Multiple Keratoacanthomas, Philadelphia Chromosome+ Acute Lymphoblastic Leukemia, and Dasatinib: A Case Report

Background: Treatment for adult Philadelphia chromosome+ acute lymphoblastic leukemia includes using dasatinib, a tyrosine kinase inhibitor. Cutaneous squamous cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors of tyrosine kinases. No documentation of dasatinib inducing multiple keratoacanthomas, squamous cell carcinomas type during treatment of Philadelphia chromosome+ acute lymphoblastic leukemia is currently available. Case: A 77-year-old Caucasian male presented to the dermatology clinic two months after starting treatment with dasatinib for Philadelphia chromosome positive+ acute lymphoblastic leukemia. Biopsies confirmed the lesions on the arms, chest, legs and back as keratoacanthoma (KA) type of squamous cell carcinomas (SCCs). The cutaneous lesions were surgically removed and no new or recurrent lesions were detected since their initial rapid onset despite continued dasatinib therapy. Conclusion: This report of the rapid onset of keratoacanthoma type squamous cell carcinomas in a patient with Philadelphia chromosome+ acute lymphoblastic leukemia treated with dasatinib is presumed to be the first due to the rarity of adult Philadelphia chromosome+ acute lymphoblastic leukemia. This report documents another tyrosine kinase inhibitor that is associated with the eruption of keratoacanthomas, and adds to the literature regarding the regularity of this relatively common side effect, which may have treatment other than surgery if only a few lesions are present

Secondary Localized Cutaneous Amyloidosis Associated with Actinic Keratosis

Histochemically identifiable amyloid associated with actinic keratosis was studied with the electron microscope. Typical amyloid filaments forming islands identical to collagen strands were found in the upper dermis. Beyond the lesion of actinic keratosis, no amyloid was found. In the healing wound of a previously biopsied lesion, amyloid was regenerated only when the epidermis covered the wound. In such epidermis-covered granulation tissue, electron-dense amorphous substance was initially formed in the upper dermis and amyloid filaments subsequently emerged within it. In both original and regenerated lesions, perivascular spaces were free from amyloid, and actinic elastosis was absent. It was concluded that secondary amyloidosis associated with actinic keratosis is produced by local fibroblastic cells under an abnormal influence of the epidermis

The EGF/TGFα Receptor in Skin

In responsive cells, all known effects of epidermal growth factor (EGF), transforming growth factor a (TGFα), and related proteins are mediated through binding to a specific membrane receptor. The EGF/TGFα receptor is a single- chain glycoprotein (1186 amino acids) containing three functional domains: 1) an extracellular, glycosylated portion that binds EGF; 2) a small transmembrane portion; and 3) a cytoplasmic portion that has the intrinsic tyrosine kinase activity and multiple sites that can be phosphorylated. When EGF binds to the receptor its intrinsic tyrosine kinase is activated, resulting in increased phosphorylation of intracellular tyrosine residues both on the receptor (autophosphorylation sites) and on exogenous proteins involved in regulating cellular functions. Site-specific mutagenesis has established that the tyrosine-kinase activity of the receptor is essential for nearly all of the effects of EGF including its ability to elevate cellular calcium levels and to induce DNA synthesis. The binding of EGF and the kinase activity of the receptor are both regulated by the phosphorylation of the receptor on specific threonine/serine sites catalyzed by other protein kinases. Specific lipids such as sphingosine also can regulate kinase activity. Tyrosine-specific phosphoprotein phosphatases and perhaps proteases must be important in terminating the cellular response to EGF. In human skin, the response to EGF/TGFα is determined by the location and number of receptors and is modulated by processes affecting the binding affinity, internalization, and tyrosine-kinase activity of the receptor. Specific patterns of EGF binding and of immunoreactive receptors characterize normal growth and differentiation and these are altered during the abnormal growth and differentiation associated with diseases such as psoriasis, viral infections, neoplasms, and paraneoplastic syndromes. It is not clear if the altered patterns reflect the consequence of the disease or are the cause of the disease. As a cause, the EGF receptor may have undetected point mutations that result in internalization and degradation defects, aberrant phosphorylation, and dephosphorylation or abnormal glycosylation

Visualization of Epidermal Growth Factor Receptors in Human Epidermis

The localization of epidermal growth factor (EGF) receptors in normal human epidermis was examined with two independent experimental methods. The distribution of EGF receptor sites was studied using light microscopic autoradiography with [125I]EGF and direct immunocytochemical techniques with EGF receptor antibodies and protein A-colloidal gold complexes. Direct visualization by autoradiography indicated that the concentration of EGF receptors was greatest in the lower epidermal layers. Ultrastructural morphometric analysis of protein A-gold complexes showed that EGF receptors were primarily associated with the plasma membranes although intranuclear and cytoplasmic localization was also evident. This postembedment immunolocalization method also confirmed the relative differences in the number of EGF receptors found in individual epidermal layers (basalis > spinosum > granulosum corneum layers). This inverse relationship between numbers of EGF receptors and the degree of epidermal differentiation and/or keratinization may suggest a physiologic role for EGF in these processes in human epidermis

Autoantibodies to Hair Follicles in C3H/HeJ Mice With Alopecia Areata–Like Hair Loss

We have previously described spontaneous but reversible hair loss that clinically and histologically resembles human alopecia areata in a colony of C3H/HeJ mice. Alopecia areata in humans is associated with antibodies to hair follicles. This study was conducted to determine whether C3H/HeJ mice with hair loss have a similar abnormal antibody response to hair follicles. Eighteen C3H/HeJ mice with alopecia, 12 unaffected littermates, and 15 control mice were examined for circulating antibodies to C3H/HeJ anagen hair follicles by indirect immunofluorescence and against extracts of isolated C3H/HeJ and human anagen hair follicles by immunoblotting. Using both procedures, antibodies to anagen hair follicles were present in all C3H/HeJ mice with alopecia but in none of the control mice. The antibodies were also present in some unaffected C3H/HeJ littermates but were absent in mice of an unrelated strain with inflammatory skin disease and alopecia, indicating that their appearance did not result from the hair loss. These antibodies reacted to hair follicle–specific antigens of 40–60kDa present in murine and human anagen hair follicles. These antigens were also reactive with human alopecia areata antibodies. Some of the antibodies in both C3H/HeJ mice and humans with alopecia areata reacted to antigens of 44 and 46 kDa, which were identified as hair follicle–specific keratins. This study indicates that C3H/HeJ mice with hair loss have circulating antibodies to hair follicles similar to those present in humans with alopecia areata. These findings confirm that these mice are an appropriate model for human alopecia areata and support the hypothesis that alopecia areata results from an abnormal autoimmune response to hair follicles

Detecting Determinacy in Prolog Programs: 22nd International Conference, ICLP 2006, Seattle, WA, USA, August 17-20, 2006. Proceedings

In program development it is useful to know that a call to a Prolog program will not inadvertently leave a choice-point on the stack. Determinacy inference has been proposed for solving this problem yet the analysis was found to be wanting in that it could not infer determinacy conditions for programs that contained cuts or applied certain tests to select a clause. This paper shows how to remedy these serious deficiencies. It also addresses the problem of identifying those predicates which can be rewritten in a more deterministic fashion. To this end, a radically new form of determinacy inference is introduced, which is founded on ideas in ccp, that is capable of reasoning about the way bindings imposed by a rightmost goal can make a leftmost goal deterministic

The genetic basis for adaptation of model-designed syntrophic co-cultures.

Understanding the fundamental characteristics of microbial communities could have far reaching implications for human health and applied biotechnology. Despite this, much is still unknown regarding the genetic basis and evolutionary strategies underlying the formation of viable synthetic communities. By pairing auxotrophic mutants in co-culture, it has been demonstrated that viable nascent E. coli communities can be established where the mutant strains are metabolically coupled. A novel algorithm, OptAux, was constructed to design 61 unique multi-knockout E. coli auxotrophic strains that require significant metabolite uptake to grow. These predicted knockouts included a diverse set of novel non-specific auxotrophs that result from inhibition of major biosynthetic subsystems. Three OptAux predicted non-specific auxotrophic strains-with diverse metabolic deficiencies-were co-cultured with an L-histidine auxotroph and optimized via adaptive laboratory evolution (ALE). Time-course sequencing revealed the genetic changes employed by each strain to achieve higher community growth rates and provided insight into mechanisms for adapting to the syntrophic niche. A community model of metabolism and gene expression was utilized to predict the relative community composition and fundamental characteristics of the evolved communities. This work presents new insight into the genetic strategies underlying viable nascent community formation and a cutting-edge computational method to elucidate metabolic changes that empower the creation of cooperative communities

A low-absorption disk zone at low Galactic latitude in Centaurus

We investigate the properties of two stellar concentrations in a low-absorption disk zone in Centaurus, located respectively at $\ell=306.47^{\circ}$, $b=-0.61 ^{\circ}$, and $\ell=307.01^{\circ}$, $b=-0.74 ^{\circ}$. The present analysis is based mostly on 2MASS photometry, as well as optical photometry. Based on colour-magnitude diagrams and stellar radial density profiles, we show that these concentrations are not open star clusters. Instead, they appear to be field stars seen through a differentially-reddened window. We estimate that the bulk of the stars in both stellar concentrations is located at $\sim1.5$ kpc from the Sun, a distance consistent with that of the Sgr-Car arm in that direction. This low-absorption window allows one to probe into distant parts of the disk besides the Sgr-Car arm, probably the tangent part of the Sct-Cru arm, and/or the far side of the Sgr-Car arm in that direction. The main sequence associated to the Sgr-Car arm is reddened by \ebv\sim0.5, so that this window through the disk is comparable in reddening to Baade's window to the bulge. We also investigate the nature of the open cluster candidate Ru 166. The presently available data do not allow us to conclude whether Ru 166 is an actual open cluster or field stars seen through a small-scale low-absorption window

Multiplicativity of completely bounded p-norms implies a new additivity result

We prove additivity of the minimal conditional entropy associated with a quantum channel Phi, represented by a completely positive (CP), trace-preserving map, when the infimum of S(gamma_{12}) - S(gamma_1) is restricted to states of the form gamma_{12} = (I \ot Phi)(| psi >< psi |). We show that this follows from multiplicativity of the completely bounded norm of Phi considered as a map from L_1 -> L_p for L_p spaces defined by the Schatten p-norm on matrices; we also give an independent proof based on entropy inequalities. Several related multiplicativity results are discussed and proved. In particular, we show that both the usual L_1 -> L_p norm of a CP map and the corresponding completely bounded norm are achieved for positive semi-definite matrices. Physical interpretations are considered, and a new proof of strong subadditivity is presented.Comment: Final version for Commun. Math. Physics. Section 5.2 of previous version deleted in view of the results in quant-ph/0601071 Other changes mino

The Ursinus Weekly, January 15, 1962

Shadowy figure of Ursinus\u27 past publishes volume of 66 poems • Dr. Snyder, Forum speaker, outlines seven strong forces in Africa today • Spontaneous fun object of new social committee • Prof casts critical eye over Lantern; Discovers sound creative instincts • Bursting water pipe sends Alumni Office to 620 Main • Student teachers\u27 light-hearted talk explains what\u27s not in the Ed. book • Best-dressed co-ed sought by Weekly • Shares of the pecuniary pie • Pre-medders hear about corneal transplant work • Editorial: Appeal of wrestling • Ursinus in the past • Letters to the editor • Obituary for a timid intellectual • Dryfoos sets two Ursinus cage marks; Dean ties record with quick pin • Pair of heartbreaking losses catch grapplers last week • Basketball begins • Frymen flounder; Lose to PMC, 92-80; Drop thriller to Swarthmore, 89 to 85 • Greek gleaningshttps://digitalcommons.ursinus.edu/weekly/1309/thumbnail.jp