Ruksana Huda

• Doctor of Philosophy
• Associate Professor at The University of Texas Medical Branch at Galveston

Porphyrins and porphyrin precursors are normally detected in small amounts in healthy individuals but are found in large quantities in the urine, feces, blood, plasma, bone marrow, and liver in patients with various types of porphyrias. These are intermediates, or are derived from intermediates, in the pathway for heme biosynthesis. Heme is synthes...

Background Givosiran is an interfering RNA therapeutic targeting hepatic ALAS1 mRNA, and the first-in-its-class drug approved for treatment of acute hepatic porphyrias (AHP). It reduces ALAS1 expression, thus reducing delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) over-production and accumulation. Here, we present a case of a patient wit...

Beginning in her 20s, this 70-year-old female experienced episodes of abdominal pain accompanied by nausea, fatigue, and fecal and urinary urgency. Porphyria was considered in her 30s, but urine porphobilinogen (PBG) was normal. At age 60, she developed blistering on sun-exposed skin when taking an estrogen-medroxyprogesterone combination for menop...

Background Accurate assessment of iron status is important in patients with acute hepatic porphyrias (AHP) since iron overload may develop after repeated administration of hemin. Serum ferritin is a useful measure of iron status; however, ferritin is also an acute-phase protein that may be elevated by inflammation or dysmetabolic conditions. We con...

Serological testing for anti-acetylcholine receptor (AChR) autoantibodies is not only crucial for the diagnosing, disease monitoring, and treatment management of patients with myasthenia gravis (MG) but also for preclinical studies utilizing MG disease models. However, there are no specific guidelines on which methods to use in clinical diagnostic...

Background: Accurate assessment of iron status is important in acute hepatic porphyrias (AHP) especially after repeated administration of hemin, which can cause iron overload. Although useful for assessing iron status, serum ferritin is an acute-phase protein that may be elevated by inflammatory or dysmetabolic conditions. We considered that subcl...

Conjugates of monoclonal antibodies (mAbs) and siRNA have been used for target cell-specific gene repression. B cells are integrally involved in the anti-Acetylcholine receptor autoantibody-mediated pathogenic development of autoimmune myasthenia gravis (MG). Here we show that simultaneous targeting of the critical receptors expressed on pathogenic...

Myasthenia gravis (MG) is a debilitating autoimmune disease characterized by muscle fatigue and weakness caused by autoantibody- and complement-mediated damage to the neuromuscular junction. This study sought to compare the efficacy of unique sets of monoclonal antibody–siRNA conjugates, individually (mono) or in combination (duo), against the cruc...

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial co...

Myasthenia gravis (MG) is an autoimmune disease characterized by chronic muscle fatigue and weakness caused by autoantibodies and complement-mediated damage at neuromuscular junctions. Histone deacetylases (HDACs) are crucial epigenetic regulators of proinflammatory gene expression; however, it is unclear whether HDACs modulate chronic inflammation...

Background: Heterozygosity at HLA class I loci is generally considered beneficial for host defense. We report here an element of HLA class I homozygosity that may or may not help preserve its existence in populations but which could indicate a new avenue for antiviral research. Methods: Lymphocytes from serologically HLA-homozygous or -heterozyg...

Acute flaccid myelitis (AFM) is a sudden-onset polio-like neuromuscular disability found commonly in young children. There is an increasing incidence of confirmed AFM cases in the USA and other countries in recent years, and in association with nonpolio enterovirus infection. This represents a significant challenge to clinicians and causes signific...

Current therapies for myasthenia gravis (MG) are limited, and many investigations have recently focused on target-specific therapies. B cell-targeting monoclonal antibody (mAb) therapies for MG are increasingly attractive due to their specificity and efficacy. The targeted B cell biomarkers are mainly the cluster of differentiation (CD) proteins th...

We have prepared a unique set of monoclonal antibody-siRNA conjugates which will target two different subsets of pathogenic B cells in a mouse model of autoimmune myasthenia gravis (EAMG). At the optimum dose, our duo-conjugates significantly reduced two crucial receptors, CD268 and -269, of pathogenic B220 positive cells in PBMCs, lymph node cells...

We investigated potential therapeutic effect of a conjugate of BAFF receptor specific- monoclonal antibody and short interference RNA in a mouse model of myasthenia gravis (EAMG). We found that at high dose, conjugate treatment caused significant accumulation of Fas expressing CD19+/ B220+ cells and increased type 1 interferon in lymph nodes. Low d...

Myasthenia gravis (MG) is an autoimmune disease of muscle weakness caused by Acetylcholine receptor- autoantibody and complement mediated damage of neuro-muscular junction (NMJ). We have recently shown a greater advantage of using siRNA over other conventional therapeutic tools in an experimental mouse model of MG (EAMG). However, the major drawbac...

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of...

Abstract While the complement system is desired for protective immunity, antibody- and complement-mediated neuromuscular junction (NMJ) destruction, a hallmark of myasthenia gravis (MG) or experimental autoimmune MG (EAMG), is a significant concern. Evidence suggests that the binding of complement factors to the pathogenic anti-acetylcholine recept...

Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune neuromuscular disease. Antibodies to the nicotinic acetylcholine receptor (AChR) destroy the AChR, thus leading to defective neuromuscular transmission of electrical impulse and to muscle weakness. This unit is a practical guide to the induction and evaluation of experimental...

Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune neuromuscular disease. Antibodies to the nicotinic acetylcholine receptor (AChR) destroy the AChR, thus leading to defective neuromuscular transmission of electrical impulse and to muscle weakness. This unit is a practical guide to the induction and evaluation of experimental...

Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to neuromuscular junction damage caused by anti-acetylcholine receptor (AChR) antibody and complement. In this study, we investigated the effect of complement depletion with HC3-1496, a recombinant humanized CVF, in EAMG in C57Bl6/J male mice (8 weeks). Mice were immuni...

Interleukin-6⁻¹⁷⁴ (IL-6⁻¹⁷⁴) and tumor necrosis factor α⁻³⁰⁸ (TNFα⁻³⁰⁸) are high-cytokine-producing genotypes that are known to increase the susceptibility to infectious diseases, but their influence on cytokine production induced by respiratory viruses is unknown. We exposed human monocyte-derived macrophages from IL-6⁻¹⁷⁴, TNFα⁻³⁰⁸, and normal ge...

Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study. After 5 days' recovery, tracheostomy was performe...

To investigate ceftazidime in acute lung injury (ALI) and sepsis. Prospective, randomized, controlled animal study in an investigational ICU at a university hospital. Eighteen female Merino sheep were prepared for chronic study and subjected to smoke inhalation and septic challenge according to an established protocol. Whereas global hemodynamics a...

Reduced bioavailability of endothelium-derived nitric oxide associated with reperfusion could potentially exacerbate the inflammatory response during reperfusion. Evidence suggests the pharmacologic effects of inhaled nitric oxide may extend beyond the pulmonary vasculature, and this is attributed to nitric oxide-derived complexes in blood that ult...

To investigate the effects of recombinant human activated protein C (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke inhalation in association with a bacterial challenge. Prospective, randomized, controlled, experimental animal study with repeated measurements. Investigational intensive care unit at a university hospita...

Remote ischemic preconditionining (IPC) has been defined as a brief episode of ischemia/reperfusion in an organ that protects another remote organ from the damage induced by subsequent and prolonged ischemia. As yet, no study has been conducted with the purpose of elucidating a precise association between remote IPC and patterns of gene-transcripti...

Respiratory syncytial virus (RSV) is a paramyxovirus that produces airway inflammation, in part by inducing interleukin-8 (IL-8) expression, a CXC-type chemokine, via the NF-kappaB/RelA and STAT/IRF signaling pathways. In RSV-infected A549 cells, IL-8 transcription attenuates after 24 h in spite of ongoing viral replication and persistence of nucle...

The objective of this study was to identify cellular and plasma marker(s) of post-I/R (ischaemia/reperfusion) in patients undergoing elective knee surgery where a tourniquet was used to facilitate a bloodless surgical field. We evaluated the inflammatory and redox response by measuring the mRNA levels of ICAM-1 (intercellular cell-adhesion molecule...

Circulatory neutrophils are known to be critical mediators of inflammation and oxidative stress during ischemia reperfusion (I/R) injury. Recent studies have shown an important role for protein kinase C (PKC) in neutrophil survival and function. Activation of specific isotypes of PKC are known to be involved in membrane alteration and motility, oxi...

The occurrence and accumulation of dicentric marker (dic) chromosomes with terminal centromeres have been documented in a murine ascites sarcoma cell line (S180) during in vivo progression of the tumour for many years. Initially, in 1975, the cell line had only one such "dic" but currently the predominant clone is represented by three such "dics"....

The involvement of NOR-bearing chromosome in the formation of two stable and transmissible Robertsonian markers is reported in ascitic form of mouse Sarcoma 180 (S180) adapted in vivo to outbred strain of Swiss albino mice. The chromosomes involved in Robertsonian fusion included t(8;12) and t(16;17).

Induction of differentially stained sister chromatids at G2/M and determination of baseline sister chromatid exchanges (SCEs) in ascites form of mouse sarcoma 180 cell line have been done by in vivo incorporation of 5-bromodeoxyuridine (BrdU) for two consecutive DNA replication cycles. The baseline SCE frequency is 6.24 at log phase of tumour growt...