Toxic Shock Syndrome and Other Related Severe Infections
Botros Rizk, A. Mostafa Borahay, Abdel Maguid Ramzy in Clinical Diagnosis and Management of Gynecologic Emergencies, 2020
The pathogenesis resulting from invasive GAS infections is due to virulence factors associated with this microorganism. These factors enable GAS to attach to the host tissue, evade the immune response, and spread by penetrating host tissue layers. There are several virulence factors, all of which have unique pathologic features that result in invasive disease [124]. However, of these factors, M protein is considered the major somatic virulence factor. This protein allows GAS to adhere to endothelium of blood vessels, causing vascular leakage and hypercoagulability. Even with treatment, this protein can cause DIC, multiorgan failure, and death. In addition, M protein resists the human immune response by preventing macrophage phagocytosis. It is not clear why some patients with GAS progress to widespread disseminated invasive disease while others do not. With the right environment and specific trigger, such as surgery or a vaginal laceration after a delivery, GAS can release its virulence factors and quickly progress to an acute highly lethal state.
Proteins in plasma and urine
Martin Andrew Crook in Clinical Biochemistry & Metabolic Medicine, 2013
Protein electrophoresis should be carried out on serum to detect a paraprotein or M protein and, importantly, also on urine to detect BJP. The diagnosis of myelomatosis should be confirmed by microscopic inspection of a bone marrow aspirate or biopsy and usually also a skeletal survey. Plasma immunoglobulin concentrations should be measured to assess the degree of immune paresis. To evaluate apparently abnormal concentrations or changes in concentrations of a protein-bound substance Estimation of plasma albumin concentration should always accompany that of total plasma calcium. If changes in this or other protein-bound substances parallel those of albumin, they are probably due to changes in protein concentrations.As part of the investigation of hypogammaglobulinaemia A low total plasma protein concentration, if not due to hypoalbuminaemia, may be due to hypogammaglobulinaemia. Plasma immunoglobulin concentrations can be measured as part of the assessment of the adequacy of the immune system.
Multiple myeloma
Anju Sahdev, Sarah J. Vinnicombe in Husband & Reznek's Imaging in Oncology, 2020
In addition to CRAB, biopsy proven plasmacytoma or clonal bone marrow cells >10%, any one of the following can be used as diagnostic criteria: ≥60% clonal bone marrow cells.Serum involved-to-uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC ratio is 100 mg/L or higher).>1 focal lesion on MRI, each at least 5 mm in size.CT or PET-CT evidence of osteolytic bone deposits.Creatinine clearance <40 mL/min can be used as cutoff for renal failure.Only suspected or biopsy-proven light chain cast nephropathy is allowed as a renal MDE.An M protein is not required for the diagnosis of myeloma but is used to classify myeloma into secretory and non-secretory types.Osteoporosis, compression fractures, infections, hyperviscosity, or peripheral neuropathy occurring alone are not considered as MDE.
Targeting viral proteins for restraining SARS-CoV-2: focusing lens on viral proteins beyond spike for discovering new drug targets
Published in Expert Opinion on Drug Discovery, 2023
Tao Yang, Si Chun Wang, Linyan Ye, Yasen Maimaitiyiming, Hua Naranmandura
The membrane glycoprotein (M protein), the most abundant protein in the coronavirus virion, exhibits multiple functions in the process of viral life cycle including viral modification, protein trafficking, virion assembly and secretion [115]. M protein also contributes to compromise the host innate immunity as an interferon antagonist [116]. The M protein of SARS-CoV-2 is a 222-amino acid protein that shares 90.5% sequence identity with the M protein of SARS-CoV [117]. It contains three domains, namely, a short N-terminal domain, a triple transmembrane domain and a longer C-terminal domain (Figure 2(g)). The M protein related assembly process includes multiple steps: first, the M protein self-associates and is mainly localized in the ER and Golgi apparatus; second, the M protein interacts with the N protein and forms a complex in Golgi or ER-Golgi compartment, enabling further binding of viral RNA to the N protein [112]; third, the M protein recruits spike protein and other factors to enable viral release and budding process.
Platelet interaction with bacterial toxins and secreted products
Published in Platelets, 2015
Streptococcus pyogenes sepsis is associated with haemostasis dysfunction [86]. M protein is a cell wall-anchored protein of S. pyogenes that participates in multiple aspects of virulence [87]. The M protein of S. pyogenes emm1 serotype can also be released into the extracellular medium through the action of bacterial and host proteases [88, 89]. This soluble M1-protein forms a complex with plasma fibrinogen and this complex has been detected in abscess material from a patient suffering from S. pyogenes sepsis [90]. The M1 protein is a powerful platelet agonist. The M protein–fibrinogen complex binds to the surface of resting platelets and stimulates platelet activation [91, 92]. An inter-individual variation in the ability of platelets to become activated in response to M protein has been observed and this is correlated to the level of anti-M protein IgG present in the individual’s plasma. This may represent an important strategy to cause thrombi at a distance from the bacteria and avoid entrapment of the bacteria in platelet aggregates. Furthermore, platelet thrombi may occlude the vessels and contribute to organ damage in sepsis.
Efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy to treat multiple myeloma
Published in Hematology, 2022
Yigang Guo, Lulu Zhang, Rongyao Zhang, Meiling Zhou, Xu Chen, Chucheng Wan, Ping Hu, Yuanyuan He, Hua Jiang, Wei Geng, Weixing Zhang, Fariha Kanwal, Muhammad Fayyaz ur Rehman, Zhangzhi Li
Our study shows sequential chemotherapy of plasma exchange without plasma is effective, safe, and feasible in the treatment of MM. By analyzing clinical characteristics, in the experimental group patients with later stages, globulin levels increased significantly, whereas more than 90% of patients had apparent renal dysfunction. Through the plasma free plasma exchange sequential chemotherapy treatment, the total response rate of patients reached 75%. In comparison, the control group's 63% response suggests that plasma exchange treatment without plasma may improve the efficacy of high-risk MM patients. By comparing the levels of plasma globulin, microglobulin, VEGF, and IL-6 levels in the experimental group before and after the exchange, it is found that the plasma exchange without plasma can significantly reduce the levels of globulin, microglobulin, VEGF, and IL-6 β Microglobulin, VEGF and IL-6 in plasma were measured. The two groups of patients through chemotherapy can significantly reduce the level of globulin, serum albumin. The microglobulin levels, VEGF, and IL-6 in the experimental group were significantly lower than those in the control group. The results show that sequential chemotherapy without plasma exchange can substantially benefit patients with multiple high-risk myeloma, especially in patients with renal damage. The mechanism is related to the fact that plasma exchange without plasma transfusion can rapidly reduce M protein and inflammatory factors, VEGF, and IL-6 in plasma. It can reduce the deposition of M protein in the kidney and immune injury. By clearing inflammatory factors, it may inhibit the clonal proliferation and abnormal secretion of myeloma cells.
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