scholarly journals Primary immune deficiencies with defects in neutrophil function

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Mary C. Dinauer
Keyword(s):  
Fungal Infections ◽  
Leukocyte Adhesion ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Adaptor Protein ◽  
Invasive Fungal Disease ◽  
Neutrophil Function ◽  
Microbial Pathogens ◽  
Immune Deficiencies

Abstract Immune deficiencies resulting from inherited defects in neutrophil function have revealed important features of the innate immune response. Although sharing an increased susceptibility to bacterial and fungal infections, these disorders each have distinctive features in their clinical manifestations and characteristic microbial pathogens. This review provides an update on several genetic disorders with impaired neutrophil function, their pathogenesis, and treatment strategies. These include chronic granulomatous disease, which results from inactivating mutations in the superoxide-generating nicotinamide dinucleotide phosphate oxidase. Superoxide-derived oxidants play an important role in the control of certain bacterial and fungal species, and also contribute to the regulation of inflammation. Also briefly summarized are updates on leukocyte adhesion deficiency, including the severe periodontal disease characteristic of this disorder, and a new immune deficiency associated with defects in caspase recruitment domain–containing protein 9, an adaptor protein that regulates signaling in neutrophils and other myeloid cells, leading to invasive fungal disease.

Genetic Disorders and Asthma

Asthma ◽  
2014 ◽  
pp. 115-138
Author(s):  
Neetu Talreja ◽  
Ronald Dahl
Keyword(s):  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Hereditary Diseases ◽  
Great Promise ◽  
Diagnostic Strategies ◽  
Antitrypsin Deficiency ◽  
Emerging Treatments ◽  
Important Challenge ◽  
Definition Of

Primary ciliary dyskinesia, cystic fibrosis, and α‎1-antitrypsin deficiency are autosomal recessive hereditary diseases. These diseases should always be considered in cases of asthma. The diagnosis and management of these diseases, particularly with asthma, is an important challenge for clinicians. However, the diagnosis of these chronic diseases is evolving with better definition of phenotypic features and expansion of diagnostic tests. Optimizing and expanding access to the nongenetic tests is critical for ensuring a timely and accurate diagnosis. Early diagnostic strategies, better understanding of the complex interactions underlying the pathophysiology of lung disease, and emerging treatments show great promise for the future. The discovery of genetic and biomarker studies that will predict individuals at risk to develop the clinical manifestations of these diseases can lead to more personalized treatment strategies and a better prognosis.

scholarly journals Mucormycosis Amid COVID-19 Crisis: Pathogenesis, Diagnosis, and Novel Treatment Strategies to Combat the Spread

2022 ◽  
Vol 12 ◽  
Author(s):  
Shreya Dogra ◽  
Akanksha Arora ◽  
Aashni Aggarwal ◽  
Gautam Passi ◽  
Akanksha Sharma ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Behavior Pattern ◽  
Fungal Infections ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Antifungal Drugs ◽  
Invasive Infection ◽  
Multiple Organs ◽  
Global Pandemic ◽  
Novel Treatment Strategies

The havoc unleashed by COVID-19 pandemic has paved way for secondary ominous fungal infections like Mucormycosis. It is caused by a class of opportunistic pathogens from the order Mucorales. Fatality rates due to this contagious infection are extremely high. Numerous clinical manifestations result in damage to multiple organs subject to the patient’s underlying condition. Lack of a proper detection method and reliable treatment has made the management of this infection troublesome. Several reports studying the behavior pattern of Mucorales inside the host by modulation of its defense mechanisms have helped in understanding the pathogenesis of this angio-invasive infection. Many recent advances in diagnosis and treatment of this fungal infection have not been much beneficial. Therefore, there is a need to foster more viable strategies. This article summarizes current and imminent approaches that could aid effective management of these secondary infections in these times of global pandemic. It is foreseen that the development of newer antifungal drugs, antimicrobial peptides, and nanotechnology-based approaches for drug delivery would help combat this infection and curb its spread.

scholarly journals Inflammatory consequences of inherited disorders affecting neutrophil function

Blood ◽  
2019 ◽  
Vol 133 (20) ◽  
pp. 2130-2139 ◽  
Author(s):  
Mary C. Dinauer
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Leukocyte Adhesion ◽  
Neutrophil Function ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Inherited Disorders ◽  
Molecular Defects ◽  
Inflammatory Stimuli ◽  
Increased Susceptibility

Abstract Primary immunodeficiencies affecting the function of neutrophils and other phagocytic leukocytes are notable for an increased susceptibility to bacterial and fungal infections as a result of impaired leukocyte recruitment, ingestion, and/or killing of microbes. The underlying molecular defects can also impact other innate immune responses to infectious and inflammatory stimuli, leading to inflammatory and autoimmune complications that are not always directly related to infection. This review will provide an update on congenital disorders affecting neutrophil function in which a combination of host defense and inflammatory complications are prominent, including nicotinamide dinucleotide phosphate oxidase defects in chronic granulomatous disease and β2 integrin defects in leukocyte adhesion deficiency.

Using Naïve Bayes Algorithm to Estimate the Response to Drug in Lung Cancer Patients

2019 ◽  
Vol 21 (10) ◽  
pp. 734-748 ◽  
Author(s):  
Baoling Guo ◽  
Qiuxiang Zheng
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Drug Response ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Cancer Resistance ◽  
Lung Cancer Patients ◽  
Bayes Algorithm

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.

scholarly journals Dry Eye Syndrome in Patients with Diabetes Mellitus: Prevalence, Etiology, and Clinical Characteristics

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xinyuan Zhang ◽  
Lin Zhao ◽  
Shijing Deng ◽  
Xuguang Sun ◽  
Ningli Wang
Keyword(s):  
Diabetes Mellitus ◽  
Dry Eye ◽  
Keratoconjunctivitis Sicca ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Dry Eye Syndrome ◽  
Surface System ◽  
Patients With Diabetes ◽  
Function Unit ◽  
Substantial Progress

There has been substantial progress in our understanding of the ocular surface system/lacrimal function unit in the past 15 years. Keratoconjunctivitis sicca, more commonly referred to as dry eye syndrome (DES), is the most frequently encountered condition and diabetes mellitus (DM) has been identified as one of the leading causes of DES. Poor glycemic control affects both the anterior and the posterior segments of the eye and increasing prevalence of diabetes-associated DES (DMDES) has been reported in recent years. The pathogenesis and specific features of DMDES remain uncertain and interventions are limited to those used in DES. This review outlines the pathogenesis, clinical manifestations, and the current preventive and treatment strategies for diabetes-related DES.

scholarly journals Microbial pathogens in urogenital infection in pregnant women

2019 ◽  
pp. 13-20
Author(s):  
A. V. Karaulov ◽  
M. S. Afanasiev ◽  
Yu. V. Nesvizhsky ◽  
S. S. Afanasiev ◽  
E. A. Voropaeva ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Pregnancy Termination ◽  
Clinical Manifestations ◽  
Microbial Pathogens ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cervical Canal ◽  
Type I ◽  
Urogenital Infection ◽  
In Pregnancy

Introduction. Chronic and latent infections are often activated during pregnancy.Aim - to asses the pathogenetic role of microbial pathogens in urogenital tract infection (UTI) in pregnant women.Materials and methods. 89 pregnant women underwent general clinical examination, examination of smears from urethra, vagina, cervical canal; bacteriological analysis of vaginal contents; enzyme-linked immunosorbent assay, polymerase chain reaction and determination of specific antibodies for verification of herpes simplex virus (HSV) type I and II, cytomegalovirus (CMV), Epstein-Barr (EBV) and UTI pathogens in pregnant women in blood and mucosal scrapes.Results. Prevalence of Herpesviridae was revealed (90-100% -EBV, HSV type I and II, CMV); in 41% of cases - bacterial pathogens, in 57% of cases - Mycoplasma, Ureaplasma.Discussion. In preterm birth and pregnancy termination mycoplasma and ureaplasma were more often revealed, and in pregnancy termination - association of HSV type I and II in comparison with urgent birth; in the last equally often - HSV type I and association of HSV type I and II; in urgent birth (infection) more often - HSV type I, than association of HSV type I and II; in preterm birth more often - HSV type I, than the association of HSV types I and II, and less often than combination of HSV type I and association of HSV types I and II in pregnancy termination; in the last, the association of HSV types I and II is more common than HSV type I. Increase of TLRs genes expression levels depends on HSV type I less than from association of HSV types I and II, less than from combination of HSV type I and association of HSV types I and II (it determines the clinical manifestations of genital herpes).Conclusion. Microbial pathogens determine the character of pregnancy course, and HSV types I and II- are the triggers of the infectious process, prognosing its course.

scholarly journals Clinical observation of Сhronic granulomatous disease in a 6-year-old child

2020 ◽  
Vol 19 (4) ◽  
pp. 69-72
Author(s):  
G. A. Kharchenko ◽  
O. G. Kimirilova
Keyword(s):  
Chronic Granulomatous Disease ◽  
Clinical Observation ◽  
Fungal Infections ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Hereditary Disease ◽  
Laboratory Method ◽  
Granulomatous Disease ◽  
Hematopoietic Stem ◽  
Nbt Test

Chronic granulomatous disease (CGD) is a hereditary disease caused by a genetic defect of violations of oxygen — dependent mechanisms of phagocytosis. Clinical manifestations of the disease are recurrent bacterial or fungal infections of the skin, hepatic abscesses, pneumonia, osteomyelitis, sepsis, meningitis et al. Most available laboratory method for the diagnosis of CGD is the test of histochemical nitro blue tetrazolium recovery (NBT-test). Allogeneic hematopoietic stem cell transplantation is considered a radical treatment for chronic granulomatous disease. The article presents a clinical observation of the manifestation of chronic granulomatous disease with an unfavorable outcome in a child aged 6 years.

scholarly journals Sterol-response pathways mediate alkaline survival in diverse fungi

2020 ◽  
Author(s):  
Hannah E. Brown ◽  
Calla L. Telzrow ◽  
Joseph W. Saelens ◽  
Larissa Fernandes ◽  
J. Andrew Alspaugh
Keyword(s):  
Fungal Pathogens ◽  
Fungal Infections ◽  
Membrane Integrity ◽  
Microbial Pathogens ◽  
Alkaline Ph ◽  
Ph Response ◽  
Ph Tolerance ◽  
Alkaline Conditions ◽  
Host Infection ◽  
The Impact

AbstractThe ability for cells to maintain homeostasis in the presence of extracellular stress is essential for their survival. Stress adaptations are especially important for microbial pathogens to respond to rapidly changing conditions, such as those encountered during the transition from the environment to the infected host. Many fungal pathogens have acquired the ability to quickly adapt to changes in extracellular pH to promote their survival in the various micro-environments encountered during a host infection. For example, the fungal-specific Rim/Pal alkaline response pathway has been well characterized in many fungal pathogens, including Cryptococcus neoformans. However, alternative mechanisms for sensing and responding to host pH have yet to be extensively studied. Recent observations from a genetic screen suggest that the C. neoformans sterol homeostasis pathway is required for growth at elevated pH. This work explores interactions among mechanisms of membrane homeostasis, alkaline pH tolerance, and Rim pathway activation. We find that the sterol homeostasis pathway is necessary for growth in an alkaline environment, and that an elevated pH is sufficient to induce Sre1 activation. This pH-mediated activation of the Sre1 transcription factor is linked to the biosynthesis of ergosterol, but is not dependent on Rim pathway signaling, suggesting that these two pathways are responding to alkaline pH independently. Furthermore, we discover that C. neoformans is more susceptible to membrane-targeting antifungals in alkaline conditions highlighting the impact of micro-environmental pH on the treatment of invasive fungal infections. Together, these findings further connect membrane integrity and composition with the fungal pH response and pathogenesis.

scholarly journals Challenges and opportunities to understanding genetics of fungal diseases: towards a functional genomics approach

2021 ◽  
Author(s):  
Mariolina Bruno ◽  
Vasiliki Matzaraki ◽  
Frank L van de Veerdonk ◽  
Vinod Kumar ◽  
Mihai G. Netea
Keyword(s):  
Infectious Diseases ◽  
Fungal Infections ◽  
Critical Role ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Fungal Diseases ◽  
Human Pathogens ◽  
Challenges And Opportunities ◽  
Patients At Risk ◽  
Immune Related Genes

Infectious diseases are a leading cause of morbidity and mortality worldwide and human pathogens have long been recognized as one of the main sources of evolutionary pressure, resulting in a high variable genetic background in immune-related genes. The study of the genetic contribution to infectious diseases has undergone tremendous advances over the last decades. Here, focusing on genetic predisposition to fungal diseases, we provide an overview of the available approaches for studying human genetic susceptibility to infections, reviewing current methodological and practical limitations. We describe how the classical methods available, such as family-based studies and candidate-gene studies, have contributed to the discovery of crucial susceptibility factors for fungal infections. We will also discuss the contribution of novel unbiased approaches to the field, highlighting their success but also their limitations for the fungal immunology field. Finally, we show how a systems genomics approach can overcome those limitations and can lead to efficient prioritization and identification of genes and pathways with a critical role in susceptibility to fungal diseases. This knowledge will help stratify patients at risk groups and, subsequently, develop early appropriate prophylactic and treatment strategies.

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