Rational design of a SOCS1-edited tumor-infiltrating lymphocyte therapy using CRISPR/Cas9 screens.

Cell therapies such as tumor-infiltrating lymphocyte (TIL) therapy have shown promise in the treatment of patients with refractory solid tumors, with improvement in response rates and durability of responses nevertheless sought. To identify targets capable of enhancing the antitumor activity of T cell therapies, large-scale in vitro and in vivo clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens were performed, with the SOCS1 gene identified as a top T cell-enhancing target. In murine CD8+ T cell-therapy models, SOCS1 served as a critical checkpoint in restraining the accumulation of central memory T cells in lymphoid organs as well as intermediate (Texint) and effector (Texeff) exhausted T cell subsets derived from progenitor exhausted T cells (Texprog) in tumors.

Structure and Glycan Binding of a New Cyanovirin-N Homolog.

The HIV-1 envelope glycoprotein gp120 is heavily glycosylated and bears numerous high mannose sugars. These sugars can serve as targets for HIV-inactivating compounds, such as antibodies and lectins, which bind to the glycans and interfere with viral entry into the target cell. We determined the 1.

Focused Vascular Ultrasound for the Assessment of Atherosclerosis: A Proof-of-Concept Study.

Background: Current decisions to refer for angiographic coronary assessment are based on pain character, risk scores, stress testing, and occasionally calcium scoring. Carotid plaque has emerged as an effective vascular biomarker, but the cost and time of a full carotid ultrasound examination are disadvantageous. Focused vascular ultrasound (FOVUS) is a rapid limited assessment of carotid plaque that can be conducted by non-vascular-trained operators.

Batch variations.

One of the basic principles in the investigation of suspected contact dermatitis is always to test with the patient's "own" product or chemical, the one to which he or she was actually exposed. An equally basic second principle is not to rely solely on a positive test reaction. The author discusses a case of contact dermatitis involving only certain batches of a particular branded product.

Studies in the guinea-pig with ICI 185,282: a thromboxane A2 receptor antagonist.

The effects of ICI 185,282 (5(Z)-7-([ 2,4,5-cis]-4-O-hydroxyphenyl-2-trifluoromethyl-1, 3-dioxan-5-yl)heptenoic acid) have been studied on guinea-pig platelets and pulmonary smooth muscle in-vitro and in-vivo. When tested on guinea-pig lung parenchyma in-vitro. ICI 185,282 (1 x 10(-7) M) produced a significant shift in U-46619 response curves (concentration ratio of 13:3); the antagonist (1 x 10(-5) M) did not modify histamine responses.

Contact and photocontact allergy to musk ambrette.

Musk ambrette, a contact and photocontact allergen, is a synthetic fragrance present in aftershave lotions and many toiletries. Thirty-four patients with contact and photocontact allergy to musk ambrette were studied. All had a facial eczema.

Lichen aureus: a localized persistent form of pigmented purpuric dermatitis.

Localized persistent pigmented macules and plaques due to a chronic form of pigmented purpuric dermatitis are described in forty-two patients. The designation 'lichen aureus' for this eruption can be justified because of the striking yellowish or bronze-like colour assumed by many of the lesions. The lower legs were the commonest sites but other body regions can be affected also.

Thalidomide in actinic prurigo.

Fourteen patients suffering from actinic prurigo were treated with thalidomide. Eleven patients showed lasting improvement on the drug and three of these remained symptom-free after discontinuing therapy. No major side-effects were observed.

Allergy to phenyl salicylate.

Six cases of contact dermatitis from a lip salve are described. Five were allergic to phenyl salicylate and one to geraniol in the fragrance. The dermatitis spread in a ring around the mouth.