Both connective tissue mast cells and mast cells grown in vitro are derived from multipotential hematopoietic stem cells, but these two mast cell populations exhibit many differences in morphology, biochemistry, and function. We investigated whether the phenotype of cultured mast cells or their progeny was altered when the cells were transferred into different locations in vivo. Cultured mast cells were immature by ultrastructure, and stained with alcian blue but with neither safranin or berberine sulfate, a fluorescent dye that binds to the heparin of connective tissue mast cell granules. By contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient (WB X C57BL/6)F1-W/Wv (WBB6F1-W/Wv) mice 10 wk after intraperitoneal injection of cultured WBB6F1-+/+ or C57BL/6-bgJ/bgJ mast cells stained with both safranin and berberine sulfate. Staining with berberine sulfate was prevented by treatment of the cells with heparinase but not chondroitinase ABC, suggesting that the adoptively transferred mast cell population had acquired the ability to synthesize and store heparin. Furthermore, the recovered mast cells were indistinguishable by ultrastructure from the normal mature peritoneal mast cells of WBB6F1-+/+ mice, and contained substantially more histamine than mast cells studied directly from culture. Intravenous injection of cultured mast cells resulted in the development of safranin-and berberine sulfate-positive mast cells in the peritoneal cavity, spleen, skin, and glandular stomach muscularis propria. Mast cells also developed on the glandular stomach mucosa, but these cells stained with alcian blue rather than safranin, and did not stain with berberine sulfate. This result suggests that cultured mast cells can give rise to mast cells of either the connective tissue type or mucosal phenotype, depending on anatomical location. Furthermore, transplantation of cultured mast cells into WBB6F1-W/Wv mice had no measurable effect on the anemia of the recipient mice, suggesting a possible strategy for repairing the mast cell deficiency of WBB6F1-W/Wv mice without affecting other bone marrow-derived populations such as erythrocytes. Intravenous injection of representative connective tissue type mast cells (30-50% pure peritoneal mast cells derived from WBB6F1-+/+ mice) gave results similar to those obtained with cultured mast cells: mast cells developing in the peritoneal cavity, skin, spleen, and glandular stomach muscularis propria of WBB6F1-W/Wv recipients stained with safranin and berberine sulfate, whereas mast cells developing in the mucosa of the glandular stomach stained only with alcian blue.(ABSTRACT TRUNCATED AT 400 WORDS)
Fifty-seven cases of juvenile xanthogranuloma that fulfilled the classic description of histologic findings of the disease were analyzed clinicopathologically and immunohistochemically. Two forms could be distinguished: 47 cases of the infantile form and 10 of the adolescent and young adult form. The infantile lesion was found at birth in 8 patients (17%), and was noted within 1 year after birth in 33 (70%). Twenty-two had multiple lesions and five of the six for whom follow-up was feasible had spontaneous involution. About half of the lesions were located on the head and neck, 30% on the trunk, and 20% on the extremities. All six adolescents had a solitary tumor located in the head and neck region. Comparison of the latter form with reticulohistiocytoma and cutaneous fibrous histiocytoma was established from a differential point of view. Immunohistochemically, most lesions of juvenile xanthogranuloma displayed a positive reaction for lysozyme and alpha-1-antichymotrypsin and were negative for S-100 protein, thereby suggesting that the essential constituents of this lesion would derive from the mononuclear phagocyte system.
In three patients with hepatocellular carcinoma (HCC), implanted metastases occurred in the peritoneal or pleural cavity after rupture of the tumors; in one patient this was caused by trauma, and in two others this complication became obvious during resection of the tumor. Hepatic resection was successful, and the postoperative status was satisfactory. Implanted metastases were present in the peritoneal or pleural cavity of these three patients 6 years, 10 months, and 6 months after surgery, respectively. We wish to emphasize that a ruptured HCC may lead to implanted metastases.
Abstract. Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/β-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.
A case of dedifferentiated hepatocellular carcinoma with osteoclast‐like giant cells resembling those of giant cell tumor of bone is presented. The clinicopathologic findings are described, and the literature concerning this type tumor is reviewed. The tumor differed histologically from a pleomorphic variant of hepatocellular carcinoma in that there were numerous osteoclast‐like giant cells with numerous, small, uniform, benign‐appearing nuclei. To the knowledge of the authors, there has been only one report of this type of tumor arising in the liver. The tumor contained a separate area of a histologically conventional hepatocellular carcinoma, in addition to the above giant cell areas.
Recommender systems aim to increase user actions such as clicks and purchases. Typical evaluations of recommenders regard the purchase of a recommended item as a success. However, the item may have been purchased even without the recommendation. An uplift is defned as an increase in user actions caused by recommendations. Situations with and without a recommendation cannot both be observed for a specifc user-item pair at a given time instance, making uplift-based evaluation and optimization challenging. This paper proposes new evaluation metrics and optimization methods for the uplift in a recommender system. We apply a causal inference framework to estimate the average uplift for the ofine evaluation of recommenders. Our evaluation protocol leverages both purchase and recommendation logs under a currently deployed recommender system, to simulate the cases both with and without recommendations. This enables the ofine evaluation of the uplift for newly generated recommendation lists. For optimization, we need to defne positive and negative samples that are specifc to an uplift-based approach. For this purpose, we deduce four classes of items by observing purchase and recommendation logs. We derive the relative priorities among these four classes in terms of the uplift and use them to construct both pointwise and pairwise sampling methods for uplift optimization. Through dedicated experiments with three public datasets, we demonstrate the efectiveness of our optimization methods in improving the uplift. CCS CONCEPTS • Information systems → Recommender systems; • Computing methodologies → Learning from implicit feedback.
From September 1981 to December 1988, 163 patients underwent hepatic resection for hepatocellular carcinoma. The patients were divided into two groups: those operated on from September 1981 to March 1985 (n = 58) and those operated on from April 1985 to December 1988 (n = 105). There was an increase in the number of relatively small hepatocellular carcinomas in 1987-88. Differences in the incidence of accompanying liver cirrhosis (72 versus 62 per cent) were not statistically significant; however, values of the indocyanine green test (21.5 versus 17.0 per cent, P less than 0.01) aided in strict patient selection. In more recent years, initial hepatic hilar dissection for control of vascular structures was undertaken and an ultrasonic dissector was used in about three-quarters of these patients. Consequently, the mean estimated blood loss (2500 versus 1300 ml, P less than 0.001) and mean intraoperative blood replacement (2200 versus 560 ml, P less than 0.001) were significantly less than in the earlier period. Among the 58 patients treated in the early period, hospital morbidity and mortality rates were 52 and 29 per cent respectively. In contrast, the rates were 23.8 and 1.9 per cent respectively among the 105 patients operated on during the recent period (P less than 0.01). The decline in hospital mortality is attributed to the careful selection of patients, use of modern tools, and a diminished blood loss.
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