scholarly journals Antibody Prophylaxis and Therapy against West NileVirus Infection in Wild-Type and ImmunodeficientMice

2003 ◽  
Vol 77 (24) ◽  
pp. 12941-12949 ◽  
Author(s):  
Michael J. Engle ◽  
Michael S. Diamond
Keyword(s):  
B Cell ◽  
Gamma Globulin ◽  
Polyclonal Antibodies ◽  
Current Treatment ◽  
Mouse Serum ◽  
Wild Type ◽  
Viral Reservoirs ◽  
In The Wild ◽  
Human Gamma Globulin ◽  
Immune Antibody

ABSTRACT West Nile virus (WNV) is a mosquito-borne Flavivirus that causes encephalitis in a subset of susceptible humans. Current treatment for WNV infections is supportive, and no specific therapy or vaccine is available. In this study, we directly tested the prophylactic and therapeutic efficacy of polyclonal antibodies against WNV. Passive administration of human gamma globulin or mouse serum prior to WNV infection protected congenic wild-type, B-cell-deficient (μMT), and T- and B-cell-deficient (RAG1) C57BL/6J mice. Notably, no increased mortality due to immune enhancement was observed. Although immune antibody completely prevented morbidity and mortality in wild-type mice, its effect was not durable in immunocompromised mice: many μMT and RAG1 mice eventually succumbed to infection. Thus, antibody by itself did not completely eliminate viral reservoirs in host tissues, consistent with an intact cellular immune response being required for viral clearance. In therapeutic postexposure studies, human gamma globulin partially protected against WNV-induced mortality. In μMT mice, therapy had to be initiated within 2 days of infection to gain a survival benefit, whereas in the wild-type mice, therapy even 5 days after infection reduced mortality. This time point is significant because between days 4 and 5, WNV was detected in the brains of infected mice. Thus, passive transfer of immune antibody improves clinical outcome even after WNV has disseminated into the central nervous system.

scholarly journals IKZF1 Status As an Independent Prognostic Marker in Adult Common B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1075-1075
Author(s):  
Qiumei Yao ◽  
Kaiyan Liu ◽  
Bing Jiang ◽  
Yanrong Liu ◽  
Qian Jiang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Prognostic Marker ◽  
Lymphoblastic Leukemia ◽  
Wild Type ◽  
Survival Curves ◽  
Free Survival ◽  
Pcr Multiplex ◽  
In The Wild ◽  
Group 5

Abstract Previous studies have suggested that IKZF1 gene deletions are associated with an adverse prognosis in acute lymphoblastic leukemia (ALL). However, the prognostic value of IKZF1 deletions in adult common B-cell ALL (Com-B ALL) has not been well-defined, especially in the context of different post-remission therapies. The objectives of this study were to evaluate the prognostic role of IKZF1 deletions in adult Com-B ALL. Overall, 162 untreated adult Com-B ALL patients were recruited between April 2006 and April 2013. Patients received one or two cycles of induction therapy and, if in remission, were allowed to select either ongoing systemic chemotherapy or hematopoietic stem cell transplantation (HSCT). BCR-ABL positive patients were additionally treated with tyrosine kinase inhibitors (TKIs). Deletions in the IKZF1 gene were detected using multiplex RQ-PCR, multiplex fluorescent PCR, multiplex ligation-dependent probe amplification (MLPA) and sequence analysis. High-risk (HR) was defined as having any of the following factors: central nervous system involvement at diagnosis; age ¡Ý50 years; WBC count ¡Ý30x109/L; hypodiploidy; mixed lineage leukemia (MLL) gene rearrangements; BCR-ABL rearrangements; t(1;19) translocations; or a complicated karyotype (¡Ý5 chromosomal abnormalities); failure to achieve remission after two cycles of induction therapy. The study end points included relapse-free survival (RFS), disease-free survival (DFS) and overall survival (OS), which was analyzed using the Kaplan-Meier method. The cumulative incidence of relapse (CIR) was estimated, adjusting for competing risks of death, and compared by Gray's test. IKZF1 deletions were detected in 79 (48.8%) out of 162 adult Com-B ALL patients. Patients with an IKZF1 deletion (n=79) had a significantly inferior prognosis than those with wild-type IKZF1 (n=83) (Fig.1). The prognosis of patients with IKZF1 deletions with or without the BCR-ABL rearrangements was significantly inferior compared to those of patients with neither IKZF1 deletions nor BCR-ABL rearrangements. The power of IKZF1 deletion status as a prognostic factor remained in both non-HR group (5-yr OS: 52.5%¡À13.1% for IKZF1 deletions (n=25) vs. 72.2%¡À8.8% for wild-type IKZF1 (n=42), P=0.048) and HR group (5-yr OS: 36.7%¡À8.2% for IKZF1 deletions (n=54) vs. 69.3%¡À8.3% for wild-type IKZF1 (n=41), P=0.015). Among patients who received chemotherapy as post-remission therapy (n=52), IKZF1 deletions were associated with an unfavorable OS (P=0.003). In this group, the median OS time for IKZF1-deletion patients (n=28) was 10.0¡À1.0 months, while the median OS time for IKZF1-wild-type carriers (n=24) was not achieved. Among those that received HSCT as post-remission therapy (n=94), IKZF1 status did not affect the prognosis. For patients with IKZF1 deletions, HSCT (n=40) was significantly superior to chemotherapy (n=28) as a post-remission therapy. In the wild-type IKZF1 HR group, patients that received HSCT (n=24) achieved a longer DFS and RFS while the OS did not significantly differ from that of patients who received chemotherapy alone (n=12). In the wild-type IKZF1 non-HR group, there was no significant difference between patients that received HSCT (n=30) and those who received chemotherapy (n=12) as a post-remission therapy. Comparing survival curves of HSCT to chemotherapy are shown in Fig.2. Multivariate analysis confirmed the negative impact of IKZF1 deletions on OS (RR 2.3; 95% CI, 1.3-4.3; P=0.007), DFS (RR 1.8; 95% CI, 1.1-3.0; P=0.029), RFS (RR 2.1; 95% CI, 1.3-3.9; P=0.018) and favorable impact of HSCT on OS (RR 0.2; 95% CI, 1.0-0.5; P=0.000), DFS (RR 0.2; 95% CI, 0.1-0.4; P=0.000), RFS (RR 0.2; 95% CI, 0.1-0.4; P=0.000). These results indicated that IKZF1 status served as an independent negative prognostic marker in adult Com-B ALL and surpassed conventional HR features in the era of TKIs. Patients may benefit from therapy stratified by IKZF1 deletions and conventional HR features. Fig. 1 Fig. 1. Survival curves related to status of IKZF1 in Com-B-ALL cohort. Abbreviation: IKZF1 WT, IKZF1 wide type; IKZF1 DEL, IKZF1 deletion. Fig. 2 Fig. 2. Comparing survival curves of HSCT to chemotherapy in IKZF1-deleted group, wild-type IKZF1 HR group and wild-type IKZF1 non-HR group. Disclosures No relevant conflicts of interest to declare.

scholarly journals B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus- dependent and independent forms of the same hapten

1977 ◽  
Vol 145 (3) ◽  
pp. 778-783 ◽  
Author(s):  
JC Cambier ◽  
ES Vitetta ◽  
JW Uhr ◽  
Kettman JR
Keyword(s):  
B Cells ◽  
B Cell ◽  
Gamma Globulin ◽  
Tolerance Induction ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Adult Mice ◽  
Human Gamma Globulin ◽  
Induction Of Tolerance

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those required to produce the same degree of unresponsiveness in neonates. In contrast to these results, studies with T-independent (TI) antigens indicate that neonatal and adult splenic B cells are equally susceptible to tolerance induction (3,4). However, such studies have not ascertained whether the neonate is more resistant to tolerance induction or the adult is hypersusceptible, i.e., does the induction of tolerance in cells responsive to TI antigens resemble that of adult or neonatal cells responsive to TD antigens? The answer is pertinent to determining the relative maturity of the B cells which can be tolerized or respond to TI or TD antigens. We report here the direct comparison of tolerogen sensitivity of adult and neonatal TD and TI responses by inducing tolerance in vitro with trinitophenyl human gamma globulin (TNP(17)HgG) and assaying unresponsiveness with TD and TI forms of the TNP determinant.

scholarly journals Defective B cell tolerance in adult (NZB X MZW)F1 mice.

1980 ◽  
Vol 152 (3) ◽  
pp. 730-735 ◽  
Author(s):  
E A Goldings ◽  
P L Cohen ◽  
S F McFadden ◽  
M Ziff ◽  
E S Vitetta
Keyword(s):  
B Cells ◽  
Autoimmune Disease ◽  
B Cell ◽  
Gamma Globulin ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Epitope Density ◽  
Human Gamma Globulin ◽  
Specific Tolerance

Hapten-specific tolerance was induced in vitro by trinitrophenyl-human gamma globulin (TNP32HGG) to a comparable degree in B cells from adult autoimmune (NZB X NZW)F1 (B/W) mice and normal BDF1, CBA/J, and DBA/1J mice. When a lower epitope density tolerogen (TNP7HGG) was used, B/W mice were significantly less sensitive than normal mice to the induction of B cell tolerance. This finding of defective B cell tolerance in adult B/W mice is consistent with previous reports that document other B cell abnormalities that may relate to the expression of autoimmune disease.

scholarly journals B-Cell RANKL Contributes to Pathogen-Induced Alveolar Bone Loss in an Experimental Periodontitis Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Rajendra P. Settem ◽  
Kiyonobu Honma ◽  
Sreedevi Chinthamani ◽  
Toshihisa Kawai ◽  
Ashu Sharma
Keyword(s):  
B Cells ◽  
Bone Resorption ◽  
Bone Loss ◽  
Mouse Model ◽  
B Cell ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Conditional Knockout ◽  
Wild Type ◽  
In The Wild

Periodontitis is a bacterially-induced inflammatory disease that leads to tooth loss. It results from the damaging effects of a dysregulated immune response, mediated largely by neutrophils, macrophages, T cells and B cells, on the tooth-supporting tissues including the alveolar bone. Specifically, infiltrating B cells at inflamed gingival sites with an ability to secrete RANKL and inflammatory cytokines are thought to play roles in alveolar bone resorption. However, the direct contribution of B cells in alveolar bone resorption has not been fully appreciated. In this study we sought to define the contribution of RANKL expressing B cells in periodontitis by employing a mouse model of pathogen-induced periodontitis that used conditional knockout mice with B cell-targeted RANKL deletion. Briefly, alveolar bone loss was assessed in the wild-type, B-cell deficient (Jh), or B-cell-RANKL deleted (RANKLΔB) mice orally infected with the periodontal pathogen Tannerella forsythia. The RANKLΔB mice were obtained by crossing Cd19-Cre knock-in mice with mice homozygous for conditional RANKL-flox allele (RANKLflox/flox). The alveolar bone resorption was determined by morphometric analysis and osteoclastic activity of the jaw bone. In addition, the bone resorptive potential of the activated effector B cells was assessed ex vivo. The data showed that the RANKL producing B cells increased significantly in the T. forsythia-infected wild-type mice compared to the sham-infected mice. Moreover, T. forsythia-infection induced higher alveolar bone loss in the wild-type and RANKLflox/flox mice compared to infection either in the B cell deficient (Jh) or the B-cell specific RANKL deletion (RANKLΔB) mice. These data established that the oral-pathogen activated B cells contribute significantly to alveolar bone resorption via RANKL production.

Freeze-substituted fungal cells of Nectria haematococca: A comparison of the macroconidial walls of the adhesion-competent wild type with an adhesion-reduced mutant

1990 ◽  
Vol 48 (3) ◽  
pp. 688-689
Author(s):  
Thecan Caesar-Ton That ◽  
Lynn Epstein
Keyword(s):  
Freeze Substitution ◽  
Uranyl Acetate ◽  
Wild Type ◽  
Nectria Haematococca ◽  
Fruit Extract ◽  
Dialysis Tubing ◽  
Tube Emergence ◽  
Contrast Microscopy ◽  
In The Wild ◽  
Freeze Damage

Nectria haematococca mating population I (anamorph, Fusarium solani) macroconidia attach to its host (squash) and non-host surfaces prior to germ tube emergence. The macroconidia become adhesive after a brief period of protein synthesis. Recently, Hickman et al. (1989) isolated N. haematococca adhesion-reduced mutants. Using freeze substitution, we compared the development of the macroconidial wall in the wild type in comparison to one of the mutants, LEI.Macroconidia were harvested at 1C, washed by centrifugation, resuspended in a dilute zucchini fruit extract and incubated from 0 - 5 h. During the incubation period, wild type macroconidia attached to uncoated dialysis tubing. Mutant macroconidia did not attach and were collected on poly-L-lysine coated dialysis tubing just prior to freezing. Conidia on the tubing were frozen in liquid propane at 191 - 193C, substituted in acetone with 2% OsO4 and 0.05% uranyl acetate, washed with acetone, and flat-embedded in Epon-Araldite. Using phase contrast microscopy at 1000X, cells without freeze damage were selected, remounted, sectioned and post-stained sequentially with 1% Ba(MnO4)2 2% uranyl acetate and Reynold’s lead citrate. At least 30 cells/treatment were examined.

scholarly journals Rad51-Independent Interchromosomal Double-Strand Break Repair by Gene Conversion Requires Rad52 but Not Rad55, Rad57, or Dmc1

2007 ◽  
Vol 28 (3) ◽  
pp. 897-906 ◽  
Author(s):  
Thomas J. Pohl ◽  
Jac A. Nickoloff
Keyword(s):  
Gene Conversion ◽  
Strand Break ◽  
Double Strand Break ◽  
Single Strand ◽  
Homology Search ◽  
Wild Type ◽  
Dsb Repair ◽  
Single Strand Annealing ◽  
In The Wild ◽  
Break Induced Replication

ABSTRACT Homologous recombination (HR) is critical for DNA double-strand break (DSB) repair and genome stabilization. In yeast, HR is catalyzed by the Rad51 strand transferase and its “mediators,” including the Rad52 single-strand DNA-annealing protein, two Rad51 paralogs (Rad55 and Rad57), and Rad54. A Rad51 homolog, Dmc1, is important for meiotic HR. In wild-type cells, most DSB repair results in gene conversion, a conservative HR outcome. Because Rad51 plays a central role in the homology search and strand invasion steps, DSBs either are not repaired or are repaired by nonconservative single-strand annealing or break-induced replication mechanisms in rad51Δ mutants. Although DSB repair by gene conversion in the absence of Rad51 has been reported for ectopic HR events (e.g., inverted repeats or between plasmids), Rad51 has been thought to be essential for DSB repair by conservative interchromosomal (allelic) gene conversion. Here, we demonstrate that DSBs stimulate gene conversion between homologous chromosomes (allelic conversion) by >30-fold in a rad51Δ mutant. We show that Rad51-independent allelic conversion and break-induced replication occur independently of Rad55, Rad57, and Dmc1 but require Rad52. Unlike DSB-induced events, spontaneous allelic conversion was detected in both rad51Δ and rad52Δ mutants, but not in a rad51Δ rad52Δ double mutant. The frequencies of crossovers associated with DSB-induced gene conversion were similar in the wild type and the rad51Δ mutant, but discontinuous conversion tracts were fivefold more frequent and tract lengths were more widely distributed in the rad51Δ mutant, indicating that heteroduplex DNA has an altered structure, or is processed differently, in the absence of Rad51.

scholarly journals Effects of Mutations of RAD50, RAD51, RAD52, and Related Genes on Illegitimate Recombination in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (2) ◽  
pp. 383-391 ◽  
Author(s):  
Yasumasa Tsukamoto ◽  
Jun-ichi Kato ◽  
Hideo Ikeda
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quantitative Analysis ◽  
Structural Analysis ◽  
Recombination Rate ◽  
Type Strain ◽  
Negative Selection ◽  
Wild Type Strain ◽  
Illegitimate Recombination ◽  
Wild Type ◽  
In The Wild

Abstract To examine the mechanism of illegitimate recombination in Saccharomyces cerevisiae, we have developed a plasmid system for quantitative analysis of deletion formation. A can1 cyh2 cell carrying two negative selection markers, the CAN1 and CYH2 genes, on a YCp plasmid is sensitive to canavanine and cycloheximide, but the cell becomes resistant to both drugs when the plasmid has a deletion over the CAN1 and CYH2 genes. Structural analysis of the recombinant plasmids obtained from the resistant cells showed that the plasmids had deletions at various sites of the CAN1-CYH2 region and there were only short regions of homology (1-5 bp) at the recombination junctions. The results indicated that the deletion detected in this system were formed by illegitimate recombination. Study on the effect of several rad mutations showed that the recombination rate was reduced by 30-, 10-, 10-, and 10-fold in the rad52, rad50, mre11, and xrs2 mutants, respectively, while in the rud51, 54, 55, and 57 mutants, the rate was comparable to that in the wild-type strain. The rad52 mutation did not affect length of homology at junction sites of illegitimate recombination.

scholarly journals Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 618
Author(s):  
Yue Jin ◽  
Shihao Li ◽  
Yang Yu ◽  
Chengsong Zhang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Underlying Mechanism ◽  
Biological Processes ◽  
Wild Type ◽  
Expression Levels ◽  
In The Wild ◽  
Cuticle Proteins ◽  
Apolipoprotein D ◽  
High Level ◽  
Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

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