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Experimental cryoglobulinaemia: Production and properties of streptococcus-induced rabbit cryoglobulins 总被引:4,自引:0,他引:4
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Zana L. Herd 《Immunology》1973,25(6):931-939
Cryoglobulin production in rabbits immunized with streptococcal vaccines began about 3 weeks after immunization began and maximum yields from fresh immune sera ranged from <0.1 mg/ml to >6 mg/ml in individual rabbits. The cryoglobulins contained IgM and IgG, antiglobulin that was mainly IgM, IgG homogeneous antibodies to streptococci, and DNA. It is postulated that cryoglobulins are formed in two stages: alteration of IgG followed by antigen—antibody precipitation with antiglobulin. 相似文献
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The increased prevalence of atrial fibrillation (AF) has led to specialized AF clinics (AFCs) to facilitate management of AF patients. In this article we report on outpatient AFCs in Canada, which is essential to health policies required to standardize the performance of existing AFCs and help design new AFCs. We surveyed 14 clinics in 5 provinces; 100% provided responses to a detailed questionnaire on clinic processes and care practices. Fourteen care maps were analyzed, and 5 models of care were identified; 4 were specific to AFCs. An online survey with 49 questions included items on: (1) process before visit; (2) process at visit; (3) patient education provided; (4) outreach; and (5) specific clinic information. Clinicians’ advice to patients on self-care items such as: (1) amount of alcohol and (2) caffeine intake; (3) exercise activity; (4) stressful events; (5) “when to go to the emergency department”; and (6) lifestyle changes, were evaluated to assess consistency in practice. There were moderate variances in clinicians’ advice to patients in 5 of 6 self-care items. The 1 item that had 100% consistent practice recommendation was when to go to the emergency department. A guideline-based clinical assessment checklist (CAC) was piloted to obtain feedback on its usability in real-world practice; revisions finalized the “simplified CAC” for AF care encompassing 35 data points with rationale. There was 100% positive feedback on its ability to provide baseline elements in AF care. When validated, a “simplified CAC” can facilitate a standardized clinical assessment tool in clinical practice. 相似文献
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Jacopo Millul Gabriele Bassi Jacqueline Mock Abdullah Elsayed Christian Pellegrino Aureliano Zana Sheila Dakhel Plaza Lisa Nadal Andreas Gloger Eleonore Schmidt Ilaria Biancofiore Etienne J. Donckele Florent Samain Dario Neri Samuele Cazzamalli 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(16)
We describe the development of OncoFAP, an ultra-high-affinity ligand of fibroblast activation protein (FAP) for targeting applications with pan-tumoral potential. OncoFAP binds to human FAP with affinity in the subnanomolar concentration range and cross-reacts with the murine isoform of the protein. We generated various fluorescent and radiolabeled derivatives of OncoFAP in order to study biodistribution properties and tumor-targeting performance in preclinical models. Fluorescent derivatives selectively localized in FAP-positive tumors implanted in nude mice with a rapid and homogeneous penetration within the neoplastic tissue. Quantitative in vivo biodistribution studies with a lutetium-177–labeled derivative of OncoFAP revealed a preferential localization in tumors at doses of up to 1,000 nmol/kg. More than 30% of the injected dose had already accumulated in 1 g of tumor 10 min after intravenous injection and persisted for at least 3 h with excellent tumor-to-organ ratios. OncoFAP also served as a modular component for the generation of nonradioactive therapeutic products. A fluorescein conjugate mediated a potent and FAP-dependent tumor cell killing activity in combination with chimeric antigen receptor (CAR) T cells specific to fluorescein. Similarly, a conjugate of OncoFAP with the monomethyl auristatin E-based Vedotin payload was well tolerated and cured tumor-bearing mice in combination with a clinical-stage antibody-interleukin-2 fusion. Collectively, these data support the development of OncoFAP-based products for tumor-targeting applications in patients with cancer.Small organic ligands which selectively bind with high affinity to tumor-associated antigens are increasingly applied as targeting delivery vehicles of small payloads such as radionuclides (1, 2), drugs (3–5), and fluorophores (6, 7) to tumor sites. In principle, the use of small ligands for targeting applications offers several advantages compared to intact immunoglobulins, including superior penetration of solid neoplastic lesions (8), lower immunogenicity (9), and a reduced cost of goods (10). Low molecular weight compounds may reach their target in vivo in a matter of seconds, thanks to rapid extravasation after intravenous administration (8). A strikingly selective accumulation of small ligands in neoplastic masses has been demonstrated for a small number of targets including somatostatin receptor type 2 (SSTR-2) (11), prostate-specific membrane antigen (PSMA) (12), and carbonic anhydrase IX (CAIX) (13), for which high-affinity small organic ligands are available. Those ligands are typically specific for defined tumor entities, such as neuroendocrine tumors (11), prostate cancer (3), and clear cell renal cell carcinoma (2).177Lu-DOTATATE (Lutathera), a small-molecule product targeting SSTR-2, has been approved based on phase III data in which a clinically meaningful 82% reduction in the risk of disease progression or death was demonstrated in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) (14). Similar data are expected from the currently ongoing phase III VISION trial for 177Lu-PSMA-617 (clinical trial no. ), a radiolabeled small molecule that binds with high affinity to PSMA and that enables targeted beta particle therapy in metastatic castration-resistant prostate cancer patients ( NCT0351166415). PHC-102, a 99mTc-labeled small-molecule derivative targeting CAIX, exhibited favorable uptake in primary and metastatic lesions in patients with renal cell carcinoma (RCC) (2). In light of the promising performance of small organic ligands, it would be desirable to discover and develop small molecules with a broader tumor-targeting potential, therefore covering multiple cancer types.Fibroblast activation protein (FAP) is a type II integral membrane serine protease which is abundantly expressed in the stroma of more than 90% of the epithelial cancers, including malignant breast, colorectal, skin, prostate, and pancreatic cancers (16, 17), while exhibiting a restricted expression in normal adult tissues (18, 19). Haberkorn and coworkers (1, 20, 21) have recently described a series of FAP ligands capable of selective accumulation in FAP-positive tumors in mice and in patients. One of these products (named FAPI-04) showed impressive tumor to background ratios at early time points (i.e., few hours after administration) in a broad range of different cancer types in patients. More than 28 tumor types including breast, lung, pancreatic, head and neck, esophagus, and colorectal cancer presented a remarkably high uptake of a FAP-targeted small molecule labeled with gallium-68 (1, 20, 21). For this reason, FAP has recently been dubbed as “the next billion-dollar target for theranostic products” (22).Here, we describe how the chemical modification of a quinoline moiety in position 8 led to the discovery of OncoFAP, a small organic FAP ligand with a dissociation constant in the subnanomolar concentration range. OncoFAP exhibited a strikingly selective and efficient tumor-targeting performance when equipped with various types of payloads, including radionuclides, fluorophores, and cytotoxic drugs. The targeting delivery of radionuclides to solid tumors is rapidly gaining in popularity, as it may open theranostic opportunities, associated with the use of gallium-68 for positron emission tomography (PET) imaging and of lutetium-177 for therapeutic applications (23). The delivery of fluorescein to tumors enables the conditional activation of chimeric antigen receptor (CAR) T cells, which display a potent biocidal activity only in the presence of fluorescein-labeled adaptor molecules specific to a tumor antigen (24, 25). Finally, small-molecule–drug conjugates (SMDCs) promise to represent a valid alternative to antibody–drug conjugates for cancer therapy, with better tumor penetration and a lower cost of goods (8, 26, 27). 相似文献
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Cheryl Cusack Benita Cohen Javier Mignone Mariette J. Chartier Zana Lutfiyya 《Journal of advanced nursing》2018,74(7):1544-1553
Aim
This article explores and describes participatory action research (PAR) as a preferred method in addressing nursing practice issues. This is the first study that used PAR with public health nurses (PHNs) in Canada to develop a professional practice model.Background
Participatory action research is a sub‐category of action research that incorporates feminist and critical theory with foundations in the field of social psychology. For nurses, critical analysis of long‐established beliefs and practices through PAR contributes to emancipatory knowledge regarding the impact of traditional hierarchies on their practice.Design
This study used participatory action, a non‐traditional but systematic research method, which assisted participants to develop a solution to a long‐standing organizational issue.Method
The stages of generating concerns, participatory action, acting on concerns, reflection and evaluation were implemented from 2012 ‐ 2013 in an urban Canadian city, to develop a professional practice model for PHNs.Findings
Four sub‐themes specific to PAR are discussed. These are “participatory action research engaged PHNs in development of a professional practice model;” “the participatory action research cycles of “Look, Think, Act” expanded participants’ views;” “participatory action research increased awareness of organizational barriers;” and “participatory action research promoted individual empowerment and system transformation.”Conclusions
This study resulted in individual and system change that may not have been possible without the use of PAR. The focus was engagement of participants and recognition of their lived experience, which facilitated PHNs’ empowerment, leadership and consciousness‐raising. 相似文献8.
Sogole Moin Zana Kalajzic Achint Utreja Jun Nihara Sunil Wadhwa Flavio Uribe Ravindra Nanda 《The Angle orthodontist》2014,84(6):1086
Objective:To investigate the time course of osteocyte death in a mouse model of orthodontic tooth movement (OTM) and its association to the caspase-3 activation pathway and osteoclast formation.Materials and Methods:Twenty-five male wild type CD-1 mice (8–12 weeks old) were loaded with an orthodontic appliance. A spring delivering 10–12 g of force was placed between the right first molar and the incisor to displace the first molar mesially. The contralateral unloaded sides served as the control. The animals were equally divided into five different time points: 6, 12, 24, and 72 hours and 7 days of orthodontic loading. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, caspase-3 immunostaining, and tartrate-resistant acid phosphatase (TRAP) staining was performed on histologic sections of the first molars. The labeling was quantified in osteocytes on the compression side of the alveolar bone at each time point.Results:TUNEL labeling significantly increased at 12, 24, and 72 hours after orthodontic loading; the peak was observed at 24 hours. Elevated caspase-3 labeling was noted at 12, 24, and 72 hours and 7 days after loading, although the increase was not significant. Significant osteoclast formation was initially evident after 72 hours and progressively increased up to 7 days.Conclusions:Osteocyte death during OTM peaks at 24 hours, earlier than initial osteoclast activation. However, only a slight trend for increased caspase-3 activity suggests that other mechanisms might be involved in osteocyte death during OTM. 相似文献
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The ultrasonic properties (velocity at 2·81 and 5·04 MHz, absorption in the range 1–15 MHz and vibration potential at 200 kHz) of amniotic liquid have been investigated. The results indicate that at physiological pH the absorption is essentially due to the proteins found in amniotic liquid, its vibration potential to the sodium chloride contained in this fluid while the velocity appears to be determined both by the proteins and sodium chloride. In the acid range (pH ~ 3) and alkaline range (pH ~ 9·6), proton transfer processes involving a low molecular weight component of amniotic liquid, in addition to those involving the proteins, contribute to the absorption of ultrasound by amniotic liquid. 相似文献
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Bumbulienè Z 《Ginekologia polska》2003,74(4):267-273
OBJECTIVES: Menstrual disorders are very common during the early postmenarcheal years. This study was undertaken to determine the causes of menstrual disorders in adolescents. MATERIALS AND METHODS: In the research there were included 117 girls 14-18 years old without evidence of androgen excess (hirsutism, acne): the study group consisted of 87 adolescents with menstrual disorders and the control group of 30 girls with regular menstrual cycles. All the patients underwent gynecological and ultrasound examination and an analysis of the hormonal status. RESULTS: The data from our investigation show that 43.7% of adolescents with menstrual dysfunction have eating disorders, 16.1%--immaturity of hypothalamic-pituitary-ovarian axis, 13.8%--polycystic ovary syndrome, 9.2%--hyperprolactinemia, 4.6%--delayed puberty, 3.4%--genetic defect and 9.2% other reasons. CONCLUSIONS: A thorough history and physical examination focusing on the basic understanding of pubertal and menstrual physiology and pathology allows to obtain an accurate diagnosis. The prognosis for later fertility depends on the preventive measures token in adolescence. 相似文献