A5032369387- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Bacillus and Francisella bacterial research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Nail Diseases and Treatments
- Microbial Inactivation Methods
- Long-Term Effects of COVID-19
- Bacterial Genetics and Biotechnology
- Viral Infections and Outbreaks Research
- Inhalation and Respiratory Drug Delivery
- Bacterial Infections and Vaccines
- Cytomegalovirus and herpesvirus research
- Antimicrobial Peptides and Activities
- Studies on Chitinases and Chitosanases
- COVID-19 and healthcare impacts
- Pneumonia and Respiratory Infections
- SARS-CoV-2 detection and testing
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Hepatitis B Virus Studies
- Research on Leishmaniasis Studies
- Respiratory viral infections research
- Structural and Chemical Analysis of Organic and Inorganic Compounds
Albert Einstein College of Medicine
2013-2024
Montefiore Medical Center
2013-2024
Children's Hospital at Montefiore
2008-2018
Columbia University
2013
Long Island University
2011
Office of Infectious Diseases
2003-2006
Bipar
1998-2005
Universitat de València
1998
University College London
1998
Central University of Ecuador
1998
Extracellular vesicle production is a ubiquitous process in Gram-negative bacteria, but little known about such Gram-positive bacteria. We report the isolation of extracellular vesicles from supernatants Bacillus anthracis, bacillus that powerful agent for biological warfare. B. anthracis formed at outer layer bacterial cell had double-membrane spheres and ranged 50 to 150 nm diameter. Immunoelectron microscopy with mAbs protective antigen, lethal factor, edema toxin, anthrolysin revealed...
ABSTRACT The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(κ)] is in preclinical development for treatment of Cryptococcus neoformans infections. In anticipation its use humans, we defined the serological and biological properties MAb detail. Structural comparison to related protective 2H1 revealed conservation antigen binding site despite several amino acid differences. was shown by immunofluorescence agglutination studies bind all four serotypes C. , opsonize A D, enhance human...
To optimize the use of modified adenoviruses as vectors for gene delivery to myocardium, we have characterized infection cultured fetal and adult rat cardiac myocytes in vitro vivo by using a replication-defective adenovirus carrying chloramphenicol acetyltransferase (CAT) reporter driven cytomegalovirus promoter (AdCMVCATgD). In vitro, virtually all or cardiocytes express CAT when infected with 1 plaque-forming unit virus per cell. enzymatic activity can be detected these cells early 4 hr...
There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.To determine the safety and efficacy of CCP compared placebo receiving noninvasive supplemental oxygen.CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial adults was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The enrolled 941 participants who were 3 or less days presented 7 after symptom onset required oxygen supplementation.A unit...
Abstract Despite a century of study, the relationship between Ag-specific Ig concentration and protection remains poorly understood for majority pathogens. In certain conditions, administration high Ab doses before challenge with an infectious agent can be less effective than smaller doses, phenomenon which is consistent prozone-like effect. this IgG1, IgG2a, IgG2b, IgG3 dose, infective inocula, was investigated in mouse model Cryptococcus neoformans infection. The activity each IgG subclass...
Abstract Neutrophils are generally considered to contribute host defense through their potent microbicidal activity. However, there is accumulating evidence that neutrophils also have an important regulatory role in establishing the balance of Th1 and Th2 responses. This study investigated against pulmonary Cryptococcus neoformans infection using neutrophil‐depleted BALB/c mice generated by administering mAb RB6–8C5. Neutropenic with survived significantly longer than control mice, but was...
Cryptococcus neoformans (Cn) is a pathogenic yeast and the cause of cryptococcal meningitis. Prevalence disease between males females skewed, with having an increased incidence disease. Based on reported gender susceptibility differences to Cn in literature, we used clinical isolates from Botswanan HIV-infected patients test hypothesis that different environments exerted selective pressures Cn. When examined this data set, found men had significantly higher risk death despite CD4+ T...
Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for 2019 (COVID-19). We compared the mortality and clinical outcome of patients COVID-19 who received 200 mL CCP spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours admission propensity score-matched controls cared at medical center in Bronx, between April 13 May 4, 2020. Matching criteria were age, sex, body mass index, race, ethnicity,...
Abstract Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have mixed, potentially due to heterogeneous nature CP. Here we perform deep profiling SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, well from hospitalized COVID-19 patients before after administration. The show that, although all recipients exhibit expanded humoral immune...
Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering ‘booster’ doses of vaccines beyond the standard two-dose series, for this group patients. Therefore, studying efficacy these additional vaccine against SARS-CoV-2 variants concern is utmost importance in immunocompromised patient population Methods: We conducted a prospective single arm clinical trial enrolling cancer that...
In studies of murine infection, the capsule thickness Cryptococcus neoformans varied depending on organ. The relative order was as follows: lung > brain in vitro isolates. differences suggest that there are organ-related expression genes responsible for thickness.
ABSTRACT CBA/J mice were highly susceptible to intratracheal (i.t.) Cryptococcus neoformans infection relative BALB/c mice, while both strains equally intravenous (i.v.) infection. Increased susceptibility in i.t. was associated with higher brain CFU, lower serum immunoglobulin M (IgM) and IgG responses glucuronoxylomannan (GXM), lack of IgE regulation during infection, alveolar macrophage permissiveness intracellular replication vitro. In contrast, for resistance increased interleukin-12...
For both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. However, there are unresolved issues regarding vesicle synthesis stability, including the fact that vesicular packaging for factors involved virulence must also mechanism unloading. Consequently, we studied kinetics of production stability using [1-(14) C] palmitic acid metabolic labelling dynamic light scattering...
Summary The encapsulated fungus Cryptococcus neoformans is a common cause of life‐threatening disease in immunocompromised individuals. Its major virulence determinant the polysaccharide (PS) capsule. An unsolved problem cryptococcal biology whether PSs composing capsule are linear or complex branched polymers, as well implications this structural composition pathogenesis. In study we approached by combining static and dynamic light scattering, viscosity analysis, high‐resolution microscopy...
The polysaccharide capsule surrounding Cryptococcus neoformans comprises manose, xylose and glucuronic acid, of which mannose is the major constituent. GDP‐mannose biosynthesis pathway highly conserved in fungi consists three key enzymes: phosphomannose isomerase (PMI), phosphomannomutase (PMM) pyrophosphorylase (GMP). MAN1 gene, encoding for PMI enzyme, was isolated sequenced from C. , a disruption gene generated. One mutant, man1 showed poor formation, reduced secretion morphological...
Abstract We investigated the pathogenesis of pulmonary Cryptococcus neoformans infection and passive Ab efficacy in mice deficient inducible NO synthase (NOS2−/−) parental strain. Parental lived significantly longer than NOS2−/− after intratracheal infection, despite having a higher lung fungal burden. Administration reduced CFU both mice, but prolonged survival increased inflammatory response only mice. administration was associated with serum nitrite polysaccharide levels Eosinophils were...
Abstract Cryptococcus neoformans is a fungal pathogen with unique intracellular pathogenic strategy that includes nonlytic exocytosis, phenomenon whereby cells are expunged from macrophages without lysing the host cell. The exact mechanism and specific proteins involved in this process have yet to be completely defined. Using murine deficient membrane phospholipid binding protein, annexin A2 (ANXA2), we observed significant decrease both phagocytosis of yeast frequency exocytosis....
ABSTRACT The pathogenesis of pulmonary Cryptococcus neoformans infection and the efficacy passive immunoglobulin G1 (IgG1) administration were investigated in B-cell-deficient C57BL/6J mice. mice lived longer than after both intratracheal intravenous infections. Administration IgG1 prior to prolonged survival but had no effect on or numbers CFU lungs C. resulted significantly higher levels gamma interferon (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory...
ABSTRACT Does the age of a microbial cell affect its virulence factors? To our knowledge, this question has not been addressed previously, but answer is great relevance for chronic infections where cells persist and in hosts. Cryptococcus neoformans an encapsulated human-pathogenic fungus notorious causing variable tissue. The major factor C. polysaccharide (PS) capsule. understand how chronological could impact cryptococcal capsule properties, we compared elastic permeabilities, zeta...
Antibody (Ab) responses to Bacillus anthracis toxins are protective, but relatively few protective monoclonal antibodies (MAbs) have been reported. Protective antigen (PA) is essential for the action of B. lethal toxin (LeTx) and edema toxin. In this study, we generated two MAbs PA, 7.5G 10F4. These did not compete binding consistent with specificities different epitopes. The were tested their ability protect a monolayer cultured macrophages against toxin-mediated cytotoxicity. MAb 7.5G,...
Protective antigen (PA), the binding subunit of anthrax toxin, is major component in current vaccine, but fine antigenic structure PA not well defined. To identify linear neutralizing epitopes PA, 145 overlapping peptides covering entire sequence protein were synthesized. Six monoclonal antibodies (mAbs) and antisera from mice specific for tested their reactivity to by enzyme-linked immunosorbent assays. Three immunodominant B-cell mapped residues Leu(156) Ser(170), Val(196) Ile(210),...
Abstract The protective efficacy of mAbs to Cryptococcus neoformans glucuronoxylomannan depends on Ab isotype. Previous studies in A/JCr and C57BL/6J mice showed relative IgG1, IgG2a ≫ IgG3. However, we now report that × 129/Sv mice, IgG3 is while IgG1 not protective, with neither isotype being mice. IgG2a, had different effects IFN-γ expression infected IgG1-treated significantly more pulmonary eosinophilia than IgG2a- IgG3-treated C. infection administration FcγRI, FcγRII, FcγRIII...