Comprehensive gene-expression profile in murine oxygen-induced retinopathy.

BACKGROUND/AIMS: To investigate the correlation between the clinical course and gene-expression pattern in murine oxygen-induced retinopathy (OIR), a commonly used model of retinopathy of prematurity (ROP). METHODS: OIR was induced in C57BL/6N mice by placing postnatal day 7 (P7) pups in 75% oxygen for 5 days. The clinical course of the OIR was evaluated on retinal flat-mounts after fluorescein isothiocyanate-conjugated dextran perfusion from P12 to P21. The expression values of 94 genes, selected by microarray analyses, were determined daily from P12 through P21 by RT-PCR with TaqMan low-density array (TLDA) and analysed by hierarchical clustering. RESULTS: TLDA cluster analyses showed a homology of gene-expression pattern between P12 and P13 and between P16 and P17. Many genes associated with inflammation were upregulated on P12 and P13 when the degree of both central avascular area and central vasoconstriction were maximal, and the upregulation of the genes continued to P21. At P16 and P17 when extraretinal neovascularisation became most noticeable, several genes associated with angiogenesis, for example, vascular endothelial growth factor-A and angiopoietin-2, were most upregulated. CONCLUSION: The gene-expression pattern was well correlated with the clinical appearance in murine OIR. These findings should contribute to the understanding of the pathological conditions in ROP.

Comparison of three techniques of foveal translocation in patients with subfoveal choroidal neovascularization resulting from age-related macular degeneration.

PURPOSE: To report the results of three methods of foveal translocation in the presence of subfoveal choroidal neovascular membrane resulting from age-related macular degeneration. METHODS: We treated 51 eyes of 51 consecutive patients with subfoveal choroidal neovascular membranes resulting from age-related macular degeneration with one of three techniques of foveal translocation surgery: foveal translocation with partial retinotomy (n = 6), limited translocation (n = 9), and translocation with 360-degree retinotomy (n = 36). All patients were followed for at least 6 months postoperatively. The size of the choroidal neovascular membrane and the amount of foveal displacement, the best-corrected visual acuity, and complications were recorded preoperatively and postoperatively. RESULTS: The mean distance of the foveal translocation was greater in the 360-degree retinotomy group (3340 microm) than in the partial retinotomy (1060 microm, P <.001) and the limited translocation groups (1120 microm, P <.001). A final visual acuity of 20/200 or better was achieved in two eyes (33%) in the partial retinotomy group, seven eyes (78%) in the limited translocation group, and 23 eyes (64%) in the 360-degree retinotomy group. The final visual acuity improved by 0.2 logarithm of minimal angle of resolution (logMAR) unit or more in one eye (17%), one eye (11%), and seven eyes (19%), respectively. The final visual acuity was maintained within 1 line in zero eyes, five eyes (56%), and 19 eyes (53%), respectively. A retinal detachment developed postoperatively in five eyes (83%), zero eyes (0%), and 15 eyes (42%), respectively. CONCLUSIONS: A significant number of patients improved or maintained best-corrected visual acuity after translocation with 360-degree retinotomy, and limited translocation, whereas translocation with 360-degree retinotomy is suitable for larger choroidal neovascular membranes because it resulted in the greatest foveal displacement among the three translocation procedures.

Clonal composition of malignant fibrous histiocytoma: analysis by PCR-based assay of the human androgen receptor gene (HUMARA).

Malignant fibrous histiocytoma (MFH), the most common soft-tissue sarcoma, consists mainly of two different cell populations: histiocytelike and fibroblastlike cells. It has been suggested to contain a large amount of reactive histiocytes and fibroblasts hard to distinguish from the tumor cells. In this study, the clonality of MFH was determined by analyzing the patterns of X chromosome inactivation at the human androgen receptor gene (HUMARA) using DNA samples from archival snap-frozen and paraffin-embedded tissues. All the eleven informative female heterozygotes without severe inflammation showed the monoclonal pattern; 8 storiform-pleomorphic (6 distinct, 2 relative monoclonal pattern) and 3 myxoid (3 distinct monoclonal pattern) subtype. Although normal tissue DNA, amplifiable by the polymerase chain reaction, valid for the assay was not available in these cases, statistically at least 5 cases are monoclonal (p = 0.037 <0.05), even when markedly skewed lyonization were to primarily exist in the normal tissue at the highest rate as ever reported (33%). Experiments using the mixture of monoclonal and polyclonal DNA at varying ratios have suggested that a distinct monoclonal pattern is obtained only when the monoclonal component exceeds 80%. Our study demonstrates that most cells that are present in MFH are monoclonal in origin which may be the population of tumor cells.

Anisocoria--a pupillary sign of hippocampal lesions: an experimental study in the cat by using neurotoxins.

Pupillary inequality developed after unilateral lesions of the hippocampal formation (HF) of the cat. Lesions were made by an injection of a small amount of colchicine, ibotenic acid or kainic acid. In all anisoric cats, the pupil on the side of the lesions was invariably smaller than its partner. Evident pupillary inequality developed in the cats with dorsal HF lesions. Although there was a considerable variation in the extent and the location of lesions among these cats, the involvement of the giganto-pyramidal CA 3-2 appeared very responsible for the development of the pupillary sign. However, an evidently anisoric cat hat a lesion affecting only the prosubiculum and the subiculum in the posterior part of the dorsal HF. Despite a large involvement of CA 3-2 with or without coincident injuries to CA1, the prosubiculum and the subiculum, only slight pupillary inequality developed following ventral HF lesions. Evident anisocoria in the cats with large dorsal HF lesions disappeared after bilateral cervical sympathectomy, implying that the asymmetry of sympathetic nervous activity might be critically involved in the development of the pupillary sign. The hippocampo-spinal pathway relayed by the lateral septal nucleus and, then, by the lateral hypothalamic area to terminate in the intermedio-lateral cell column of the spinal cord was considered to be most concerned with anisocoria caused by HF lesions.

Intestinal absorption of carboxyfluorescein entrapped in liposomes in comparison with its administration with lipid-surfactant mixed micelles.

The absorption of carboxyfluorescein (CF) entrapped in liposomes from the small intestine was investigated in vivo using bile fistula rats. Within the intestine CF was not metabolized, but 32% of the entrapped CF was released for 3 h from the liposomes when incubated with luminal incubation solution. The data of CF disappearance from the intestinal lumen and of CF plasma concentration showed that no apparent difference was observed between administration of the liposomal CF and that of free dye. Especially in initial 60 min after administration of liposomal CF, the plasma concentration was obviously lower than that in free CF administration. On the contrary, the coadministration of 40 mM lipid-surfactant mixed micelles induced a remarkable promotive effect on the absorption of free CF already in the early periods of the initial 60 min. When liposomal CF was administered into the intestinal lumen of thoracic duct-cannulated rats, the concentration in lymph was lower than that in plasma. Intramural injection of liposomal CF into intestinal wall, however, showed a much higher concentration in lymph than that in plasma. These findings suggest that liposomal entrapment of CF has rather difficulty to be absorbed through the intestinal mucosa, while lipid-surfactant mixed micelles exert a remarkable promotive effect on the absorption of CF.