Atezolizumab-induced psoriasiform drug eruption successfully treated with ixekizumab: a case report and literature review.

Immune-related cutaneous adverse events (ircAE) are commonly seen with immune checkpoint inhibitors such as atezolizumab. Atezolizumab-induced psoriasis has been previously reported as an ircAE, especially in patients with pre-existing psoriasis. The severity of the reaction influences treatment of the cutaneous eruption. Biologics should be considered as a treatment option for severe refractory psoriasiform eruptions even in patients with complex medical conditions like chronic infections and malignancy. This is the first reported case of successful treatment of atezolizumab-induced psoriasiform eruption with ixekizumab, a neutralizing IL17A monoclonal antibody, to the best of our knowledge. Herein, we present a 63-year-old man with a history of human immunodeficiency virus and psoriasis who presented with atezolizumab-induced psoriasiform eruption while being treated for metastatic hepatocellular carcinoma. After initiating ixekizumab, atezolizumab was restarted without cutaneous eruption.

Experience-dependent expression of rat hippocampal Arc and Homer 1a after spatial learning on 8-arm and 12-arm radial mazes.

The expression of Arc and Homer 1a (H1a) depends on neural activity. This study was designed to determine hippocampal Arc and H1a mRNA expression levels after spatial learning with differing behavioral task demands. Forty-four male rats were distributed into 11 groups of four. One group received no training or trial sessions. Of the ten remaining groups, three were tested on the 8-arm maze, three on the 12-arm maze, two on the 8-arm maze and then the 12-arm maze, and two on the 12-arm maze and then the 8-arm maze. Each animal was sacrificed 30 min after the last session of maze testing and its hippocampus was immediately dissected and stored at -80°C. The level of mRNA expression at different stages of maze learning was determined using real-time reverse-transcription polymerase chain reaction (qRT-PCR). Significantly elevated expression of both Arc and H1a was observed. The orchestrated expression levels of both genes were correlated with the behavioral task demand level and behavioral performance.

A model for anteroposterior patterning of the vertebrate limb based on sequential long- and short-range Shh signalling and Bmp signalling.

It has been proposed that digit identity in chick limb bud is specified in a dose-dependent fashion by a long-range morphogen, produced by the polarising region. One candidate is Sonic hedgehog (Shh) protein, but it is not clear whether Shh acts long or short range or via Bmps. Here we dissect the relationship between Shh and Bmp signalling. We show that Shh is necessary not only for initiating bmp2 expression but also for sustaining its expression during the period when additional digits are being specified. We also show that we can reproduce much of the effect of Shh during this period by applying only Bmp2. We further demonstrate that it is Bmps that are responsible for digit specification by transiently adding Noggin or Bmp antibodies to limbs treated with Shh. In such limbs, multiple additional digits still form but they all have the same identity. We also explored time dependency and range of Shh signalling by examining ptc expression. We show that high-level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb. Furthermore, we find that high-level ptc expression is first widespread but later more restricted. All these data lead us to propose a new model for digit patterning. We suggest that Shh initially acts long range to prime the region of the limb competent to form digits and thus control digit number. Then later, Shh acts short range to induce expression of Bmps, whose morphogenetic action specifies digit identity.

L-Arginine inhibits vasopressin-stimulated mesangial cell Ca2+.

L-Arginine (L-Arg) affects various parameters that modulate the progression of renal disease. These same factors [e.g., glomerular filtration rate, changes in mesangial cell (MC) tension, and production of NO] are all controlled at least in part by changes in MC intracellular Ca2+ concentration ([Ca2+]i). We therefore evaluated the effect of L-Arg on MC [Ca2+]i. We found that L-Arg inhibits the vasopressin-stimulated rise in MC [Ca2+]i both in rat and murine cell cultures. This effect does not appear to be due to metabolism of L-Arg to either NO or L-ornithine (L-Orn). Blocking the metabolism of L-Arg with Nomega-monomethyl-L-arginine, an NO synthase inhibitor, or with 20 mM L-valine (L-Val), an inhibitor of Orn formation, does not reverse the inhibition. However, other cationic amino acids, as well guanidine, the functional group of L-Arg, all inhibit the vasopressin-stimulated rise in [Ca2+]i, consistent with a structural basis for this effect. We conclude that 1) L-Arg inhibits vasopressin-stimulated murine and rat MC [Ca2+]i rise, 2) this inhibition is not mediated by metabolism of L-Arg to either NO or L-Orn, and 3) the effect of L-Arg is due to its cationic functional group, guanidine.

A proximo-distal gradient of FGF-like activity in the embryonic chick limb bud.

In a microassay for anchorage-independent growth in soft agar, NR6 cells form colonies in a dose-dependent manner in the presence of fibroblast growth factor (FGF). Using this assay system, the ability of thin sequential slices of embryonic chick limb bud to promote colony formation was investigated. A functional gradient of colony-promoting ability along the proximo-distal axis of the developing chick limb bud (stages 22-26) was observed. The highest number of colonies was observed in the presence of the most distal slices, and colony number decreased progressively at proximal levels. This gradient was specifically eliminated by the addition of anti-FGF antibody to the assay, indicating that it was caused by a functional gradient of an FGF-like molecule. Limbs of stages 21-26 were assayed: before this time limb buds are too small to slice in the proximo-distal axis in the required manner. The FGF-like gradient was observed at stages 22 to 26.