Podcasts about cd16

While our podcast takes a brief break, Labiotech invites you to enjoy some of our favorite episodes. We will return with a brand-new episode on January 3rd, 2025! Have an awesome holiday season!On this podcast, we speak to Artiva Biotherapeutics' CEO, Fred Aslan, M.D.The company has demonstrated the potential for efficacy and safety with natural killer (NK) cells in two cancer clinical trials. In August 2023, the company announced FDA clearance for an IND for lupus – marking a first for an allogeneic, off-the-shelf NK or CAR-T cell therapy in autoimmune disease.AlloNK (also known as AB-101) is a non-genetically modified, cord blood-derived, allogeneic, cryopreserved, ADCC-enhancing NK cell therapy candidate for use in combination with monoclonal antibodies or innate-cell engagers in the out-patient setting. Artiva is investigating AlloNK in a phase 1/2 multicenter clinical trial to assess the safety and clinical activity of AlloNK alone and in combination with the anti-CD20 monoclonal antibody, rituximab, in patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (B-NHL). Artiva is also investigating the safety and clinical activity of AlloNK in combination with rituximab in patients with lupus nephritis. In addition, Artiva is collaborating with Affimed in a phase 2, open-label, multi-center, multi-cohort study, testing a combination therapy, comprised of AlloNK and the innate cell engager AFM13, for the treatment of patients with relapsed/refractory CD30-positive lymphomas. Artiva selects cord blood units with the high affinity variant of the CD16 receptor and a KIR-B haplotype for enhanced product activity. Using the company's cell therapy manufacturing platform, Artiva can generate thousands of doses of pure, cryopreserved, infusion-ready NK cells from a single umbilical cord blood unit while retaining the high and consistent expression of CD16 and other activating NK receptors, without the need for engineering. AlloNK is being administered in the outpatient setting over multiple doses and multiple cycles.Artiva's pipeline also includes AB-201, an anti-HER2 CAR-NK cell therapy candidate for the treatment of HER2-overexpressing tumors, such as breast, gastric, and bladder cancers, and for which an IND has been allowed by FDA, and a pipeline of CAR-NK candidates targeting both solid and hematopoietic cancers. Artiva has also entered into therapeutic NK cell collaborations with Merck Sharp & Dohme. Interested in being a sponsor of an episode of our podcast? Discover how you can get involved here! Stay updated by subscribing to our newsletter

El programa "T'agrada el blues?" d'aquesta setmana t

This week, we speak to Artiva Biotherapeutics' CEO, Fred Aslan, M.D. The company has demonstrated the potential for efficacy and safety with natural killer (NK) cells in two cancer clinical trials. In August, the company announced FDA clearance for an IND for lupus – marking a first for an allogeneic, off-the-shelf NK or CAR-T cell therapy in autoimmune disease.AlloNK (also known as AB-101) is a non-genetically modified, cord blood-derived, allogeneic, cryopreserved, ADCC-enhancing NK cell therapy candidate for use in combination with monoclonal antibodies or innate-cell engagers in the out-patient setting. Artiva is investigating AlloNK in a phase 1/2 multicenter clinical trial to assess the safety and clinical activity of AlloNK alone and in combination with the anti-CD20 monoclonal antibody, rituximab, in patients with relapsed or refractory B-cell-non-Hodgkin lymphoma (B-NHL). Artiva is also investigating the safety and clinical activity of AlloNK in combination with rituximab in patients with lupus nephritis. In addition, Artiva is collaborating with Affimed in a phase 2, open-label, multi-center, multi-cohort study, testing a combination therapy, comprised of AlloNK and the innate cell engager AFM13, for the treatment of patients with relapsed/refractory CD30-positive lymphomas. Artiva selects cord blood units with the high affinity variant of the CD16 receptor and a KIR-B haplotype for enhanced product activity. Using the company's cell therapy manufacturing platform, Artiva can generate thousands of doses of pure, cryopreserved, infusion-ready NK cells from a single umbilical cord blood unit while retaining the high and consistent expression of CD16 and other activating NK receptors, without the need for engineering. AlloNK is being administered in the outpatient setting over multiple doses and multiple cycles.Artiva's pipeline also includes AB-201, an anti-HER2 CAR-NK cell therapy candidate for the treatment of HER2-overexpressing tumors, such as breast, gastric, and bladder cancers, and for which an IND has been allowed by FDA, and a pipeline of CAR-NK candidates targeting both solid and hematopoietic cancers. Artiva has also entered into therapeutic NK cell collaborations with Merck Sharp & Dohme. 

CytoDyn Inc. CEO Nader Pourhassan tells Proactive its contract research organization in Brazil has met with the Brazilian Health Regulatory Agency and received its agreement to modify the CD16 trial for critically ill coronavirus patients. It also submitted a Phase 3 trial with the FDA to treat critically ill patients with COVID-19. Pourhassan said separately, it has filed a request with the FDA for approval of expanded access use of leronlimab for multi-drug resistance (MDR) HIV patients.

CytoDyn Inc's Nader Pourhassan tells Proactive that Brazil's regulatory authority Agência Nacional de Vigilância Sanitária (ANVISA) has approved the start of an additional Phase 3 CD16 clinical trial of its flagship drug leronlimab to treat critically ill coronavirus patients. Pourhassan says the new clinical trial will focus on hospitalized COVID-19 patients in critical condition who require mechanical and invasive ventilation or Extracorporeal Membrane Oxygenation (ECMO).

Welcome! The cats and I used a decent makeshift podcasting setup to record in the kitchen and it doesn't sound too bad! I talk about this:What's in my podcasting bag? I need a checklist: Enter Bullet JournalingMore to come in this quest for accountability. Be well,jFind out more at https://creativedrive.pinecast.co

Corridor Digital has amassed over 6 million subscribers by creating visually entertaining viral videos. Sam Gorski and Niko Pueringer co-founded Corridor Digital in 2010, a year later Jake Watson came on as a partner. They have gone on to win several Streamys including the “Visual and Special Effects Award” in 2017. Creative Disruption Podcast with Ricky Ray Butler and Derral Eves Insights and stories from leading creators, writers, producers and marketers on how the worlds of advertising, entertainment, and data science are converging. https://www.youtube.com/channel/UCUA8eH81InvAPd9kNoHQtWw

CD16 - Modeling Respect For Others And Proper Speech by Shaare Mussar

Session 25 Dr. Karen Shackelford form BoardVitals joins us once again as we dig deep into a question about the hematopoietic and immune system. Listen to this podcast episode with the player above, or keep reading for the highlights and takeaway points. [01:05] About BoardVitals If you're ready to prepare for your Step 1 or Level 1, go to BoardVitals. Their QBank system is set up to simulate the real USMLE Step 1 and COMLEX Level 1 exams. They have questions that are equally as hard to get you prepared for your exam. Use the promo code BOARDROUNDS to save 15% off when you purchase any of their products. [02:20] Question of the Week A 16-year-old male presents with a complaint of sore throat, fatigue and low-grade fever for three days. Exam reveals glossopharyngeal erythema with white exudates on his tonsils. He has enlarged posterior cervical lymph nodes and the posterior auricular lymph nodes are slightly enlarged. His spleen is palpable on abdominal exam. The throat culture is negative for strep and the monospot is positive. Which of the following findings are associated with the patient's diagnosis? (A) Atypical lymphocyte (B) Eosinophilia (C) Howell-Jolly bodies (D) Sickled erythrocytes (E) Target cells [Related episode: USMLE and COMLEX Prep: Glossopharyngeal Nerve Anatomy] [03:20] Thought Process Behind the Right Answer The correct answer here is A. The enlarged spleen could throw students off as it may make you think about Howell-Jolly bodies. But this is a case of classical mononucleosis with fever, exudative pharyngitis, the tender lymphadenopathy, particularly posterior in the cervical and posterior auricular nodes. Adenopathy in the anterior nodes and the atypical lymphocytosis are the hallmarks of classic infectious mononucleosis. The explanation to this question goes on to discuss the infection of the Epstein-Barr virus. It's a viral replication that begins in the oral pharyngeal epithelial cells with dissemination and infection of B-lymphocytes and the oropharyngeal lymphoid tissue. There is more Step 1 detail here. The infected B-lymphocytes produce antibodies to the viral antigens. But they also produce another type of antibody which could be heterophile antibodies that are not antibodies to the virus, but antibodies to other tissues. Active infection and the reinfection are regulated basically by the Epstein-Barr virus-specific T-lymphocyte. And atypical lymphocytes are activated. CDA plus T-cells and CD16 after killer cells appear in the blood at least 1-3 weeks after symptom onset. Fatigue can persist forever – 6 months or longer in 13% of patients. The splenic enlargement is a big caution for practitioners to remind their patients to avoid contact. The enlargement usually resolves after about 3 weeks. But even without contact, spontaneous splenic rupture is responsible throughout half of the cases. This usually occurs 2 weeks after symptom onset. [06:50] Understanding the Other Answer Choices Eosinophilia is usually associated with parasitic infection. The Howell-Jolly bodies were good distractor. They refer to the basophilic remnants of DNA. The circulating erythrocyte is usually removed in the spleen so they're found in patients who have either no spleen or 07:15. Sickled erythrocytes are associated with sickle cell disease. Target cells are associated with this disorder where the erythrocyte's cell surface is increased disproportionately to the cell volume. An example would be spherocytosis. Links: BoardVitals (Use the promo code BOARDROUNDS to save 15% off when you purchase any of their products.)

2019DJ苏打-打碟现场开场-中文车载串烧CD16

Dr Carolyn Lam:                Welcome to Circulation on the Run. Your weekly podcast summary and backstage pass to the Journal and its editors. I'm Doctor Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. This week's journal features an international external validation study of the 2014 ESE Guidelines on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy. A very exciting discussion coming right up after these summaries.                                                 The first original paper this week suggests that proteomics, a tool of precision medicine may prove useful in improving the safety and efficiency of drug development. First author, Doctor Williams, Corresponding Author, Doctor Ganz, from the Zuckerberg San Francisco General Hospital retrospectively applied large scale proteomics to blood samples from Illuminate, the trial of Torcetrapib, a cholesterol estrotransfer protein inhibitor, which raised HDL and lowered LDL cholesterol. Recall that this trial was terminated due to increases in cardiovascular events and mortality.                                                 In the current study, the authors found that plasma concentrations of 200 proteins changed significantly with Torcetrapib. Their pathway analysis revealed unexpected and widespread changes in immune and inflammatory functions, as well as changes in aldosterone function and glycemic control. A previously validated nine protein risk score was similar in the two treatment arms at baseline, but higher in participants with subsequent events. At three months, the absolute nine protein derived risk increased in the Torcetrapib plus Atorvastatin arm compared to the Atorvastatin only arm. Thus, this protein-based risk score predicted harm from Torcetrapib within just three months. A protein-based risk assessment embedded within a large proteomic survey may prove to be useful in the evaluation of therapies to prevent harm to patients. This is discussed in an accompanying editorial entitled "Harnessing the Power of Proteomics to Assess Drug Safety and Guide Clinical Trials" by Doctor Maggie Lam and Ying Ge.                                                 The next study suggests that personalized monitoring of heart transplant outcomes may be achieved by profiling the genetic and phenotypic markers of the CD16-dependent natural killer cell activation pathway. First and corresponding author Dr. Paul from Vascular Research center in Marseilles in France and his colleagues collected blood samples from 103 patients undergoing routine coronary angiography for cardiac allograph vasculopathy diagnosis, a median of five years since their heart transplantation. They used a non-invasive natural killer cellular-humoral activation test to evaluate the association between genetic and phenotypic markers of the CD16 dependent natural killer cell activation pathway. They showed that the Fc-gamma receptor IIIAVV polymorphic variant, which encodes the highly responsive CD16-Fc receptor, was an independent baseline predictor of cardiac allograph vasculopathy, and may be useful for stratifying patients at higher risk of rejection. The implications of these findings also include the fact that individualized natural killer cell targeted therapies may limit vascular damage in responsive patients.                                                 The next study suggests that estimation of polygenic atrial fibrillation risk is feasible, and together with clinical risk factor burden, can explain lifetime risk of atrial fibrillation. Co-first authors Dr. Weng and Preis, corresponding author Dr. Lubitz from Massachusetts General Hospital, and colleagues estimated the lifetime risk of atrial fibrillation in individuals from the community-based Framingham Heart Study. Polygenic risk for atrial fibrillation was derived using a score of approximately 1000 atrial fibrillation-associated SNPs. Clinical risk factor burden was calculated for each individual using a validated risk score for incident atrial fibrillation comprised of height, weight, systolic and diastolic blood pressure, current smoking, anti-hypertensive medication use, diabetes, history of myocardial infarction, and history of heart failure.                                                 They found that the lifetime risk of atrial fibrillation after age 55 years was 37 percent was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of atrial fibrillation at the age of 55 years, those in the low polygenic and clinical risk tertiles, had a lifetime risk of 22 percent, whereas those in the high risk tertiles had a risk of 48 percent. Atrial fibrillation developed at an older age among individuals with a favorable clinical risk profile regardless of genetic predisposition. Nevertheless, the lifetime risk of atrial fibrillation in individuals with high genetic predisposition was substantial, even when the clinical risk factor burden was low. Thus, individualized projections of lifetime risk of atrial fibrillation may be refined by accounting for both genetic predisposition and clinical risk factor burden.                                                 The final study tells us that in contrast to previous perceptions, Takotsubo cardiomyopathy has long-lasting clinical consequences. First and corresponding author Dr. Skally from University of Aberdeen in the UK and their colleagues did an observational case controlled study of 37 patients with prior Takotsubo cardiomyopathy and 37 age, sex, and co-morbidity matched controls. Although Takotsubo cardiomyopathy occurred 20 months before the study, the majority of patients had persisting symptoms compatible with heart failure and cardiac limitation on exercise testing. Despite a normal left ventricular ejection fraction in serum biomarkers, patients with prior Takotsubo cardiomyopathy had impaired cardiac deformation indices on echo cardiography, increased native T1 mapping values on cardio magnetic residence imaging and impaired cardiac energetic status on p31 spectroscopy. Taken together, these findings demonstrate that after Takotsubo cardiomyopathy, patients appear to develop a persistent long-term heart failure phenotype.                                                 Well that wraps it up for our summaries. Now for our featured discussion.                                                 Sudden cardiac death prevention and hypertrophic cardiomyopathy. Always such an important topic. I'm so pleased to have with us the author from our featured paper this week, Dr. Perry Elliot from University College London, nd our associate editor, Dr. Mark Link from UT Southwestern who also wrote a beautiful accompanying editorial with Tera Lynn Ho. So welcome both of you. Perry, I think to set us up, I'd really love if you could tell us a little bit more about the 2014 ESE guidelines for sudden cardiac death prevention and hypertrophic cardiomyopathy. And particularly pointing out how they may differ from the 2011 ACC AHA guidelines please. Dr Perry Elliot:                   So, the 2014 guideline on sudden death prevention HCM, the aim of that guideline was to try to quantify the risk of sudden cardiac death. As you pointed out, sudden death is a significant complication of hypertrophic cardiomyopathy and one which we all as clinicians spend a lot of time trying to determine. If we look back over at, I don't know, a period of twenty, thirty years the approach we've developed is based upon the recognition of a number of clinical features of the disease that we know associate with a higher risk of sudden death. So things such as, you know, unexplained syncope or severity of hypertrophy. And it was that model of sort of taking those so called major risk factors which form the basis of the 2011 US guidelines and the essential model was the more of those things you have, the greater is your risk, and I suppose the  higher indication for an ICD.                                                 One of the problems with that approach was that it's not quantitative so you know, you could say, "Okay. Well I think you're at higher risk, but I can't say how much that risk is." And another problem with that way of doing things is when you start to think about some of the individual risk factors, it doesn't make a great deal of sense clinically.                                                 And I suppose a good example of that is wall thickness. You know we have this magical number of 30 millimeters, above which we say you're at risk, but of course are we really saying that if your wall thickness is 29 millimeters you're at low risk? We know it doesn't really work that way in biology. So when we drew up the 2014 guideline we wanted to say, "Okay let's develop a model in exactly the same way that we do with atrial fibrillation or primary prevention in coronary disease so that we can say to the patient sitting in front of us, 'Based on your clinical assessment we think you've got a one, five, ten percent risk of something bad happening to you in the next five years.'" And then we can use that information to inform our decision about ICD implantation.                                                 The model itself is not so revolutionary. I mean, it uses a lot of the conventional risk factors such as wall thickness, such as non-sustained VT on Holter monitoring, but what it did introduce was the factor of age, because we know that the age of the patient certainly determines their risk. We brought in [inaudible 00:10:12] obstruction because we've now got reasonable evidence showing that if you've got a big gradient, that certainly modulates your risk. And also probably for the first time, I suppose, left atrial size, which was one of those missing things I think in previous assessments. You know, it's a fantastic surrogate for restrictive physiology and certainly when we added it to the model it improved the predictive power of that model.                                                 So I suppose in summary what we've done is to produce a tool which allows you to estimate risk and then use that to help you decide on whether an individual needs a defibrillator in the clinic. Dr Carolyn Lam:                You know Perry I believe you led those guidelines and I just want to congratulate you as well as that was such a beautiful explanation of what was going on behind those. Yup, but the proof is in the pudding isn't it? But you're providing that proof in today's paper. Tell us about it. So it's an external validation, a large international multi-centers study to actually validate these 2014 guidelines. Dr Perry Elliot:                   That's right. I mean, I think when we generate these kind of models it's really important to test those models in different settings. The original model was based upon a relatively small number of European centers and I think what this paper does is it brings insights into different geographies and different health care systems. So we have participating centers from North America from the Middle East from the Far East and the idea here is to get as diverse a population as we can and just see if the model performs in the same way. And you know in a study just short of 4000 people, I think that we've shown that the model does indeed seem to behave in the same way. In fact, the numbers were remarkably similar. You know the ability of this model to discriminate between high and low risk patients was almost exactly the same as in the original paper, which I think gives us a level of reassurance that this model, this tool that we've developed, can be used in different health care settings. Dr Carolyn Lam:                Mark. I really enjoyed your editorial. I love the way that you started out with a case that really shows why this is so important. And I also love that you discuss some other studies that tried to validate the 2014 ESE guidelines as well. Could you just give us some of your thoughts there. Dr Mark Link:                     Yeah. I first want to congratulate Perry and his fellow authors for this paper. I think it was a very nice paper. I was a champion of this paper from the time it got sent into circulation. And, you know, the big change in the 2014 European guidelines compared to the American guidelines is really the linear risk of age, wall thickness, and I'll put tract gradient. And as Perry says, I agree, it's not a simple you have it or you don't, it's a linear risk and I applaud them for including that in their risk factor stratifier. And if you look at the current paper, I mean it was very good at picking out high risk patients. So if you have greater than a four percent, six percent risk over five years, you did. And so for picking out the high risk patients it was very good. And for picking out the medium risk patients, it didn't function as well. It was best for separating out the high risk and the low risk population.                                                 And I will say, based on this paper, I've started using the European risk stratifier in my clinical practice. So I do want to applaud them, you know, for the risk stratifier tool and this paper. But I do want to say, and I'm sure Perry will agree, that we're not there yet. We need better tools, because not only in this data set but in other data sets, because more of these individuals reside in the low risk population, more of the sudden deaths are in that population. And we need better tools. And over time they will come. You know, they may be MRI tools. They may be scar tools. They may be other tools that we aren't even aware of that are coming on the horizon, but we do need better tools as we move forward to identify those at risk for sudden death in hypertrophic cardiomyopathy. Dr Perry Elliot:                   Yeah. No. I agree. I mean I think what I would say is if you sort of take a step back and look at the overall perspective in this paper, despite the fact that, you know, we've got nearly 4000 people and they're followed in different health care settings, the overall sudden death rate in hypertrophic cardiomyopathy pretty low. You know, so that's good for patients 'cause I think it shows that at least in managed populations, the risk of sudden death which is real and we've got to assess it, but I think it's really important to get that message over to patients that for most people with HCM they're at low risk. It is of course the challenge because when you're dealing with rare events, it's really hard to predict them. And this model is far from perfect. I would argue it's probably the best we've got for the moment, but you know, it's not that bad. It's not that bad.                                                 I mean agree with you absolutely Mark, 'cause you know, either end it performs pretty well. In the middle there it's not as predictive, although what it tends to do is overpredict, rather than underpredict. So you know, I think if you use this model in your every day practice just the greatest risk is that you'd end up putting in probably more ICDs then you really need to rather than missing a lot of patients. You know, we really want to prevent every sudden death if we possibly can, but that's always going to be really hard I think and I think the fight goes on. We got to look for new risk predictors. It may be that we can interchange some of these predictors. They might be easier to assess in some practices, but I'm not a born optimist, but I really think it's amazing just how well in such a complex heterogeneous disease that this relatively simple assessment works. You know? Dr Mark Link:                     Going forward, what do you think the future of HCM [inaudible 00:15:47] stratification will include? We've got the risk stratifiers in your calculator ready. And more specifically where do you think gadolinium enhancement will play a role in the future? So MRI findings of scar or gadolinium enhancement. Dr Perry Elliot:                   The base we have at the moment show that the more scar you have, the greater risk of sudden death. It sort of makes sense, doesn't it? It's part of that substrate for ventricular arrhythmia. My own reading of it just so far is that I'm not sure what it adds to the existing way of doing things. I mean I think this is true of any biomarker, you know. I've got a new biomarker, what does it tell me that I don't already know? And with scar, we know the greater amount of scar, it often tracks with wall thickness. You're likely to have a thicker heart, you're more likely to have non-sustained VT. But I'm openminded on that front. The beauty about this model, for me, is that it's a tool to into which you can plug other things and you know, if we can get big enough data sets and we can use gads and the amount of scar and put that into the model and if it improves the performance of the model that's great. Those studies are underway at the moment and I think we eagerly wait the results of those studies.                                                 For me, one of the missing things is the genetics. This is a heterogeneous disease with quite a complex genetic architecture, and despite the fact that you know it's 20, 30 years now since we identified the first gene, we haven't really factored that in to our risk models and I think that for me is one of the big challenges and opportunities over the coming years is to put together really large international data sets so that we can answer once and for all whether your mutation determines your prognosis. Dr Mark Link:                     Yeah. I agree with the genetics also I think getting more information on that. And it's been 30 years it still is not helping us prognosticate the risk of sudden death, but it should. I mean it really should. And I do think hopefully we will find other tools also as time goes on because it really is imprecise and it's very difficult when you're sitting there in front of ... You know, I just had a 20 year old yesterday come in with his family and he's got a three centimeter septum and he's got 12 percent scar and he's saying, "Gee what would you do and what would you do if I were your son?" And it's easy when you're looking at it in the aggregate. It's much more difficult when you're sitting there one on one with a patient in front of you. Dr Perry Elliot:                   Of course. Of course. And I think another factor I think which is changing the dynamic of that kind of discussion is the evolution of ICD technology. You know, I think when you're dealing with young people the fear is long-term complications with leads isn't it? And I think with the advent of the SICD I sense it's already tipping the balance into perhaps a slightly more liberal approach to ICD implantation exactly in the kind of scenario you've just described Mark, you know you've got guy who's 20. He's got a really severe hypertrophy. Well you know, if you and mess ICD you know your threshold for implantation might be a bit lower. Dr Mark Link:                     Yeah and in fact, after a two hour discussion that's what we decided on is that subcu ICD was the right thing for him. And everyone's very happy with that choice. Dr Perry Elliot:                   Yep. I think it also raises another thing which I often think about is that as medics we're also probably not good at considering what acceptable risk actually is. You know? We develop models in different settings and hyeprtrophic cardiomyopathy, coronary disease, heart failure, and actually if you go back and critically look at the thresholds that are used to put in defibrillators, the absolute risks vary enormously. So you know, here in [inaudible 00:19:02] we're talking about an approximate annual risk of sudden death of about one percent per annum is sufficient to put in an ICD, but in long-QT world it's quite a different threshold that's used and of course that's because there is no defined number. You know the number's we used in the ESE model of greater than six percent you should have an ICD, well yeah that's the consensus number, there's nothing magical about it. There's nothing biological about it. And I think we've probably had greater debates at what acceptable risks really are. Dr Mark Link:                     And that's become a big shared decision now in the States and actually everywhere. It's become a big word because it sued to be that the physicians would decide on who gets an ICD and who doesn't. And it's no longer that way it's a discussion with the patient, with the family. How much risk are they willing to take, both with an ICD and without an ICD, because there are issues with ICD, even though I'm a big fan. There are issues and especially with transvenous ICDs, but also with subcutaneous ICDs. Dr Perry Elliot:                   Absolutely. Absolutely. Dr Mark Link:                     You know, it's a different world now than it was 15 20 years ago. Dr Carolyn Lam:                Perry and Mark, this has been one of the most wonderful conversations I've had on these podcasts. I just can't thank you enough. I'm sure all our listeners are thanking you too. You've been listening to Circulation on the Run. You must tune in again next week for more beautiful conversations.  

It took us long enough, but we finally had a chance to sit down with Yash Mistry (@yashyog), a Charlotte Digital Storyteller and a Day 1 fan of Carolina Desi! Yash runs Mistry Design Co. where he does Graphic Design, Web Dev, and everything in between. Join the Carolina Desis this week as they discuss with Yash, the process of pursuing and owning a business within the creative field, working for yourself, and the value of connections. Follow @thecarolinadesi on social media to join the conversation.

Hyperstyles. CD16 | Draw Darker |   Tracklist can be found at: https://soundcloud.com/lentej/   Happy Halloween :)

Thu, 20 May 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/11548/ https://edoc.ub.uni-muenchen.de/11548/1/Beeck_Stefan.pdf Beeck, Stefan

Background: MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates peritoneal metastasis of ovarian tumors. Both sMUC16 and csMUC16 also protect cancer cells from cytotoxic responses of natural killer (NK) cells. In a previous study we demonstrated that sMUC16 binds to specific subset of NK cells. Here, we identify the csMUC16/sMUC16 binding partner expressed on immune cells. Results: Analysis of immune cells from the peripheral blood and peritoneal fluid of ovarian cancer patients indicates that in addition to NK cells, sMUC16 also binds to B cells and monocytes isolated from the peripheral blood and peritoneal fluid. I-type lectin, Siglec-9, is identified as the sMUC16 receptor on these immune cells. Siglec-9 is expressed on approximately 30-40% of CD16(pos)/CD56(dim) NK cells, 20-30% of B cells and > 95% of monocytes. sMUC16 binds to the majority of the Siglec-9(pos) NK cells, B cells and monocytes. sMUC16 is released from the immune cells following neuraminidase treatment. Siglec-9 transfected Jurkat cells and monocytes isolated from healthy donors bind to ovarian tumor cells via Siglec-9-csMUC16 interaction. Conclusions: Recent studies indicate that csMUC16 can act as an anti-adhesive agent that blocks tumor-immune cell interactions. Our results demonstrate that similar to other mucins, csMUC16 can also facilitate cell adhesion by interacting with a suitable binding partner such as mesothelin or Siglec-9. Siglec-9 is an inhibitory receptor that attenuates T cell and NK cell function. sMUC16/csMUC16-Siglec-9 binding likely mediates inhibition of anti-tumor immune responses.

Thu, 9 Oct 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9157/ https://edoc.ub.uni-muenchen.de/9157/1/Joeinig_Anke.pdf Joeinig, Anke ddc:600, ddc:610, Med

Schizophrenia has often been observed to be associated with alterations of the cellular immune system. In this study we monitored numerous immune parameters in the course of antipsychotic treatment. 40 patients diagnosed with an acute exacerbation of schizophrenia were tested before and during treatment with antipsychotics. The percentual distribution of lymphocyte subgroups (CD3, CD4, CD8, CD19, CD5, CD16/56, CD25, HLA-DR, gd, CD11a, CD11b and CD49d) was measured by FACS analysis. 20 healthy volunteers served as controls. In the acute state of psychosis a significant elevation of the B-lymphocyte fraction was observed, while the percentage of T-lymphocytes was decreased. These values levelled to those of the control group in the course of treatment. Natural killer cells, integrine expressing cells and CD5+ B-cells showed alterations in numbers after several months of treatment. The latter may be a side effect of antipsychotic treatment. The findings in the acute state of schizophrenia could be seen as a nonspecific stress reaction or an effect of the altered metabolism of neurotransmitters. On the other hand the observed changes in the immune system could be due to infectious diseases or autoimmune processes provoking the symptoms of schizophrenia.

Fragestellung: Um mögliche proinflammatorische Zeichen bzw. Frühindikatoren (sog. Mikroinflammation) bei Patienten mit chronischem Nierenversagen und nierentransplantierten Patienten aufzuspüren, die an späteren Organkomplikationen (chronische Transplantatdysfunktion, Herz-Kreislaufmorbidität, endotheliale Dysfunktion, Infektanfälligkeiten) beteiligt sein können, untersuchten wir die Expression funktioneller monozytärer Oberflächenantigene. Als immunologischen Marker der Aktivität einer Entzündungsreaktion verglichen wir die in der Durchflusszytometrie (fluorescence-activated cell sorter (FACS))gemessene Expression sog. mCD14-Rezeptoren und der CD14+CD16++-Rezeptoren auf peripheren Blut-Monozyten mit serologischen Parametern wie C-reaktives Protein und Leukozytenzahl. Die Frage, ob die beiden Oberflächenantigene CD14 und CD16 sowie die Koexpression beider Antigene (proinflammatorisch aktivierte Monozyten) zum „immunologischen Monitoring“ geeignet sind, sollte erstmalig klinisch an Gesunden, Patienten nach Nierentransplantation sowie Patienten mit chronischer Niereninsuffizienz im Endstadium ohne Dialysebehandlung untersucht werden. Ergänzend wurden nichtorgantransplantierte Patienten mit akuten infektiösen Komplikationen auf mögliche Modulationen proinflammatorischer Blutmonozyten (CD14+/CD16++-Zellen) hin untersucht. CD14 existiert membrangebunden (mCD14) und in löslicher Form (sCD14) und ist verantwortlich für die Interaktion von Endotoxin (LPS) mit Monozyten und Neutrophilen. LPS ist ein Glykoprotein der äußeren Membranschicht gramnegativer Bakterien. CD14 ist der wichtigste Rezeptor für gram-negative bakterielle Lipopolysaccharide (Endotoxin), jedoch auch für Peptidoglykan und Lipoteichonsäure gram-positiver Erreger. CD 16 ist der funktionell wichtige Fcγ–Rezeptor Typ III (FcγRIII, IgG-Rezeptor Typ III), der mit niedriger Affinität monomeres IgG sowie polymeres IgG oder Immunkomplexe bindet. Er vermittelt wichtige immunphysiologische Funktionen wie antikörperabhängige zellvermittelte Zytotoxizität, Beseitigung zirkulierender Immunkomplexe, Superoxidbildung und ist auch an der Signaltransduktion beteiligt. Die untersuchten CD14+CD16++-Monozyten bewirken im Zusammenwirken von TNFα, IL-1, IL-6 und IL-10 bewirkt eine stärkere Entzündungsreaktion als die konventionellen CD14++CD16negativen-Zellen; sie sind sehr potente Antigen-präsentierende Zellen, besitzen eine hohe Phagozytoseaktivität und verstärken die endotheliale Adhäsion. Untersuchungsaufbau: Wir untersuchten 69 Patienten nach Nierentransplantation (23 Frauen, 46 Männer) im Alter von durchschnittlich 52,63 +/- 11,42 Jahren (Median 53,84 Jahre). Die Patienten erhielten durchschnittlich vor 6,38 +/- 5,2 Jahren ein Nieren- Transplantat (Median 8,16 Jahre). Wir unterschieden diese Patienten hinsichtlich ihrer Immunsuppression in folgende Gruppen: 1) Mycophenolat-Mofetil-Monotherapie (MMFmono), 2) Cyclosporin-Monotherapie (CyAmono) und 3) einer Kombination aus MMF und CyA (MMF-CyAkombi). In die Gruppe mit MMF-Monotherapie wurden16 Personen eingeschlossen (3 Frauen, 13 Männer) im Alter von durchschnittlich 51,29 +/- 10,47 Jahren (Median 51,15 Jahre). In der Gruppe der CyA-monotherapierten Patienten befanden sich 11 Personen (3 Frauen, 8 Männer) im Durchschnittsalter von 58,43 +/- 8,01 Jahren (Median 59,96 Jahre). Zur Gruppe der MMF-CyA-kombinationstherapierten Patienten gehörten 18 Patienten (3 Frauen, 15 Männer) im Alter von 46,69 +/- 10,22 Jahren (Median 47,44 Jahre). Des weiteren wurden 13 Patienten mit chronischer Niereninsuffizienz (12 Männer, eine Frau) im Alter von 32 bis 74 Jahren (Median 65,0 Jahre; Mittelwert 63,5 Jahre +/- 10,3 Jahre) in die Analysen miteinbezogen. Parallel wurden 8 Patienten (6 Frauen, 2 Männer) im Verlauf einer akuten Infektion erfasst (Mittelwert 74,6 +/- 10,53 Jahre; Median 78 Jahre). Unser Kontrollkollektiv bestand aus 18 klinisch gesunden freiwilligen Probanden im Alter zwischen 24 und 54 Jahren (Median 31Jahre; Mittelwert 33,42 +/- 9,91 Jahre; 10 Frauen, 8 Männer). Ergebnisse: 1. Patienten mit chronischer Niereninsuffizienz hatten signifikant höhere CRP-Serumkonzentrationen als Gesunde (p=0,010)(Gesunde 0,33 mg/dl vs. Urämiker 0,7 mg/dl). 2. Die mCD14-Expression auf peripheren Blutmonozyten war bei Urämikern (p=0,024) und bei nierentransplantierten Patienten (p=0,026) signifikant niedriger als bei Gesunden.(Gesunde 517 MFI vs. Urämiker 426 MFI vs. NTX 433 MFI) 3. Der prozentuale Anteil CD14+CD16++-Monozyten im Blut war sowohl bei Patienten mit chronischer Niereninsuffizienz (p=0,00000487; MFI= 13,0%) als auch bei Patienten nach Nierentransplantation (p=0,00298; MFI=9,3%) signifikant höher. 4. Die Leukozytenzahl im Blut war weder bei immunsupprimierten Nierentransplantierten noch bei Patienten mit chronischer Niereninsuffizienz im Endstadium signifikant gegenüber Gesunden verändert. 5. Hinsichtlich der verschiedenen Strategien der immunsuppressiven Therapie ließen sich keine Unterschiede zwischen den Gruppen der MMF-mono, der CyA-mono und der MMF-CyA-kombi-behandelten Nt-Patienten feststellen. 6. Die Absolutzahl CD14+CD16++-Monozyten war sowohl bei urämischen Patienten (p=0,003; 430/µl) als auch bei nierentransplantierten Patienten (p=0,005; 413/µl) gegenüber Gesunden signifikant erhöht. 7. Bei Nierentransplantierten fiel die CRP-Konzentration im Serum mit steigendem Alter des Transplantates logarithmisch ab (p=0,065), die mCD14-Expression fiel linear ab (p=0,063) wohingegen der prozentuale Anteil der CD14+CD16++- Monozyten invers ansteigt (p=0,0036). 8. Im Verlauf akuter infektiöser Erkrankungen war der Anteil der CD14+CD16++- Monozyten signifikant höher als bei Gesunden (p=0,000049) und fiel bis zur stationären Entlassung so signifikant ab (p=0,012), so dass kein Unterschied mehr zwischen Gesunden und Kranken mehr nachweisbar war. Schlußfolgerungen: 1. Sowohl bei Patienten mit chronischer Niereninsuffizienz wie bei Nierentransplantierten finden sich anhand erhöhter Zahlen proinflammatorischer Blutmonozyten (CD14+CD16++-Phänotyp) eindeutig Zeichen einer sog. „Mikroinflammation“; dies ausdrücklich auch bei NTX-Patienten, obwohl diese unter einer dauerhaften immunsuppressiven Behandlung stehen. 2. Proinflammatorische Blutmonozyten sind Ziel- und Effektorzellen der Immunabwehr. Darüber hinaus sind sie pathophysiologisch an den Vorgängen einer Atheromatose beteiligt. CD14+CD16++-Blutmonozyten entsprechen dem Phänotyp von Gewebsmakrophagen. Erhöhte Anteile CD14+CD16++-Blutmonozyten gehen möglicherweise parallel mit der erhöhten Progressionsrate der Atheromatose von Organtransplantierten und Patienten mit Niereninsuffizienz. Andererseits sind sie an der Auslösung und Perpetuation der chronischen Transplantatdysfunktion (chronisches Transplantatversagen) ursächlich beteiligt, was aus Biopsiedaten hervorgeht. Die hier erfolgten Blutzellanalysen unterstützen diese These. 3. Dauerimmunsuppression bei Nierentransplantierten vermag nicht den proinflammatorischen Status diese Patienten zu unterdrücken. Damit gilt für alle NTXPatienten, dass sich mehr oder weniger schnell trotz potenter Immunsuppression irgendwann ein Transplantatversagen einstellt. Es spricht alles dafür, dass aktivierte Blutmonozyten hier die Schlüsselrolle spielen. Wir postulieren, dass dies nur dann abgeschwächt oder vermindert werden könnte, wenn sich die zellulären Marker, die auf chronische inflammatorische Aktivität hinweisen, pharmakologisch günstig beeinflussen ließen.

We aimed to investigate the natural killer (NK) cell activity in hGH-deficient adults and to analyze the effect of insulin-like growth factor (IGF)-I in uivo and in vitro on NK cell activity. NK cell activity was measured in a 4-h nonisotopic assay with europium-labeled and cryopreserved K-562 cells. NK-cell numbers were measured after incubation with murine monoclonal CD3 and CD16 antibodies by flow cytometry analysis. In a cross-sectional study, the basal and interferon- p (IFN-P) stimulated (1000 IU/ml) NK cell activity of 15 hGHdeficient patients and 15 age- and sex-matched controls was measured. The percentages and absolute numbers of CD3./16+ NK-cells were not significantly different in the patient vs. control group. The basal and IFN-P stimulated NK cell activity however was significantly decreased in the patient vs. control group at all effecter/target (E/T) cell ratios from 12.5-100 (e.g. 17 ? 3 vs. 28 ? 3% lysis without IFN-P, P < 0.05, and 42 t 4 vs. 57 2 4% lysis with IFN-0, P < 0.05; both at E/T 50). IGF-I levels of patients and controls showed a significant positive correlation with NK cell activity (r = 0.37; P < 0.05). In an IGF-I in vitro study (IGF-I in vitro 250-1250 kg/L), the basal and IFN-P stimulated NK cell activity of 13 hGH-deficient patients and of 18 normal subjects was significantly enhanced by IGF-I in vitro (e.g. GH-deficient patients: 9 ? 2 us. 10 2 2% lysis without IFN-P, P < 0.05 and 25 + 4 vs. 30 + 4% lysis with IFN-/3, P < 0.005; and normal subjects: 15 + 3 vs. 23 ? 3% lysis without IFN-/3, P < 0.001 and 35 2 4 us. 44 + 5% lysis with IFN-P, P < 0.001; both at IGF-I 500 pg/L). In summary, in our cross-sectional study, adult GH-deficient patients showed a significantly lower basal and IFN-P stimulated NK cell activity than matched controls, despite equal NK cell numbers. IGF-I levels of patients and controls showed a weak positive correlation with NK cell activity. In an in vitro study, IGF-I significantly enhanced basal and IFN-P stimulated NK cell activity of hGH-deficient patients and also of normal subjects. The decreased NK cell activity in GHdeficient patients may be caused at least in part by low serum IGF-I levels. IGF-I appears to be an independent coregulatory modulator of NK cell activity. (Endocrinology 137: 5332-5336, 1996)