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Article ; Online: Cytokines as predictors of COVID-19 severity: evidence from a meta-analysis. Authors' reply.

Kosmaczewska, Agata / Frydecka, Irena

2021 Volume 131, Issue 1, Page(s) 99–100

MeSH term(s)	COVID-19 ; Cytokines ; Humans ; SARS-CoV-2
Chemical Substances	Cytokines
Language	English
Publishing date	2021-01-29
Publishing country	Poland
Document type	Letter ; Comment
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15793
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Dysregulation of the immune system as a driver of the critical course of novel coronavirus disease 2019.

Kosmaczewska, Agata / Frydecka, Irena

Polish archives of internal medicine

2020 Volume 130, Issue 9, Page(s) 779–788

Abstract: Novel coronavirus disease 2019 (COVID‑19) is a highly contagious, respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). Given that inflammatory immune cells may induce severe lung injury, the ... ...

Abstract	Novel coronavirus disease 2019 (COVID‑19) is a highly contagious, respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). Given that inflammatory immune cells may induce severe lung injury, the involvement of immunological factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses have developed mechanisms of immune evasion, making themselves invisible to the immune system at an early stage of infection. The mechanism relies on inhibiting the antiviral response of type I interferons, which enhances uncontrolled viral replication in epithelial cells. There has been a growing body of evidence showing that fatal hyperinflammation (cytokine storm) responsible for the severe course of COVID‑19 is a consequence of massive SARS‑CoV‑2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, the suppressed antiviral innate immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminant systemic inflammation. The occurrence of virus transmission even in asymptomatic individuals infected with SARS‑CoV‑2 clearly strengthens the evidence for the key role played by the sufficient immune control of viral replication in a subset of cases (eg, in children, a population with a highly effective innate immune response). Although administration of immunomodulatory drugs is recommended under certain conditions by the guidelines for COVID‑19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS‑CoV‑2 still exist. Extending clinicians' knowledge on the dysregulated immune response, which is a driver of the COVID‑19 outcome, may improve both therapeutic strategies and the prognosis of patients infected with SARS‑CoV‑2.
MeSH term(s)	COVID-19 ; Coronavirus Infections/immunology ; Cytokines/immunology ; Female ; Humans ; Immune System/immunology ; Immunity, Innate ; Inflammation ; Male ; Pandemics ; Pneumonia, Viral/immunology
Chemical Substances	Cytokines
Keywords	covid19
Language	English
Publishing date	2020-07-06
Publishing country	Poland
Document type	Journal Article ; Review
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15482
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Are patients with lung cystic fibrosis at increased risk of severe and fatal COVID-19? Interleukin 6 as a predictor of COVID-19 outcomes. Authors' reply.

Kosmaczewska, Agata / Frydecka, Irena

Polish archives of internal medicine

2020 Volume 130, Issue 10, Page(s) 920–921

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus ; Coronavirus Infections ; Cystic Fibrosis ; Humans ; Immune System ; Interleukin-6 ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
Chemical Substances	Interleukin-6
Keywords	covid19
Language	English
Publishing date	2020-10-29
Publishing country	Poland
Document type	Letter ; Comment
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15660
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Low-dose interleukin-2 therapy: a driver of an imbalance between immune tolerance and autoimmunity.

Kosmaczewska, Agata

International journal of molecular sciences

2014 Volume 15, Issue 10, Page(s) 18574–18592

Abstract: For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, ... ...

Abstract	For many years, the role of interleukin-2 (IL-2) in autoimmune responses was established as a cytokine possessing strong pro-inflammatory activity. Studies of the past few years have changed our knowledge on IL-2 in autoimmune chronic inflammation, suggesting its protective role, when administered at low-doses. The disrupted balance between regulatory and effector T cells (Tregs and Teffs, respectively) is a characteristic of autoimmune diseases, and is dependent on homeostatic cytokines, including IL-2. Actually, inherent defects in the IL-2 signaling pathway and/or levels leading to Treg compromised function and numbers as well as Th17 expansion have been attributed to autoimmune disorders. In this review, we discuss the role of IL-2 in the pathogenesis of autoimmune diseases. In particular, we highlight the impact of the dysregulated IL-2 pathway on disruption of the Treg/Th17 balance, reversal of which appears to be a possible mechanism of the low-dose IL-2 treatment. The negative effects of IL-2 on the differentiation of follicular helper T cells (Tfh) and pathogenic Th17 cells, both of which contribute to autoimmunity, is emphasized in the paper as well. We also compare the current IL-2-based therapies of animal and human subjects with immune-mediated diseases aimed at boosting the Treg population, which is the most IL-2-dependent cell subset desirable for sufficient control of autoimmunity. New perspectives of therapeutic approaches focused on selective delivery of IL-2 to inflamed tissues, thus allowing local activity of IL-2 to be combined with its reduced systemic and pleiotropic toxicity, are also proposed in this paper.
MeSH term(s)	Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; Autoimmune Diseases/therapy ; Autoimmunity ; Humans ; Immune Tolerance ; Immunotherapy/methods ; Interleukin-2/administration & dosage ; Interleukin-2/immunology ; Interleukin-2/therapeutic use ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology ; Th17 Cells/immunology ; Th17 Cells/pathology
Chemical Substances	Interleukin-2
Language	English
Publishing date	2014-10-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms151018574
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Dysregulation of the immune system as a driver of the critical course of novel coronavirus disease 2019

Kosmaczewska, Agata / Frydecka, Irena

Pol Arch Intern Med

Abstract: Novel coronavirus disease 2019 (COVID19) is a highly contagious, respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARSCoV2). Given that inflammatory immune cells may induce severe lung injury, the ... ...

Abstract	Novel coronavirus disease 2019 (COVID19) is a highly contagious, respiratory disease caused by the newly emerged severe acute respiratory syndrome coronavirus 2 (SARSCoV2). Given that inflammatory immune cells may induce severe lung injury, the involvement of immunological factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses have developed mechanisms of immune evasion, making themselves invisible to the immune system at an early stage of infection. The mechanism relies on inhibiting the antiviral response of type I interferons, which enhances uncontrolled viral replication in epithelial cells. There has been a growing body of evidence showing that fatal hyperinflammation (cytokine storm) responsible for the severe course of COVID19 is a consequence of massive SARSCoV2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, the suppressed antiviral innate immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminant systemic inflammation. The occurrence of virus transmission even in asymptomatic individuals infected with SARSCoV2 clearly strengthens the evidence for the key role played by the sufficient immune control of viral replication in a subset of cases (eg, in children, a population with a highly effective innate immune response). Although administration of immunomodulatory drugs is recommended under certain conditions by the guidelines for COVID19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARSCoV2 still exist. Extending clinicians' knowledge on the dysregulated immune response, which is a driver of the COVID19 outcome, may improve both therapeutic strategies and the prognosis of patients infected with SARSCoV2.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #634302
Database	COVID19

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Article: Are patients with lung cystic fibrosis at increased risk of severe and fatal COVID-19? Interleukin 6 as a predictor of COVID-19 outcomes. Authors' reply

Kosmaczewska, Agata / Frydecka, Irena

Pol Arch Intern Med

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #895813
Database	COVID19

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Article ; Online: Inappropriate Expression of PD-1 and CTLA-4 Checkpoints in Myeloma Patients Is More Pronounced at Diagnosis: Implications for Time to Progression and Response to Therapeutic Checkpoint Inhibitors.

Kulikowska de Nałęcz, Anna / Ciszak, Lidia / Usnarska-Zubkiewicz, Lidia / Pawlak, Edyta / Frydecka, Irena / Szmyrka, Magdalena / Kosmaczewska, Agata

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Multiple myeloma (MM) is a hematologic malignancy characterized by severely profound immune dysfunction. Therefore, the efficacy of drugs targeting the immune environments, such as immune checkpoint inhibitors (ICIs), is of high clinical importance. ... ...

Abstract	Multiple myeloma (MM) is a hematologic malignancy characterized by severely profound immune dysfunction. Therefore, the efficacy of drugs targeting the immune environments, such as immune checkpoint inhibitors (ICIs), is of high clinical importance. However, several clinical trials evaluating ICIs in MM in different therapeutic combinations revealed underwhelming results showing a lack of clinical efficacy and excessive side effects. The underlying mechanisms of resistance to ICIs observed in the majority of MM patients are still under investigation. Recently, we demonstrated that inappropriate expression of PD-1 and CTLA-4 on CD4 T cells in active MM is associated with adverse clinical outcomes and treatment status. The aim of the current study was to determine the usefulness of immune checkpoint expression assessment as a predictive biomarker of the response to therapeutic inhibitors. For this purpose, along with checkpoint expression estimated by flow cytometry, we evaluated the time to progression (TTP) of MM patients at different clinical stages (disease diagnosis and relapse) depending on the checkpoint expression level; the cut-off point (dividing patients into low and high expressors) was selected based on the median value. Herein, we confirmed the defective levels of regulatory PD-1, CTLA-4 receptors, and the CD69 marker activation in newly diagnosed (ND) patients, whereas relapsed/refractory patients (RR) exhibited their recovered values and reactivity. Additionally, substantially higher populations of senescent CD4
MeSH term(s)	Humans ; CTLA-4 Antigen ; Multiple Myeloma/diagnosis ; Multiple Myeloma/drug therapy ; Multiple Myeloma/genetics ; Programmed Cell Death 1 Receptor ; Neoplasm Recurrence, Local/etiology ; Immunotherapy/methods
Chemical Substances	CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-03-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065730
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Archaeobotanical evidence and ethnobotanical interpretation of plants used as coffin pillow fillings in burials in Poland (17th-18/19th centuries)

Badura, Monika / Jarosińska, Marta / Noryśkiewicz, Agnieszka M. / Kosmaczewska, Agata / Sady-Bugajska, Agata / Święta-Musznicka, Joanna / Pińska, Katarzyna / Latałowa, Małgorzata

Veget Hist Archaeobot. 2023 Jan., v. 32, no. 1 p.85-103

2023

Abstract: The aim of this article is the study of the botanical material in the fillings of 54 coffin pillows from Catholic and Protestant burials dated to the 17th-18/19th centuries, collected during the investigation of 15 church crypts in different regions of ... ...

Abstract	The aim of this article is the study of the botanical material in the fillings of 54 coffin pillows from Catholic and Protestant burials dated to the 17th-18/19th centuries, collected during the investigation of 15 church crypts in different regions of Poland, and consideration of the role of the plants used for this purpose. In a large part of the dataset, a comprehensive picture of the botanical composition of the pillow fills has been obtained through the parallel studies of plant macroremains and pollen. Advantages and pitfalls in the use of pollen analysis on these specific remains are discussed. The results show that a large number of taxa were used in pillow fillings. The choice of plants was mostly dictated by their aromatic, insect repellent and preservative properties as well as their symbolic meanings, but the morphology and other physical properties of plants used in the fillings was also of importance. In some cases, the use of plants from bouquets which had been blessed in specific Catholic church ceremonies is suggested. The possible season of burial according to the botanical composition of the pillows is discussed.
Keywords	archaeobotany ; botanical composition ; data collection ; insect repellents ; pollen ; pollen analysis ; Poland
Language	English
Dates of publication	2023-01
Size	p. 85-103.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	1481434-1
ISSN	1617-6278 ; 0939-6314
ISSN (online)	1617-6278
ISSN	0939-6314
DOI	10.1007/s00334-022-00884-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Deregulated Expression of Immune Checkpoints on Circulating CD4 T Cells May Complicate Clinical Outcome and Response to Treatment with Checkpoint Inhibitors in Multiple Myeloma Patients.

Kulikowska de Nałęcz, Anna / Ciszak, Lidia / Usnarska-Zubkiewicz, Lidia / Frydecka, Irena / Pawlak, Edyta / Szmyrka, Magdalena / Kosmaczewska, Agata

International journal of molecular sciences

2021 Volume 22, Issue 17

Abstract: Unlike solid-tumor patients, a disappointingly small subset of multiple myeloma (MM) patients treated with checkpoint inhibitors derive clinical benefits, suggesting differential participation of inhibitory receptors involved in the development of T-cell- ...

Abstract	Unlike solid-tumor patients, a disappointingly small subset of multiple myeloma (MM) patients treated with checkpoint inhibitors derive clinical benefits, suggesting differential participation of inhibitory receptors involved in the development of T-cell-mediated immunosuppression. In fact, T cells in MM patients have recently been shown to display features of immunosenescence and exhaustion involved in immune response inhibition. Therefore, we aimed to identify the dominant inhibitory pathway in MM patients to achieve its effective control by therapeutic interventions. By flow cytometry, we examined peripheral blood (PB) CD4 T cell characteristics assigned to senescence or exhaustion, considering PD-1, CTLA-4, and BTLA checkpoint expression, as well as secretory effector function, i.e., capacity for IFN-γ and IL-17 secretion. Analyses were performed in a total of 40 active myeloma patients (newly diagnosed and treated) and 20 healthy controls. At the single-cell level, we found a loss of studied checkpoints' expression on MM CD4 T cells (both effector (Teff) and regulatory (Treg) cells) primarily at diagnosis; the checkpoint deficit in MM relapse was not significant. Nonetheless, PD-1 was the only checkpoint distributed on an increased proportion of T cells in all MM patients irrespective of disease phase, and its expression on CD4 Teff cells correlated with adverse clinical courses. Among patients, the relative defect in secretory effector function of CD4 T cells was more pronounced at myeloma relapse (as seen in declined Th1/Treg and Th17/Treg cell rates). Although the contribution of PD-1 to MM clinical outcomes is suggestive, our study clearly indicated that the inappropriate expression of immune checkpoints (associated with dysfunctionality of CD4 T cells and disease clinical phase) might be responsible for the sub-optimal clinical response to therapeutic checkpoint inhibitors in MM.
MeSH term(s)	Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CTLA-4 Antigen/antagonists & inhibitors ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/metabolism ; Case-Control Studies ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Tolerance/immunology ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/immunology ; Multiple Myeloma/metabolism ; Multiple Myeloma/mortality ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/immunology ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/mortality ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; Receptors, Immunologic/antagonists & inhibitors ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Survival Rate ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology
Chemical Substances	BTLA protein, human ; Biomarkers, Tumor ; CTLA-4 Antigen ; CTLA4 protein, human ; Immune Checkpoint Inhibitors ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Immunologic
Language	English
Publishing date	2021-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22179298
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: CD4

Kosmaczewska, Agata / Ciszak, Lidia / Stosio, Malgorzata / Szteblich, Aleksandra / Madej, Marta / Frydecka, Irena / Wiland, Piotr / Szmyrka, Magdalena

Lupus

2020 Volume 29, Issue 7, Page(s) 705–714

Abstract: Background: Pathogenic CD4: Methods: We examined the levels of circulating CD4: Results: In patients, we found elevated CD4: Conclusion: SLE with a moderately active clinical course is characterized by peripheral blood expansion of ... ...

Abstract	Background: Pathogenic CD4 Methods: We examined the levels of circulating CD4 Results: In patients, we found elevated CD4 Conclusion: SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4
MeSH term(s)	Adult ; CD28 Antigens/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Female ; Flow Cytometry ; Humans ; Interferon-gamma/immunology ; Lupus Erythematosus, Systemic/immunology ; Male ; Middle Aged ; Severity of Illness Index
Chemical Substances	CD28 Antigens ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2020-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1154407-7
ISSN	1477-0962 ; 0961-2033
ISSN (online)	1477-0962
ISSN	0961-2033
DOI	10.1177/0961203320917749
Database	MEDical Literature Analysis and Retrieval System OnLINE

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