Familial Hyperaldosteronism Type 3 with a Rapidly Growing Adrenal Tumor: An In Situ Aldosterone Imaging Study

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic β-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings.     

A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis

In the screening for cisplatin (CDDP)-resistance related genes by a mRNA differential display method, we detected some increased bands in CDDP resistant ovarian tumor cell line 2008/C13*5.25. One of them, named DD9, was a positive fragment on Northern blot analysis. We cloned it as a full length cDNA by 5'RACE and found a novel gene, CRR9 (Cisplatin Resistance Related gene 9). The CRR9 gene was transcribed into a 2.0 kb mRNA, encoding 512 amino acids. The putative protein had transmembrane-like domains and well conserved on C terminus with human CLPTM1 and the homologs found in Drosophila and C. elegans. Transfection assay showed that the CDDP-sensitive strain 2008 with CRR9 was more sensitive to CDDP, indicating that CRR9 was not associated with the CDDP-resistance, but the CDDP-induced apoptosis.     

Tau-tubulin kinase phosphorylates tau at Ser-208 and Ser-210, sites found in paired helical filament-tau

Hyperphosphorylated tau protein is known to be a major component of the paired helical filaments (PHFs) that accumulate in the brain of Alzheimer's patients. The kinase that phosphorylated Ser-208 and Ser-210 in PHF-tau had remained unknown. We used anti-pS208 and anti-pS210 antibodies and Western blots to confirm that the tau-tubulin kinase (TTK) phosphorylates tau at Ser-208 and at Ser-210. Using partial amino acid sequences of purified bovine brain TTK, a mouse cDNA of TTK was isolated and the sequence was determined. Its 963 bp coding region is composed of 320 amino acids and encodes a 36 kDa protein indistinguishable in size from authentic bovine brain TTK. Our immunoblot analysis demonstrated that TTK is ubiquitously distributed in the rat tissues, and that it is developmentally regulated in the rat brain.     

Study of color variation in the solitary ascidian Halocynthia roretzi, collected in the Inland Sea of Japan

In the vicinity of Yashiro Island in the Inland Sea of Japan, the solitary ascidian (tunicate) Halocynthia roretzi with tunics of various colors were collected. Samples of these animals were sorted into three groups on the basis of visual observation of tunic color. The red group includes animals with dark-red, light-red, or orange tunics. The pink group includes animals with tunic colors ranging between red and white. The white group includes only animals with completely white tunics. Animals in the white group lacked color internally, with the exception of the hepatopancreas and the gonads in breeding season; the epidermis and gill basket were white. In contrast, animals of both the red group and the pink group were colored internally, with red-orange epidermis and yellow gill basket. Alloreactivity was tested by mixed-hemocyte incubation between different animals belonging to the same color group and between animals belonging to different color groups. Alloreactivity between animals of the white group was 56.3%, between animals of the pink group was 60.0%, and between animals of the red group was 69.3%. The relatively high frequency of compatible combinations among the white animals is discussed.     

Cloning and expression analysis of a MAPKKK gene and a novel nodulin gene of Lotus japonicus

We isolated a cDNA encoding mitogen-activated protein kinase kinase kinase alpha, designated LjM3Kalpha, from Lotus japonicus, a model legume. The gene was expressed constitutively in roots, root nodules, and shoots. We also identified a novel nodulin gene, LjNUF, that shows specific expression in nodules. LjNUF resembles the C-terminal half of a hypothetical protein (pir//D85436), the N-terminal half of which is similar to a portion of mitogen-activated protein kinase kinase kinase gamma. Although LjNUF was predicted to be a secreted protein, its function remains to be clarified.     

Secular trends of sizes at birth in Japanese healthy infants born between 1962 and 1988

Body sizes at birth are important clinical indicators widely used for evaluation of prenatal growth. Japan had significant socioeconomic improvement around the 1960s, and these environmental changes may influence physiologically prenatal growth. Furthermore, in Japan, measurements of size at birth for birth certificates are weight and height. Thus, we can refer to annual data on weight and height, but not on head and chest circumference at birth. In this study we measured the weight, height, and head and chest circumference at birth among 6,563 Japanese singleton healthy infants, annually in 1962 and 1988, and examined secular trends of these anthropometric measurements. The boys consistently exceeded the girls in all four variables. Birth weight and height increased significantly from the 1960s to '70s, but did not differ between the '70s and '80s in both boys and girls. Secular trends of head and chest circumference were different from them. In both boys and girls, head and chest circumference increased significantly from the '60s to the '70s, but decreased significantly from the '70s to the '80s. No difference of head circumference during the '60s and '80s was found, but the difference of chest circumference was found. Size at birth was likely to increase from the '60s to '70s in Japan. These findings suggest that the environmental changes such as socioeconomic improvements influence the prenatal growth.