ABSTRACT
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Subject(s)
Humans , Male , Adult , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/therapy , Photochemotherapy/methods , Biopsy , Leishmania/cytology , Leishmania/drug effects , Meglumine Antimoniate/therapeutic use , Administration, Topical , Combined Modality TherapyABSTRACT
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Subject(s)
Humans , Male , Adult , Leishmaniasis/diagnosis , Leishmaniasis/therapy , Meglumine Antimoniate/administration & dosage , Antiprotozoal Agents/administration & dosage , Photochemotherapy , Treatment Outcome , Injections, Intralesional , Combined Modality TherapyABSTRACT
1 in 8 women will be affected by breast cancer, which is the most diagnosed malignancy among women. Although breast cancer was regarded as "immunologically cold", recent studies demonstrate that immunotherapy can be successful employed in combination regimens for the treatment of triple negative breast cancer, an aggressive type of breast cancer without many treatment options available. In March 2019, the US Food and Drug Administration granted accelerated approval for the first immunotherapy-based regimen comprising atezolizumab in combination with protein-bound paclitaxel for patients with advanced metastatic TNBC, expressing programmed cell death-ligand 1 (PD-L1) and without previous systemic treatment for metastatic disease. This immunotherapy-based regimen is not only a promising therapy for the TNBC patients, but it also represents an inspiring proof of concept for the development of more efficient advanced immunotherapy-based strategies for breast cancer treatment in the future.
Subject(s)
Fellowships and Scholarships/organization & administration , Internship and Residency/organization & administration , Radiology/organization & administration , Societies, Medical/organization & administration , Female , Humans , Male , Organizational Innovation , Outcome Assessment, Health Care , Program Evaluation , United StatesABSTRACT
Few autoantibodies directed against thyroglobulin (TgAbs) have been fully characterized in man. The present study was designed to characterize TgAbs from patients with unusually high titers (greater than 1:5(12] using tanned red cell hemagglutination technique (TRC). IgG was isolated from the sera of subjects with Hashimoto's thyroiditis (n = 4), subacute thyroiditis (n = 1) and Graves' disease (n = 1) using DEAE-Sephacel chromatography. Isolated TgAbs were substituted as first antibody in a double antibody thyroglobulin (Tg) RIA and the Ka's were determined by Scatchard analysis. Molecular ratios of antibody to antigen, TgAb: Tg, were calculated from quantitative precipitin curves. The clonality of each antibody was determined using agarose isoelectric focusing and 131I labeled Tg as an autoradiographic probe. All six TgAbs were polyclonal. The Ka's were on the order of 10(9)-10(10). In two sera TgAb:Tg ratios of 20:1 and 8:1 were obtained. These results are significant when compared to previously characterized Tg autoantibodies which have been of low titer, low Ka (10(5], and have been directed towards a restricted portion of the Tg molecule (TgAb: Tg ratios of 2:1 to 6:1). In view of their high affinity constants and recognition of a less restricted portion of the Tg molecule, some of the TgAb's with unusually high titers behave more like Tg heteroantibodies than autoantibodies.
Subject(s)
Antibodies/analysis , Thyroglobulin/immunology , Antibody Affinity , Antibody Specificity , Autoradiography , Epitopes/analysis , Humans , Isoelectric Focusing , Thyroiditis, Autoimmune/immunologyABSTRACT
In a prospective study carried out on a group of 1210 patients with liver cirrhosis (LC), the diagnosis was based on clinical, biological and histological criteria, as well as on the prognostic significance of 20 clinical, biochemical and histological parameters. The group, including 830 males (68.59%) and 380 females (31.41%), with an average age of 49.27 +/- 13.18 years, was studied during periods of 6 to 16 months, the initial investigations being periodically repeated. The statistical significance of the prognosis factors was studied by uni- and multivariative methods, according to the model of Cox, with the help of an IMB computer. The survival rate for the group studied ranged from 6 to 204 months, with an average period of survival of 38.29 months. The multivariative analysis demonstrated that the prognosis factor with a best correlation with the death power is ascites, which has additional predictive significance in association with encephalopathy and/or jaundice. The multivariative analysis selects as clinical factors of unfavourable prognosis the cholestasis, the hepatocytolytic syndrome, the syndrome of liver deficiency and the age over 50. The limits of the biochemical parameters with unfavourable significance were: bilirubinemia level greater than 3 mg%, ASAT/ALAT = 50.24/70.33 u.i., prothrombinemic index less than 50% and albuminemia greater than 3 g%. The multivariative method proved also superior in appreciating the interrelations of the prognostic factors, emphasizing the significance of the clinical parameters (ascites, encephalopathy, jaundice), while the multivariative analysis differentiated the biochemical prognosis factors (bilirubinemia, ASAT/ALAT, prothrombinemic index, albuminemia) and their level of significance.
Subject(s)
Liver Cirrhosis/diagnosis , Adult , Ascites/epidemiology , Cholestasis/epidemiology , Edema/epidemiology , Female , Hemorrhage/epidemiology , Hepatic Encephalopathy/epidemiology , Humans , Liver Cirrhosis/mortality , Liver Function Tests , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
The present study reports the biochemical and immunohistochemical findings in the cytosol of a Hürthle cell carcinoma as compared with that of normal thyroid tissue. Sephadex G-200 chromatography of the extract derived from a Hürthle cell carcinoma and from normal thyroid tissue revealed three identical pools. Pool I consisted mainly of thyroglobulin (Tg), pool II corresponded to albumin, while pool III contained unidentified low molecular weight fragments which could not be studied further. Hürthle cell carcinoma, pool I, had a Tg content of 12.9 micrograms Tg/mg equivalent tissue and a 127I content of 5,6 mole/mole of Tg. Its sialic acid content was undetectable, however. In pool I of the normal thyroid gland, the respective values were 62.8 micrograms Tg/mg equivalent tissue, 21.3 +/mole 127I/mole Tg, and 15.4 mole sialic acid/mole Tg. The albumin contained in both pools II was shown to be ioidinated at the following levels: 0.025 mole 127I/mole albumin in Hürthle tumor pool II vs 1.28 mole 127I/mole albumin in normal thyroid pool II. Immunohistochemical studies confirmed the presence of Tg and albumin in the malignant Hürthle cells and acini and colloid. Thus, Hürthle cell carcinoma contained Tg and albumin. The Tg content was five times less compared with control tissue. Both proteins (Tg and albumin) were poorly iodinated in Hürthle carcinoma tissue, and the iodination of albumina seemed to be more severely impaired. The site of synthesis of both proteins could not be derived from the present studies.
Subject(s)
Carcinoma/analysis , Neoplasm Proteins/analysis , Thyroid Neoplasms/analysis , Electrophoresis, Polyacrylamide Gel , Histocytochemistry , Humans , Immunoenzyme Techniques , Male , Middle Aged , Molecular Weight , Thyroglobulin/analysisABSTRACT
The in vivo kinetics of hepatic clearance of 125I-asialo-orosomucoid and 125I-asialofetuin was determined with a portal vein injection technique in barbiturate-anesthetized rats. Nonlinear regression analyses of saturation data gave the following parameters for asialo-orosomucoid, Km = 0.26 +/- 0.06 mg/ml, Vmax = 320 +/- 70 micrograms/min/g, and for asialofetuin, Km = 0.32 +/- 0.07 mg/ml, Vmax = 240 +/- 40 micrograms/min/g. Unlabeled asialofetuin inhibited the clearance of 125I-asialo-orosomucoid with a Ki = 0.25 +/- 0.04 mg/ml. Based on a model assuming that in vivo receptor concentration much greater than receptor KD, then the maximal binding capacity of the external surface of liver cells in vivo for asialo-orosomucoid is 2Km or 520 micrograms/ml or 52 micrograms/g of liver, assuming the liver interstitial space is 0.1 ml/g. Our estimate of in vivo binding capacity approximates in vitro estimates of total hepatic binding capacity, but is 10-fold greater than in vitro estimates of binding capacity on the external surface of liver cells. These results suggest the large majority of asialoglycoprotein receptors are located on the external surface of liver cells. The saturability of 125I-asialo-orosomucoid clearance was also demonstrated with a portal vein double bolus technique, wherein the portal injection of 20-1000 micrograms of unlabeled asialo-orosomucoid was followed 30 s later by the portal injection of tracer. Maximal inhibition of uptake was obtained with a portal vein injection of greater than or equal to 500 micrograms of asialo-orosomucoid. The specific extraction of the 125I-asialo-orosomucoid, which was near zero shortly after a 400-micrograms loading dose, gradually increased toward normal levels with a t1/2 of 21 min. This t1/2 may represent the in vivo rate of receptor recycling, since the gradual increase in unoccupied receptor sites is consistent with the model of receptor binding, internalization, and recycling.