[Profile and immune environment of upper tract urothelial carcinoma]. / Profil et environnement immunitaires des tumeurs de la voie excrétrice supérieure.

INTRODUCTION AND OBJECTIVES: Upper Tract Urothelial Carcinoma (UTUC) are tumors that share similarities with bladder tumors. Immunotherapy is already used for bladder locations and appears to have interest for UTUC. In order to rationalize the immunotherapy development pipeline it seemed necessary to describe the immune infiltrate of a cohort of UTUC treated with nephroureterectomy and to determine the expression of a panel of immune checkpoints and co-stimulatory molecules on tumor cells as well as on infiltrating and circulating lymphocytes. MATERIALS AND METHODS: This is a monocentric, prospective and exploratory work. Patients treated with total nephroureterectomy or segmental ureterectomy for presumably infiltrative (≥ T1) UTUC managed at the Saint-Louis Hospital were included from January 2019 to July 2020. A set of markers and immune checkpoints were studied by flow fluorocytometry on circulating lymphocytes (PBMCs) and tumor-infiltrating lymphocytes (TILs). Some markers were also studied by immunohistochemistry on tumor sample. RESULTS: In total, 14 patients were included and 13 patients could be analyzed. 1 patient had no residual tumor. 5 tumors out of the 12 (41.7%) showed a lymphocytic inflammatory infiltrate. PD1 was the most represented checkpoint with a median expression rate of 41.4% on CD4+ TILs and 3.89% on circulating CD4+ T cells. This rate was 62.4% and 7.45% respectively on CD8+ T cells. TIGIT was the second most represented marker with a median expression rate on tumor-infiltrating CD4+ T cells of 25% and 2.9% on circulating CD4+ T cells. The median expression level of TIGIT on tumor-infiltrating CD8+ T cells was 23.3% and 3.2% on circulating CD8+ T cells. ICOS was highly expressed on CD4+ TILS with a median of 33.9% in contrast to CD8+ TILS (median: 6.67%). Variable expression of other checkpoints (ILT2, TIM3, LAG3 and OX40) was found without clear trend. CONCLUSION: This exploratory work highlighted that PD1 was the most represented checkpoint. TIGIT was the second most represented checkpoint while ICOS, TIM3 and LAG3 were 3 other checkpoints whose expression was found to be less important. ILT2 and OX40 appeared to be weakly expressed. LEVEL OF EVIDENCE: II.

A novel covalent modification of nitrogenase in a cyanobacterium.

In extracts of the unicellular cyanobacterium Gloeothece, the Fe-protein of nitrogenase can be separated by SDS-PAGE into two antigenically identifiable components. Unlike the situation in photosynthetic bacteria such as Rhodospirillum rubrum, these two forms do not arise from covalent modification of the protein by ADP-ribosylation. Rather, the Fe-protein of Gloeothece nitrogenase is subjected to modification by palmitoylation.

Interaction of maternal photoperiod history and food type on growth and reproductive development of laboratory meadow voles (Microtus pennsylvanicus).

The interaction of maternal photoperiod history and four diets were tested by measuring body growth, reproductive development, and pelage development in 9-week-old juvenile meadow voles. Meadow vole dams were housed in long daylengths (LD; 14 h light/day), short daylengths for 2 weeks (SD; 10 h light/day), or short daylengths for 26 weeks (PR; photorefractory) prior to mating. Immediately following parturition, one of four diets was available to dams and pups; (a) a control diet containing no 6-methoxy-2-benzoxazolinone (6-MBOA); (b) the control diet plus sprouted wheat (which contains 6-MBOA); (c) the control diet plus alfalfa harvested in spring (no 6-MBOA); and (d) the control diet plus alfalfa harvested in autumn (no 6-MBOA). By 9 weeks of age, juvenile meadow voles born to photorefractory dams and fed either spring or fall alfalfa or sprouted wheat were significantly larger and more had achieved puberty than juveniles fed only the control diet. Juveniles born to LD dams demonstrated a smaller increase in developmental rate than photorefractory juveniles when fed alfalfa and spring wheat, and juveniles of SD dams showed the smallest effect of alfalfa and sprouted wheat on development. Supplements of spring wheat and both forms of alfalfa had similar positive effects on growth and reproduction. The authors suggest that juvenile meadow voles rely on the interaction of maternal photoperiod history and the availability of nutrient-rich food such as sprouted wheat and alfalfa to time the onset of growth and puberty.

Biosynthesis of the tropane-related cyanobacterial toxin anatoxin-a: role of ornithine decarboxylase.

A study was made of the biosynthesis by Anabaena flos-aquae of the tropane-related alkaloid anatoxin-a. Evidence is presented that the toxin arises from ornithine via putrescine (1,4-diaminobutane) and that ornithine decarboxylase (EC 4.1.1.17) is involved. An ornithine decarboxylase preparation, with optimal activity at pH 8, was obtained from Anabaena flos-aquae and partially purified by gel-filtration chromatography on DEAE-cellulose. One major and one minor peak of enzymic activity were obtained with Km values of 1.25 and 2.5 mM, respectively. Plasmid DNA (10 Kb; Mr 6.5 x 10(6] was detected in the toxic strain of Anabaena flos-aquae but not in a non-toxic strain. DNA from the toxin-producing strain of Anabaena flos-aquae transforms the non-toxic into a toxic strain.

[Arteriopathies of the lower extremities before 40. Their nature and prognosis]. / Artériopathies des membres inférieurs avant 40 ans. Nature et pronostic.

Sixty-three patients with arteriopathies confirmed by arteriography when they were under 40 years of age were followed up for between 1 and 7 years. The arteriopathy was due to atheroma in 23 cases, to miscellaneous in 22 cases, and to Buerger's disease less frequently (18 cases), suggesting that atheroma should be suspected as being at the origin of an arteriopathy initially in young subjects. Confirmation of the basic nature of the affection is based on several criteria, the most reliable being results of angiography and the detection of associated lesions in other localizations. Histology is a decisive element, but biopsy may involve risks and results are sometimes difficult to interpret. Treatment depends more on clinical symptomatology and the localizations of arterial occlusion than on the nature of the arteriopathy. Sympathectomy is effective in distal lesions, whereas revascularization, adapted to the often small size of the vessels involved and potential impairment in distal vessel circulation, is necessary for proximal lesions. Overall prognosis is more satisfactory in Buerger's disease than in arteriopathy of atheromatous origin, rapid progression occurring in half of the latter cases.