Podcasts about Monocyte

Reference: Agnello et al. Monocyte distribution width (MDW) as a screening tool for early detecting sepsis: a systematic review and meta-analysis. Clinical Chemistry and Laboratory Medicine 2022; 60(5):786-792 Clin Chem Lab Med. 2022 Date: February 21, 2025 Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School […] The post SGEM#468: Wide Open Monocytes – Using MDW to Diagnose Sepsis first appeared on The Skeptics Guide to Emergency Medicine.

When you visit your doctor for a routine physical, the protocol often includes ordering blood work. Why? What can the results indicate?Your doctor looks at your lab results to help diagnose and monitor treatment for many conditions. However, many patients, probably even you, have experienced being told that their labs are normal, but they feel awful. What if you could read your blood work and determine what's going on inside your body? Today, I'll walk you through reading blood work, but instead of looking at the normal ranges, we will look at the functional ranges and understand what the numbers mean. Specifically, we will look at the five markers inside your CBC with differential. This episode is the first part of a 3-hour Blood Work and Business Intensive session. Watch out for Parts 2 and 3.Have you ever wished you had a step-by-step process to create a treatment plan for any client seeking your help? One you felt confident with and only needed their regular blood work to create? That's what we are doing during the one-day event: Functional Medicine Made Easy. Get the details and register at drkylieburton.com/fm"Today's episode is brought to you by StarWalker Organic Farms. We're a third-generation family-run farm deeply committed to producing the highest quality organic beef, pork, and artisanal jerky. With a strong belief in the power of regenerative farming, we aim to produce not only richer, more nutritious products but also to nurture the land for generations to come. Our dedication to organic and humane practices means every cut of meat supports wellness, the environment, and the well-being of our animals. And the best part? We ship nationwide, bringing the StarWalker difference directly to your door. Elevate your health with sustainably sourced meats. Visit us at starwalkerorganicfarms.com to discover more."My favorite place for ordering labs is virtualclinic.MD. Make your account and order functional medicine labs and regular blood work at any Labcorp facility across the country. Yes, you can order labs as a health coach through this platform. As long as you have a healthcare business, you can order labs. Make your account and start ordering today - tell them Dr. Kylie Burton sent you.Leave a review, share it with your colleagues, and let people on social media know you love what you're hearing. Spread the message, and I'll be very grateful for it!“We're not reading the labs to diagnose. We're reading them to figure out what the heck is wrong with our patient.”- Dr. Kylie Burton In This Episode:Do you need a license to read blood work?What is the purpose of reading a patient's blood work?Normal range vs. Functional rangeThe CBC with differentialWBC and what the range meanWhat does the Neutrophil count indicate?What does the Lymphocyte count indicate?What does the Monocyte count indicate?What do the Eosinophil and Basophil ranges indicate?WBC breakdown and what the numbers mean Practical application (let's read some blood work)Resources:Build Your Virtual Platform in 90 Days - https://drkylieburton.com/business/Join the 90-day...

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

Carla Kim, Ph.D., explains how aging impacts lung cell biology and its potential to reshape our understanding of diseases, including lung cancer. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39254]

In this week's episode, we'll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.

Listen in as Dr. Nally discussed the history of gout, why Hippocrates only thought it happened to royalty and how you can treat and prevent it with a ketogenic or carnivorous lifestyle. Show Note Sources: Kanbara A., Seyama I. Effect of urine pH on uric acid excretion by manipulating food materials. Nucleosides, Nucleotides Nucleic Acids. 2011;30(12):1066–1071. Towiwat P., Li Z.G. The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout. Int J Rheum Dis. 2015;18(5):495–501. Bedir A., Topbas M., Tanyeri F., Alvur M., Arik N. Leptin might be a regulator of serum uric acid concentrations in humans. Jpn Heart J. 2003;44(4):527–536. Garrod AB. The Nature and Treatment of Gout and Rheumatic Gout, 2nd ed, Walton and Maberly, London 1863. Dalbeth N, Phipps-Green A, Frampton C, et al. Relationship between serum urate concentration and clinically evident incident gout: an individual participant data analysis. Ann Rheum Dis 2018; 77:1048. Hall AP, Barry PE, Dawber TR, McNamara PM. Epidemiology of gout and hyperuricemia. A long-term population study. Am J Med 1967; 42:27. Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 1987; 82:421. Zalokar J, Lellouch J, Claude JR, Kuntz D. Epidemiology of serum uric acid and gout in Frenchmen. J Chronic Dis 1974; 27:59. BRILL JM, MCCARTY DJ. "STUDIES ON THE NATURE OF GOUTY TOPHI" BY MAX FREUDWEILER, 1899. (AN INFLAMMATORY RESPONSE TO INJECTED SODIUM URATE, 1899). AN ABRIDGED TRANSLATION, WITH COMMENTS. Ann Intern Med 1964; 60:486. McCarty DJ, Hollander JL. Identification of urate crystals in gouty synovial fluid. Ann Intern Med 1961; 54:452. Seegmiller JE, Howell RR, Malawista SE. The inflammatory reaction to sodium urate: its possible relationship to the genesis of acute gouty arthritis. JAMA 1962; 180:469. Hutton J, Fatima T, Major TJ, et al. Mediation analysis to understand genetic relationships between habitual coffee intake and gout. Arthritis Res Ther 2018; 20:135. Fanning N, Merriman TR, Dalbeth N, Stamp LK. An association of smoking with serum urate and gout: A health paradox. Semin Arthritis Rheum 2018; 47:825. Lin KC, Lin HY, Chou P. Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen. J Rheumatol 2000; 27:1045. Zhang Y, Woods R, Chaisson CE, et al. Alcohol consumption as a trigger of recurrent gout attacks. Am J Med 2006; 119:800.e13. Hunter DJ, York M, Chaisson CE, et al. Recent diuretic use and the risk of recurrent gout attacks: the online case-crossover gout study. J Rheumatol 2006; 33:1341. Chhana A, Lee G, Dalbeth N. Factors influencing the crystallization of monosodium urate: a systematic literature review. BMC Musculoskelet Disord 2015; 16:296. Loeb JN. The influence of temperature on the solubility of monosodium urate. Arthritis Rheum 1972; 15:189. Horvath SM, Hollander JL. INTRA-ARTICULAR TEMPERATURE AS A MEASURE OF JOINT REACTION. J Clin Invest 1949; 28:469. Martinon F, Pétrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440:237. Guerne PA, Terkeltaub R, Zuraw B, Lotz M. Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Arthritis Rheum 1989; 32:1443. Terkeltaub R, Zachariae C, Santoro D, et al. Monocyte-derived neutrophil chemotactic factor/interleukin-8 is a potential mediator of crystal-induced inflammation. Arthritis Rheum 1991; 34:894. di Giovine FS, Malawista SE, Thornton E, Duff GW. Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest 1991; 87:1375. Guerne PA, Terkeltaub R, Zuraw B, Lotz M. Inflammatory microcrystals stimulate interleukin-6 production and secretion by human monocytes and synoviocytes. Arthritis Rheum 1989; 32:1443.

TWiV explains why this season's influenza vaccine is not protecting against mild to moderate disease caused by H3N2 virus, and that antibody-dependent entry of SARS-CoV-2 into monocytes is a major contributor to severe COVID-19. Hosts: Vincent Racaniello, Dickson Despommier, Rich Condit, and Amy Rosenfeld Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Seasonal influenza vaccine effectiveness (MMWR) Properties of a dominant H3N2 variant (bioRxiv) Scott Henley on influenza vaccine growth in eggs (TWiV 480) Fc receptor dependent entry of SARS-CoV-2 into monocytes (Nature) Timestamps by Jolene. Thanks! Weekly Picks Dickson – Ketanji Brown Jackson confirmed to US Supreme Court Amy – Some threats just keep coming in waves Rich – Lady Bird Johnson Wildflower Center Vincent – Martijn Doolaard Listener Picks Ann – Immunological memory to SARS-CoV-2 infection and vaccines Chris – Isoplexis Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150In the season finale, Chalke is determined to undo the damage he's done....no matter how many times he has to try, and the true nature of the Monocyte comes to light.Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150While the Monocyte attempts to thwart Chalke's plan, it reaches out to an unlikely ally--Emissary Fralgon...Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Trying to find a cure for his nightmares, CHalke has a long talk with Crewman #7...or is it Crewman #7? And the Monocyte makes Doctor Montana an offer she can't refuse. Or can she?Written byNina Ki and Donaldson Cardenas Directed by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150The crew of the Monocyte is rocked by a sudden death; Chief Murtaugh and the Monocyte both come to realizations about themselves.Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Phineas Q. Progress returns to the Monocyte with a companion in tow, looking for a favor. Then all hell breaks loose.Written by Nina Ki and Donaldson CardenasDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Fralgon invites Chalke to their quarters for drinks and, it turns out, Fralgonese therapy. Meanwhile, The Monocyte has a heart-to-heart with the Auto-Translator. Did we mention there were drinks?Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Fralgon, Montana, and Chalke all have moments where they remember their first time aboard the Monocyte. With music and everything. And that memory offers up a BIG revelation for Chalke.Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Somehow, things get both better AND worse simultaneously. Chalke's nightmares continue, and the Monocyte ends up in both the film The Black Hole AND Groundhog Day....Written byDonaldson Cardenas and Nina KiDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Transphobic Microagressions, Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Feeling underappreciated on the Monocyte, Emissary Fralgon makes the decision to go back to Fralgon, where they and Doctor Montana run headlong into the most powerful force in the universe...sibling rivalry!Written byNina Ki and Donaldson CardenasDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

Content Warning: Mental Health issues, including depression and suicidal ideation. If you or someone you know is in crisis, help is out there. Contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or the Crisis Text Line by texting TALK to 741741 If you or someone you know is struggling with mental health issues and needs help, contact NAMI at 888-958-7150Fan Favorite Phineas Q. Progress visits the Galactic Medical Cruiser, Monocyte. There's nothing we can tell you about that that Phineas can't tell better himself.Written byNina Ki and Donaldson CardenasDirected by Natividad SalgadoStarring the voice talents of: Rae Hamilton-Vargo, Chris Davis, Serina Johnston*, Luis Bermudez, Andre Luc Martinez, Aryn Rozelle, and Rue DickeySound Design by Andrew Pond*. *Denotes EFCT Company MemberSupport this podcast at — https://redcircle.com/monocyte/donations

A chat with Monocyte director, Natividad Salgado, about her love for science fiction, space, and directing via chat windows Monocyte Launches March 24th!Support this podcast at — https://redcircle.com/monocyte/donations

Is blood a connective tissue. Blood cells. Romanovsky type mixtures/ different staining. Haematopoiesis. Erythropoiesis. Granulopoiesis. Platelet formation. Monocyte/ lymphocytes formation --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/oge-osondu/message

An interview with the writers of Monocyte, Donaldson Cardenas and Nina ki, as they talk about the process, fan service, and sad poetry...Support this podcast at — https://redcircle.com/monocyte/donations

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.25.354399v1?rss=1 Authors: Quek, H., Cuni-Lopez, C., Stewart, R., Colletti, T., Notaro, A., Sun, Y., Guo, C. C., Lupton, M. K., Nguyen, T. H., Oikari, L. E., Roberts, T. L., Lim, Y. C., La Bella, V., White, A. R. Abstract: Aims: Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Neuroinflammation mediated by microglial activation is evident in post-mortem brain tissues, and in brain imaging of patients with ALS. However, the exact role of microglia in ALS remains to be elucidated partly due to the lack of an accurate microglial model system that is able to recapitulate the clinical pathology of ALS. Moreover, direct sampling of microglia from patients with ALS is not feasible, further limiting the study of microglial function in ALS. To address this shortcoming, we describe an approach that generates monocyte-derived microglia (MDMi) that are capable of expressing molecular markers, and functional characteristics similar to resident human brain microglia. Importantly, MDMi can be routinely and reproducibly generated from ALS patient blood, and reveal patient heterogeneity associated with age, sex and disease subgroup. Methods: MDMi were successfully established from all 30 ALS patients, including 15 patients with slow disease progression, 6 with intermediate progression, and 9 with rapid progression, together with 20 non-affected heathy controls (HC). Results: Our ALS MDMi model recapitulated canonical pathological features of ALS including non-phosphorylated and phosphorylated-TDP-43-positive pathological inclusions. We further observed significantly impaired phagocytosis, altered cytokine expression and microglial morphology, as well as elevated DNA damage in ALS compared to HC MDMi. Abnormal phagocytosis was observed in all ALS cases, and was correlated to the progression of disease. Moreover, in-depth analysis of individual microglia revealed cell-specific variation in phagocytic function that was significantly altered, and exacerbated in rapid disease progression. Conclusions: Our approach enabled us to generate ALS patient microglia from peripheral blood samples using a rapid, robust, cost-effective, and reproducible protocol. We have shown that ALS monocyte-derived microglia have significantly altered functional behaviour compared to age-matched HCs, with a major deficit in phagocytic activity. This is also the first demonstration of abnormal TDP-43 localisation in microglia grown from ALS patients. Overall, this approach is highly applicable to monitor disease progression and can be applied as a functional readout in clinical trials for anti-neuroinflammatory agents. Additionally, this model system can be used as a basis for personalised therapeutic treatment for ALS, as well as other neurodegenerative diseases. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.136275v1?rss=1 Authors: Harwood, J. C., Leonenko, G., Sims, R., Escott-Price, V., Williams, J., Holmans, P. Abstract: More than 50 genetic loci have been identified as being associated with Alzheimer's disease (AD) from genome-wide association studies (GWAS) and many of these are involved in immune pathways and lipid metabolism. Therefore, we performed a transcriptome-wide association study (TWAS) of immune-relevant cells, to study the mis-regulation of genes implicated in AD. We used expression and genetic data from naive and induced CD14+ monocytes and two GWAS of AD to study genetically controlled gene expression in monocytes at different stages of differentiation and compared the results with those from TWAS of brain and blood. We identified nine genes with statistically independent TWAS signals, seven are known AD risk genes from GWAS: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR and two, LACTB2 and PLIN2/ADRP, are novel candidate genes for AD. Three genes, SPI1, PLIN2 and LACTB2, are TWAS significant specifically in monocytes. LACTB2 is a mitochondrial endoribonuclease and PLIN2/ADRP associates with intracellular neutral lipid storage droplets (LSDs) which have been shown to play a role in the regulation of the of immune response. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.04.077065v1?rss=1 Authors: Xu, E., Boddu, R., Abdelmotilib, H. A., Kelly, K., Sokratian, A., Harms, A. S., Schonhoff, A. M., Bryant, N., Harmsen, I. E., Schlossmacher, M., Chandra, S., Krendelshchikova, V., Liu, Z., West, A. B. Abstract: Missense mutations in the LRRK2 gene that lead to LRRK2 kinase hyperactivity can cause Parkinson's disease (PD). The link between LRRK2 and a-synuclein aggregation in PD remains enigmatic. Numerous reports suggest critical LRRK2 functions in microglial responses. Herein, we find that LRRK2-positive immune cells in the brain represent CD68-positive pro-inflammatory, monocyte-derived macrophages, distinct from microglia. Rod a-synuclein fibrils stimulate LRRK2 kinase activity in monocyte-derived macrophages, and LRRK2 mutations lead to enhanced recruitment of classical monocytes into the midbrain in response to a-synuclein. LRRK2 kinase inhibition blocks a-synuclein fibril induction of LRRK2 protein in both human and murine macrophages, with human cells demonstrating much higher LRRK2 levels and kinase activity than equivalent murine cells. Further, interferon-g strongly induces LRRK2 kinase activity in primary human macrophages in comparison to weak effects observed in murine cells. These results highlight peripheral immune responses in LRRK2-linked paradigms that further connect two central proteins in PD. Copy rights belong to original authors. Visit the link for more info

CHEST 2019 Recap Part 2 featuring random pearls and highlights from #CHEST2019 in New Orleans including: tips for addressing futile end-of-life care, bleeding in the ICU, DOAC reversal agents, use of procalcitonin and monocyte distribution width to identify sepsis, vitamin C for sepsis treatment, small particles and lung cancer risk, augmented reality/virtual learning, and tech as a teaching tool. Special thanks to Dr. Bill Kelly and his team at CHEST (@accpchest) for their hospitality.  Full show notes available at https://thecurbsiders.com/episode-list. Join our mailing list and receive a PDF copy of our show notes every Monday. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Credits Written, produced, and co-hosted by: Sarah Phoebe Roberts MPH; Paul Williams MD, FACP; Stuart Brigham MD; Matthew Watto MD, FACP Edited by: Matthew Watto MD, FACP Special Guests: Nina Maouelainin DO, MBA (@lungsolutions); Erin Narewski DO, FCCP (@erinnarewski); Chidinma Chima-Melton MD, FCCP (@LABritishLady), Kim Fabyan MD (@kfabsMD) Time Stamps 00:00 Pun, Disclaimer, Intro 03:58 Dr Erin Narewski on end of life conversations 13:30 Bleeding in the ICU 15:40 DOACs and reversal agents 18:40 Dr Chidinma Chima-Melton on ICU visiting hours 22:50 Vitamin C use in the ICU, Stuart’s Vitamin C rant 29:22 Monocyte distribution width for identifying patients with sepsis 30:55 Sarah Phoebe Roberts on Procalcitonin and CRP for sepsis 39:36 Dr Nina on technological innovations in MedEd: Virtual bronchoscopy; Dropping a computer in a remote village 46:49 Sarah Phoebe Roberts on Small particles and lung cancer risk 54:48 Outro Citation Narewski E, Chima-Melton C, Maouelainin N, Roberts SP, Williams P, Brigham S, Fayban K, Watto MF. “CHEST 2019 Recap Part 2”. The Curbsiders Internal Medicine Podcast https://thecurbsiders.com/episode-list. October 30, 2019.

Dr. Kelly Diehl talks about equine herpes virus with Dr. Tracy Stokol, Professor of Clinical Pathology at Cornell University. The two cover this devastating disease, as well as Dr. Stokol’s recent Morris Animal Foundation-funded research into certain white blood cells, called monocytes, to help horses fight equine herpesvirus type 1 (EHV1) infections.

We launched the Blood Chemistry Calculator six months ago and have come to rely on it for our Elite Performance Program clients as an initial screening tool and measure of ongoing progress. With the input of 39 basic blood chemistry markers, the calculator uses a machine-learning algorithm to predict health status in 6 specific areas: immune balance, toxicity, metabolic health, nutrition, oxidative balance, and a general 5-year wellness score. On this podcast, Tommy and I are talking specifically about the Immune Balance Score, the domain that forecasts immune system health and inflammation from 13 out of the 39 input markers and one forecasted value (CRP). Tommy discusses these markers in detail, citing research that supports using them to predict health outcomes. He also shares ideas for next steps to improve functioning in the area of immune balance. You can now try some features of the Blood Chemistry Calculator for free by visiting bloodcalculator.com and clicking “Free Report”. Here’s the outline of this interview with Tommy Wood: [00:00:30] Florida Institute for Human & Machine Cognition (IHMC); Podcast: Optimal Diet and Movement for Healthspan, Amplified Intelligence and More with Ken Ford. [00:00:49] Blood Chemistry Calculator. [00:01:03] Peer Review. [00:02:32] Immune Balance Score. [00:04:00] Dashboard of Blood Chemistry Calculator scores (example). [00:04:08] Predicted Age Score. [00:05:12] Who is the calculator for? [00:06:09] Building a health coach referral network. [00:07:05] Podcast: How to Measure Hormones, with Mark Newman. [00:08:31] Combining 2+ reports for longitudinal tracking. [00:09:08] Markers that make up the Immune Balance Score. [00:10:49] Sensitivity and specificity. [00:13:40] All-cause mortality: dying from any cause. [00:17:05] Evaluating scientific research: PubMed + Google. [00:19:53] C-Reactive Protein (CRP) > 0.5 associated with 75% increase in all-cause mortality; Study: Li, Yunwei, et al. "Hs-CRP and all-cause, cardiovascular, and cancer mortality risk: a meta-analysis." Atherosclerosis 259 (2017): 75-82. [00:21:10] Jeremy Powers; Podcast: National Cyclocross Champion Jeremy Powers on Racing, Training and the Ketogenic Diet. [00:22:30] Dr. Bryan Walsh - Timing of blood testing for athletes. [00:24:49] Albumin: less than 4 g/dL = increased risk of all-cause mortality; Studies: 1. Fulks, Michael, Robert L. Stout, and Vera F. Dolan. "Albumin and all-cause mortality risk in insurance applicants." J Insur Med 42.1 (2010): 11-17; 2. Proctor, Michael J., et al. "Systemic inflammation predicts all-cause mortality: a glasgow inflammation outcome study." PloS one 10.3 (2015): e0116206; 3. Lee, Won-Suk, et al. "Population Specific Biomarkers of Human Aging: A Big Data Study Using South Korean, Canadian, and Eastern European Patient Populations." (2018). [00:27:25] Gamma Gap (globulins): > 3 g/dL = increase in all-cause mortality; Studies: 1. Juraschek, Stephen P., et al. "The gamma gap and all-cause mortality." PloS one 10.12 (2015): e0143494; 2. Yang, Ming, et al. "The gamma gap predicts 4-year all-cause mortality among nonagenarians and centenarians." Scientific reports 8.1 (2018): 1046. [00:29:58] Table that shows reference ranges, scores assigned. [00:30:39] Ferritin - iron overload vs. indicator of inflammation; >200 ng/mL = 50% increase risk of all-cause mortality; Study: Kadoglou, Nikolaos PE, et al. "The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English longitudinal study of ageing." PloS one 12.6 (2017): e0178994. [00:34:20] Iron overload podcast: Iron overload and the impact it can have on performance and health, with Dr. Tommy Wood; Blood donation. [00:34:37] Podcast: Rethinking Positive Thinking, with Gabriele Oettingen. [00:36:31] Hemoglobin - higher = more aerobic power; Lower = chronic inflammation or nutritional deficiency.   [00:37:27] Hemoglobin has U-shaped curve - increased all-cause mortality if too low or too high. Optimal: from 14.5 g/dL (13 for women) + 1.5-2 g/dL; Study: Fulks, Michael, Vera F. Dolan, and Robert L. Stout. "Hemoglobin Screening Independently Predicts All-Cause Mortality." (2015): 75-80. [00:39:02] Christopher Kelly’s combined report. [00:39:18] Fasting blood glucose: >100 mg/dL = higher all-cause mortality. Study: Bjørnholt, JØRGEN V., et al. "Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men." Diabetes care 22.1 (1999): 45-49. [00:40:57] Red Cell Distribution Width (RDW): ideal is below 12%; Study: Al-Kindi, Sadeer G., et al. "Red Cell Distribution Width Is Associated with All-Cause and Cardiovascular Mortality in Patients with Diabetes." BioMed research international 2017 (2017). [00:41:17] White Blood Cells. [00:41:28] Eosinophils >0.275 x10E3/uL= increased risk of 30-year all-cause mortality; Study: Hospers, Jeannette J., et al. "Eosinophilia is associated with increased all-cause mortality after a follow-up of 30 years in a general population sample." Epidemiology (2000): 261-268. [00:42:21] Ratios between markers. [00:43:20] Platelets - High is associated with increased risk of mortality after heart attack; Study: Tsai, Ming-Tsun, et al. "U-shaped mortality curve associated with platelet count among older people: a community-based cohort study." Blood 126.13 (2015): 1633-1635. [00:43:39] Lymphocyte:Monocyte ratio; Study: Xiang, Fangfang, et al. "Monocyte/lymphocyte ratio as a better predictor of cardiovascular and all‐cause mortality in hemodialysis patients: A prospective cohort study." Hemodialysis International 22.1 (2018): 82-92. [00:45:23] Where to go from here?   [00:45:40] Acute vs. chronic inflammation. [00:47:07] Antimicrobials: Monolaurin, Lauricidin, Selenomethionine; antibody testing. [00:47:40] Malcolm Kendrick Podcast: Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think about Instead). [00:48:51] bloodcalculator.com; Quest lab locator. [00:49:11] UK: Fibrhealth. [00:49:15] Australia: https://stephenanderson.com.au/nbt/; Podcast: How to Get Help and Feel Great in Australia Using Advanced Blood Interpretation, with Stephen Anderson.   [00:49:38] support@nourishbalancethrive.com

Commentary by Dr. Valentin Fuster

Article Summary by Benjamin Bowe, Tingting Li, and Ziyad Al-Aly: In this podcast, Benjamin Bowe, Tingting Li and Ziyad Al-Aly discuss their recent CJASN article entitled, "Association between Monocyte Count and Risk of Incident CKD and Progression to...

Article Summary by Benjamin Bowe, Tingting Li, and Ziyad Al-Aly: In this podcast, Benjamin Bowe, Tingting Li and Ziyad Al-Aly discuss their recent CJASN article entitled, "Association between Monocyte Count and Risk of Incident CKD and Progression to...

Hosts: Vincent Racaniello, Michele Swanson, and Michael Schmidt. Vincent, Michael, and Michele reveal how a fungal protease blunts the innate immune response and promotes pathogenicity. Subscribe to TWiM (free) on iTunes, Stitcher, RSS, or by email. You can also listen on your mobile device with the Microbeworld app. Links for this episode Michele on Flint Legionella outbreak (Detroit News) Fungal mimicry of a mammalian aminopeptidase (Cell Host Micr)   This episode is sponsored by ASM Agar Art Contest and ASM Microbe 2016 Send your microbiology questions and comments (email or mp3 file) to twim@twiv.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twim.

Ivan Bogeski explains how redox-insensitive ORAI calcium channels enable monocytes to sustain calcium signaling while still producing bactericidal reactive oxygen species.

Can you tell the difference between a monocyte and a basophil? Would you know what an eosinophil looked like if it came up to you and introduced itself? Where do platelets come from? If I have worms, what cells are responsible for killing them? All this and much more answered as Susan Anderson takes you on a tour of blood on a microscopic scale, teaching you how to identify red cells, granulocytes, lymphocytes, platelets, monocytes, basophils, eosinophils and neutrophil polymorphs and going through what each cell type is for. Don't miss this if you are a medical student or doctor taking early postgrad exams. Susan Anderson is Associate Professor of Surgery at the University of Nottingham, UK

Background: Radiotherapy, administered in fractionated as well as ablative settings, is an essential treatment component for breast cancer. Besides the direct tumor cell death inducing effects, there is growing evidence that immune mechanisms contribute - at least in part - to its therapeutic success. The present study was designed to characterize the type and the extent of cell death induced by fractionated and ablative radiotherapy as well as its impact on the release of monocyte migration stimulating factors by dying breast cancer cells. Methods: Cell death and senescence assays were employed to characterize the response of a panel of breast cancer cell lines with different receptor and p53 status towards.-irradiation applied in a fractionated (daily doses of 2 Gy) or ablative setting (single dose of 20 Gy). Cell-free culture supernatants were examined for their monocyte migration stimulating potential in transwell migration and 2D chemotaxis/chemokinesis assays. Irradiation-induced transcriptional responses were analyzed by qRT-PCR, and CD39 surface expression was measured by flow cytometry. Results: Fast proliferating, hormone receptor negative breast cancer cell lines with defective p53 predominantly underwent primary necrosis in response to.-irradiation when applied at a single, ablative dose of 20 Gy, whereas hormone receptor positive, p53 wildtype cells revealed a combination of apoptosis, primary, and secondary (post-apoptotic) necrosis. During necrosis the dying tumor cells released apyrase-sensitive nucleotides, which effectively stimulated monocyte migration and chemokinesis. In hormone receptor positive cells with functional p53 this was hampered by irradiation-induced surface expression of the ectonucleotidase CD39. Conclusions: Our study shows that ablative radiotherapy potently induces necrosis in fast proliferating, hormone receptor negative breast cancer cell lines with mutant p53, which in turn release monocyte migration and chemokinesis stimulating nucleotides. Future studies have to elucidate, whether these mechanisms might be utilized in order to stimulate intra-tumoral monocyte recruitment and subsequent priming of adaptive anti-tumor immune responses, and which breast cancer subtypes might be best suited for such approaches.

We are back for another special issue of Talking Comics, and this time we have the creators of Monocyte and founders of 44Flood Kasra Ghanbari and Menton3 on the show.  Be sure to check them out over at http://44flood.com. Bobby: @ bobbyshortle Steve: @ dead_anchoress Stephanie: @ hellocookie And Bob's email is  bobreyer@talkingcomicbooks.com FYI: the crew have gone all superhero on the world, thanks to the wonderful  Hanie Mohd. Like them? Make sure to follow her and let us know what you think of our new superhero pictures.

Accumulation of classical monocytes is imperative for the progression ofatherosclerosis. Hence, therapeutic interference with mechanisms oflesional monocyte recruitment, the primary mechanism controllingmacrophage accumulation, may allow for targeting atheroprogression andits clinical complications. Here, we review the important role ofclassical monocytes in atheroprogression as well as their routes ofarterial recruitment. We specifically highlight the role of celladhesion molecules as well as of platelet-derived chemokines andneutrophil-borne alarmins.

Thu, 8 Nov 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15036/ https://edoc.ub.uni-muenchen.de/15036/1/Lam_Isong_Veronique.pdf Lam Isong, Veronique ddc:610, ddc:600, Medizinische

Its spring time. The sun is out. Time for a chillsky then. MonocyteSaltillo “If Wishes Were Catholics” (mp3) from “Monocyte”

Talking Comics' gang is down right buzzing about the podcast this week as they welcome ** Batman, Swamp Thing, American Vampire**  and  Severed  writer Scott Snyder to the show. During the spoiler free conversation Mr. Snyder tells our hosts the great responsibility of writing the caped crusader, how he came up with the Court of Owls, the impending Night of the Owls crossover event and even the origins of the Bat taser! In addition Bobby, Stephanie, Steve and Bob talk about  Amazing Spider-Man, Lobster Johnson, and Brilliant  in the book of the week segment and go far off the beaten path with Steve to take in a review of Saltillo's  Monocyte  concept album. The crew even manages to get into a little Academy Awards debate. So sit back, relax, grab your bat-a-rang and let's talk some comics!

Background: Infections and immunological processes are likely to be involved in the pathogenesis of Tourette's syndrome (TS). To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. Methods: In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP) in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), soluble CD14 (sCD14), IL1-receptor antagonist (IL1-ra), and serum neopterin were detected by immunoassays. Results: We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. Conclusions: The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

Human peritoneal mesothelial cells (MC) play an important role in inflammatory processes of the peritoneal cavity by producing various cytokines and chemokines, such as monocyte chemoattractant protein-1 (MCP-1). The present study was designed to assess the effect of the peroxisome proliferator-activated receptor-gamma- (PPAR gamma-) activator rosiglitazone on the mesothelial MCP-1 expression and release. Primary cultures of MC were obtained from omental tissue. MCP-1 antigen concentrations were measured in the cell supernatant by ELISA and MCP-1 mRNA levels by real-time polymerase chain reaction. The presence of PPAR. on MC was assayed in a Western Blot analysis. MC constitutively express PPAR gamma. Activation of this receptor via rosiglitazone (0,1-10 mu mol/L) resulted in significantly reduced amounts of mesothelial MCP-1 release as well as MCP-1 mRNA. The use of the PPAR gamma inhibitor GW-9662 could completely prevent the rosiglitazone effects. Rosiglitazone was also effective in reducing TNF alpha-induced enhanced secretion of MCP-1. Our findings indicate that glitazones are effective in reducing constitutive and TNF alpha-stimulated mesothelial MCP-1 mRNA expression and release.

Reviews: Dead Man's Run #0, Helldorado #1, The Incredible Hulk #1, Legion Secret Origin #1, Spaceman #1, Stitched #1, War of the Independents #1, Wolverine and the X-Men #1 Jimmy is joined again by Mike Cho to bring you the last of the New York Comic Con interviews! Jimmy chats with Ashley Eckstein ("Ahsoka Tano" on the Star Wars: The Clone Wars animated series), Bruce Time (Green Lantern, Batman animated series), and Monocyte creators Menton Matthews III & Kasra Ghanbari. The boys also discuss Halloween, famous tweets, Burke & Hare film, Beavis & Butt-Head and Good Vibes cartoons, Grimm, Grace Helbig wins King of the Web, 10th Doctor Who musical and other nonsense. News includes: Topps and IDW bring back Mars Attacks! in a comic book series, DC Universe Online is free, Rob Liefeld returns Extreme to Image, and Trip City is here. As always, Listener Feedback, the Top 3 and more! Leave your iTunes comments! 5 stars and nothing but love!

Background: Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS) and neuromyelitis optica (NMO) generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE) attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naive B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods: Myelin oligodendrocyte glycoprotein (MOG) peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg) and cytokine production of CD11b(+) antigen presenting cells (APC) were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM). Results: We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b(+) APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions: These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and effectiveness may further advance by selectively targeting pathogenic B-cell function.

In this study the ability of different Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) strains to survive in bovine monocyte-derived macrophages (MDMs) was investigated. The following hypotheses were tested: 1) Infection status of a cow does not affect the ability of its macrophages to kill M. paratuberculosis 2) Killing capacity of bovine macrophages is not dependent on the M. paratuberculosis strain MDMs for conducted experiments were obtained from Johne’s disease-positive (n = 3) and age and stage of lactation matched Johne’s disease-negative (n = 3) multiparious cows. Animals were kept on the same dairy operation, thus non-infected cows had been exposed to M. paratuberculosis strains present on the farm premises. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by density gradient centrifugation. After a five-day differentiation period in cell culture using Teflon jars MDMs were obtained and subsequently challenged in vitro with four M. paratuberculosis strains of different host specificity (bovine, ovine). MDMs were harvested at 2 hours, 2 days, 4 days and 7 days following infection. For each time point ingestion and intracellular survival of M. paratuberculosis strains were determined by fluorescence microscopy. There was no effect of the origin of MDMs (Johne’s disease-positive or control animals) on phagocytosis, survival of bacteria, or macrophage survival. In contrast, important strain differences were observed. These findings suggest that some M. paratuberculosis strains interfere more successfully than others with the ability of macrophages to kill intracellular pathogens which may make it important to include strain typing when designing control programs.

Oxidized LDL and platelets play a central role in the pathogenesis of atherosclerosis and ischemic cardiovascular diseases. Lysophosphatidic acid (LPA) is a thrombogenic substance that accumulates in mildly-oxidized LDL and in human atherosclerotic lesions, and is responsible for the initial platelet activation, shape change, induced by mildly-oxidized LDL and extracts of lipid-rich atherosclerotic plaques (Siess et al., 1999 Proc Natl Acad Sci USA 1999). LPA directly induced platelet shape change in blood and platelet-rich plasma (PRP) obtained from all blood donors. Albumin was one of the main inhibiting factors of platelet shape change in plasma. Interestingly LPA, at concentrations slightly above plasma levels, induced platelet shape change and aggregation in blood. 1-alkyl-LPA (16:0) was almost 20-fold more potent than 1-acyl-LPA (16:0). LPA-stimulated platelet aggregation in blood and PRP was donor-dependent. LPA-induced aggregation in blood could be completely blocked by the ADP- scavenging enzyme, apyrase, and antagonists of the platelet ADP-receptors P2Y1 and P2Y12. These substances also inhibited LPA-induced aggregation of platelet-rich plasma, and aggregation and serotonin secretion of washed platelets. These results indicate a central role for ADP-mediated P2Y1 and P2Y12 receptor activation in supporting LPA-induced platelet aggregation and show that LPA synergistically with ADP induces platelet aggregation in blood. Thus antagonists of platelet P2Y1 and P2Y12 receptors, especially in donors highly sensitive to LPA, might be useful in preventing LPA-elicited thrombus formation in patients with cardiovascular diseases. The mechanism of LPA plus ADP-induced aggregation was independent of the Rho/Rho kinase pathway which mediated LPA-induced platelet shape change in blood. LPA, activating G13, but not Gi or Gq synergized also with epinephrine, activating Gi, and serotonin, activating Gq, in amplifying LPA-induced platelet aggregation in washed platelets. LPA/serotonin-induced aggregation was blocked by either ADP-receptor antagonist whereas synergistic aggregation induced by LPA/epinephrine was independent from ADP-receptor antagonists. The latter results demonstrate an additional mechanism for aggregation independent of P2Y1 and P2Y12. Most surprising, LPA-induced platelet aggregation was insensitive to inhibition by aspirin. LPA at low concentrations, starting slightly above plasma level, was also capable of eliciting platelet-monocyte conjugate formation. LPA-induced platelet-monocyte formation was independent of the blood donor. ADP mediated P2Y1 and P2Y12 receptor activation played only a minor role. Platelet-monocyte aggregate formation stimulated by LPA was P-selectin-mediated and insensitive to inhibition by aspirin. Pathophysiolocical events such as sudden plaque rupture or progressive enrichment of circulating oxidized LDL at critical sites of turbulent flow might lead to higher local blood concentration of LPA. This can induce platelet shape change, platelet aggregation and platelet-monocyte formation at atherosclerotic sites. LPA receptor antagonists could be of possible benefit not only preventing arterial thrombosis, but also retarding vascular inflammation in patients with cardiovascular disease.

Background: Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2(+) T cells accumulate in pediatric ILD and are related to disease severity. Methods: Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2(+), CCR4(+), CCR3(+), CCR5(+) and CXCR3(+) T cells were quantified by flow-cytometry. Results: CCR2(+) T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2(+) T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion: The results indicate that pulmonary CCR2(+) T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.

Human peritoneal mesothelial cells (HMC) contribute to the activation and control of inflammatory processes in the peritoneum by their potential to produce various inflammatory mediators. The present study was designed to assess the effect of glucose, the osmotic active compound in most commercially available peritoneal dialysis fluids, on the synthesis of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured HMC. The MCP-1 concentration in the cell supernatants was determined by enzyme-linked immunosorbent assay and the MCP-1 mRNA expression was examined using Northern blot analysis. Incubation of HMC with glucose (30-120 mM) resulted in a time- and concentration-dependent increase in MCP-1 protein secretion and mRNA expression. After 24 h the MCP-1 synthesis was increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p < 0.05) in HMC treated with 60 mM glucose. In contrast, osmotic control media containing either the metabolically inert monosaccharide mannitol or NaCl did not influence MCP-1 production. The stimulating effect of high glucose on MCP-1 expression in HMC was mimicked by activation of protein kinase C (PKC) with the phorbol ester PMA (20 nM). Coincubation of the cells with glucose and the specific PKC inhibitor Ro 31-8220 completely blunted glucose-mediated MCP-1 expression. In summary, our results indicate that glucose induces MCP-1 synthesis by a PKC-dependent pathway. Since osmotic control media did not increase MCP-1 release, it is suggested that the effect of glucose is mainly related to metabolism and not to hyperosmolarity. These data may in part explain elevated steady-state levels of MCP-1 found in the dialysis effluent of continuous ambulatory peritoneal dialysis patients. Copyright 2001 S. Karger AG. Basel.