Deoxycorticosterone-producing adenoma concomitant with aldosterone-producing microadenoma: a challenging combination.

OBJECTIVE: To describe the challenging case of a 59-year-old male with a deoxycorticosterone (DOC)-producing adrenal adenoma concomitant with an aldosterone-producing microadenoma. METHODS: We measured the patient's aldosterone and progesterone levels during adrenal venous sampling (AVS). The steroidogenic enzyme expression was studied with in situ hybridization (ISH). Steroids profiles were determined in the peripheral serum obtained before and after the operation, as well as in the main adrenal tumor. RESULTS: The patient was diagnosed with primary aldosteronism (PA) based on typical clinical findings. He had an adrenal tumor located at the lower pole of the left adrenal gland. The aldosterone concentration in the adrenal vein proximal to the adrenal tumor was higher than that of the ipsilateral adrenal vein distal to the tumor during the AVS. Progesterone was only elevated in the adrenal vein proximal to the tumor, suggesting that the tumor produced steroids other than aldosterone. The postoperative findings revealed that the main tumor was accompanied by 2 microadenomas. The main adrenal tumor was diagnosed as a DOC-producing adenoma, and one of the microadenomas was diagnosed as aldosterone-producing based on the ISH and the determination of the steroid profiles. CONCLUSIONS: Concomitant PA masked the key findings of a DOC-producing tumor; the suppression of aldosterone in this patient. Multiple sampling in the adrenal vein considering the location of the adrenal tumor provided a clue to the diagnosis. Progesterone measurement during AVS is easy and may be useful in diagnosing rare adrenal tumors that produce intermediate products in adrenal steroid biosynthesis.

Genome evolution of a nonparasitic secondary heterotroph, the diatom Nitzschia putrida.

Secondary loss of photosynthesis is observed across almost all plastid-bearing branches of the eukaryotic tree of life. However, genome-based insights into the transition from a phototroph into a secondary heterotroph have so far only been revealed for parasitic species. Free-living organisms can yield unique insights into the evolutionary consequence of the loss of photosynthesis, as the parasitic lifestyle requires specific adaptations to host environments. Here, we report on the diploid genome of the free-living diatom Nitzschia putrida (35 Mbp), a nonphotosynthetic osmotroph whose photosynthetic relatives contribute ca. 40% of net oceanic primary production. Comparative analyses with photosynthetic diatoms and heterotrophic algae with parasitic lifestyle revealed that a combination of gene loss, the accumulation of genes involved in organic carbon degradation, a unique secretome, and the rapid divergence of conserved gene families involved in cell wall and extracellular metabolism appear to have facilitated the lifestyle of a free-living secondary heterotroph.

Folic acid prevents congenital malformations in the offspring of diabetic mice.

It is well known that maternal diabetes causes various congenital malformations. Although there are many reports that folic acid (FA) administration in pregnancy reduces the risk of birth defects including neural tube defects (NTDs), a precise analysis on the preventive effect of FA against diabetic embryopathy has not been done yet. In this study, we analyzed the preventive effects of FA on congenital malformations including NTDs, cardiovascular, and skeletal malformations using a diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were examined for congenital malformations. FA did not affect plasma glucose levels. In the DM control group, the incidence of NTDs, cardiovascular, and skeletal malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of embryos from DM control group on day 9.5, and the apoptosis was decreased by FA treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly lowered in DM control group compared with those in non-DM group, and FA treatment did not show a significant effect. These results indicate that FA is effective for the prevention of various diabetic embryopathy including NTDs, cardiovascular, and skeletal malformations, and suggested that this effect is independent from homocysteine metabolism and possibly mediated by decreasing the abnormal apoptosis during organogenesis.

HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis.

Plants strictly regulate the levels of sterol in their cells, as high sterol levels are toxic. However, how plants achieve sterol homeostasis is not fully understood. We isolated an Arabidopsis thaliana mutant that abundantly accumulated sterol esters in structures of about 1 µm in diameter in leaf cells. We designated the mutant high sterol ester 1 (hise1) and called the structures sterol ester bodies. Here, we show that HISE1, the gene product that is altered in this mutant, functions as a key factor in plant sterol homeostasis on the endoplasmic reticulum (ER) and participates in a fail-safe regulatory system comprising two processes. First, HISE1 downregulates the protein levels of the ß-hydroxy ß-methylglutaryl-CoA reductases HMGR1 and HMGR2, which are rate-limiting enzymes in the sterol synthesis pathway, resulting in suppression of sterol overproduction. Second, if the first process is not successful, excess sterols are converted to sterol esters by phospholipid sterol acyltransferase1 (PSAT1) on ER microdomains and then segregated in SE bodies.