Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, we present such a guide, which uses objective, well-defined, and reproducible criteria and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in sub-optimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field.
Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3-6 hours after 50-100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.
Nonsurgical treatment has become the standard of care in hemodynamically stable patients with blunt liver trauma. The use of helical computed tomography (CT) in the diagnosis and management of blunt liver trauma is mainly responsible for the notable shift during the past decade from routine surgical to nonsurgical management of blunt liver injuries. CT is the diagnostic modality of choice for the evaluation of blunt liver trauma in hemodynamically stable patients and can accurately help identify hepatic parenchymal injuries, help quantify the degree of hemoperitoneum, and reveal associated injuries in other abdominal organs, retroperitoneal structures, and the gastrointestinal tract. The CT features of blunt liver trauma include lacerations, subcapsular or parenchymal hematomas, active hemorrhage, juxtahepatic venous injuries, periportal low attenuation, and a flat inferior vena cava. It is important that radiologists be familiar with the liver injury grading system based on these CT features that was established by the American Association for the Surgery of Trauma. CT is also useful in the assessment of delayed complications in blunt liver trauma, including delayed hemorrhage, hepatic or perihepatic abscess, posttraumatic pseudoaneurysm and hemobilia, and biliary complications such as biloma and bile peritonitis. Follow-up CT is needed in patients with high-grade liver injuries to identify potential complications that require early intervention.
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