Rescue of replication failure by Fanconi anaemia proteins

Chromosomal aberrations are often associated with incomplete genome duplication, for instance at common fragile sites, or as a consequence of chemical alterations in the DNA template that block replication forks. Studies of the cancer-prone disease Fanconi anaemia (FA) have provided important insights into the resolution of replication problems. The repair of interstrand DNA crosslinks induced by chemotherapy drugs is coupled with DNA replication and controlled by FA proteins. We discuss here the recent discovery of new FA-associated proteins and the development of new tractable repair systems that have dramatically improved our understanding of crosslink repair. We focus also on how FA proteins protect against replication failure in the context of fragile sites and on the identification of reactive metabolites that account for the development of Fanconi anaemia symptoms

Parathyroid Localization and Preservation during Transcervical Resection of Substernal Thyroid Glands

Objective The feasibility of parathyroid preservation during thyroidectomy has not been well documented for cases in which the thyroid gland extends into the mediastinum. Study Design Retrospective chart review. Setting Tertiary academic referral center. Subjects and Methods In this retrospective cohort study, 70 consecutive patients who had substernal thyroid glands treated with a transcervical thyroidectomy between 1993 and 2013 were compared with 286 thyroidectomies that did not entail substernal extension within that same time period. All localized parathyroid glands were confirmed histologically. Results Of 160 possible parathyroid glands in the substernal cases, 119 (74%) were histologically confirmed intraoperatively (67 superior and 52 inferior). In nonsubsternal cases, 725 (89%) were histologically confirmed (372 superior and 353 inferior). There was a statistically significant difference between the substernal and nonsubsternal cases in the total number of glands found (P \u3c .0001) and the number of superior and inferior glands that were identified (P = .009 and \u3c 0.0001). Conclusions Even when the thyroid gland extends into the mediastinum, it is often possible, although with reduced efficiency, to identify and preserve the parathyroid glands

PNL2 melanocytic marker in immunohistochemical evaluation of primary mucosal melanoma of the head and neck.

BACKGROUND: Histologic diagnosis of mucosal melanoma of the head and neck is difficult, requiring immunohistochemical stains which are less reliable than in cutaneous lesions. PNL-2 is a novel marker that has not been examined in mucosal melanoma. METHODS: Nine formalin-fixed tissue sections of mucosal melanoma were stained with PNL-2, human melanoma black (HMB)-45, Melan-A, S-100, and microphthalmia transcription factor (MITF). RESULTS: Disease in all 9 patients arose from the sinonasal mucosa. Rates of diffuse positive staining with the 4 stains were PNL-2 (77.8%), HMB-45 (77.8%), Melan-A (50%), S-100 (87.5%), and MITF (40%). In 3 patients, PNL2 staining was superior to Melan-A or MITF. CONCLUSION: We report the first characterization of PNL-2 staining in head and neck mucosal melanoma. PNL-2 demonstrates high sensitivity for mucosal melanoma, likely superior to Melan-A and MITF, and comparable to HMB-45, with specificity superior to S-100. We advocate inclusion of PNL2 as an important adjunctive marker in the evaluation of these lesions

PNL2 melanocytic marker in immunohistochemical evaluation of primary mucosal melanoma of the head and neck.

BACKGROUND: Histologic diagnosis of mucosal melanoma of the head and neck is difficult, requiring immunohistochemical stains which are less reliable than in cutaneous lesions. PNL-2 is a novel marker that has not been examined in mucosal melanoma. METHODS: Nine formalin-fixed tissue sections of mucosal melanoma were stained with PNL-2, human melanoma black (HMB)-45, Melan-A, S-100, and microphthalmia transcription factor (MITF). RESULTS: Disease in all 9 patients arose from the sinonasal mucosa. Rates of diffuse positive staining with the 4 stains were PNL-2 (77.8%), HMB-45 (77.8%), Melan-A (50%), S-100 (87.5%), and MITF (40%). In 3 patients, PNL2 staining was superior to Melan-A or MITF. CONCLUSION: We report the first characterization of PNL-2 staining in head and neck mucosal melanoma. PNL-2 demonstrates high sensitivity for mucosal melanoma, likely superior to Melan-A and MITF, and comparable to HMB-45, with specificity superior to S-100. We advocate inclusion of PNL2 as an important adjunctive marker in the evaluation of these lesions

Downhill from devaluation: The battle for sterling, 1967–1972

The devaluation of 1967 and the float of 1972 have become two of the key cornerstones in the analysis of sterling under the Bretton Woods system. Sterling’s fortunes between 1968 and 1972 have not been so well documented. This article uncovers new evidence about the pound for this period, including the British government’s contingency plans for blocking the sterling balances as a means to negate the weakness of sterling following the 1967 devaluation, the discussions with the United States on the reform of the international monetary system, and the preparations made for floating the pound