropane alkaloids. The applicability of the developed method for analysis of plant samples was examined by analyzing samples of transgenic Egyptian henbane Hyoscyamus muticus (L.) plants. A simple 40 mM phosphate buffer at pH 7.8 using a voltage of 20 kV was found the best for this purpose. The main tropane alkaloids, atropine and scopolamine as well as nor-(-)-scopolamine, and tropic acid, the precursor of tropane alkaloids, could be separated in less than 13 min. The linear concentration range for atropine was 5.00-140 microg ml(-1), for scopolamine 7.50-210 microg ml(-1) and for tropic acid 2.50-70.0 microg ml(-1).     

Expression of the mnb (dyrk) protein in adult and embryonic mouse tissues

Remission of Graves' disease (GD) during pregnancy with recrudescence after delivery is commonly observed. However, as pregnancy is associated with type 2 rather than type 1 cytokine production, a decrease in thyroid-stimulating antibody (TSAb) activity alone is unlikely to account for the remission during pregnancy. We hypothesized that a change in the antibody characteristics may occur as pregnancy advances. Fifteen women were studied in the first, second, and third trimesters of pregnancy and 4 months postpartum. TSH receptor antibodies were determined using human thyroid cell cultures, and lymphocyte subsets were measured by flow cytometry. Median TSAb (determined by cAMP release) decreased from 280% (96-3200) to 130% (range, 35-350; P < 0.05) during pregnancy, but no significant change was noted with the TSH binding inhibitory antibody (TBII; determined by RRA). Thyroid stimulation-blocking antibody (TSBAb; inhibition of TSH-stimulated cAMP release) increased from 16 +/- 9% to 43 +/- 16% (mean +/- SD; P < 0.005). The increase in TSBAb was observed even among those patients who were in clinical remission before pregnancy. Overall, a negative correlation was observed between TSBAb activities and free T4 levels during pregnancy (r = -0.279; P < 0.05). Reciprocal changes in TSAb, TBII, and TSBAb levels were observed in the seven patients who relapsed during the postpartum period. In comparison, the healthy pregnant women (n = 14) were all negative for TSAb, TBII, and TSBAb throughout pregnancy. The absolute number of T lymphocytes, T helper cells, and natural killer cells, but not B cells, decreased significantly during pregnancy in both healthy women and GD patients. GD patients had significantly more CD5+ B cells at all stages of pregnancy compared to controls. In conclusion, a change in specificity from stimulatory to blocking antibodies was observed in GD patients during pregnancy and may contribute to the remission of GD during pregnancy.