[Recommended diagnostics for pruritus affecting primary non-lesional skin]. / Empfohlene Diagnostik bei Pruritus auf primär unveränderter Haut.

BACKGROUND: Chronic pruritus affecting primary non-lesional skin (CPNL) manifests as a common symptom across a spectrum of diseases spanning various medical specialties. Given the diverse etiological factors involved, diagnosing the underlying condition poses a significant challenge. OBJECTIVES: To provide a comprehensive overview of clinical, laboratory, and imaging diagnostics for CPNL. MATERIALS AND METHODS: A thorough literature search on the diagnostics of chronic pruritus was conducted using PubMed with specific keywords "chronic pruritus AND non-lesional skin", "chronic itch AND non-lesional skin", "chronic pruritus AND diagnostics", "chronic itch AND diagnostics", "CKD-aP", "hepatic pruritus", "cholestatic pruritus", and "myeloproliferative neoplasms AND pruritus". RESULTS: A systematic diagnostic approach is recommended for patients with CPNL, guided by the prevalence of pruritus-associated diseases. Initial basic diagnostics facilitate a cost-effective and focused evaluation during the initial medical assessment. Information pertaining to underlying diseases can be further refined through specialized diagnostic procedures. CONCLUSIONS: CPNL often presents a diagnostic dilemma. Adopting a stepwise diagnostic strategy facilitates the identification of underlying etiologies, which is crucial for recognizing diseases and administering pruritus-specific pharmacotherapy.

adapt78, a stress-inducible mRNA, is related to the glucose-regulated protein family of genes.

We have recently reported a new oxidant- and calcium-inducible mRNA, adapt78, from hamster HA-1 cells. The adapt78 mRNA is induced in HA-1 cells under conditions where a protective adaptive response is observed and contains a translatable open reading frame whose protein product shows strong homology to a human sequence. Computer analysis of the predicted Adapt78 protein sequence also revealed a stretch of amino acids homologous to a portion of the glucose-regulated protein78 (Grp78). Based on this homology, we tested the hypothesis that adapt78 may be a new member of the grp gene family. Toward this, we assessed the modulation of adapt78 mRNA by stress agents known to induce grp78. In HA-1 cells, adapt78 mRNA was induced by the calcium ionophore A23187, 2-deoxyglucose, brefeldin A, tunicamycin, thapsigargin, and cyclopiazonic acid, with thapsigargin being the most potent inducer (7.3-fold). As expected, grp78 mRNA was also induced by these agents in our model system. In contrast, heat shock treatment produced little if any modulation of either grp78 or adapt78. Differences were also observed, as adapt78 mRNA but not grp78 mRNA was induced by 160 microM hydrogen peroxide, and adapt78 demonstrated earlier induction kinetics for certain agents compared with grp78. adapt78 mRNA was also found to be induced in several different human cell lines. A23187 had the strongest effect on adapt78 mRNA levels in human cells, inducing greater than 20-fold in all human cell cultures tested. Furthermore, in vitro transcription translation of human adapt78 cDNA produced an Adapt78 protein product. We conclude that adapt78 may be a new member of the grp family of genes and may represent an early response grp that complements the actions of grp78 and grp94.

Extension of chromatin accessibility by nuclear matrix attachment regions.

Transcription of the variable region of the rearranged immunoglobulin mu gene is dependent on an enhancer sequence situated within one of the introns of the gene. Experiments with transgenic mice have shown that activation of the promoter controlling this transcription also requires the matrix-attachment regions (MARs) that flank the intronic enhancer. As this mu gene enhancer can establish local areas of accessible chromatin, we investigated whether the MARs can extend accessibility to more distal positions. We eliminated interactions between enhancer- and promoter-bound factors by linking mu enhancer/MAR fragments to the binding sites for bacteriophage RNA polymerases that were either close to or one kilobase distal to the enhancer. The mu enhancer alone mediated chromatin accessibility at the proximal site but required a flanking MAR to confer accessibility upon the distal promoter. This long-range accessibility correlates with extended demethylation of the gene construct but not with whether it is being actively transcribed. MARs thus collaborate with the mu enhancer to generate an extended domain of accessible chromatin.

Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development.

Targeted inactivation of the murine gene encoding the transcription factor LEF-1 abrogates the formation of organs that depend on epithelial-mesenchymal tissue interactions. In this study we have recombined epithelial and mesenchymal tissues from normal and LEF-1-deficient embryos at different stages of development to define the LEF-1-dependent steps in tooth and whisker organogenesis. At the initiation of organ development, formation of the epithelial primordium of the whisker but not tooth is dependent on mesenchymal Lef1 gene expression. Subsequent formation of a whisker and tooth mesenchymal papilla and completion of organogenesis require transient expression of Lef1 in the epithelium. These experiments indicate that the effect of Lef1 expression is transmitted from one tissue to the other. In addition, the finding that the expression of Lef1 can be activated by bone morphogenetic protein 4 (BMP-4) suggests a regulatory role of this transcription factor in BMP-mediated inductive tissue interactions.