Profile of Transforming Growth Factor-β Responses During the Murine Hair Cycle

Transforming growth factor-β (TGF-β) appears to promote the regression phase of the mammalian hair cycle, in vivo in mice and in organ culture of human hair follicles. To assess the relationship between TGF-β activity and apoptosis of epithelial cells during the murine hair cycle, we identified active TGF-β responses using phospho-Smad2/3-specific antibodies (PS2). Strong, nuclear PS2 staining was observed in the outer root sheath throughout the anagen growth phase. Some bulb matrix cells were positive for PS2 during late anagen. Extensive, but weak, staining was observed in this region at the anagen-catagen transition. We also examined expression of TGF-β-stimulated clone-22 (TSC-22), which is associated with TGF-β-induced apoptosis of some cell lines. Recombinant rat TSC-22 was used to generate a rabbit anti-TSC-22 antibody useful for immunohistochemistry. TSC-22 RNA accumulation and immunoreactivity were observed in follicles throughout the murine hair cycle, including the dermal papilla and lower epithelial strand of late-catagen hair follicles. Neither the expression pattern nor the presence of nuclear TSC-22 correlated with the sites of apoptosis, suggesting that TSC-22 is not an effector of apoptosis in mouse catagen hair follicles. These studies support a complex role for TGF-β in regulating the regression phase of the cycle, with potential for indirect promotion of apoptosis during the anagen–catagen transition

Rapid Multiorgan Dissemination of Low-Grade Myxofibrosarcoma: A Case Report

Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly people. It is characterized by a high frequency of local recurrence due to an infiltrative growth property. In contrast, the overall risk of distant metastases is generally low. This makes the prognosis for the patients with myxofibrosarcoma definitely good. In this paper, we will report the case of a 79-year-old female with very aggressive metastatic low-grade myxofibrosarcoma. The disease progression was really unexpected and misled every possible medical interpretation, leading to rapid worsening of the patient's clinical conditions and no chance for therapy. The tumor developed diffuse infiltration in lung, spine, skeletal bone, abdomen, paravertebral muscles, and liver. The patient died 8 months after the diagnosis of remote metastases due to rapid tumor progression

Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo

The regression phase of the hair cycle (catagen) is an apoptosis‐driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor β1 (TGF‐β1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF‐β1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF‐β1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF‐β1 null mice and age‐matched wild‐type littermates, and assessed the effects of TGF‐β1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF‐β1 —/— mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF‐β1 — /— mice displayed more Ki‐67‐positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF‐β1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratino‐cytes was reduced and the number of TUNEL + cells was increased in the TGF‐β1‐treated mice compared to controls. Double visualization of TGF‐β type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF‐β1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TGF‐βRII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism).—Foitzik, K., Lindner, G., Mueller‐Roever, S., Maurer, M., Botchkareva, N., Botchkarev, V., Handjiski, B., Metz, M., Hibino, T., Soma, T., Dotto, G. P., Paus, R. Control of murine hair follicle regression (catagen) by TGF‐β1 in vivo. FASEB J. 14, 752–760 (2000

Thermal and Electrochemical Stability of Tetraglyme–Magnesium Bis(trifluoro­methane­sulfonyl)amide Complex: Electric Field Effect of Divalent Cation on Solvate Stability

Phase behavior of binary mixtures of tetraglyme (G4) and Mg­[TFSA]₂ (TFSA: bis­(trifluoro­methane­sulfonyl)­amide) was investigated. In a 1:1 molar ratio, G4 and Mg­[TFSA]₂ formed a stable complex with a melting point of 137 °C. X-ray crystallography of a single crystal of the complex grown from a G4-Mg­[TFSA]₂ binary mixture revealed that the G4 molecule wraps around Mg²⁺ to form a complex [Mg­(G4)]²⁺ cation, and the two [TFSA]⁻ anions also participate in the Mg²⁺ coordination in the crystal. The thermal stability of [Mg­(G4)]­[TFSA]₂ was examined by thermogravimetry, and it was found that the complex is stable up to 250 °C. Above 250 °C, desolvation of the Mg²⁺ ion takes place and G4 evaporates. On the other hand, the weight loss starts at around 140 °C in solutions containing excess G4 (<i>n</i> > 1 in Mg­[TFSA]₂:G4 = 1:<i>n</i>) due to the evaporation of free (uncoordinated) G4. The suppression of G4 volatility in the [Mg­(G4)]­[TFSA]₂ complex is attributed to strong electrostatic and induction interactions between divalent Mg²⁺ and G4. In addition, complexation of G4 with Mg²⁺ is effective in enhancing the oxidative stability of G4. Linear sweep voltammetry revealed that the oxidative decomposition of [Mg­(G4)]­[TFSA]₂ occurs at electrode potentials >5 V vs Li/Li⁺, while the oxidation of uncoordinated G4 occurs at around 4.0 V. This oxidative stability enhancement occurs because the HOMO energy level of G4 is reduced by complexation with Mg²⁺, which is supported by the <i>ab initio</i> calculations