scholarly journals Identification and Characterization of Novel Rat Polyomavirus 2 in a Colony of X-SCID Rats by P-PIT assay

mSphere ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Lora H. Rigatti ◽  
Tuna Toptan ◽  
Joseph T. Newsome ◽  
Patrick S. Moore ◽  
Yuan Chang
Keyword(s):  
T Cell ◽  
Potential Model ◽  
Treatment Options ◽  
Pneumocystis Carinii ◽  
Preclinical Studies ◽  
Content Type ◽  
Laboratory Rats ◽  
Wide Range ◽  
Disseminated Disease ◽  
Human Polyomaviruses

ABSTRACT Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies. Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.

scholarly journals Protection againstStaphylococcus aureusColonization and Infection by B- and T-Cell-Mediated Mechanisms

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Fan Zhang ◽  
Olivia Ledue ◽  
Maria Jun ◽  
Cibelly Goulart ◽  
Richard Malley ◽  
...  
Keyword(s):  
T Cell ◽  
Soft Tissue ◽  
Bacterial Infections ◽  
Vaccine Development ◽  
Pathological Condition ◽  
Treatment Options ◽  
Immune Defense ◽  
Invasive Infection ◽  
Content Type ◽  
Increased Risk

ABSTRACTStaphylococcus aureusis a major cause of morbidity and mortality worldwide.S. aureuscolonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management.S. aureusvaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by anS. aureusvaccine in protection againstS. aureusbacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-inducedS. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality duringS. aureusbacteremia, whereas Th1 or Th17 responses are essential for prevention ofS. aureusskin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention ofS. aureusdermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses toS. aureusantigens may be critical to achieve effective and comprehensive immune defense against this pathogen.IMPORTANCES. aureusis a leading cause of healthcare- and community-associated bacterial infections.S. aureuscauses various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections.S. aureuscolonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development againstS. aureushas been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses toS. aureusantigens in conferring enhanced and broad protection againstS. aureusinvasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.

Primary central nervous system T-cell lymphoma

1991 ◽  
Vol 74 (4) ◽  
pp. 668-672 ◽  
Author(s):  
Martin M. Bednar ◽  
Anthony Salerni ◽  
Martin E. Flanagan ◽  
William W. Pendlebury
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
T Cell ◽  
Cell Lymphoma ◽  
Case Reports ◽  
Treatment Options ◽  
T Cell Lymphoma ◽  
Content Type ◽  
Diagnostic Measures ◽  
T Cell Lymphomas

✓ Primary central nervous system (CNS) T-cell lymphoma is extremely rare. The present case report provides immunocytochemical evidence for a cerebellar CNS T-cell lymphoma. The patient underwent surgery followed by radiation therapy and is alive and well 36 months postoperatively. The clinical and pathological features of primary CNS T-cell lymphoma as well as diagnostic measures and treatment options are discussed, together with a compilation of all previous case reports of primary CNS T-cell lymphomas.

scholarly journals β-Lactam Combinations That Exhibit Synergy against Mycobacteroides abscessus Clinical Isolates

2020 ◽  
Vol 65 (4) ◽  
Author(s):  
Elizabeth Story-Roller ◽  
Christos Galanis ◽  
Gyanu Lamichhane
Keyword(s):  
Pulmonary Disease ◽  
Treatment Guidelines ◽  
Treatment Options ◽  
Current Treatment ◽  
Clinical Isolates ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Content Type ◽  
Wide Range

ABSTRACT Mycobacteroides abscessus (Mab) is an opportunistic environmental pathogen that can cause chronic pulmonary disease in the setting of structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. These infections are often incurable and associated with rapid lung function decline. Mab is naturally resistant to most of the antibiotics available today, and current treatment guidelines require at least 1 year of daily multidrug therapy, which is often ineffective and is associated with significant toxicities. β-Lactams are the most widely used class of antibiotics and have a demonstrated record of safety and tolerability. Here, using a panel of recent clinical isolates of Mab, we evaluated the in vitro activities of dual-β-lactam combinations to identify new treatments with the potential to treat infections arising from a wide range of Mab strains. The Mab clinical isolates were heterogeneous, as reflected by the diversity of their genomes and differences in their susceptibilities to various drugs. Cefoxitin and imipenem are currently the only two β-lactams included in the guidelines for treating Mab disease, yet they are not used concurrently in clinical practice. However, this dual-β-lactam combination exhibited synergy against 100% of the isolates examined (n = 21). Equally surprising is the finding that the combination of two carbapenems, doripenem and imipenem, exhibited synergy against the majority of Mab isolates. In the setting of multidrug-resistant Mab disease with few therapeutic options, these combinations may offer viable immediate treatment options with efficacy against the broad spectrum of Mab strains infecting patients today.

Update on psychopharmacology for autism spectrum disorders

2016 ◽  
Vol 10 (1) ◽  
pp. 6-26 ◽  
Author(s):  
Marco O. Bertelli ◽  
Michele Rossi ◽  
Roberto Keller ◽  
Stefano Lassi
Keyword(s):  
Autism Spectrum Disorders ◽  
Animal Studies ◽  
Treatment Options ◽  
Autism Spectrum ◽  
Psychotropic Medications ◽  
Cochrane Library ◽  
Content Type ◽  
Wide Range ◽  
Spectrum Disorders ◽  
The Cochrane Library

Purpose – The management of individuals with autism spectrum disorders (ASDs) requires a multimodal approach of behavioural, educational and pharmacological treatments. At present, there are no available drugs to treat the core symptoms of ASDs and therefore a wide range of psychotropic medications are used in the management of problems behaviours, co-occurring psychiatric disorders and other associated features. The purpose of this paper is to map the literature on pharmacological treatment in persons with ASD in order to identify those most commonly used, choice criteria, and safety. Design/methodology/approach – A systematic mapping of the recent literature was undertaken on the basis of the following questions: What are the most frequently used psychoactive compounds in ASD? What are the criteria guiding the choice of a specific compound? How effective and safe is every psychoactive drug used in ASD? The literature search was conducted through search engines available on Medline, Medmatrix, NHS Evidence, Web of Science and the Cochrane Library. Findings – Many psychotropic medications have been studied in ASDs, but few have strong evidence to support their use. Most commonly prescribed medications, in order of frequency, are antipsychotics, antidepressants, anticonvulsants and stimulants, many of them without definitive studies guiding their usage. Recent animal studies can be useful models for understanding the common pathogenic pathways leading to ASDs, and have the potential to offer new biologically focused treatment options. Originality/value – This is a practice review paper applying recent evidence from the literature.

Long-term survival of the nasal NK/T cell lymphoma

2008 ◽  
Vol 149 (17) ◽  
pp. 801-805
Author(s):  
Péter Rajnics ◽  
László Krenács ◽  
András Kenéz ◽  
Zoltán Járay ◽  
Enikő Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Guidelines ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
T Cell Lymphoma ◽  
Term Survival ◽  
Barr Virus ◽  
Significant Difference ◽  
Nk T Cell

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein–Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

scholarly journals Transfer of Plasmid DNA to Clinical Coagulase-Negative Staphylococcal Pathogens by Using a Unique Bacteriophage

2015 ◽  
Vol 81 (7) ◽  
pp. 2481-2488 ◽  
Author(s):  
Volker Winstel ◽  
Petra Kühner ◽  
Bernhard Krismer ◽  
Andreas Peschel ◽  
Holger Rohde
Keyword(s):  
Plasmid Dna ◽  
Genetic Manipulation ◽  
Current Knowledge ◽  
Virulence Determinants ◽  
Coagulase Negative Staphylococci ◽  
Reliable Technique ◽  
Content Type ◽  
Research Activities ◽  
Wide Range ◽  
Genetic Barriers

ABSTRACTGenetic manipulation of emerging bacterial pathogens, such as coagulase-negative staphylococci (CoNS), is a major hurdle in clinical and basic microbiological research. Strong genetic barriers, such as restriction modification systems or clustered regularly interspaced short palindromic repeats (CRISPR), usually interfere with available techniques for DNA transformation and therefore complicate manipulation of CoNS or render it impossible. Thus, current knowledge of pathogenicity and virulence determinants of CoNS is very limited. Here, a rapid, efficient, and highly reliable technique is presented to transfer plasmid DNA essential for genetic engineering to important CoNS pathogens from a uniqueStaphylococcus aureusstrain via a specificS. aureusbacteriophage, Φ187. Even strains refractory to electroporation can be transduced by this technique once donor and recipient strains share similar Φ187 receptor properties. As a proof of principle, this technique was used to delete the alternative transcription factor sigma B (SigB) via allelic replacement in nasal and clinicalStaphylococcus epidermidisisolates at high efficiencies. The described approach will allow the genetic manipulation of a wide range of CoNS pathogens and might inspire research activities to manipulate other important pathogens in a similar fashion.

scholarly journals Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Susan L. Brockmeier ◽  
Crystal L. Loving ◽  
Tracy L. Nicholson ◽  
Jinhong Wang ◽  
Sarah E. Peters ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccine Trial ◽  
Streptococcus Suis ◽  
Protein Subunit ◽  
Content Type ◽  
Degree Of Protection ◽  
Wide Range ◽  
Associated Proteins ◽  
Clinical Protection ◽  
Cellular Immune

ABSTRACT Streptococcus suis is a bacterium that is commonly carried in the respiratory tract and that is also one of the most important invasive pathogens of swine, commonly causing meningitis, arthritis, and septicemia. Due to the existence of many serotypes and a wide range of immune evasion capabilities, efficacious vaccines are not readily available. The selection of S. suis protein candidates for inclusion in a vaccine was accomplished by identifying fitness genes through a functional genomics screen and selecting conserved predicted surface-associated proteins. Five candidate proteins were selected for evaluation in a vaccine trial and administered both intranasally and intramuscularly with one of two different adjuvant formulations. Clinical protection was evaluated by subsequent intranasal challenge with virulent S. suis . While subunit vaccination with the S. suis proteins induced IgG antibodies to each individual protein and a cellular immune response to the pool of proteins and provided substantial protection from challenge with virulent S. suis , the immune response elicited and the degree of protection were dependent on the parenteral adjuvant given. Subunit vaccination induced IgG reactive against different S. suis serotypes, indicating a potential for cross protection.

scholarly journals CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

2021 ◽  
Vol 22 (10) ◽  
pp. 5394
Author(s):  
Tomas Lidak ◽  
Nikol Baloghova ◽  
Vladimir Korinek ◽  
Radislav Sedlacek ◽  
Jana Balounova ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Ubiquitin Ligase ◽  
Cell Activation ◽  
Rna Helicase ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Risc Complex ◽  
Wide Range

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

scholarly journals Polymer-Drug Conjugates as Nanotheranostic Agents

2021 ◽  
Vol 2 (1) ◽  
pp. 63-81
Author(s):  
Sajana Manandhar ◽  
Erica Sjöholm ◽  
Johan Bobacka ◽  
Jessica M. Rosenholm ◽  
Kuldeep K. Bansal
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Treatment Options ◽  
The Body ◽  
Drug Conjugates ◽  
Imaging Characteristics ◽  
Wide Range ◽  
Systemic Side Effects ◽  
Theranostic Agents ◽  
The Stability

Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.

scholarly journals 'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies

2021 ◽  
Vol 9 (2) ◽  
pp. e001608
Author(s):  
Debottam Sinha ◽  
Sriganesh Srihari ◽  
Kirrliee Beckett ◽  
Laetitia Le Texier ◽  
Matthew Solomon ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Nuclear Antigen ◽  
T Cell Therapy ◽  
In Vivo Models ◽  
Hla Alleles ◽  
Cell Therapies ◽  
Wide Range

BackgroundEpstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.MethodsTaking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.ResultsThese allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.ConclusionThese findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response.

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