scholarly journals Mathematical Analysis of an Autoimmune Diseases Model: Kinetic Approach

Mathematics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 1024 ◽  
Author(s):  
Mikhail Kolev

A new mathematical model of a general autoimmune disease is presented. Basic information about autoimmune diseases is given and illustrated with examples. The model is developed by using ideas from the kinetic theory describing individuals expressing certain functions. The modeled problem is formulated by ordinary and partial equations involving a variable for a functional state. Numerical results are presented and discussed from a medical view point.

2020 ◽  
Vol 5 (2) ◽  
pp. 439-456
Author(s):  
Jenny L. Pierce

Purpose This review article provides an overview of autoimmune diseases and their effects on voice and laryngeal function. Method A literature review was conducted in PubMed. Combinations of the following keywords were used: “autoimmune disease and upper airway,” “larynx,” “cough,” “voice,” “dysphonia,” and “dyspnea.” Precedence was given to articles published in the past 10 years due to recent advances in this area and to review articles. Ultimately, 115 articles were included for review. Results Approximately 81 autoimmune diseases exist, with 18 of those highlighted in the literature as having laryngeal involvement. The general and laryngeal manifestations of these 18 are discussed in detail, in addition to the clinical implications for a laryngeal expert. Conclusions Voice, breathing, and cough symptoms may be an indication of underlying autoimmune disease. However, these symptoms are often similar to those in the general population. Appropriate differential diagnosis and timely referral practices maximize patient outcomes. Guidelines are provided to facilitate correct diagnosis when an autoimmune disease is suspected.


2020 ◽  
Vol 16 ◽  
Author(s):  
Mariam Ahmed Saad ◽  
Mostafa Alfishawy ◽  
Mahmoud Nassar ◽  
Mahmoud Mohamed ◽  
Ignatius N Esene ◽  
...  

Introduction: Over 4.9 million cases of Coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide pandemic began. Since the emergence of COVID-19, a number of confirmed cases reported autoimmune manifestations. Herein, we reviewed the reported COVID-19 cases with associated autoimmune manifestations. Methods: We searched PubMed database using all available keyword for COVID-19. All related studies between January 1st, 2020 to May 22nd, 2020 were reviewed. Only studies published in English language were considered. Articles were screened based on titles and abstract. All reports of confirmed COVID-19 patients who have associated clinical evidence of autoimmune disease were selected. Results: Among 10006 articles, searches yielded, Thirty-two relevant articles for full-text assessment. Twenty studies meet the eligibility criteria. The twenty eligible articles reported 33 cases of confirmed COVID-19 diagnosis who developed an autoimmune disease after the onset of covid-19 symptoms. Ages of patients varied from a 6 months old infant to 89 years old female (Mean=53.9 years of 28 cases); five cases had no information regarding their age. The time between symptoms of viral illness and onset of autoimmune symptoms ranged from 2 days to 33 days (Mean of the 33 cases=9.8 days). Autoimmune diseases were one case of subacute thyroiditis (3%), two cases of Kawasaki Disease (6.1%), three cases of coagulopathy and antiphospholipid syndrome (9.1%), three cases of immune thrombocytopenic purpura (9.1%), eight cases of autoimmune hemolytic anemia (24.2%), and sixteen cases of Guillain–Barré syndrome (48.5%). Conclusions: COVID-19 has been implicated in the development in a range of autoimmune diseases which may shed a light on the association between autoimmune diseases and infections.


2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Tan Chan Sin ◽  
Ryspek Usubamatov ◽  
M. A. Fairuz ◽  
Mohd Fidzwan B. Md. Amin Hamzas ◽  
Low Kin Wai

Productivity rate (Q) or production rate is one of the important indicator criteria for industrial engineer to improve the system and finish good output in production or assembly line. Mathematical and statistical analysis method is required to be applied for productivity rate in industry visual overviews of the failure factors and further improvement within the production line especially for automated flow line since it is complicated. Mathematical model of productivity rate in linear arrangement serial structure automated flow line with different failure rate and bottleneck machining time parameters becomes the basic model for this productivity analysis. This paper presents the engineering mathematical analysis method which is applied in an automotive company which possesses automated flow assembly line in final assembly line to produce motorcycle in Malaysia. DCAS engineering and mathematical analysis method that consists of four stages known as data collection, calculation and comparison, analysis, and sustainable improvement is used to analyze productivity in automated flow assembly line based on particular mathematical model. Variety of failure rate that causes loss of productivity and bottleneck machining time is shown specifically in mathematic figure and presents the sustainable solution for productivity improvement for this final assembly automated flow line.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1321.1-1321
Author(s):  
S. Nagpal ◽  
S. Cole ◽  
A. Floudas ◽  
M. Wechalekar ◽  
Q. Song ◽  
...  

Background:Immune checkpoint blockade with agents targeting CTLA4 and PD-1/PD-L1 alone or in combination has demonstrated exceptional efficacy in multiple cancer types by “unleashing” the cytotoxic action of quiescent, tumor-infiltrating T cells. However, the therapeutic action of these immunotherapies goes hand in hand with the loss of immune tolerance and appearance of immune-related adverse events such as colitis, arthralgia and inflammatory arthritis in responsive patients. Therefore, immune checkpoint molecules have been proposed as targets for the treatment of autoimmune diseases.Objectives:Herein, we interrogate the potential of BTLA/HVEM axis as a target for restoring immune homeostasis in rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome (SjS) by examining their expression patterns in autoimmune disease tissues.Methods:Message and protein expression of BTLA and HVEM were examined in RA and SLE synovial tissues, SLE cutaneous lesions, SjS salivary glands and peripheral blood samples of autoimmune disease by RNA sequencing and flow cytometry.Results:Tissue dysregulation of the BTLA-HVEM axis was observed: Increased BTLA RNA level in RA synovium, SLE-affected skin, and SjS salivary gland samples, whereas HVEM level was affected only in the RA synovium when compared to unaffected tissues. Detailed immunophenotyping of B, T, and myeloid cell populations in RA, SLE, SjS and healthy control PBMCs revealed differential modulation of the BTLA+ or HVEM+ immune cell subsets in a disease-context dependent manner. SjS patients showed an overall decrease in memory B cells and most of the BTLA+ B cell subsets while a decrease in HVEM+ B cells was observed only in SLE PBMC samples and not RA and SLE samples. Immunophenotyping with a T cell panel exhibited decreased BTLA and HVEM expression on T cell subsets in SjS and SLE but not in RA patients. In addition, protein levels of HVEM were differentially decreased in SLE myeloid cell subsets. Finally, we demonstrate tissue-specific surface expression patterns of BTLA in RA and SLE samples: higher surface BTLA levels on RA and SLE PBMC B cells than matched tissue-derived B cells.Conclusion:Our results demonstrate a dysregulation of the BTLA/HVEM axis in either lesional tissue or peripheral blood in an autoimmune disease context-dependent manner. These results also indicate the potential of targeting BTLA-HVEM axis for the treatment of multiple autoimmune diseases.Disclosure of Interests:Sunil Nagpal Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Suzanne Cole Shareholder of: Janssen Research & Development employee, Employee of: Janssen Research & Development employee, Achilleas Floudas: None declared, Mihir Wechalekar Grant/research support from: Grant from Janssen Research & Development, Qingxuan Song Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research, Tom Gordon: None declared, Roberto Caricchio Grant/research support from: Financial grant from Janssen Research & Development, Douglas Veale: None declared, Ursula Fearon: None declared, Navin Rao Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Ling-Yang Hao Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1347.2-1347
Author(s):  
S. Y. Ki ◽  
H. Shin ◽  
Y. Lee ◽  
H. R. Bak ◽  
H. Yu ◽  
...  

Background:Janus kinases (JAK1, JAK2, JAK3, and TYK2) play critical roles in mediating various cytokine signaling, and has been developed as a target for autoimmune diseases such as RA. Tofacitinib, oral Pan-JAK inhibitor, demonstrated efficacy in RA patients, but its widespread use is limited by safety issues. Baricitinib, JAK1/2 inhibitor, is also known to interfere with the hematopoiesis system, such as anemia and thrombocytopenia associated with suppression of JAK2 signals. Therefore, it is necessary to develop a new potent compound that selectively inhibits JAK1 over JAK2, 3Objectives:To identify the pharmacological characteristic based on efficacy of CJ-15314 as potent and selective JAK1 inhibitor for treatment of autoimmune disease.Methods:In vitro, cell-based, kinase panel, Kd value and human whole blood assay were performed to determine the inhibition potency and selectivity for JAK subfamily kinases. In vivo therapeutic potential was evaluated by RA model including rat Adjuvant-Induced Arthritis (AIA) and collagen-induced arthritic (CIA). To confirm the possibility of further expansion into the autoimmune disease, BioMAP® Diversity PLUS® Panel was performed by discoverX.Results:In vitro assay, CJ-15314 inhibited JAK kinase family in a concentration-dependent manner with IC50 values of 3.8 nM against JAK1, Selectivity for JAK1 over JAK2, 3 was approximately 18, 83 fold greater for CJ-15314. In 1mM ATP condition, CJ-15314 has been confirmed to have the highest JAK1 selectivity over competing drugs, under 1 mM ATP condition that reflects the physiological environment in the body. Similarly, Kd values has also confirmed the selectivity of JAK1, which is 10 fold higher than JAK2, 3. Accordingly, in human whole blood assays, CJ-15314 is 11 fold more potent against IL-6 induced pSTAT1 inhibition through JAK1 (IC50 value: 70 nM) than GM-CSF-induced pSTAT5 inhibition (JAK2) whereas baricitinib and filgotinib exhibited only 2 fold and 7 fold respectively.In vivo efficacy model, CJ-15314 inhibited disease severity scores in a dose dependent manner. In the rat AIA model, CJ-15314 at 30 mg/kg dose showed 95.3% decrease in arthritis activity score, 51.2% in figotinib at 30 mg/kg, 97.7% showed baricitinib at 10 mg/kg. CJ-15314 showed superior anti-arthritic efficacy than filgotinib. CJ-15314 also minimally affected anemia-related parameters but not bricitinib end of the 2-week treatment. In the rat CIA model, like 10 mg/kg of bricitinib, 30 mg/kg of CJ-15314 also has a similar effect, with a significant reduction in histopathological scores.In biomap diversity panel, CJ-15314 inhibited the expression of genes such as MCP-1, VCAM-1, IP-10, IL-8, IL-1, sTNF-α and HLA-DR confirming the possibility of expansion into other diseases beyond arthritis.Conclusion:CJ-15314 is a highly selective JAK1 inhibitor, demonstrates robust efficacy in RA animal model and is good candidate for further development for inflammatory diseases.* CJ-15314 is currently conducting a phase I trial in south Korea.References:[1]Clark JD et al. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem. 2014; 57(12):5023-38.[2]Burmester GR et al. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol. 2014; 10(2):77-88[3]Jean-Baptiste Telliez et al. Discovery of a JAK3-selective inhibitor: functional differentiation of JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition. ACS Chem. Biol., 2016; 11 (12):3442-3451Disclosure of Interests:so young Ki Employee of: CJ healthcare, hyunwoo shin Employee of: CJ healthcare, yelim lee Employee of: CJ healthcare, Hyoung rok Bak Employee of: CJ healthcare, hana yu Employee of: CJ healthcare, Seung Chan Kim Employee of: CJ healthcare, juhyun lee Employee of: CJ healthcare, donghyun kim Employee of: CJ healthcare, Dong-hyun Ko Employee of: CJ Healthcare, dongkyu kim Employee of: CJ healthcare


Small ◽  
2021 ◽  
Vol 17 (25) ◽  
pp. 2170126
Author(s):  
Yanan Zhang ◽  
Yingni Li ◽  
Jianlin Zhang ◽  
Xuehui Chen ◽  
Ruofei Zhang ◽  
...  

2019 ◽  
Vol 28 (8) ◽  
pp. 1045-1052
Author(s):  
Li-Li Sun ◽  
Wen-Xiong Tang ◽  
Min Tian ◽  
Lu Zhang ◽  
Zun-Jing Liu

It is important to investigate the clinical characteristics and identify the stroke mechanisms of patients with autoimmune disease-related stroke, which are necessary for early etiology diagnosis, accurate treatment and preventive strategies. In this article we retrospectively studied eight cases of acute ischemic stroke associated with autoimmune diseases, and without competing conventional stroke etiologies. The characteristics of stroke (clinical and radiological features), the laboratory tests especially serum D-dimer levels (as a marker of hypercoagulable state), and embolic signals on transcranial Doppler were evaluated for all eight patients. High-resolution magnetic resonance imaging (HRMRI), which can help to evaluate vasculitis was performed in four patients. The possible underlying mechanisms of these cases were discussed based on these manifestations. As a result, autoimmune diseases in our study included systemic lupus erythematosus ( n=5), mixed connective tissue disease ( n=1), central nervous system vasculitis ( n=1), and Takayasu arteritis ( n=1). All eight patients presented with acute infarction lesions in ≥2 vascular territories. Most patients presented with numerous small and medium infarction lesions located in the cortical and subcortical areas. Multiple stroke mechanisms were involved in these cases, including hypercoagulability ( n=4), cardiac embolism ( n=1) and vasculitis ( n=3). Embolic signals could be detected on transcranial Doppler in all three stroke mechanisms. In conclusion, our study revealed the characteristics of autoimmune disease-related stroke. For patients with multiple acute cerebral infarcts within non-single arterial territories, autoimmune disease is an important etiology not to be neglected. Multiple stroke mechanisms were involved in these cases.


2002 ◽  
Vol 4 (1) ◽  
pp. 21-38 ◽  
Author(s):  
C. E. Kelly ◽  
R. D. Leek ◽  
H. M. Byrne ◽  
S. M. Cox ◽  
A. L. Harris ◽  
...  

In this paper a mathematical model that describes macrophage infiltration into avascular tumours is presented. The qualitative accuracy of the model is assessed by comparing numerical results with independent experimental data that describe the infiltration of macrophages into two types of spheroids: chemoattractant-producing (hepa-1) and chemoattractant-deficient (or C4) spheroids. A combination of analytical and numerical techniques are used to show how the infiltration pattern depends on the motility mechanisms involved (i.e. random motion and chemotaxis) and to explain the observed differences in macrophage infiltration into the hepa-1 and C4 spheroids. Model predictions are generated to show how the spheroid's size and spatial structure and the ability of its constituent cells influence macrophage infiltration. For example, chemoattractant-producing spheroids are shown to recruit larger numbers of macrophages than chemoattractant-deficient spheroids of the same size and spatial structure. The biological implications of these results are also discussed briefly.


1992 ◽  
Vol 106 (3) ◽  
pp. 288-295 ◽  
Author(s):  
Ilsa Schwartz ◽  
Sean O. McMenomey ◽  
Nancy J. Russell ◽  
Jane I. Morton ◽  
Dennis R. Trune

The stria vascularis in the C3H/ lpr autoimmune strain mouse was ultrastructurally examined in order to better understand the potential mechanisms by which systemic autoimmune disease affects the ear. The inner ears from C3H/ lpr mice before disease onset and C3H/HeJ controls showed no apparent pathology. However, the stria vascularis from older C3H/ lpr mice after systemic autoimmune disease onset showed considerable intercellular edema around the stria capillaries and thickening of the capillary basement membrane, compared to controls. These observations suggest that perivascular abnormalities, which are the hallmark of systemic autoimmune diseases, may underlie the stria dysfunction and hearing loss seen in autoimmune diseases in humans.


Sign in / Sign up

Export Citation Format

Share Document