Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrome, which is caused by mutations in KMT2D or KDM6A, genes also involved in histone methylation. KMT2A mutations and clinical features are summarized in our six patients together with eight previously reported patients. Furthermore, clinical comparison of the two syndromes is discussed in detail.

Possible mechanism of regulating adenylate cyclase activity in adipocyte membranes from exercise-trained male rats.

(-)-Isoproterenol-stimulated adenylate cyclase activities were significantly greater in membranes from exercise-trained male rats than in sedentary male rats. GTP-inhibition of forskolin (10 microM)-stimulated cyclase activities were observed in sedentary membranes, whereas the inhibitory actions of GTP were significantly reduced in membranes from trained rat adipocytes. Treatment of membranes with islet-activating protein, a pertusis toxin, completely abolished the differences in GTP-inhibition of forskolin-stimulated cyclase activities between the two groups. The amounts of the inhibitory regulatory protein (41kDa/40kDa polypeptides) were about 40% less in membranes from trained rats than in sedentary membranes, whereas that of the stimulatory regulatory protein (a 45kDa polypeptide) was equivalent. It is concluded that the enhanced cyclase activities of adipocyte membranes from trained male rats appear to result from, in part, an attenuation of the inhibitory pathway due to a specific decrease in the amount of the inhibitory regulatory proteins.

Augmentation of catecholamine-stimulated [3H]GDP release in adipocyte membranes from exercise-trained rats.

The effects of exercise training on the catecholamine-stimulated [3H]GDP release in rat adipocyte membranes prelabeled with [3H]GTP and the adenylate cyclase activity were investigated. Exercise training significantly increased the release of [3H]GDP in response to (-)isoproterenol. The adenylate cyclase activity induced by a nonhydrolyzable guanine nucleotide analogue, Gpp(NH)p, was significantly greater in exercise-trained rats.

[Effects of Ca2+ and calmodulin inhibitors on lipolysis induced by epinephrine, norepinephrine, caffeine and ACTH in rat epididymal adipose tissue].

The effects of Ca2+ and calmodulin inhibitors on lipolysis induced by epinephrine, norepinephrine, caffeine and ACTH in rat epididymal adipose tissue were investigated. 1. Omission of Ca2+ from the incubation medium slightly depressed lipolysis induced by epinephrine, norepinephrine and ACTH. Lipolysis induced by caffeine was significantly depressed. 2. Lipolysis induced by epinephrine, norepinephrine, caffeine and ACTH was strongly depressed when Ca2+-deficient tissue was incubated in Ca2+-free Ringer solution. 3. In Ca2+-deficient tissue, the addition of 0.75mM Ca2+ apparently restored lipolysis induced by epinephrine, norepinephrine and ACTH, whereas that by caffeine was restored to only approximately 89%. 4. The addition of La3+ markedly inhibited lipolysis induced by each agonist. 5. The Ca2+ antagonists such as verapamil and diltiazem dose-dependently inhibited lipolysis induced by each agonist. 6. The specific calmodulin inhibitors such as chlorpromazine, trifluoperazine and W-7 markedly inhibited lipolysis induced by each agonist. These results strongly support the possible key role that the redistribution and influx of Ca2+ may play in lipolysis induced by epinephrine, norepinephrine, caffeine and ACTH, and further suggest that calmodulin may affect lipolysis.