A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease, which requires differential diagnosis from relatively common primary hyperparathyroidism (PHPT) in order to avoid unnecessary surgery. CASE PRESENTATION: A 16-year-old female had been followed by the department of psychosomatic medicine at our institution. Throughout the follow-up period, her plasma calcium levels were high, plasma Pi levels were relatively low, and plasma intact PTH was relatively high. She was referred to our department to determine the cause of her hypercalcemia. Her 24 h urinary calcium excretion was as low as 100 mg/day, and calcium creatinine clearance ratio was below 0.01. Moreover, she had a family history of hypercalcemia (proband, her brother, and her father). The genetic testing for her family revealed that she, her brother, and her father were definitively diagnosed with FHH type 1 due to the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu). CONCLUSION: We experienced a 16-year-old female with FHH, in whom genetic testing identified the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu) as pathogenic, permitting a definitive diagnosis of FHH type 1. The genetic testing for calcium sensing receptor is beneficial to distinguish asymptomatic primary hyperparathyroidism from FHH.

An inhibitory effect of the sequence-conserved upstream open-reading frame on the translation of the main open-reading frame of HsfB1 transcripts in Arabidopsis.

Plants have as many as 20 heat shock factors (Hsfs) grouped into three classes, A, B and C, based on sequence similarity and modular structures. Through screening for cell death-inducing factor(s) in Nicotiana benthamiana, we identified Arabidopsis HsfB2b and thus subjected all other members of Arabidopsis Hsf class B (HsfB1, HsfB2a, HsfB2b, HsfB3 and HsfB4) to the same cell death assay. When expressed in N. benthamiana leaves, only HsfB1 and HsfB2b elicited mild cell death. Simultaneously we found that HsfB1 has a post-transcriptional control mechanism, in which a sequence-conserved upstream open-reading frame (sc-uORF) is involved. The known repressor function of the respective HsfBs was confirmed and the difference in cell death-inducing activity of HsfBs was explained by the fact that HsfB1 and HsfB2b are transcriptional repressors but the others are not. Indeed, the cell death symptom by HsfB1 and HsfB2b required not only their repression activity but also their nuclear localization activity. HsfB1 expression was drastically and transiently induced by heat shock (HS) and the intactness of sc-uORF was required for its HS response. Based on the results, the physiological significance of cell death-inducing activity of HsfB1 and HsfB2b and the sc-uORF in the HsfB1 transcript during HS response is discussed.

Quantitative analysis of plant polyamines including thermospermine during growth and salinity stress.

Arabidopsis thaliana was thought to contain two spermine synthase genes, ACAULIS 5 (ACL5) and SPMS. Recent investigations, however, revealed that the ACL5 gene encodes thermospermine synthase. In this study, we have established a simple method to separate two isomers of tetraamine, spermine and thermospermine, in extracts from plant tissues of less than 500 mg. Polyamines (PAs) extracted from plant tissues were benzoylated, and the derivatives were completely resolved by high-performance liquid chromatography on a C18 reverse-phase column, by eluting with 42% (v/v) acetonitrile in water in an isocratic manner at 30 degrees C and monitoring at 254 nm. The relevance of the method was confirmed by co-chromatography with respective PAs and by the PA analysis of the single- and double-mutants of acl5 and spms, which could not synthesize thermospermine and/or spermine, respectively. Furthermore, with this method, we monitored the thermospermine contents in various tissues of A. thaliana and found that stems and flowers contain two- to three-fold more thermospermine compared to whole seedlings and mature leaves. The presence of thermospermine was confirmed in Oryza sativa and Lycopersicon pesculentum. Finally we addressed whether salinity stress changes the contents of PAs including thermospermine in Arabidopsis.

Leptin modulates the response to oleic acid in the pharynx.

Leptin released from the adipose tissues is known to inhibit obesity by regulating food intake. In this study, we investigated the effect of leptin on afferent nerve responses to fats and fatty acid in the pharyngolaryngeal region. The afferent nerve activities were recorded from the whole nerve bundle or pauci-fiber bundles of the pharyngeal branch of the glossopharyngeal nerve (GPN-ph) in Wistar normal and fatty rats. Oleic acid (long-chain fatty acid), mineral oil (nonfat oil) and safflower oil (vegetable oil; middle-chain fatty acid) were applied to the surface of pharyngolaryngeal mucous membrane. Oleic acid elicited vigorous stimulation of the GPN-ph activity in both normal and fatty rats but other oils had no significant effect on the activity. After intravenous administration of leptin (30 ng/kg, 1 ml), the response to oleic acid was significantly decreased in normal rats, whereas such a decrease was not found in fatty rats. These results are the first findings to indicate the existence of a suppressive mechanism of leptin on the response of the GPN-ph to fatty acid in normal rats, but that such a mechanism is lacking in fatty rats.