The filling of the gills and head vascular space of a teleost fish was measured in vitro by perfusing an isolated head of a trout with a Ringer solution containing 131I-labeled human serum albumin. The presence of epinephrine in the Ringer solution significantly increased afferent (ventral aortic) flow rate and efferent (dorsal aorta) flow rate, whereas branchial venous system circulation was reduced. When perfused with an epinephrine-free Ringer, the branchial vascular space appears 5-6 times greater than the head vascular space (per 100 g of tissue). Epinephrine, 10(-5) M, in the Ringer solution significantly decreased the branchial vascular space without modifying that of the head. The increase in perfusion rate and decrease in branchial vascular space due to the epinephrine can only be interpreted by taking into account a branchial nonlamellar compartment of a considerable volume.
The cervico-vaginal secretions of 58 women were shown to contain IgG and IgA globulins in high concentration. The ratio IgG/IgA was found to be 1.5. IgM globulin was demonstrated only occasionally. Agglutinating antibodies to Candida albicans were present in 48% of the samples and antibodies to E.Coli in 77%. The opsonizing property of genital tract secretions against Enterococcus, Kleb-siella, Proteus vulgaris and Pseudomonas was found to be present in 207 tests (79%). Absorption of the material with a rabbit anti-human y-globulin anti-serum removed almost all the opsonizing activity. Lysozyme and complement were shown to enhance the phagocytic properties of these external secretions. Local immunological mechanisms are likely to play a significant role in the protection of human genital tract against infection.
35 insulin-treated diabetics and 25 control persons were studied for in vivo and in vitro manifestations of hypersensitivity to insulin and its isolated polypeptide chains. Delayed hypersensitivity reactions were determined by skin testing, and blastogenic conversion tests were done with peripheral blood lymphocytes. None of the controls and 62.9% of the patients gave positive reactions in the blastogenic test, most of these reacted to the intact molecule, fewer patients responded to B chains, and very few responded to A chains. None of the controls and only three of the patients produced positive delayed hypersensitivity reactions to insulin, and all of these were to the intact insulin molecule.
LA | munities at a rate which makes it one of our most urgent environmenltal problems1. The ventilation limit of many z2.5s2sS2sWS~of our cities-their ability to dispose harmiessly of poisonOUS gases, soot particles, and fly ash into thle upper atmospheric trashbasket-has already been approached. Every newr power plant, smokestack, refinery, home furnacce, incinerator, aUtolnobile, bus or truck adds to the burden, and during the ncxt decade or so these sources of contamination will increase by at least 25 per cent. For air pollution iS a disease of increasing population2, and it has been estimated that by I975 there will be in America alone j,0ooo,ooo more persons to be serviced by means of devices that wvill produce air pollution. The fin-Incial burden of air pollution is already staggering. Crop damage in the-Los Angeles area in I957 was estimated at $5sooo,ooo' 4; the deterioration of stonelbuildings and the corrosion of metals and paint, directly traceable to air pollution, play a large role in cvery city budget. "It is estimated conservatively that the cost of air pollution to the citizens of the City of New York is approximatelTy $I2 per person per year, or $IOO000,000", laccording to the Department of Air Pollution'. Thle chemical industry wvas recently reported as spending $40,000,-000 yearly and the automotive industry is said to have devoted $sooo,-000 in so far unsuccessful attempts to develop oxidizers or afterburners which will eliminate the harmful hydrocarbons in gasoline and diesel motor exhausts. There are few cities in the LUnited States of over 25,000 population without some form of air pollution control7. In I955, after President Eisenhower, in hlis State of the Union address, called attention to thle growing menace, Congress authorized the appropriation of $5,ooo,ooo ePrepared for the Subcomtmittee oo Air Pollution and Health. Committee on1 Pu1bIiC 1 lealtlh 'The Netv York Academy of Medicine. F room the I)epmartnenit of 'Medicitie (ollege of Physic;iis aoil Surgeoti, Colntim ia 1 vTniersity, anti the t resbyterilai Hospmital NeV York, N. V.
Even if lymphocyte presence within tumor tissues and its impact on cancer patient prognosis have been well documented past few years, the type of tumor vessels governing infiltration of effector cells into tumors remain to be determined. High endothelial venules (HEV) are specialized vessels for lymphocyte recruitment physiologically present in secondary lymphoidorgans also found in chronic inflammation that may impact lymphocyte recruitment and cancer patient's clinical outcome. We recently identified HEV like vessels in the peritumoral stroma of human solid tumors including melanomas, breast, colon, ovarian, and lung carcinomas. In order to better analyse the functional consequence of HEV presence within human solid tumors, we quantified HEV and tumor infiltrating lymphocytes by immunohistochemistry on serial tumor sections of 146 breast cancer patients. We demonstrate that HEV like vessels density within tumor stroma is an important predictor of CD3+, CD8+ T and B lymphocyte tumor infiltration suggesting an active role played by these vessels in peripheral blood lymphocyte migration into tumors. The breast tumor infiltrating lymphocyte phenotype associated with HEV presence was further characterized by large scale flow cytometry analysis in 30 freshly operated breast tumors. Breast tumors with a high density of HEV (HEVhi) have increased numbers of effector memory T cells (CD45RA-CD62L-) that display an activated mature phenotype (CD69+, Granzyme A+, Granzyme B+, perforin+). T cells with a naïve (CD45RA+CD62L+) and a central memory (CD45RA-CD62L+) phenotype are also specifically increased within HEVhi tumors as compared to HEVlo tumors. Finally, we analyzed the prognostic value of HEV in a retrospective cohort of 146 invasive breast cancer patients and demonstrate that HEV density within tumor stroma is an independent predictor of good clinical outcome. Indeed, HEVhi patients have a significantly longer metastasis free survival (MFS) (p< 0,004), disease free survival (DFS) (P<0,012) and overall survival (OS) (P<0,023) than HEVlo patients. HEV like vessels, through the recruitment of high number of T lymphocytes and B lymphocytes from the periphery could limit the dissemination of primary breast tumors and prevent metastatic recurrence. Therefore, signals and cells that stimulate HEV differentiation within tumor stroma represent important solid tumors therapeutic target to modulate immune infiltration and patient's clinical outcome. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-04-02.
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