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Biomedical subjects

I Kurihara

Publications and source records attributed to I Kurihara.

26 records · Page 2Linked to original sources

Lipoprotein glomerulopathy. Report of a normolipidemic case and review of the literature.

Lipoprotein glomerulopathy is a disease characterized by intraglomerular lipoprotein thrombi and abnormal lipid metabolism similar to type III hyperlipoproteinemia. Recently, glomerular lesions compatible with lipoprotein glomerulopathy were found in a 38-year-old man. In this case, plasma apolipoprotein (apo) E level was elevated, and the apo E isoform was heterozygous E2/3, similar to most of the reported cases of lipoprotein glomerulopathy. However, the plasma levels of triglyceride and total cholesterol were within their respective normal ranges. Review in 11 cases revealed that lipoprotein glomerulopathy was not always associated with hyperlipidemia, and that apo E abnormality was always recognized. These findings suggest that lipoprotein thrombi associated with lipoprotein glomerulopathy are not induced via systemic hyperlipidemia but may be formed by intraglomerular accumulation of lipoprotein composed of abnormal apo E.

Adult↗

Studies of ocular murine cytomegalovirus infection.

The pathogenesis of ocular cytomegalovirus (CMV) infection in mice was studied in detail as a model of ocular involvement of human CMV infection. Smith strain of mouse CMV (MCMV) was inoculated into the anterior chamber of the eye and viral antigen was located by immunofluorescence. When salivary gland passaged MCMV (SG-MCMV) was inoculated into the 12- to 18-day-old ICR/Sic mice, it elicited transient uveitis, retinitis, and scleritis during the early phase of infection followed by spread into the lacrimal glands, extraocular muscles and salivary glands. Mouse embryonic fibroblasts (MEF) passaged attenuated MCMV (CC-MCMV) caused mild uveitis with a short duration even inoculated into young mice, and the viral antigen was detected only in salivary glands thereafter. SG-MCMV titer in the eye taken from the young mice decreased from 10(4.5) TCID50/0.1 g at 2 days postinfection (PI) to 10(3.0) TCID50/0.1 g at 21 days PI, whereas in the salivary glands, it became detectable at 5 days PI with a titer of 10(5.0) TCID50/0.1 g, which increased up to 10(8.7) TCID50/0.1 g at 21 days PI. CC-MCMV was detectable only in the young mice salivary glands ranging from 10(4.7) TCID50/0.1 g at 9 days PI to 10(7.3) TCID50/0.1 g at 21 days PI. When the lens capsule had been damaged during the inoculation procedure, the mice developed cataracts with evidence of viral growth in the lens. When SG-MCMV was inoculated onto the cornea, viral antigen was not detected during the period of the present experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and adrenocortical tumors: possible implications in steroidogenesis.

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF), DAX-1, and steroidogenic factor-1 (SF-1) are orphan members of the nuclear hormone receptor superfamily. COUP-TF and DAX-1 have been shown to negatively regulate the transcriptional activity of SF-1, a steroidogenic cell-specific activator of various steroidogenic cytochrome P450 genes. We therefore examined the expression levels and immunolocalization of COUP-TF, DAX-1, and SF-1 in human adrenal gland (NL) and adrenocortical adenomas, and compared the results with CYP17 expression levels and its enzyme activities to study their potential correlation with adrenocortical steroidogenesis. In NL (n = 10), expressions of COUP-TF, DAX-1, and SF-1 were detected in the nuclei of adrenocortical cells, but not in the medulla. In cortisol-producing adenomas causing Cushing syndrome (CS, n = 20), CYP17 expression was upregulated (298 +/- 2% vs NL 98 +/- 4%), whereas expression levels of both COUP-TFs (COUP-TFI, 52 +/- 5% vs NL 98 +/- 4%; COUP-TFII, 18 +/- 4% vs NL 98 +/- 4%) and DAX-1 (42 +/- 4% vs NL 100 +/- 4%) were reduced. In deoxycorticosterone-producing adenomas (DOC, n = 2), on the other hand, CYP17 expression was extremely reduced (8 and 12% vs NL 98 +/- 4%), whereas DAX-1 expression increased markedly (350 and 360% vs NL 100 +/- 4%). Expression levels of SF-1 did not differ between NL (100 +/- 8%) and CS (106 +/- 10%), but its expression appeared to be decreased in DOC (25 and 20%). These results showed CYP17 expression to be upregulated and downregulated in CS and DOC, respectively, in a manner reciprocal to that of its repressors, COUP-TF and/or DAX-1. In summary, the results indicate that co-localization of COUP-TF, DAX-1, and SF-1 in NL was lost in adrenocortical tumors and that these orphan receptors play an important role in the regulation of steroidogenesis in human adrenals.

Adenoma↗

Differential expression of an orphan receptor COUP-TFI and corepressors in adrenal tumors.

Recently, it has been shown that CYP17 gene transcription is activated by SF-1 (Steroidogenic Factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, whereas it is inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) binding to the sequence. We have shown that transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor). Therefore, we compared the expression of COUP-TFI, N-CoR and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands. We found significantly higher expression of COUP-TFI mRNA in non-hyperfunctioning adenomas (n=5, 227+/-18%) than in normal adrenals (n=5, 96+/-4%). Interestingly, the pattern of N-CoR and SMRT expression was different compared with COUP-TFI expression. These data suggest that COUP-TFI, N-CoR, and SMRT may play a differential role in steroid biosynthesis of non-hyperfunctioning adenomas.

Adenoma↗

The possible role of apoptosis-suppressing genes, bcl-2 and mcl-1/EAT in human adrenal tumors.

The expression levels of bcl-2, mcl-1/EAT, and bax were examined by Northern blot analysis and semi-quantitative RT-PCR method in 25 adrenal tumors, including seven adrenal pheochromocytomas (PHE), seven aldosterone-producing adenomas (APA), four adrenal cortisol-producing adenomas (CS), one deoxycorticosterone-producing adenoma (DOC) and six non-hyperfunctioning adrenal cortical adenomas (NF). Northern blot analysis revealed both bcl-2 and mcl-1/EAT mRNAs in all of the adrenal tumors. The expression levels differed greatly among the tumor samples. Mcl-1/EAT mRNA levels were enhanced in APA and CS compared with those in NF. In contrast, bcl-2 levels in NF were higher than in other tumors. Our results suggest that deregulation of such apoptosis-suppressing genes may contribute to the multistep tumorigenesis of human adrenal tumors and that mcl-1/EAT, one of the bcl-2 family genes, has a different role from that of bcl-2 in such pathways.

Adrenal Gland Neoplasms↗